SUPPLEMENTARY INFORMATION - Nature · 2012-07-24 · Compound 21: A 2 L round bottom ﬂask equipped with a stir bar and a septum, previously ﬂame-dried under vacuum, was charged

NATURE CHEMISTRY | www.nature.com/naturechemistry 1

SUPPLEMENTARY INFORMATIONDOI: 10.1038/NCHEM.1385

Guided Desaturation of Unactivated Aliphatics

Ana-Florina Voica, Abraham Mendoza,† Will R. Gutekunst,† Jorge Otero Fraga and Phil S.

Baran*

Contribution from the Department of Chemistry, The Scripps Research Institute,

10550 North Torrey Pines Road, La Jolla, California 92037

SUPPORTING INFORMATION

Part 1: Experimental Procedures and Characterization Data

Table of Contents

.....................................................................................General Experimental page S-3...............................................................................Experimental Procedures page S-4 – S-45

................................................................ Synthesis of the Directing Group page S-4 – S-5 Compound S2 .................................................................................... page S-4 Compound 21..................................................................................... page S-5 ...............................................................................Synthesis of Substrates page S-6 – S-18

.............................................................................. General procedure page S-6 Compound S3..................................................................................... page S-6 Compound S4..................................................................................... page S-7 Compound S5..................................................................................... page S-8 Compound S6..................................................................................... page S-8 Compound S7..................................................................................... page S-9 Compound S8..................................................................................... page S-9 Compound 22..................................................................................... page S-10 Compound S10................................................................................... page S-10 Compound 57 .................................................................................... page S-11 Compound S11 .................................................................................. page S-12 Compound S12 .................................................................................. page S-12 Compound S13................................................................................... page S-13 Compound S14 .................................................................................. page S-14 Compound S15 .................................................................................. page S-14 Compound (–)-S16 ............................................................................ page S-15 Compound 40 .................................................................................... page S-16 Compound 42..................................................................................... page S-17 Compound 45 .................................................................................... page S-18 Compound 47 .................................................................................... page S-19

................................................................................. Synthesis of Products page S-20 – S-36............................................................................ General procedures page S-20

1

© 2012 Macmillan Publishers Limited. All rights reserved.



Compound 26 ................................................................................... page S-21 Compound 27 ................................................................................... page S-22 Compound 28 ................................................................................... page S-22 Compound 29 ................................................................................... page S-23 Compound 30a, b, c.......................................................................... page S-24 Compound 31a, b, c ......................................................................... page S-25 Compound 23 ................................................................................... page S-25 Compound 32a, b ............................................................................. page S-26 Compound 33 ................................................................................... page S-26 Compound 34 ................................................................................... page S-27 Compound 35a, b ............................................................................. page S-28 Compound 36 ................................................................................... page S-29 Compound 37 ................................................................................... page S-29 Compound 38a, b ............................................................................. page S-30 Compound (–)-39 ............................................................................. page S-31 Compound 41a, b ............................................................................. page S-32 Compound 43 ................................................................................... page S-33 Compound 44 ................................................................................... page S-34 Compound 46a ................................................................................. page S-35 Compound 48 ................................................................................... page S-36

................................................................................... Mechanistic Studies page S-37 – S-45 Compound S17 ................................................................................. page S-37 Compound S18 ................................................................................. page S-39 Compound 49 ................................................................................... page S-40 Compound 50a ................................................................................. page S-41 Compound 51 ................................................................................... page S-42 Compound 54 ................................................................................... page S-42 Compound 55 ................................................................................... page S-43 Compound 60 ................................................................................... page S-44Chiral HPLC data for (±)-39 and (–)-39 ....................................................... page S-45MS fragmentation data for 23 and 50 ........................................................... page S-47X-ray crystallography data for 21 ................................................................. page S-48 X-ray crystallography data for 33 ................................................................. page S-54X-ray crystallography data for (–)-39 ........................................................... page S-59 X-ray crystallography data for 41 ................................................................. page S-64 X-ray crystallography data for 43 ................................................................. page S-71 X-ray crystallography data for 44 ................................................................. page S-79

.....................................................................................................References page S-85

2




General procedures. All reactions were carried out under a nitrogen atmosphere with dry

solvents using anhydrous conditions unless otherwise stated. Dry diethyl ether (Et2O),

dichloromethane (CH2Cl2), acetonitrile (CH3CN), methanol (MeOH) and triethylamine (Et3N)

were obtained by passing these previously degassed solvents through activated alumina columns.

Dry nitromethane (CH3NO2) was obtained by distillation from CaH2 and stored under Ar over

4Å MS. Reagents were purchased at the highest commercial quality and used without further

purification, unless otherwise stated. Yields refer to chromatographically and spectroscopically

(1H NMR) homogeneous materials, unless otherwise stated. Reactions were monitored by thin

layer chromatography (TLC) carried out on 0.25 mm E. Merck silica gel plates (60F-254) using

UV light as the visualizing agent and an acidic mixture of anisaldehyde, phosphomolybdic acid,

or ceric ammonium molybdate, or basic aqueous potassium permangante (KMnO4), and heat as

developing agents. E. Merck silica gel (60, particle size 0.043–0.063 mm) was used for flash

column chromatography. Preparative thin layer chromatography (pTLC) separations were

carried out on 0.25 or 0.5 mm E. Merck silica gel plates (60F-254). NMR spectra were recorded

on Bruker DRX-600, DRX-500, and AMX-400 or Varian Inova-400 instruments and calibrated

using residual undeuterated solvent as an internal reference (CHCl3 @ 7.26 ppm 1H NMR, 77.16

ppm 13C NMR; DMSO-d6 @ 2.50, 3.30 ppm 1H NMR, 39.51 ppm 13C NMR). The following

abbreviations (or combinations thereof) were used to explain the multiplicities: s = singlet, d =

doublet, t = triplet, q = quartet, m = multiplet, b = broad. On inseparable mixtures, partial

assigment is provided in the NMR spectra supporting information file. High-resolution mass

spectra (HRMS) were recorded on Agilent LC/MSD TOF time-of-flight mass spectrometer by

electrospray ionization time of flight reflectron experiments. IR spectra were recorded on a

Perkin Elmer Spectrum BX FTIR spectrometer. Melting points were recorded on a Fisher-Johns

3




12-144 melting point apparatus and are uncorrected.

Experimental

Compound S21: A 250 mL round bottom flask equipped with a stir bar was charged with 5-

methyl-2-bromoaniline S1 (15 g, 80.620 mmol, 1 equiv) which was suspended in conc. HCl (81

ml) to obtain a white slurry. This mixture was cooled at 0 °C before a solution of NaNO2 (8.34 g,

120.930 mmol, 1.5 equiv) in H2O (10.4 mL) was added dropwise (Caution! Toxic gases form

during this addition). The resulting yellow solution was stirred at 0 °C for 10 min after which a

solution of diethylamine (6.5 g, 88.680 mmol, 1.1 equiv) in 1 M KOH (68.2 mL) was poured

into the reaction flask. The reaction was allowed to proceed at 0 °C for 1h before it was

quenched with 3 M NaOH (or KOH) until the pH reached 12. The product was extracted with

EtOAc (3 x 75 mL). The combined organic layers were then washed with brine, dried over

MgSO4, filtered and concentrated in vacuo. The desired product S2 (19.68 g, 91% yield) was

isolated after rapid chromatography (silica gel, 49:1 hexanes/EtOAc) as a brown oil.

Physical state: brown oil;

Rf = 0.72 (4:1 hexanes/EtOAc);

HRMS (m/z): calcd for C11H16BrN3H+, [M+H]+, 270.0600; found, 270.0606;

IR (film) νmax = 2973, 2933, 1465, 1409, 1385, 1341, 1249, 1105, 1032, 802;

1H NMR (600 MHz, CDCl3) δ 7.43 (d, J = 8.1 Hz, 1 H), 7.19 (s, 1 H), 6.80 (d, J = 7.9 Hz, 1 H),

3.79 (q, J = 7.0 Hz, 4 H), 2.30 (s, 3 H), 1.31 (s, 6 H);

13C NMR (151 MHz, CDCl3) δ 148.3, 137.8, 132.7, 127.1, 119.2, 116.6, 49.2, 41.9, 21.2, 14.6, 11.0.

4

BrNH2

Me

NaNO2 (1.5 equiv), conc HCl, 0 °C, 10 min

then Et2NH (1.1 equiv), aq. KOH (1M),0 °C, 30 min

94%

BrN

Me

NNEt2

S1 S2




Compound 21: A 2 L round bottom flask equipped with a stir bar and a septum, previously

flame-dried under vacuum, was charged with S2 (31.4 g, 116.66 mmol, 1 equiv), azeotroped

from benzene (100 mL) and kept under Ar. After addition of Et2O (1 L), the solution was cooled

at –78 ˚C and sec-BuLi (1.4 M in cyclohexane, 140.000 mmol, 100 mL, 1.2 equiv) was added

dropwise to give a red solution which was stirred for 30 min at the same temperature. After this

time, SO2(g) was condensed via cannula into the reaction flask until the mixture became a pale

yellow suspension (and the color is persistent; 5–10 min). The resulting mixture was stirred for 1

h at –78 ˚C, then at room temperature for 5 h before the solvent was removed in vacuo to give a

pale brown solid which was maintained under an atmosphere of Ar. The resulting solid (aryl

sulfonate lithium salt) was dissolved in CH2Cl2 (1 L) and the solution was cooled at 0 ˚C before

NCS (18.7 g, 140.000 mmol, 1.2 equiv) was added in one portion. The brown mixture was

stirred at 0 ˚C for 10h/overnight before being quenched with a saturated solution of NH4Cl (200

mL). The aqueous layer was extracted with EtOAc (3 x 200 mL) and the resulting organic

solution was washed with brine (500 mL), dried over MgSO4 and concentrated in vacuo. Thus

TzoCl 21 (23.26 g) was isolated after column chromatography (silica gel, 9:1 hexane/EtOAc)

(69% yield).

Physical state: orange solid;


m.p. = 74–76 ºC;

5

BrN

Me

NNEt2

SO2ClN

Me

NNEt2

1. secBuLi (1.2 equiv), Et2O-78 °C, 30 minthen SO2(g),

-78 °C, 1h to rt, 4h

2. NCS (1.2 equiv), DCM0 °C, 4h

69 %S2 21




HRMS (m/z): calcd for C11H16ClN3O2SH+ [M+H]+, 290.0724; found, 290.0727;

IR (film) νmax = 2976, 2936, 1589, 1566, 1464, 1387, 1340, 1325, 1269, 1168, 1111;


3.94 – 3.83 (m, 4 H), 2.42 (s, 3 H), 1.39 (t, J = 7.2 Hz, 3 H), 1.30 (t, J = 7.1 Hz, 3 H);

13C NMR (151 MHz, CDCl3) δ 148.8, 147.1, 134.1, 128.9, 124.8, 118.4, 49.8, 43.0, 22.0, 14.6,

11.5.

General procedure for the synthesis of alkyl triazine tosylates/tosylamines

A 5 mL vial equipped with a stir bar, previously flame-dried under vacuum and cooled under an

atmosphere of Ar, was charged with the alcohol/amine (1 equiv) and TzoCl 21 (1.25 equiv) which

were then dissolved in CH2Cl2 (0.5 M). To this mixture DMAP (2 equiv) was added2 and the

reaction was allowed to proceed at room temperature under Ar for 16–24 h (TLC control). The

resulting suspension was diluted with EtOAc (3 mL) and washed with H2O (2 mL). The layers

were then partitioned and the aqueous solution was further extracted with EtOAc (3 x 3 mL). The

combined organic layers were dried over MgSO4, filtrated and concentrated in vacuo. The

product was purified by flash chromatography (silica gel, hexanes/EtOAc).

Compound S3: Synthesized from 2,6-dimethyl-heptan-4-ol (0.400 mmol)

following the general procedure. After purification on silica gel (10:1

hexanes/EtOAc), the product was obtained in 92% yield (143.3 mg).

Physical state: yellow oil;

6

Me

Me O

Me

S

Me

NNNEt2

OO

Me

R XH +

SO2Cl

Me

NN

NEt2DMAP (2 equiv),

DCM (0.5M), rt, 16-24h

SO2

Me

NN

NEt2

XR

X = O, N 1.25 equiv

21





HRMS (m/z): calcd for C20H35N3O3SH+ [M+H]+, 398.2472; found, 398.2480;

IR (film) νmax = 2957, 2870, 1593, 1466, 1388, 1350, 1327, 1270, 1174, 1109, 922, 890;


4.65 – 4.58 (m, 1 H), 3.83 (q, J = 7.1 Hz, 4 H), 2.39 (s, 3 H), 1.65 – 1.51 (m, 4 H), 1.39 – 1.21

(m, 8 H), 0.83 – 0.70 (m, 12 H);

13C NMR (151 MHz, CDCl3) δ 149.2, 144.8, 130.1, 128.0, 125.0, 118.3, 81.3, 49.4, 44.1, 42.4,

24.3, 22.8, 22.4, 21.8, 14.7, 11.5.

Compound S4: Synthesized from 5-methyl-1-phenylhexan-3-ol (0.330

mmol) following the general procedure. After purification on silica gel

(10:1 hexanes/EtOAc), the product was obtained in 85% yield (124.8 mg).




IR (film) νmax = 2956, 2935, 2870, 1593, 1454, 1388, 1351, 1328, 1270, 1174, 1109, 889;

1H NMR (600 MHz, CDCl3) δ 7.84 (d, J = 8.1 Hz, 1 H), 7.38 (s, 1 H), 7.22 (t, J = 7.4 Hz, 2 H),

7.15 (t, J = 7.2 Hz, 1 H), 7.00 – 6.96 (m, 3 H), 4.65 (t, J = 6 Hz, 1 H), 3.86 – 3.79 (m, 4 H), 2.62

– 2.49 (m, 2 H), 2.39 (s, 3 H), 1.90 –1.80 (m, 2 H), 1.68 – 1.58 (m, 2 H), 1.41 – 1.31 (m, 4 H),

1.28 (t, J = 6.6 Hz, 3 H), 0.78 (dd, J = 11.9, 6.1 Hz, 6 H);

13C NMR (151 MHz, CDCl3) δ 149.2, 144.9, 141.6, 130.2, 128.4, 128.4, 127.9, 126.0, 125.1,

118.4, 81.9, 49.4, 43.3, 42.4, 36.4, 30.7, 24.4, 22.8, 22.4, 21.8, 14.6, 11.5.

7

Me

Me O

Ph

S

Me

NNNEt2

OO




Compound S5: Synthesized from 5-methyl-1-phenylhexan-3-ol (0.300

mmol) following the general procedure. After purification on silica gel

(10:1 hexanes/EtOAc), the product was obtained in 86% yield (109.4 mg).




IR (film) νmax = 2955, 2870, 1594, 1466, 1388, 1351, 1270, 1175, 1109, 888;


4.64 – 4.57 (m, 1 H), 3.82 (q, J = 7.0 Hz, 4 H), 2.38 (s, 3 H), 1.66 – 1.48 (m, 3 H), 1.41 – 1.23

(m, 9 H), 1.24 – 1.11 (m, 2 H), 0.98 (dd, J = 14.8, 7.3 Hz, 2 H), 0.82 – 0.73 (m, 12 H);

13C NMR (151 MHz, CDCl3) δ 149.1, 144.7, 130.1, 128.1, 125.0, 118.3, 82.7, 49.4, 43.4, 42.4,

38.8, 34.9, 27.9, 24.3, 22.9, 22.6, 22.6, 22.3, 22.2, 21.8, 14.7, 11.5.

Compound S6: Synthesized from 2-methylnon-8-en-4-ol (0.300 mmol)






IR (film) νmax = 2956, 2934, 2870, 1593, 1465, 1388, 1349, 1327, 1270, 1256, 1173, 1108, 992;


5.66 (dq, J = 12.2, 6.8 Hz, 1 H), 4.94 – 4.85 (m, 2 H), 4.65 – 4.57 (m, 1 H), 3.88 – 3.76 (m, 4 H),

2.39 (s, 3 H), 1.90 (q, J = 7.0 Hz, 2 H), 1.63 – 1.52 (m, 3 H), 1.40 – 1.22 (m, 9 H), 0.96 – 0.82

(m, 1 H), 0.76 (dd, J = 18.5, 6.1 Hz, 6 H);

8

Me

Me OS

Me

NNNEt2

OO

Me

Me OS

Me

NNNEt2

MeMe

OO




13C NMR (151 MHz, CDCl3) δ 149.2, 144.8, 138.4, 130.1, 128.0, 125.0, 118.4, 114.8, 82.3,

49.4, 43.3, 42.4, 34.0, 33.5, 24.3, 23.6, 22.9, 22.3, 21.8, 14.7, 11.5.

Compound S7: Synthesized from 3,7-dimethyl-octan-1-ol (0.410

mmol) following the general procedure. After purification on

silica gel (10:1 hexanes/EtOAc), the product was obtained in 93%

yield (158.1 mg).

Physical state: orange oil;


HRMS (m/z): calcd for C21H37N3O3SH+[M+H]+, 412.2628; found, 412.2612;

IR (film) νmax = 2954, 2927, 1466, 1389, 1353, 1176;

1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.1 Hz, 1 H), 7.37 (s, 1 H), 6.99 (d, J = 7.9 Hz, 1

H), 4.10 – 4.02 (m, 2 H), 3.83 (q, J = 7.2 Hz, 4 H), 2.39 (s, 3 H), 1.70 – 1.59 (m, 1 H), 1.53 –

1.32 (m, 6 H), 1.28 (t, J = 7.1 Hz, 3 H), 1.24 – 0.98 (m, 6 H), 0.84 (d, J = 6.6 Hz, 6 H), 0.78 (d, J

= 6.6 Hz, 3 H);

13C NMR (151 MHz, CDCl3) δ 149.3, 145.1, 130.7, 126.2, 125.2, 118.4, 68.8, 49.4, 42.4, 39.3,

37.0, 36.0, 29.3, 28.0, 24.6, 22.8, 22.7, 21.8, 19.3, 14.6, 11.5.

Compound S8: Synthesized from 3-ethylpentanol (0.250 mmol)






IR (film) νmax = 2963, 2934, 1465, 1389, 1351, 1174, 1110, 966, 810, 671;

9

Me

Me Me

OS

NNNEt2

Me

OO

OS

Me

NNNEt2

Me

Me

OO





4.05 (t, J = 6.5 Hz, 2 H), 3.83 (q, J = 6.7 Hz, 4 H), 2.39 (s, 3 H), 1.60 – 1.53 (m, 2 H), 1.36 (t, J =

7.2, 3 H), 1.31 – 1.25 (m, 4 H), 1.18 – 1.04 (m, 4 H), 0.79 (t, J = 7.2 Hz, 6 H);

13C NMR (151 MHz, CDCl3) δ 149.3, 145.2, 130.6, 126.2, 125.1, 118.3, 68.9, 49.4, 42.4, 36.5,

32.0, 25.0, 21.8, 14.6, 11.4, 10.6.

Compound 22: Synthesized from 2-cyclopentylethanol (0.500 mmol)






IR (film) νmax = 2940, 2868, 1593, 1388, 1349, 1327, 1173, 1109, 967, 930, 671;


4.02 (t, J = 6.7 Hz, 2 H), 3.86 – 3.78 (m, 4 H), 2.39 (s, 3 H), 1.88 – 1.74 (m, 1 H), 1.70 – 1.60

(m, 4 H), 1.59 – 1.50 (m, 2 H), 1.49 – 1.40 (m, 2 H), 1.35 (t, J = 7.2 Hz, 3 H), 1.27 (t, J = 7.1 Hz,

3 H), 1.04 – 0.94 (m, 2 H);

13C NMR (151 MHz, CDCl3) δ 149.3, 145.2, 130.7, 125.9, 125.1, 118.3, 69.9, 49.4, 42.4, 36.2,

35.0, 32.4, 25.0, 21.8, 14.6, 11.4.

Compound S10: Synthesized from 2-cyclohexylethanol (0.500 mmol)





10

OS

Me

NNNEt2

OO

OS

Me

NNNEt2

OO





IR (film) νmax =2922, 2850, 1593, 1448, 1388, 1349, 1172, 1108, 961, 907, 671;


4.05 (t, J = 6.5 Hz, 2 H), 3.83 (q, J = 6.7 Hz, 4 H), 2.39 (s, 3 H), 1.62 (d, J = 10.9 Hz, 3 H), 1.55

(d, J = 14.2 Hz, 3 H), 1.48 (q, J = 6.5 Hz, 2 H), 1.40 – 1.24 (m, 6 H), 1.18 – 1.04 (m, 3 H), 0.79

(q, J = 11.7 Hz, 2 H);

13C NMR (151 MHz, CDCl3) δ 149.3, 145.1, 130.7, 126.1, 125.1, 118.3, 68.4, 49.4, 42.4, 36.3,

33.7, 32.9, 26.5, 26.2, 21.8, 14.6, 11.4.

Compound 57: Synthesized from (1R, 2S, 5R)-(–)-menthol (0.400 mmol)


hexanes/EtOAc), 57 was obtained in 99% yield (162.0 mg).

Physical state: thick yellow oil;


[α]D = –108.8 º (c = 0.50, CH2Cl2);


IR (film) νmax = 2955, 2931, 2870, 1593, 1388, 1351, 1174, 943, 913, 867, 674;


4.35 (td, J = 10.8, 4.5 Hz, 1 H), 3.86 – 3.67 (m, 4 H), 2.38 (s, 3 H), 2.19 (d, J = 12.2 Hz, 1 H),

2.04 – 1.96 (m, 1 H), 1.60 (d, J = 14.6 Hz, 2 H), 1.40 – 1.22 (m, 8 H), 1.18 – 1.09 (m, 1 H), 0.98

– 0.87 (m, 1 H), 0.85 (d, J = 6.5 Hz, 3 H), 0.83 – 0.74 (m, 4 H), 0.42 – 0.34 (d, J = 6.5 Hz, 3 H);

13C NMR (151 MHz, CDCl3) δ 149.2, 144.8, 130.0, 127.9, 125.1, 118.3, 83.4, 49.4, 47.8, 42.3,

42.0, 33.9, 31.7, 25.1, 22.9, 22.0, 21.8, 21.0, 15.1, 14.7, 11.5.

11

Me

Me Me

OS

NN

Me

NEt2

OO




Compound S11: Synthesized from menthylamine3 (0.230 mmol) following

the general procedure. After purification on silica gel (10:1 hexanes/

EtOAc), the product was obtained in 74% yield (69.5 mg).

Physical state: pale yellow solid;



IR (film) νmax = 2953, 2927, 1455, 1393, 1337, 1269, 1165;


5.24 (d, J = 8.5 Hz, 1 H), 3.89 – 3.77 (m, 3 H), 3.76 – 3.68 (m, 1 H), 3.22 – 3.14 (m, 1 H), 2.38

(s, 3 H), 2.30 – 2.19 (m, 1 H), 1.76 (d, J = 12.6 Hz, 1 H), 1.61 (d, J = 10.0 Hz, 2 H), 1.41 – 1.22

(m, 8 H), 1.04 – 0.91 (m, 2 H), 0.85 (d, J = 7.0 Hz, 3 H), 0.77 – 0.61 (m, 7 H);

13C NMR (151 MHz, CDCl3) δ 147.2, 143.4, 132.3, 127.7, 125.5, 118.2, 55.4, 49.9, 48.9, 43.4,

42.2, 34.4, 31.9, 25.9, 23.8, 22.2, 21.8, 21.3, 15.4, 14.6, 11.5.

Compound S12: In a 5 mL vial equipped with a stir bar, the 2,7-dimethyl-4-

amino-heptane (107 mg, 0.750 mmol, 1.4 equiv) was added and dissolved in

CH2Cl2 (2 mL). To this mixture a solution of saturated NaHCO3 (2 mL) was

added followed by 21 (155 mg, 0.535 mmol, 1 equiv). The resulting biphasic

mixture was then stirred vigorously at room temperature for 45 min. Upon completion (TLC

control), the organic layer was separated, washed with brine (2 mL), dried over MgSO4, filtered

and concentrated in vacuo. After purification on silica gel (20:1 hexanes/EtOAc), the product

was obtained in 94% yield (199.5 mg).

Physical state: white solid;


12

Me

Me Me

NHS

NN

Me

NEt2

OO

Me

Me HN

Me

S

Me

NNNEt2

OO

Me




m.p. = 64–66 ºC;


IR (film) νmax = 2956, 2869, 1594, 1467, 1393, 1329, 1270, 1166, 1138, 1112, 1061;


5.14 (d, J = 8.0 Hz, 1 H), 3.89 – 3.80 (m, 2 H), 3.80 – 3.73 (m, 2 H), 3.37 (sextet, J = 6.6 Hz, 1

H), 2.38 (s, 3 H), 1.60 (heptet, J = 6.7 Hz, 2 H), 1.37 (t, J = 12.5 Hz, 3 H), 1.28 (t, J = 13.5 Hz, 3

H), 1.19 – 1.14 (m, 4 H), 0.74 (m, 12 H);

13C NMR (151 MHz, CDCl3) δ 147.3, 143.5, 131.8, 128.1, 125.4, 118.2, 51.5, 49.9, 45.6, 42.1,

24.6, 22.8, 22.4, 21.7, 14.6, 11.4.

Compound S13: Synthesized from L-leucine methyl ester

hydrochloride (0.250 mmol) following the general procedure (4 equiv

of DMAP were used). After purification on silica gel (4:1 hexanes/




[α]D = +344.7 º (c = 0.34, CH2Cl2);

m.p. = 55–57 ºC;


IR (film) νmax = 3272, 2957, 1742, 1593, 1467, 1393, 1339, 1270, 1167, 1139, 1112;


6.18 (d, J = 9.1 Hz, 1 H), 4.04 (q, J = 7.8 Hz, 1 H), 3.93 – 3.83 (m, 3 H), 3.77 (td, J = 14.1, 7.1

Hz, 1 H), 3.32 (s, 3 H), 2.37 (s, 3 H), 1.82 – 1.73 (m, 1 H), 1.55 – 1.47 (m, 2 H), 1.37 (dt, J =

16.7, 7.2 Hz, 6 H), 0.89 (dd, J = 6.4, 4.0 Hz, 6 H);

13

Me

CO2Me

HN SO2 N

Me

NNEt2

Me




13C NMR (151 MHz, CDCl3) δ 172.5, 147.6, 144.0, 129.5, 128.3, 125.1, 117.9, 55.0, 52.0, 49.9,

42.7, 42.3, 24.4, 22.6, 22.0, 21.8, 14.6, 11.3.

Compound S14: Synthesized from D-leucine tert-butyl ester

hydrochloride (0.223 mmol) following the general procedure (4 equiv of

DMAP were used). After purification on silica gel (10:1 hexanes/




[α]D = -383.1 º (c = 0.13, CH2Cl2);

m.p. = 78–80 ºC;


IR (film) νmax = 2959, 1731, 1393, 1340, 1167, 1137;


6.15 (d, J = 9.3 Hz, 1 H), 3.93 (dd, J = 15.3, 8.7 Hz, 1 H), 3.90 – 3.76 (m, 4 H), 2.36 (s, 3 H),

1.85 – 1.75 (m, 1 H), 1.50 – 1.41 (m, 2 H), 1.37 (dd, J = 16.7, 7.3 Hz, 6 H), 1.14 (s, 9 H), 0.92

(dd, J = 6.6, 2.9 Hz, 6 H);

13C NMR (151 MHz, CDCl3) δ 171.5, 147.8, 143.9, 130.2, 128.3, 125.1, 118.0, 81.6, 55.7, 49.8,

43.3, 42.4, 27.6, 24.5, 22.7, 22.1, 21.7, 14.6, 11.4.

Compound S15: Synthesized from L-valine methyl ester hydrochloride

(0.500 mmol) following the general procedure (4 equiv of DMAP were

used). After purification on silica gel (10:1 hexanes/EtOAc), the product

was obtained in 99% yield (190.5 mg).


14

HN S N

Me

NNEt2

OOOMe

O

Me

Me

Me HN S N

Me

NNEt2

MeO

OO

O Me

Me Me





[α]D = +440.0 º (c = 0.49, CH2Cl2);

m.p. = 89–91 ºC;


IR (film) νmax = 2969, 1741, 1467, 1393, 1340, 1269, 1167;


6.27 (d, J = 9.2 Hz, 1 H), 3.95 – 3.82 (m, 4 H), 3.81 – 3.74 (m, 1 H), 3.33 (s, 3 H), 2.37 (s, 3 H),

2.04 – 1.97 (m, 1 H), 1.37 (dt, J = 11.1, 7.2 Hz, 6 H), 0.94 (t, J = 7.8 Hz, 6 H);

13C NMR (151 MHz, CDCl3) δ 171.7, 147.6, 144.0, 129.7, 128.2, 125.1, 117.9, 61.7, 51.8, 49.9,

42.3, 32.0, 21.8, 18.8, 18.0, 14.6, 11.4.

Compound (–)-S16: Synthesized from commercially available (R)-(–)-1-

cyclohexylethylamine (94% ee) (0.480 mmol) following the general

procedure. After purification on silica gel (10:1 hexanes/EtOAc), the

product was obtained in 99% yield (180.8 mg).



[α]D = –194 º (c = 0.42, CH2Cl2);

m.p. = 77–79 ºC;


IR (film) νmax = 2925, 2852, 1593, 1450, 1391, 1328, 1269, 1165, 1111, 684;


5.31 (d, J = 7.9 Hz, 1 H), 3.88 – 3.78 (m, 3 H), 3.73 – 3.66 (m, 1 H), 3.23 (dq, J = 13.9, 6.8 Hz, 1

H), 2.38 (s, 3 H), 1.70 (d, J = 10.3 Hz, 3 H), 1.66 – 1.57 (m, 2 H), 1.37 (t, J = 7.2 Hz, 3 H), 1.34

15

Me

HNS

Me

NNNEt2

OO




– 1.28 (m, 4 H), 1.18 – 1.01 (m, 4 H), 0.98 – 0.88 (m, 1 H), 0.85 (d, J = 6.8 Hz, 3 H);

13C NMR (151 MHz, CDCl3) δ 147.3, 143.6, 131.1, 128.3, 125.5, 118.3, 54.8, 49.9, 43.8, 42.2,

28.8, 28.2, 26.5, 26.3, 26.2, 21.8, 17.2, 14.6, 11.4.

Compound 40: Synthesized from dihydrojunenol4 following a modified

procedure: In a 5 mL microwave vial, equipped with a stir bar and previously

flame dried under vacuum and cooled under an atmosphere of Ar,

dihydrojunenol (28.7 mg, 0.128 mmol, 1 equiv) and 21 (148.0 mg, 0.592

mmol, 4 equiv) were dissolved in CH2Cl2 (0.25 mL). To this mixture DMAP (94.0 mg, 0.768

mmol, 6 equiv) was added and the reaction was allowed to proceed at room temperature under

Ar for 4 days. In order to drive the reaction to completion, more triazine tosyl chloride 21 (75.0

mg, 0.256 mmol, 2 equiv) and DMAP (50.0 mg, 0.384 mmol, 3 equiv) were added and the

mixture was stirred at room temperature for another 3 days (TLC control). The resulting

suspension was diluted with EtOAc (2 mL) and washed with H2O (2 mL). The layers were then

partitioned and the aqueous solution was further extracted with EtOAc (3 x 3 mL). The organic

mixture was dried over MgSO4, filtrated and concentrated in vacuo. After purification on silica

gel (10:1 hexanes/EtOAc), the product was isolated in 65% yield (39.7 mg).

An alternative method for the synthesis of 40 is the following: To a solution of dihydrojunenol

(10 mg, 0.044 mmol, 1 equiv) in dry THF (0.25 mL) cooled at 0 ºC, a solution of nBuLi (2.4 M,

23 mL, 1.2 equiv) was added dropwise. The resulting mixture was stirred at 0 ºC for 20 mins

before a solution of TzoCl 21 (19.4 mg, 0.066 mmol, 1.5 equiv) in THF (50 µL) was added and

as a result the reaction mixture turned dark red. The reaction proceeded overnight at 4 ºC before

being quenched with saturated NH4Cl (2 mL) and extracted with EtOAc (3 x 3 mL). The organic

solution was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a

16

MeMe Me

MeOS

MeN

OO

N NEt2




crude mixture. The product 40 was isolated by pTLC (silica gel, 8:6:1 toluene/hexanes/Et2O) in

66% yield (14.1 mg).

Physical state: thick orange oil;


[α]D = +37.8 º (c = 0.23, CH2Cl2);


IR (film) νmax = 2926, 2850, 1593, 1465, 1388, 1343, 1172, 1109, 901;


4.92 (t, J = 10.6 Hz, 1 H), 3.88 – 3.79 (m, 3 H), 3.78 – 3.70 (m, 1 H), 2.37 (s, 3 H), 2.09 – 1.99

(m, 1 H), 1.91 (s, 1 H), 1.59 (q, J = 13.8 Hz, 1 H), 1.49 (bd, J = 13.8 Hz, 1 H), 1.46 –1.30 (m, 8

H), 1.30 – 1.20 (m, 6 H), 1.04 (bq, J = 13.9 Hz, 2 H), 0.87 (bs, 6 H), 0.79 (s, 3 H), 0.78 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 148.4, 144.1, 129.8, 128.6, 124.7, 117.7, 86.1, 52.7, 50.7, 49.5,

43.8, 42.6, 42.2, 36.2, 33.3, 27.3, 26.1, 21.8, 21.5, 20.7, 18.7, 17.1, 15.7, 14.8, 14.7, 11.5.

Compound 42: Synthesized from (+)-dehydroabietylamine acetate (0.300

mmol) following the general procedure. After purification on silica gel (4:1




[α]D = –3.8 º (c = 0.44, CH2Cl2);

m.p. = 68–70 ºC;

HRMS (m/z): calcd for C31H46N4O2SH+ [M+H]+, 539. 3414; found, 539.3411;

IR (film) νmax = 2958, 1593, 1456, 1391, 1331, 1269, 1163, 1141, 1112, 1063, 821;


17

Me

MeMe

Me

HN SOO

Me

NNNEt2




7.02 (d, J = 7.9 Hz, 1 H), 6.96 (d, J = 8.1 Hz, 1 H), 6.85 (s, 1 H), 5.49 (t, J = 7.3 Hz, 1 H), 3.86 –

3.78 (m, 2 H), 3.77 – 3.68 (m, 1 H), 3.67 – 3.57 (m, 1 H), 2.86 – 2.77 (m, 3 H), 2.71 (dd, J =

12.5, 7.2 Hz, 1 H), 2.57 (dd, J = 12.5, 7.7 Hz, 1 H), 2.39 (s, 3 H), 2.27 (d, J = 12.6 Hz, 1 H), 1.77

– 1.68 (m, 2 H), 1.68 – 1.54 (m, 3 H), 1.41 – 1.27 (m, 6 H), 1.28 – 1.16 (m, 12 H), 0.91 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 147.4, 147.2, 145.7, 143.9, 134.9, 129.4, 129.1, 126.9, 125.6,

124.1, 123.8, 118.4, 54.2, 49.8, 44.9, 42.2, 38.4, 37.4, 37.0, 36.1, 33.6, 29.8, 25.2, 24.2, 24.1,

21.8, 18.8, 18.7, 18.7, 14.6, 11.3.

Compound 45: Synthesized from the corresponding diol5 (0.057 mmol) following the general

procedure. After purification on silica gel (gradient from 4:1 to 2:1




[α]D = +71.1 º (c = 0.09, CH2Cl2);

m.p. = 74–76 ºC;


IR (film) νmax = 2928, 1464, 1347, 1173, 907, 729;


5.09 (t, J = 3.4 Hz, 1 H), 3.93 (d, J = 9.4 Hz, 1 H), 3.85 – 3.79 (m, 5 H), 3.21 (dd, J = 11.4, 4.4

Hz, 1 H), 2.39 (s, 3 H), 1.97 – 1.87 (m, 1 H), 1.87 – 1.77 (m, 2 H), 1.77 – 1.67 (m, 2 H), 1.64 –

1.44 (m, 8 H), 1.43 – 1.24 (m, 11 H), 1.23 – 1.17 (m, 2 H), 1.13 – 1.06 (m, 4 H), 0.98 (s, 3 H),

0.96 – 0.90 (m, 7 H), 0.85 (s, 3 H), 0.82 – 0.79 (m, 1 H), 0.78 (s, 3 H), 0.72 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 149.5, 145.2, 144.0, 130.7, 126.0, 125.1, 122.8, 118.7, 79.1,

74.1, 55.3, 49.3, 47.7, 46.5, 42.3, 41.9, 41.7, 39.9, 38.9, 38.7, 37.0, 36.3, 34.7, 32.7, 32.3, 29.5,

18

Me MeHO

Me Me

Me

H

Me

O MeSO

OMe

NNNEt2




28.2, 28.1, 27.7, 27.3, 27.2, 26.1, 23.6, 21.8, 18.4, 16.8, 15.7, 15.6, 14.6, 11.6.

Compound 47: The tetrapeptide was prepared with an automated peptide synthesizer using

standard procedures. The product was purified by preparative HPLC separation over a

Phenomenex Jupiter Proteo 90A column (250 x 21.1 mm) using an

elution gradient water/acetonitrile/TFA 91.5:9.4:0.1 → 55:44.9:0.1 over

30 min (retention time for product is 26.3 min) at a flow rate of 10 mL/

min. Next, 47 is prepared according to the following procedure: the

parent tetrapeptide (17.9 mg, 0.040 mmol, 1 equiv) and TzoCl 21 (17.3

mg, 0.060 mmol, 1.5 equiv) were dissolved in 1:1 CH2Cl2/10% aq

K2CO3 (5 mL) and the resulting heterogeneous solution was stirred at room temperature for two

days (monitored by LC-MS). After completion, the crude mixture was extracted with CH2Cl2 (5

x 2 mL) and the resulting organic solution was dried over Na2SO4, filtered and concentrated in

vacuo. The product was isolated in 75% yield (21.0 mg) after chromatography (silica gel, 20:1

CH2Cl2/MeOH).


Rf = 0.48 (10:1 CH2Cl2/MeOH);

[α]D = –95.9 º (c = 1.0, CHCl3);

m.p. = 185 ºC (decomposition);


IR (film) νmax = 2920, 2851, 1727, 1633, 1463, 1379, 1270, 1121, 1072, 698;

1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 6.9 Hz, 1 H), 7.48 (bs, 1 H), 7.39 (bd, J = 4.8 Hz, 1

H), 7.28 (s, 1 H), 7.18 – 6.97 (m, 6 H), 6.04 (bs, 1 H), 5.37 (bs, 1 H), 4.73 (ddd, J = 12.1, 8.4, 3.5

Hz, 1 H), 4.15 (qd, J = 7.4, 4.3 Hz, 1 H), 4.01 (t, J = 4.8 Hz, 1 H), 3.95 – 3.70 (m, 5 H), 3.62 –

19

HNO

HN Me

HN

Me

Me

O

O

Me

Me

HN

Ph

O

H2N

SOO MeNN

Et2N




3.53 (m, 2 H), 2.87 (dd, J = 14.3, 12.3 Hz, 1 H), 2.48 (s, 3 H), 2.14 – 2.06 (m, 1 H), 1.67 (ddd, J

= 14.8, 10.8, 3.7 Hz, 1 H), 1.53 (d, J = 7.4 Hz, 3 H), 1.52 – 1.23 (m, 9 H), 0.81 (d, J = 6.4 Hz, 3

H), 0.75 (d, J = 6.9 Hz, 3 H), 0.63 (d, J = 6.9 Hz, 3 H), 0.49 (d, J = 6.4 Hz, 3 H);

13C NMR (100 MHz, CDCl3) δ 174.3, 174.0, 173.8, 171.0, 148.0, 145.7, 138.5, 129.1, 128.9,

128.1, 126.5, 126.1, 125.4, 118.8, 61.0, 56.7, 54.7, 51.7, 50.1, 42.2, 41.3, 36.7, 28.7, 24.5, 22.9,

21.9, 20.3, 18.5, 17.3, 17.1, 14.4, 11.3.

General procedures for desaturation

General procedure A: A 20 mL vial adapted with a septum and a stir bar was flame dried under

vacuum and kept under an Ar atmosphere. The vial was charged with the SM (0.1 mmol, 1

equiv) and TEMPO (0.1 mmol, 1 equiv) which were dissolved in previously degassed CH3NO2

(4 mL) to give a pale brown solution. To this mixture TFA (0.3 mmol, 3 equiv) was added in one

portion and as a result the reaction mixture turned light yellow. The vial was then placed in a

preheated oil bath at 60 ºC and the reaction was allowed to proceed for 1.5h. Upon completion

the solvent was removed in vacuo and the resulting crude mixture was dissolved with EtOAc (3

mL) and washed with 1 N HCl (2 mL). After they layers were partitioned, the aqueous solution

was further extracted with EtOAc (3 x 3 mL) and the combined organic solution was dried over

MgSO4, filtered and concentrated in vacuo. The pure product was isolated after flash

chromatography (silica gel, hexanes/EtOAc).

20

XSO2

MeNN

Et2N

X = NH, O

TFA (3 equiv), 60 °C, 1.5 h-or-

TfOH (2 equiv), RT, 3 h

TEMPO (1 equiv)CH3NO2

H

HX

SO2

MeH

X = NH, O




General procedure B: A 20 mL vial adapted with a septum and a stir bar was flame dried under

vacuum and kept under an Ar atmosphere. The vial was charged with the SM (0.1 mmol, 1

equiv) and TEMPO (0.1 mmol, 1 equiv) which were dissolved in previously degassed CH3NO2

(4 mL) to give a pale brown solution. To this mixture TfOH (0.2 mmol, 2 equiv) was added in

one portion and as a result the reaction mixture became light yellow in color. The reaction was

then stirred at room temperature for 3h under Ar. Upon completion, the solvent was removed in

vacuo and the resulting crude mixture was dissolved with EtOAc (3 mL) and washed with 1 N

HCl (2 mL). After the layers were partitioned, the aqueous solution was further extracted with

EtOAc (3 x 3 mL) and the organic solution was dried over MgSO4, filtered and concentrated in

vacuo. The pure product was isolated after flash chromatography (silica gel, hexanes/EtOAc).

Compound 26: General procedure A was applied, starting with 39.8 mg

(0.100 mmol) of S3. The crude mixture was purified by flash chromatography

(silica gel, 19:1 hexanes/EtOAc) followed by pTLC (19:1 hexanes/EtOAc) to provide 26 (13.1

mg) in 44% yield.

Physical state: colorless oil;


HRMS (m/z): calcd for C16H24O3SH+ [M+H]+, 297.1519; found, 297.1528;

IR (film) νmax = 2958, 1598, 1451, 1363, 1175, 1097, 899, 815, 664;

1H NMR (600 MHz, CDCl3) δ 7.80 (d, J = 8.1 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 4.77 (s, 1 H),

4.74-4.70 (m, 1 H), 4.67 (s, 1 H), 2.44 (s, 3 H), 2.36 (dd, J = 13.7, 6.9 Hz, 1 H), 2.25 (dd, J =

13.9, 7.5 Hz, 1 H), 1.64 (s, 3 H), 1.62 – 1.56 (m, 1 H), 1.56 – 1.51 (m, 1 H), 1.37 – 1.31 (m, 1 H),

0.86 (d, J = 11.9 Hz, 3 H), 0.76 (d, J = 6.5 Hz, 3 H);

21

Me

OTs

Me

Me




13C NMR (151 MHz, CDCl3) δ 144.6, 140.6, 134.7, 129.7, 127.9, 114.5, 80.8, 43.6, 43.2, 24.2,

23.2, 22.6, 21.8.

Compound 27: General procedure A was applied, starting with 44.6 mg (0.1

mmol) of S4. The crude mixture was purified by flash chromatography (silica

gel, 1:0 to 99:1 hexanes/EtOAc) followed by pTLC (47:3 hexanes/EtOAc) to provide 27 (12.3

mg) in 36% yield.




IR (film) νmax = 2987, 1356, 1174, 1055, 1033, 903;

1H NMR (600 MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz, 2 H), 7.33 (d, J = 7.8 Hz, 2 H), 7.25 (t, J =

7.1 Hz, 2 H), 7.18 (t, J = 7.3 Hz, 1 H), 7.07 (d, J = 7.3 Hz, 2 H), 4.75 (s, 1 H), 4.72 – 4.65 (m, 2

H), 2.69 – 2.59 (m, 1 H), 2.55 – 2.47 (m, 1 H), 2.46 (s, 3 H), 2.39 (dd, J = 14.0, 5.2 Hz, 1 H),

2.30 (dd, J = 13.4, 7.6 Hz, 1 H), 1.89 – 1.83 (m, 2 H), 1.60 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 144.7, 141.1, 140.4, 134.6, 129.8, 128.6, 128.5, 128.0, 126.2,

114.8, 81.6, 43.0, 35.6, 31.1, 22.5, 21.8.


(0.100 mmol) of S5. The crude mixture was purified by flash

chromatography (silica gel, 1:0 to 9:1 hexanes/EtOAc) followed by pTLC (19:1 hexanes/EtOAc)

to provide 28 (13.3 mg) in 41% yield.




22

Me

OTs

Me

Me

Me

OTs

Ph




IR (film) νmax = 2954, 1365, 1176, 899, 815, 664;


4.68 (s, 1 H), 4.64 (quintet, J = 6.6 Hz, 1 H), 2.44 (s, 3 H), 2.37 (dd, J = 13.8, 5.8 Hz, 1 H), 2.27

(dd, J = 13.9, 7.2 Hz, 1 H), 1.64 (s, 3 H), 1.60 – 1.52 (m, 2 H), 1.40 (heptet, J = 6.6 Hz, 1 H),

1.31 – 1.20 (m, 1 H), 1.15 – 1.07 (m, 1 H), 1.06 – 1.00 (m, 2 H), 0.82 – 0.77 (m, 6 H);

13C NMR (151 MHz, CDCl3) δ 144.5, 140.6, 134.7, 129.7, 128.0, 114.5, 82.5, 43.2, 38.6, 34.2,

27.9, 22.6, 22.6, 22.5, 21.7.


(0.100 mmol) of S6. The crude mixture was purified by flash chromatography

(silica gel, 1:0 to 99:1 hexanes/EtOAc) followed by pTLC (19:1 hexanes/EtOAc) to provide 29

(10.6 mg) in 32% yield.



HRMS (m/z): calcd for C17H24O3SNa [M+Na]+, 331.1338; found, 331.1339;

IR (film) νmax = 2960, 1359, 1175, 902, 665;

1H NMR (600 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2 H), 7.32 (d, J = 8.1 Hz, 2 H), 5.68 – 5.64

(m, 1 H), 4.97 – 4.89 (m, 2 H), 4.74 (s, 1 H), 4.69 – 4.62 (m, 2 H), 2.44 (s, 3 H), 2.34 (dd, J =

13.9, 5.9 Hz, 1 H), 2.24 (dd, J = 13.9, 7.3 Hz, 1 H), 1.99 – 1.90 (m, 2 H), 1.62 (s, 3 H), 1.61 –

1.54 (m, 2 H), 1.46 – 1.36 (m, 1 H), 1.35 – 1.24 (m, 1 H);

13C NMR (151 MHz, CDCl3) δ 144.6, 140.5, 138.2, 134.6, 129.8, 127.9, 115.0, 114.6, 82.1,

43.1, 33.4, 33.3, 23.9, 22.5, 21.7.

23

Me

OTs




Compounds 30a, b, c: General procedure A was applied, starting with 36.5 mg (0.088 mmol) of

S7. The crude mixture was purified by flash chromatography (silica gel, 49:1 hexanes/EtOAc)

followed by pTLC (6:1 hexanes/EtOAc) to provide 14.9 mg (55% yield) of an unseparable

mixture of olefin isomers 30a:30(b+c) = 10:8.7 (NMR ratio).




IR (film) νmax = 2954, 2927, 1360, 1188, 1175, 962;

1H NMR (400 MHz, CDCl3) δ 7.83 – 7.74 (m, 12 H), 7.39 – 7.30 (m, 12 H), 5.21 (t, J = 7.2 Hz,

1 H), 5.11 (td, J = 7.1, 1.2 Hz, 2 H), 4.78 (s, 3 H), 4.69 (s, 3 H), 4.16 – 3.99 (m, 14 H), 2.45 (s,

20 H), 2.41 – 2.25 (m, 12 H), 1.99 – 1.84 (m, 12 H), 1.61 (s, 3 H), 1.55 – 1.42 (m, 12 H), 1.39 –

1.29 (m, 7 H), 1.22 – 1.03 (m, 16 H), 0.90 – 0.82 (m, 40 H), 0.82 – 0.78 (m, 3 H);

13C NMR (151 MHz, CDCl3) δ 144.8, 144.7, 144.7, 144.7, 144.3, 133.4, 133.3, 133.2, 129.9,

129.9, 129.9, 129.6, 129.0, 128.7, 128.7, 128.0, 128.0, 111.9, 69.2, 69.1, 68.9, 68.6, 39.2, 39.1,

38.8, 38.8, 38.6, 36.9, 36.3, 35.8, 35.1, 31.5, 29.3, 28.0, 27.9, 27.7, 25.9, 25.8, 25.4, 24.6, 23.5,

22.8, 22.7, 22.6, 22.6, 21.7, 19.3, 16.0.

Me

Me Me OTzo

TEMPO (1 equiv)TFA (3 equiv)

CH3NO2, 60°C, 1.5h

Me

Me OTs

Me

Me Me OTs:

30a 30(b+c)55% (a:(b+c) = 10:8.7)

S7

24




Compounds 31a, b, c: General procedure A was applied, starting with 35.4 mg (0.096 mmol) of

S8. The crude mixture was purified by flash chromatography (silica gel, 49:1 hexanes/EtOAc) to

provide 17.6 mg (69% yield) of a mixture of olefin regioisomers (31a+b:31c = 20:1, 1H NMR

ratio).



HRMS (m/z): calcd for C14H20O3SH+[M+H]+, 269.1206; found, 269.1210;

IR (film) νmax = 2963, 1598, 1358, 1175, 1097, 958;

1H NMR (400 MHz, CDCl3) δ 7.84 – 7.72 (m, 34 H), 7.34 (d, J = 8.0 Hz, 34 H), 5.40 – 5.34 (m,

1 H), 5.29 (q, J = 6.8 Hz, 8 H), 5.16 (q, J = 6.7 Hz, 7 H), 4.95 (dd, J = 10.2, 1.8 Hz, 1 H), 4.88 –

4.82 (m, 1 H), 4.09 – 3.96 (m, 37 H), 2.45 (s, 55 H), 2.39 (t, J = 7.5 Hz, 17 H), 2.34 – 2.27 (m,

16 H), 1.99 – 1.85 (m, 34 H), 1.55 (dt, J = 19.8, 6.5 Hz, 57 H), 1.28 – 1.18 (m, 7 H), 0.90 (dt, J =

11.0, 7.5 Hz, 49 H), 0.79 (dt, J = 11.6, 7.4 Hz, 9 H);

13C NMR (151 MHz, CDCl3) δ 144.7, 144.7, 140.9, 136.1, 135.6, 133.4, 129.9, 129.9, 128.0,

128.0, 121.8, 121.4, 116.2, 69.5, 69.3, 69.0, 68.7, 42.0, 36.7, 35.7, 33.5, 32.0, 29.9, 29.8, 27.7,

25.1, 22.8, 21.7, 13.4, 13.2, 12.7, 12.7, 11.5, 10.6.

Compound 23: General procedure A was applied, starting with 40 mg (0.109 mmol) of 22. The

crude mixture was purified by flash chromatography (silica gel, 49:1 hexanes/EtOAc) to provide


CH3NO2, 60°C, 1.5h :

31(a+b) 31c69% ((a+b):c) = 20:1)

S8

Me

MeOTz°

MeOTs

Me

MeOTs

OTzo

22

OTs OTs:

23 2468% (23:24 = 20:1)


CH3NO2, 60°C, 1.5h

25




19.7 mg (68 % yield) of an unseparable mixture of olefin and reduced product (23:24 =10:1).




IR (film) νmax = 2951, 2846, 1597, 1358, 1187, 1174, 1096;


4.11 (t, J = 6.9 Hz, 2 H), 2.45 (s, 3 H), 2.42 (t, J = 6.2 Hz, 2 H), 2.26 (bs, 2 H), 2.14 (t, J = 7.8

Hz, 2 H), 2.14 – 2.13 (m, 1 H), 1.80 (quintet, J = 7.8 Hz, 2 H);

13C NMR (151 MHz, CDCl3) δ 144.8, 138.8, 133.3, 129.9, 128.0, 126.7, 69.0, 35.1, 32.6, 30.7,

23.3, 21.8.

Compound 32a: The general procedure A was followed starting with 38.1 mg of S10 (0.100

mmol). The crude mixture was purified by flash chromatography (silica gel, 49:1 hexanes/

EtOAc) to provide 14.2 mg (51% yield) of an unseparable mixture of olefin and reduced product

(32a:32b =10:1). For 32a, the analytical data was identical to that of literature report.6

Compound 33: The general procedure A was followed starting with 1.062 g (2.595

mmol) of 57. The crude mixture was purified by flash chromatography (silica gel,

49:1 hexanes/EtOAc) to provide 614.7 mg (74% yield) of 33. *For the small scale

reaction, the same procedure was followed starting with 49 mg (0.119 mmol) of 57 to provide

33.9 mg (92% yield) of 33 after chromatography. **For the catalytic reaction, the same

procedure was followed starting with 41 mg (0.100 mmol) of 57 to provide 15.6 mg (51% yield)

of 33 after chromatography.

26

Me

Me

OTs

OTzo OTs OTs

S1032a 32b

51% (a:b = 10:1)


CH3NO2, 60°C, 1.5h:






[α]D = –30.2 º (c = 0.36, CH2Cl2);

m.p. = 84–86 ºC;


IR (film) νmax = 2925, 1648, 1598, 1452, 1360, 1175, 1097, 921, 872;


4.61 (s, 1 H), 4.46 (td, J = 10.7, 4.0 Hz, 1 H), 2.43 (s, 3 H), 2.24 (d, J = 12.3 Hz, 1 H), 2.12 (t, J

= 10.6 Hz, 1 H), 1.65 (t, J = 16.0 Hz, 2 H), 1.52 – 1.46 (m, 1 H), 1.44 (s, 3 H), 1.32 (q, J = 13.2

Hz, 1 H), 1.23 (q, J = 12 Hz, 1 H), 0.92 (d, J = 8.6 Hz, 4 H);

13C NMR (151 MHz, CDCl3) δ 145.0, 144.3, 134.8, 129.5, 128.0, 113.1, 83.2, 50.9, 41.9, 33.8,

31.7, 30.5, 22.0, 21.7, 19.4.

Compound 34: General procedure B was applied, starting with 40.7 mg (0.10

mmol) of S11. The crude mixture was purified by flash chromatography (silica gel,

19:1 to 9:1 hexanes/EtOAc) followed by pTLC (4:1 hexanes/EtOAc) to provide 34

(18.1 mg) in 59% yield.



m.p. = 90–92 ºC;

HRMS (m/z): calcd for C17H25NO2SH+ [M+H]+, 308.1679; found, 308.1679;

IR (film) νmax = 3288, 2925, 1449, 1323, 1159, 1093;


4.70 (s, 1 H), 4.34 (bs, 1 H), 2.84 (tt, J = 10.9, 3.8 Hz, 1 H), 2.43 (s, 3 H), 2.31 – 2.26 (m, 1 H),

27

Me

Me

NHTs




1.88 – 1.79 (m, 1 H), 1.67 – 1.57 (m, 2 H), 1.46 – 1.35 (m, 1 H), 1.35 – 1.25 (m, 1 H), 1.15 (s, 3

H), 0.97 – 0.89 (m, 2 H), 0.88 (d, J = 6.6 Hz, 3 H);

13C NMR (151 MHz, CDCl3) δ 146.1, 143.3, 137.5, 129.6, 127.4, 114.3, 53.6, 52.0, 42.6, 34.0,

31.5, 30.3, 22.1, 21.6, 17.4.

Compound 35a, 35b: The general procedure B was followed starting with 39.7 mg of S12

(0.100 mmol). The crude mixture was purified by flash chromatography (silica gel, 95:5 to 9:1

hexanes/EtOAc) followed by pTLC (5:1 hexanes/EtOAc) to provide 35a and 35b in 60% yield

(17.7 mg) as an inseparable mixture of isomers (35a:35b = 10:1, NMR ratio).

For 35a (major):


Rf = 0.25 (4:1 hexanes/Et2O);

m.p. = 67–69 ºC;


IR (film) νmax = 3276, 2956, 2869, 1648, 1598, 1448, 1425, 1325, 1159, 1093, 814;


4.62 (s, 1 H), 4.37 (d, J = 7.2 Hz, 1 H), 3.34 – 3.27 (m, 1 H), 2.42 (s, 3 H), 2.11 – 1.99 (m, 2 H),

1.63 – 1.56 (m, 1 H), 1.47 (s, 3 H), 1.31 – 1.24 (m, 2 H), 0.83 (d, J = 6.7 Hz, 3 H), 0.73 (d, J =

6.5 Hz, 3 H);

13C NMR (151 MHz, CDCl3) δ 143.4, 141.9, 138.0, 129.7, 127.3, 114.4, 50.2, 44.5, 44.4, 24.5,

22.9, 22.2, 22.0, 21.6.

28

Me

Me

HN Me

Me

Tzo

Me

NHTs Me

Me

Me

Me

NHTs Me

Me

TEMPO (1 equiv)TfOH (2 equiv)CH3NO2, rt, 3h

S12 35a 35b60% (a:b = 10:1)

:




Compound 36: A slightly modified general procedure A (2 equiv of TEMPO, 4

equiv of TFA) was applied starting with 38.4 mg (0.096 mmol) of S13. The

crude mixture was purified by pTLC (2:1 hexanes/Et2O, three elutions) to provide 13.4 mg (47%

yield) of 36.



[α]D = –5.8 º (c = 0.41, CH2Cl2);

m.p. = 64–66 ºC;


IR (film) νmax = 3272, 2953, 1743, 1437, 1337, 1161, 1092, 815 cm-1;

1H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 7.8 Hz, 2 H), 7.29 (d, J = 7.8 Hz, 2 H), 4.97 (d, J =

8.9 Hz, 1 H), 4.83 (s, 1 H), 4.72 (s, 1 H), 4.06 (ddd, J = 8.9, 7.7, 1.3 Hz, 1 H), 3.49 (s, 3 H), 2.46

– 2.31 (m, 5 H), 1.64 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 172.0, 143.8, 139.6, 136.7, 129.7, 127.4, 115.5, 54.3, 52.4, 41.7,

21.9, 21.7.

Compound 37: A slightly modified general procedure A (2 equiv of TEMPO, 4

equiv of TFA) was applied starting with 42.6 mg (0.100 mmol) of S14. The

crude mixture was purified by chromatography (silica gel, 2:1 hexanes/Et2O) and pTLC (2:1

hexanes/Et2O, two elutions) to provide 14.4 mg (40% yield) of product.



[α]D = -5.0 º (c = 0.1, CH2Cl2);

m.p. = 84–86ºC;

29

Me CO2tBu

NHTs

Me CO2Me

NHTs




HRMS (m/z): calcd for C17H25NO4SNa+ [M+Na]+, 362.1396; found, 362.1401;

IR (film) νmax = 2926, 1724, 1599, 1455, 1340, 1152, 1091, 897, 841, 814, 663 cm-1;


8.9 Hz, 1 H), 4.83 (s, 1 H), 4.74 (s, 1 H), 3.93 (ddd, J = 8.9, 7.6, 6.5 Hz, 1 H), 2.43 – 2.36 (m, 4

H), 2.32 (dd, J = 13.9, 7.6 Hz, 1 H), 1.70 (s, 3 H), 1.24 (s, 9 H);

13C NMR (151 MHz, CDCl3) δ 170.6, 143.6, 140.0, 137.0, 129.7, 127.4, 115.2, 82.6, 54.7, 42.2,

27.8, 22.0, 21.6.

Compound 38a,b: A slightly modified general procedure A (2 equiv of TEMPO, 4 equiv of

TFA) was applied starting with 38.4 mg (0.100 mmol) of S15. The crude mixture was purified by

pTLC (5:1 hexanes/EtOAc, two elutions) to provide 16.2 mg (51% yield) of an inseparable

mixture of olefin and reduction products (38a:38b = 7:1, NMR ratio). For 38b, the analytical

data was identical to that of literature report.7



[α]D = +17.6 º (c =1.6, CHCl3);

m.p. = 68–71 ºC;


IR (film) νmax = 2923, 2853, 1738, 1436, 1335, 1160, 1090, 1019, 880, 815, 663 cm-1;


7.9 Hz, 1 H), 4.97 (d, J = 10.2 Hz, 2 H), 4.43 (d, J = 8.0 Hz, 1 H), 3.58 (s, 3 H), 2.42 (s, 3 H),

30

NHTzo

CO2Me

NHTs

CO2Me

NHTs

CO2Me


CH3NO2, 60°C, 1.5h

S15 38a 38b51% (a:b = 7:1)




1.64 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 170.4, 143.8, 139.3, 136.9, 129.7, 127.4, 116.3, 61.1, 53.0, 21.7,

18.8.

Compound (–)-39: The general procedure B was followed starting with 38.1 mg

(0.100 mmol) of (–)-S16. The crude mixture was purified by flash chromatography

(silica gel, 1:0 to 9:1 hexanes/EtOAc) followed by pTLC (5:1 hexanes/EtOAc) to provide (–)-39

(14.0 mg) in 50% yield.



[α]D = –1.6 º (c = 0.24, CH2Cl2);

m.p. = 82–84 ºC;

HRMS (m/z): calcd for C15H21NO2SNa+ [M+H]+, 302.1185; found, 302.1191;

IR (film) νmax = 3272, 2926, 1434, 1320, 1156 1079;


4.32 (d, J = 7.4 Hz, 1 H), 3.83 (quintet, J = 7.0 Hz, 1 H), 2.42 (s, 3 H), 1.87 – 1.71 (m, 3 H), 1.65

– 1.56 (m, 1 H), 1.50 – 1.41 (m, 1 H), 1.40 – 1.32 (m, 2 H), 1.28 – 1.18 (m, 1 H), 1.16 (d, J = 6.9

Hz, 3 H);

13C NMR (151 MHz, CDCl3) δ 143.1, 138.2, 136.9, 129.4, 127.4, 124.1, 55.6, 24.9, 23.7, 22.3,

22.2, 21.6, 20.6.

31

Me

NHTs




Compounds 41a and 41b: The general procedure A was followed starting with 38.0 mg (0.079

mmol) of 40. The crude mixture was purified by flash chromatography (silica gel, 1:0 to 79:1

hexanes/EtOAc) to provide 13.7 mg (46% yield) of a mixture of olefin regioisomers (41a:41b =

2:1, NMR ratio). Product 41a was observed to crystallize out of the mixture, however any

attempts to isolate the minor isomer 41b by pTLC were unsuccessful.

For 41a:



[α]D = +24.5 º (c = 0.11, CH2Cl2);

m.p. = 106–108 ºC;


IR (film) νmax = 2925, 1454, 1343, 1174, 909;

1H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 7.4 Hz, 2 H), 7.24 (d, J = 7.6 Hz, 2 H), 5.03 (t, J =

10.6 Hz, 1 H), 4.58 (s, 1 H), 4.48 (s, 1 H), 2.42 (s, 3 H), 2.22 (t, J = 9.4 Hz, 1 H), 2.14 (bs, 1 H),

1.72 – 1.63 (m, 5 H), 1.61 – 1.54 (m, 1 H), 1.51 – 1.35 (m, 5 H), 1.24 (d, J = 12.1 Hz, 1 H), 1.19

– 1.06 (m, 2 H), 1.01 (d, J = 7.2 Hz, 3 H), 0.97 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 145.4, 143.6, 136.0, 129.1, 127.5, 114.0, 85.8, 54.1, 52.0, 43.5,

42.1, 36.2, 33.2, 27.3, 26.8, 21.7, 20.7, 19.3, 17.0, 14.9.

For the mixture:

IR (film) νmax =2925, 1454, 1343, 1173, 906;

32

MeMe

Me

MeOTzo

MeMe

MeOTs

MeMe

MeOTs


CH3NO2, 60°C, 1.5h:

40 41a 41b46% (a:b = 2:1)





8.1 Hz, 10 H), 5.03 (t, J = 10.7 Hz, 4 H), 4.92 (t, J = 10.7 Hz, 1 H), 4.69 (s, 1 H), 4.67 (s, 1 H),

4.58 (s, 4 H), 4.48 (s, 4 H), 2.41 (s, 12 H), 2.40 (s, 3 H), 2.28 (d, J = 10.8 Hz, 1 H), 2.26 – 2.17

(m, 5 H), 2.17 – 2.10 (m, 5 H), 1.82 (td, J = 12.8, 5.4 Hz, 1 H), 1.75 (ddd, J = 9.6, 7.1, 3.3 Hz, 1

H), 1.72 – 1.67 (m, 3 H), 1.63 (dd, J = 13.5, 3.6 Hz, 3 H), 1.60 – 1.54 (m, 11 H), 1.52 – 1.35 (m,

24 H), 1.35 – 1.21 (m, 10 H), 1.13 (dtd, J = 29.8, 13.1, 3.2 Hz, 9 H), 1.02 (t, J = 8.9 Hz, 13 H),

0.96 (s, 12 H), 0.88 (dt, J = 14.7, 7.3 Hz, 6 H);

13C NMR (151 MHz, CDCl3) δ 145.3, 145.0, 143.6, 143.4, 136.6, 136.0, 129.1, 129.1, 127.5,

127.1, 114.0, 108.2, 86.5, 85.8, 55.5, 54.1, 51.9, 49.0, 43.5, 42.1, 39.9, 39.3, 37.9, 36.2, 33.2,

27.3, 26.8, 26.0, 24.3, 21.71, 21.7, 21.2, 20.7, 19.3, 18.5, 17.6, 17.0, 15.6, 14.9.

Compounds 43 and 44: The general procedure B was followed (reaction run at 4 ºC) starting

with 53.8 mg (0.100 mmol) of 42. The crude mixture was purified by flash chromatography

(silica gel, 5:1 hexanes/EtOAc) and pTLC (5:1 hexanes/EtOAc) to provide 13.3 mg of 43 (30%

yield) and 5.4 mg of 44 (16% yield).

For 43:



[α]D = +122.9 º (c = 0.45, CH2Cl2);

m.p. = 124–126 ºC;

33

TsN

iPrMe

Me NHTzo

iPr

MeMe

iPrMe

Me NHTs

42 4330%

4416%

+

TEMPO (1 equiv)TfOH (2 equiv)CH3NO2, rt, 3h





IR (film) νmax = 2956, 2871, 1613, 1458, 1337, 1156, 1103, 1045 cm-1;

1H NMR (600 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 1 H), 7.06 (dd, J = 8.2, 2.0 Hz, 1 H), 6.86 (d,

J = 8.2 Hz, 2 H), 6.81 (d, J = 8.2 Hz, 2 H), 6.60 (d, J = 2.0 Hz, 1 H), 3.75 (d, J = 9.3 Hz, 1 H),

3.34 (d, J = 9.3 Hz, 1 H), 2.90 – 2.79 (m, 2 H), 2.57 (ddd, J = 18.4, 11.9, 7.1 Hz, 1 H), 2.27 (s, 3

H), 2.19 – 2.09 (m, 1 H), 2.06 (dd, J = 17.5, 6.6 Hz, 1 H), 1.84 – 1.75 (m, 2 H), 1.67 – 1.56 (m, 1

H), 1.37 – 1.28 (m, 2 H), 1.28 – 1.18 (m, 7 H), 0.92 (s, 3 H), 0.79 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 148.3, 141.3, 139.0, 136.6, 131.6, 129.2, 128.5, 126.2, 126.0,

123.5, 69.7, 58.6, 45.7, 41.0, 33.7, 33.4, 30.7, 26.0, 25.7, 24.2, 24.0, 21.4, 18.9, 18.5, 13.1.

For 44:



[α]D = +48.1 º (c = 0.21, CH2Cl2);

m.p. = 162–164 ºC;


IR (film) νmax = 3279, 2959, 1461, 1326, 1160, 1094 cm-1;


8.1 Hz, 1H), 7.02 (dd, J = 8.1, 1.4 Hz, 1 H), 6.87 (s, 1 H), 5.90 (ddd, J = 10.0, 6.3, 1.7 Hz, 1 H),

5.21 (dd, J = 10.0, 2.8 Hz, 1 H), 4.28 (dd, J = 10.0, 2.2 Hz, 1 H), 3.07 (dd, J = 12.0, 10.2 Hz, 1

H), 2.84 (heptet, J = 7.0 Hz, 1 H), 2.78 (dt, J = 17.0, 3.0 Hz, 1 H), 2.72 – 2.63 (m, 1 H), 2.53 (dd,

J = 17.0, 6.3 Hz, 1 H), 2.46 (dd, J = 12.3, 2.7 Hz, 1 H), 2.42 (s, 3 H), 2.10 (d, J = 17.9 Hz, 1 H),

2.05 – 1.99 (m, 1 H), 1.66 – 1.61 (m, 2 H), 1.27 – 1.20 (m, 9 H), 0.92 (s, 3 H);

34




13C NMR (151 MHz, CDCl3) δ 145.9, 144.5, 143.3, 137.3, 135.3, 132.6, 129.8, 128.9, 127.1,

126.8, 125.8, 124.3, 51.2, 40.9, 39.6, 39.4, 36.5, 33.6, 30.7, 25.5, 24.1, 24.1, 21.6, 19.8, 19.7.

Compound 46a: The general procedure A was followed starting with 25.0 mg (0.036 mmol) of

45. The crude mixture was purified by flash chromatography (silica gel, 1:0 to 49:1 DCM/Et2O)

and pTLC (2:1 hexanes/Et2O) to provide 10.1 mg (47% yield) of a mixture of product and traces

of reduced byproduct (46a:46b = 10:1, 1H NMR ratio).



[α]D = +55.5 º (c = 0.29, CH2Cl2);

m.p. = 174–176 ºC;


IR (film) νmax = 2927, 1457, 1356, 1174, 956 cm-1;

1H NMR (600 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2 H), 7.35 (d, J = 8.1 Hz, 2 H), 6.26 (dd, J =

10.6, 2.9 Hz, 1 H), 5.54 (d, J = 10.4 Hz, 1 H), 3.72 (s, 2 H), 3.24 (dd, J = 11.5, 4.6 Hz, 1 H), 2.45

(s, 4 H), 2.34 (dd, J = 14.2, 1.7 Hz, 1 H), 1.91 – 1.85 (m, 2 H), 1.75 (d, J = 14.4 Hz, 1 H), 1.72 –

1.50 (m, 7 H), 1.45 – 1.28 (m, 8 H), 1.19 – 1.13 (m, 1 H), 1.01 (s, 3 H), 0.99 (s, 3 H), 0.93 (s, 3

H), 0.88 (s, 3 H), 0.77 (s, 3 H), 0.75 (s, 3 H), 0.68 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 144.7, 135.4, 134.9, 133.2, 129.9, 128.0, 126.3, 125.4, 80.1,

79.1, 54.9, 54.3, 42.6, 40.4, 39.0, 38.1, 37.6, 37.0, 36.7, 36.0, 34.9, 32.4, 32.1, 29.6, 27.9, 27.2,

35

Me

H

MeMe

MeHO

Me Me

MeTzoO

MeMeMe

MeHO

Me Me

MeTsO

Me

H

MeMe

MeHO

Me Me

MeTsO


CH3NO2, 60°C, 1.5h +

45 46a 46b

47% (a:b = 10:1)




25.3, 24.4, 21.8, 20.3, 19.3, 18.4, 18.1, 16.6, 15.1.

Compound 48: A 5 mL vial, flame dried and maintained under Ar was charged with 47 (21 mg,

0.030 mmol, 1 equiv) and TEMPO (9.4 mg, 0.060 mmol, 2 equiv). Next, previously degassed

CH3NO2 (1.2 mL) was added and only TEMPO was observed to go into solution. Upon addition

of TFA (13.7 mg, 9.2 µL, 0.12 mmol, 4 equiv) and sonication of the reaction mixture (2–3 min) a

cloudy suspension was obtained. The vial was then immersed in a preheated oil bath at 60 ºC and

the reaction proceeded for 1.5 h (LC-MS control). During this time, a white solid was observed

to precipitate out of the solution. After the allotted reaction time (1.5 h), the crude mixture was

centrifugated to separate a white solid which was then washed with CH3NO2 (1 mL). The

resulting solid residue was taken up in CH2Cl2 and purified by chromatography (silica gel, 20:1

CH2Cl2/MeOH) to obtain 6.2 mg (35% yield) of 48. (No desired product was detected in the

remaining crude reaction solution.)


Rf = 0.44 (10:1 CH2Cl2/MeOH);

[α]D = –12.6 º (c = 0.6, CHCl3);

m.p. = 264–267 ºC;


IR (film) νmax=3263, 1628, 1537, 1161;

1H NMR (400 MHz, DMSO-d6) δ 8.12 (d, J = 7.0 Hz, 1 H), 7.85 (d, J = 8.6 Hz, 1 H), 7.82 (d, J

36

NHTzo

O

HN Me

HN

Me

Me

O

O

Me

Me

HN

Ph

O

H2N

NHTsO

HN Me

HN

Me

O

O

Me

Me

HN

Ph

O

H2N


CH3NO2, 60°C, 1.5h

35%47

48




= 9.4 Hz, 1 H) 7.62 (d, J = 8.2 Hz, 2 H), 7.53 (d, J = 8.5 Hz, 1 H), 7.31 (d, J = 8.2 Hz, 2 H), 7.25

– 7.12 (m, 6 H), 7.04 (bs, 1 H), 4.67 (bs, 2 H), 4.44 (td, J = 8.5, 5.2 Hz, 1 H), 4.07 – 3.96 (m, 2

H), 3.92 (td, J = 9.3, 5.3 Hz, 1 H), 2.97 (dd, J = 13.9, 5.1 Hz, 1 H), 2.78 (dd, J = 13.9, 9.0 Hz, 1

H), 2.36 (s, 3 H), 2.15 (dd, J = 14.1, 5.4 Hz, 1 H), 2.06 (dd, J = 14.1, 9.6 Hz, 1 H), 1.91 – 1.81

(m, 1 H), 1.57 (s, 3 H), 0.96 (d, J = 6.9 Hz, 3 H), 0.71 (d, J = 6.7 Hz, 3 H), 0.70 (d, J = 6.8 Hz, 3

H);

13C NMR (151 MHz, DMSO-d6) δ 172.7, 171.6, 170.4, 170.2, 142.3, 140.5, 138.3, 137.8,

129.1, 129.1, 128.0, 126.7, 126.2, 113.8, 57.7, 54.3, 53.5, 47.9, 40.8, 37.6, 30.5, 21.7, 21.0, 19.1,

17.9, 17.6.

Mechanistic studies

Compound S17: 1. A flame dried round bottom flask, was kept under Ar and charged with

cyclopentane-carboxylic acid (1g, 8.76 mmol, 1 equiv) which was dissolved in dry THF (8.8

mL) and the resulting solution was cooled at –78 ºC. To this, a solution of secBuLi (1.1 M in

cyclohexane, 23.9 mL, 26.28 mmol, 3 equiv) was added dropwise and the reaction was

maintained at –78 ºC for 10 min, before being transferred in an ice bath (0 ºC) and stirred for 1h.

After this time, D2O (1.75 g, 1.75 mL, 87.6 mmol, 10 equiv) was added dropwise and the

resulting mixture was kept at 0 ºC for another hour before being quenched with 1N HCl (5 mL).

After separation of the aqueous layer, the organic solution was further washed with water (2 x 5

mL) and then shaken with 3N KOH (10 mL, until pH ≈ 12). After portioning of the layers, the

37

O

OH OMs

D1. secBuLi, D2O

THF, -78 ºC → 0 ºC67%

2. LAH, THF, rt, 2h93%

3. MsCl, NEt3DCM, rt, 1h

67%

S17




resulting aqueous solution was acidified with 3N HCl (15 mL, until pH ≈ 1) and the product was

extracted with Et2O (3 x 30 mL). The resulting organic solution was washed with brine (20 mL),

dried over MgSO4, filtered and concentrated in vacuo to give the desired deuterated acid (672

mg, 67% yield) which was used without further purification.

2. A flame dried 20 mL vial was charged with LAH (332.4 mg, 5.2 mmol, 3 equiv) in THF (5

mL). To this slurry, a solution of the previously prepared α,α-bisdeuterated cyclopentane-

carboxylic acid (119.2 mg, 1.731 mmol, 1 equiv) in THF (3 mL + 2 mL rinse) was added

dropwise at 0 ºC. The resulting reaction mixture was allowed to proceed under Ar, at room

temperature for 2 h before being quenched with H2O (0.3 mL), 1N KOH (0.6 mL) and H2O (0.9

mL). To this white slurry, Et2O (5 mL) was added and after separation of the organic layer, the

aqueous mixture was further extracted with Et2O (3 x 5 mL). The combined organic solution was

then washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo (from

ice) to give the desired alcohol in 93% yield (162.4 mg).

3. A flame dried 20 mL vial was charged with the previously prepared alcohol (162.4 mg, 1.606

mmol, 1 equiv) which was dissolved in DCM (7 mL) and cooled at 0 ºC. To this solution, MsCl

(220 mg, 1.927 mmol, 1.2 equiv) was added followed by NEt3 (324.4 mg, 0.43 mL, 3.212 mmol,

2 equiv). The resulting reaction mixture was stirred under Ar for 20 min at 0 ºC, then at room

temperature for 40 min before being quenched with saturated NH4Cl (4 mL) and extracted with

EtOAc (3 x 5 mL). The combined organic layers were washed with brine, dried over MgSO4,

filtered and concentrated in vacuo. The crude mixture was further purified by chromatography

(silica gel, 10:1 hexanes/ EtOAc) to give the desired mesylate S17 in 67% (192.7 mg).



38




HRMS (m/z): calcd for C7H13DO3SNa+ [M+Na]+, 202.0618; found, 202.0620;

IR (film) νmax = 2951, 1350, 1172, 944;

1H NMR (600 MHz, CDCl3) δ 4.11 (s, 2 H), 3.00 (s, 3 H), 1.83 – 1.76 (m, 2 H), 1.68 – 1.56 (m,

4 H), 1.34 – 1.21 (m, 2 H);

13C NMR (151 MHz, CDCl3) δ 73.8, 38.5 (t, J = 19.6 Hz), 37.4, 29.0, 25.4.

Compound S18: 1. A flame dried 20 mL vial was charged with S17 (148.5 mg, 0.829 mmol, 1

equiv) and NaCN (203 mg, 4.145 mmol, 5 equiv) and then DMSO (4.2 mL) was added to

produce a cloudy suspension. This mixture was stirred at 60 ºC for 5h (TLC control) and it was

then diluted with H2O (10 mL) and extracted with Et2O (5 x 3 mL). The combined organic layers

were washed with brine (10 mL), dried over MgSO4, filtered and concentrated in vacuo. The

resulting mixture was filtered through a plug of silica (to remove traces of DMSO) (elute with

Et2O) and the resulting solution was concentrated in vacuo and used in the next reaction as such.

2. The previously prepared nitrile was transferred to a flame dried vial, kept under Ar, dissolved

in DCM (8.3 mL) and the solution was cooled at –78 ºC. To this, DIBAL-H (1M in hexanes,

1.650 mmol, 2 equiv) was added dropwise and the resulting reaction mixture was stirred at the

same temperature (-78 ºC) for 1.5h. Acetone (1 mL) was then added before the mixture was

warmed up to room temperature. The crude mixture was dissolved in Et2O (15 mL) and a

solution of Rochelle salt (15 mL) was added and the resulting slurry was vigorously stirred

overnight at room temperature. After the layers were partitioned, the aqueous solution was

further extracted with Et2O (5 x 5 mL) and the combined organic layers were washed with brine

39

OMs

D 1. NaCN, DMSO60 ºC, 5h

2. DIBAL-H, DCM-78 ºC, 1.5h, 3. LAH, THF, 0 ºC→rt, 10h,

20% (over 3 steps)

D

OH

S17 S18




(20 mL), dried over MgSO4, filtered and concentrated in vacuo (from ice!). The resulting mixture

was used in the next reaction without purification.

3. The previously synthesized aldehyde was placed in a 20 mL flame dried vial, kept under Ar

and dissolved in THF (8 mL). This solution was cooled at 0 ºC and LAH (4 M in Et2O, 2.440

mmol, 0.6 mL, 3 equiv) was added dropwise. The resulting white slurry was stirred at room

temperature overnight before being quenched with H2O (0.2 mL), 1M KOH (0.4 mL) and H2O

(0.6 mL). After the layers were partitioned, the aqueous solution was further extracted with Et2O

(3 x 5 mL) and the combined organic layers were washed with brine (10 mL), dried over MgSO4,

filtered and concentrated in vacuo. The desired product S18 was isolated after chromatography

(silica gel, 10:1 hexanes/EtOAc) in 20% yield (over three steps) (19.1 mg).



IR (film) νmax = 3316, 2945, 2859, 1451, 1048;

1H NMR (500 MHz, CDCl3) δ 3.66 (t, J = 6.9 Hz, 2 H), 1.80 – 1.72 (m, 2 H), 1.65 – 1.56 (m, 4

H), 1.56 – 1.46 (m, 2 H), 1.29 (bs, 1H), 1.15 – 1.05 (m, 2 H);

13C NMR (151 MHz, CDCl3) δ 62.6, 39.1, 36.2 (t, J = 19.3 Hz), 32.7, 25.2.

Compound 49: The product was obtained following the general procedure

for the installation of the directing group (vide supra) starting with 6.2 mg

(0.053 mmol) of S18. After purification by flash chromatography (silica gel,

10:1 hexanes/EtOAc), 49 was obtained in 63 % yield (12.5 mg).



HRMS (m/z): calcd for C18H28DN3O3SH+ [M+H]+, 369.2064; found, 369.2061;

ODSOO

N

MeN NEt2

40




IR (film) νmax = 2936, 1593, 1388, 1349, 1174;


4.03 (t, J = 6.7 Hz, 2 H), 3.83 (q, J = 6.8 Hz, 4 H), 2.39 (s, 3 H), 1.68 – 1.60 (m, 4 H), 1.60 –

1.50 (m, 2 H), 1.50 – 1.41 (m, 2 H), 1.36 (t, J = 7.1 Hz, 3 H), 1.27 (t, J = 5.8 Hz, 3 H), 1.02 –

0.94 (m, 2H);

13C NMR (151 MHz, CDCl3) δ 149.3, 145.1, 130.6, 126.1, 125.1, 118.4, 69.9, 49.4, 42.4, 35.8

(t, J = 19.6 Hz), 35.0, 32.3, 25.1, 21.8, 14.6, 11.4.

Compound 50a: The general procedure A was followed starting with

7.6 mg of 49 (0.028 mmol). After the allotted reaction time (1.5h), the

crude reaction was cooled at room temperature and the solvent was removed in vacuo. The

resulting crude mixture was dissolved in a solution of CDCl3 (0.5 mL) containing

trimethoxybenzene (3.14 mg/mL; 0.056 mmol/mL) as an internal standard and analyzed by 1H

NMR to obtain a product yield (31%).



HRMS (m/z): calcd for C14H17DO3SH+ [M+H]+, 268.1111; found, 268.1120;

IR (film) νmax = 2924, 1594, 1359, 1180, 966;

1H NMR (400 MHz, CDCl3) δ 7.82 – 7.76 (m, 1 H), 7.38 – 7.32 (m, 2 H), 5.38 – 5.31 (m, 1 H),

4.12 (t, J = 6.9 Hz, 2 H), 2.45 (s, 3 H), 2.41 (t, J = 7.2 Hz, 2 H), 2.29 – 2.22 (m, 2 H), 2.14 (t, J =

8 Hz, 2 H), 1.79 (quintet, J = 8 Hz, 2 H);

13C NMR (151 MHz, CDCl3) δ 144.8, 138.7, 133.2, 129.8 (d, J = 17.2 Hz), 128.0, 126.6, 68.9,

35.1, 32.6, 30.7, 23.3, 21.8.

41

OS

O O

MeD




Compound 51: Synthesized from 5-methylhex-1-yn-3-ol (0.300 mmol)



Physical state: pale orange oil;



IR (film) νmax= 2959, 1593, 1466, 1389, 1353, 1271, 1175, 1110, 923, 882, 675;


5.11 (dt, J = 2.1, 7.1 Hz, 1 H), 3.92 – 3.75 (m, 4 H), 2.39 (s, 3 H), 2.35 (d, J = 2.1 Hz, 1 H), 1.86

– 1.72 (m, 2 H), 1.66 – 1.60 (m, 1 H), 1.35 (t, J = 7.1 Hz, 3 H), 1.28 (t, J = 7.1 Hz, 3 H), 0.86 (d,

J = 6.5 Hz, 3 H), 0.85 (d, J = 6.5 Hz, 3 H);

13C NMR (100 MHz, CDCl3) δ 149.5, 145.3, 130.4, 127.1, 125.0, 118.3, 79.9, 75.6, 69.6, 49.4,

44.6, 42.5, 24.4, 22.6, 22.3, 21.9, 14.7, 11.5.


(0.088 mmol) of 51. The crude mixture was purified by pTLC (silica gel,

5:1 hexanes/EtOAc, two elutions) to provide 11 mg of product (47%

yield).



m.p. = 208–210 ºC;


IR (film) νmax= 1670, 1455, 1389, 1201, 836, 799, 723;


42

O

Me

MeSO

O

Me

NNEt2N

O

Me

SO O

Me




5.86 (s, 1 H), 5.62 (ddd, J = 8.7, 5.0, 1.4 Hz, 1 H), 5.40 (s, 1 H), 4.94 (s, 1 H), 4.87 (s, 1H), 2.72

(dd, J = 14.8, 8.7 Hz, 1 H), 2.66 (dd, J = 14.8, 5.0 Hz, 1 H), 2.45 (s, 3 H), 1.83 (s, 3 H);

13C NMR (151 MHz, CDCl3) δ 143.9, 139.3, 137.9, 133.6, 131.8, 130.1, 126.1, 124.6, 115.3,

115.0, 82.3, 42.0, 22.6, 21.9.

Compound 55: 1. In a flamed dried 5 mL vial, a mixture of cyclopentyl-ethanol (200 mg, 1.75

mmol, 1 equiv), ortho-nitro-benzenesulfonyl chloride (580 mg, 2.625 mmol, 1.5 equiv), DMAP

(21.4 mg, 0.175 mmol, 0.1 equiv) was dissolved in THF (2.1 mL). To this solution, NEt3 (441.8

mg, 0.6 mL, 4.375 mmol, 2.5 equiv) was added and the resulting mixture was allowed to stir at

room temperature under Ar overnight (TLC control). Upon completion, the reaction was washed

with sat NH4Cl (3 mL) and extracted with EtOAc (3 x 3 mL). The organic solution was further

washed with brine (5 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude

mixture was purified by flash chromatography (silica gel, 10:1 hexanes/EtOAc) to yield 284.3

mg of desired product (54% yield, unoptimized).

The previously synthesized ortho-nitro tosylate (150 mg, 0.5 mmol, 1 equiv) was transferred to a

flame-dried vial and kept under Ar. To this, Pd/C (10 mol%) (80 mg, 0.075 mmol, 0.15 equiv)

was added and the vial was placed under high vacuum before being filled with H2 (process

repeated 3X). Upon addition of cyclohexane (10 mL), the heterogeneous solution was stirred at

room temperature overnight (H2 balloon). The resulting mixture was filtered through a plug of

celite (eluted with EtOAc) and after evaporation of the solvent, 55 was obtained in 96% yield

43

OH

1.SO2Cl

NO2(1.5 equiv)

Et3N (2.5 equiv), DMAP (0.1 equiv)

THF (0.825M), rt, 14h54%

2. H2, Pd/C (10 mol%)Cyclohexane, rt, 12h

96%

OS

OOH2N

55




(129.4 mg).



HRMS (m/z): calcd for C13H19NO3SH+[M+H]+, 270.1158; found, 270.1156;

IR (film) νmax =3488, 3387, 2948, 1623, 1484, 1348, 1174, 1161, 928;

1H NMR (600 MHz, CDCl3) δ 7.70 (dd, J = 8.0, 1.5 Hz, 1 H), 7.35 (ddd, J = 8.6, 7.3, 1.6 Hz, 1

H), 6.82 – 6.71 (m, 2 H), 4.96 (bs, 2 H), 4.02 (t, J = 6.7 Hz, 2 H), 1.81 (heptet, J = 7.2 Hz, 1 H),

1.72 – 1.62 (m, 4 H), 1.60 – 1.51 (m, 2 H), 1.51 – 1.41 (m, 2 H), 1.07 – 0.95 (m, 2 H);

13C NMR (151 MHz, CDCl3) δ 146.3, 135.2, 130.5, 117.4, 117.2, 116.9, 70.3, 36.3, 34.9, 32.4,

25.0.

Compound 56: A flame dried 5 mL vial was kept under Ar and charged with 55 (7.9 mg, 0.029

mmol, 1 equiv) which was dissolved in degassed CH3NO2 (1 mL) and the solution was cooled at

0 ºC before the dropwise addition of tert-BuONO (4.54 mg, 3.5 µL, 0.044 mmol, 1.5 equiv). The

resulting bright yellow solution was stirred at 0 ºC for 10 min, then TEMPO (4.7 mg, 0.029

mmol, 1 equiv) was added in one portion to give a pale brown mixture. The reaction was then

allowed to proceed at room temperature for 3h (TLC control). Upon completion, the crude

mixture was concentrated in vacuo and dissolved in a solution of CDCl3 (0.5 mL) containing

trimethoxybenzene (3.28 mg/mL; 0.058 mmol/mL) as an internal standard and analyzed by 1H

NMR to obtain a product yield (44%).

44

OSOO

H2NOSO2PhH

tBuONO (1.5 equiv)CH3NO2, 0 ºC, 10 minthen TEMPO (1 equiv)

rt, 3h

55 5644%






HRMS (m/z): calcd for C13H16O3SNa+ [M+Na]+, 275.0712; found, 275.0712;

IR (film) νmax = 2952, 2846, 1448, 1358, 1184, 1096, 962;

1H NMR (600 MHz, CDCl3) δ 7.94 – 7.88 (m, 2 H), 7.66 (t, J = 7.5 Hz, 1 H), 7.56 (t, J = 7.8

Hz, 2 H), 5.35 (s, 1 H), 4.15 (t, J = 6.9 Hz, 2 H), 2.43 (t, J = 6.5 Hz, 2 H), 2.28 – 2.21 (m, 2 H),

2.14 (t, J = 6.6 Hz, 2 H), 1.80 (quintet, J = 9.6 Hz, 2 H);

13C NMR (151 MHz, CDCl3) δ 138.6, 136.3, 133.8, 129.3, 128.0, 126.7, 69.2, 35.0, 32.6, 30.6,

23.3.

HPLC method for determining the enantiomeric excess of the desaturated product, using

(±)-39 and (–)-39:

Column: Daicel Chiralcel® OD

Dimensions: 4.6 × 250 mm

Eluent: 10% isopropanol 90% hexanes

Flow rate: 0.5 mL/min

45




Figure S1. Chromatogram of (±)-39 on a chiral column, showing ≈ 0% ee.

Figure S2. Chromatogram of (–)-39 on a chiral column, showing 98% ee.

46




MS fragmentation spectrum for compounds 23 and 50.

Figure S3. MS Fragmentation spectrum showing [M+H+] (268.1120) and [M+Na+] (290.0929) for deuterated compound 50. Note the absence of the corresponding perprotio compound 23.

Figure S4. MS Fragmentation spectrum showing [M+H+] (267.1048) and [M+Na+] (289.0905) for perprotio compound 23.

+TOF MS: 0.765 min from 011012022.wiff Agilent Max. 1.1e5 counts.

258 260 262 264 266 268 270 272 274 276 278 280 282 284 286 288 290 292 294 296 298 300m/z, amu

0.0

2000.0

4000.0

6000.0

8000.0

1.0e4

1.2e4

1.4e4

1.6e4

1.8e4

2.0e4

2.2e4

2.4e4

2.6e4

2.8e4

3.0e4

3.2e4

3.4e4

3.6e4

3.8e4

4.0e4

4.2e4

4.4e4

4.6e4

Inte

nsity

, cou

nts

290.0929

291.0955 292.1050

261.1260 294.9387

259.1395 285.1371268.1120 290.3003289.1040 298.2714270.9841

293.1102279.1572273.1662 294.0538262.1558260.1530 284.2898 288.1660280.1714278.0532 299.2440271.1448267.1558266.1592 292.3130

Polarity/Scan Type: Positive Sample Name: BVAV7231 Acq. File: 011012022.wiffAcq. Date: Tuesday, January 10, 2

+TOF MS: 0.122 min from 050511303_2.wiff Agilent Max. 6.2e4 counts.

258 260 262 264 266 268 270 272 274 276 278 280 282 284 286 288 290 292 294 296 298 300 302 304 306 308m/z, amu

0.0

5000.0

1.0e4

1.5e4

2.0e4

2.5e4

3.0e4

3.5e4

4.0e4

4.5e4

5.0e4

5.5e4

6.0e46.2e4

Inte

nsity

, cou

nts

289.0905

284.1340

267.1048290.0901

285.1340

284.3399 291.0917286.1355

268.1083293.0263292.1680277.0483 305.0620276.0265269.1095261.1293 301.1454299.1341285.3424

Polarity/Scan Type: Positive Sample Name: BVAV1298 Acq. File: 050511303_2.wiffAcq. Date: Thursday, May 05, 2011

47




X-ray crystallographic data for 21:

SO2Cl

NN

Me

NEt2

21CCDC #863213

Table S1. Crystal data and structure refinement for CCDC # 863213

Identification code CCDC # 863213

Empirical formula C11 H16 Cl N3 O2 S

Formula weight 289.78

Temperature 100(2) K

Wavelength 0.71073 Å

Crystal system Monoclinic

Space group P2(1)/c

Unit cell dimensions a = 8.2757(11) Å α= 90°.

b = 16.992(2) Å β= 93.804(2)°.

c = 9.7999(13) Å γ = 90°.

Volume 1375.0(3) Å3

Z 4

Density (calculated) 1.400 Mg/m3

Absorption coefficient 0.428 mm-1

F(000) 608

Crystal size 0.21 x 0.15 x 0.05 mm3

Crystal color, habit Yellow Plate

Theta range for data collection 2.40 to 28.21°.

Index ranges -10<=h<=10, 0<=k<=22, 0<=l<=12

Reflections collected 3162

Independent reflections 3162 [R(int) = 0.0716]

Completeness to theta = 25.00° 99.8 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 0.9789 and 0.9155

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 3162 / 0 / 191

48




Goodness-of-fit on F2 1.039

Final R indices [I>2sigma(I)] R1 = 0.0571, wR2 = 0.1426

R indices (all data) R1 = 0.0820, wR2 = 0.1609

Extinction coefficient not measured

Largest diff. peak and hole 0.758 and -0.638 e.Å-3

Table S2. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103)

for CCDC # 863213. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ Cl(1) 13177(1) 4753(1) 792(1) 36(1)

S(1) 12891(1) 3657(1) 1641(1) 28(1)

O(1) 12769(3) 3774(1) 3075(2) 34(1)

O(2) 14202(3) 3197(1) 1185(2) 39(1)

N(1) 9634(3) 4378(2) 1806(3) 35(1)

N(2) 8266(3) 4543(2) 2308(3) 33(1)

N(3) 8306(4) 5278(2) 2816(4) 28(1)

N(3B) 8007(17) 5053(9) 3272(15) 28(1)

C(1) 11075(3) 3313(2) 833(3) 26(1)

C(2) 11164(4) 2658(2) -15(3) 29(1)

C(3) 9762(4) 2336(2) -616(3) 29(1)

C(4) 8241(4) 2663(2) -386(3) 28(1)

C(5) 8164(3) 3327(2) 451(3) 27(1)

C(6) 9576(3) 3668(2) 1065(3) 26(1)

C(7) 6719(4) 2306(2) -1044(4) 37(1)

C(8) 6862(6) 5500(3) 3522(6) 40(1)

C(8B) 6440(30) 5210(12) 3720(20) 40(1)

C(9) 5888(8) 6145(4) 2783(7) 44(2)

C(9B) 5700(40) 5993(16) 3260(30) 44(2)

C(10) 9630(7) 5836(3) 2690(6) 35(1)

C(10B) 9449(18) 5493(9) 3735(16) 35(4)

C(11) 11071(6) 5685(3) 3721(5) 46(1)

C(11B) 9950(30) 6077(12) 2700(30) 35(1)

________________________________________________________________________________

49




Table S3. Bond lengths [Å] and angles [°] for CCDC # 863213.

_____________________________________________________

Cl(1)-S(1) 2.0601(11)

S(1)-O(1) 1.430(2)

S(1)-O(2) 1.433(2)

S(1)-C(1) 1.752(3)

N(1)-N(2) 1.295(4)

N(1)-C(6) 1.408(4)

N(2)-N(3B) 1.310(14)

N(2)-N(3) 1.345(4)

N(3)-C(10) 1.459(6)

N(3)-C(8) 1.469(5)

N(3B)-C(8B) 1.42(2)

N(3B)-C(10B) 1.45(2)

C(1)-C(2) 1.393(4)

C(1)-C(6) 1.412(4)

C(2)-C(3) 1.379(4)

C(2)-H(2) 0.9500

C(3)-C(4) 1.408(4)

C(3)-H(3) 0.9500

C(4)-C(5) 1.398(4)

C(4)-C(7) 1.504(4)

C(5)-C(6) 1.404(4)

C(5)-H(5) 0.9500

C(7)-H(7A) 0.9800

C(7)-H(7B) 0.9800

C(7)-H(7C) 0.9800

C(8)-C(9) 1.516(8)

C(8)-H(8A) 0.9900

C(8)-H(8B) 0.9900

C(8B)-C(9B) 1.52(3)

C(8B)-H(8BA) 0.9900

C(8B)-H(8BB) 0.9900

C(9)-H(9A) 0.9800

C(9)-H(9B) 0.9800

C(9)-H(9C) 0.9800

C(9B)-H(9BA) 0.9800

C(9B)-H(9BB) 0.9800

C(9B)-H(9BC) 0.9800

C(10)-C(11) 1.533(8)

C(10)-H(10A) 0.9900

C(10)-H(10B) 0.9900

C(10B)-C(11B) 1.49(3)

C(10B)-H(10C) 0.9900

C(10B)-H(10D) 0.9900

C(11)-H(11A) 0.9800

C(11)-H(11B) 0.9800

C(11)-H(11C) 0.9800

C(11B)-H(11D) 0.9800

C(11B)-H(11E) 0.9800

C(11B)-H(11F) 0.9800

O(1)-S(1)-O(2) 119.15(14)

O(1)-S(1)-C(1) 112.14(14)

O(2)-S(1)-C(1) 108.75(14)

O(1)-S(1)-Cl(1) 106.80(10)

O(2)-S(1)-Cl(1) 104.87(11)

C(1)-S(1)-Cl(1) 103.73(10)

N(2)-N(1)-C(6) 112.4(3)

N(1)-N(2)-N(3B) 127.3(7)

N(1)-N(2)-N(3) 109.9(3)

N(3B)-N(2)-N(3) 28.3(6)

N(2)-N(3)-C(10) 124.9(3)

N(2)-N(3)-C(8) 114.3(3)

C(10)-N(3)-C(8) 120.8(4)

N(2)-N(3B)-C(8B) 122.9(14)

N(2)-N(3B)-C(10B) 113.3(12)

C(8B)-N(3B)-C(10B) 123.5(15)

50




C(2)-C(1)-C(6) 121.3(3)

C(2)-C(1)-S(1) 117.3(2)

C(6)-C(1)-S(1) 121.4(2)

C(3)-C(2)-C(1) 119.7(3)

C(3)-C(2)-H(2) 120.1

C(1)-C(2)-H(2) 120.1

C(2)-C(3)-C(4) 120.7(3)

C(2)-C(3)-H(3) 119.6

C(4)-C(3)-H(3) 119.6

C(5)-C(4)-C(3) 119.2(3)

C(5)-C(4)-C(7) 120.5(3)

C(3)-C(4)-C(7) 120.3(3)

C(4)-C(5)-C(6) 121.0(3)

C(4)-C(5)-H(5) 119.5

C(6)-C(5)-H(5) 119.5

C(5)-C(6)-N(1) 125.1(3)

C(5)-C(6)-C(1) 118.0(3)

N(1)-C(6)-C(1) 116.7(3)

C(4)-C(7)-H(7A) 109.5

C(4)-C(7)-H(7B) 109.5

H(7A)-C(7)-H(7B) 109.5

C(4)-C(7)-H(7C) 109.5

H(7A)-C(7)-H(7C) 109.5

H(7B)-C(7)-H(7C) 109.5

N(3)-C(8)-C(9) 112.5(4)

N(3)-C(8)-H(8A) 109.1

C(9)-C(8)-H(8A) 109.1

N(3)-C(8)-H(8B) 109.1

C(9)-C(8)-H(8B) 109.1

H(8A)-C(8)-H(8B) 107.8

N(3B)-C(8B)-C(9B) 115.4(17)

N(3B)-C(8B)-H(8BA) 108.4

C(9B)-C(8B)-H(8BA) 108.4

N(3B)-C(8B)-H(8BB) 108.4

C(9B)-C(8B)-H(8BB) 108.4

H(8BA)-C(8B)-H(8BB) 107.5

C(8B)-C(9B)-H(9BA) 109.5

C(8B)-C(9B)-H(9BB) 109.5

H(9BA)-C(9B)-H(9BB) 109.5

C(8B)-C(9B)-H(9BC) 109.5

H(9BA)-C(9B)-H(9BC) 109.5

H(9BB)-C(9B)-H(9BC) 109.5

N(3)-C(10)-C(11) 113.0(4)

N(3)-C(10)-H(10A) 109.0

C(11)-C(10)-H(10A) 109.0

N(3)-C(10)-H(10B) 109.0

C(11)-C(10)-H(10B) 109.0

H(10A)-C(10)-H(10B) 107.8

N(3B)-C(10B)-C(11B) 112.8(15)

N(3B)-C(10B)-H(10C) 109.0

C(11B)-C(10B)-H(10C) 109.0

N(3B)-C(10B)-H(10D) 109.0

C(11B)-C(10B)-H(10D) 109.0

H(10C)-C(10B)-H(10D) 107.8

C(10B)-C(11B)-H(11D) 109.5

C(10B)-C(11B)-H(11E) 109.5

H(11D)-C(11B)-H(11E) 109.5

C(10B)-C(11B)-H(11F) 109.5

H(11D)-C(11B)-H(11F) 109.5

H(11E)-C(11B)-H(11F) 109.5

51




Table S4. Anisotropic displacement parameters (Å2x 103) for CCDC # 863213. The anisotropic

displacement factor exponent takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12 ]______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

Cl(1) 35(1) 35(1) 38(1) 13(1) -6(1) -11(1)

S(1) 25(1) 34(1) 25(1) 1(1) -1(1) 0(1)

O(1) 34(1) 43(1) 25(1) 0(1) -3(1) 0(1)

O(2) 27(1) 49(1) 40(1) -7(1) -1(1) 6(1)

N(1) 31(1) 36(1) 36(2) -8(1) -7(1) 6(1)

N(2) 37(1) 37(1) 26(1) -2(1) -2(1) 9(1)

N(3) 32(2) 32(2) 22(2) -2(1) 4(1) 3(1)

N(3B) 32(2) 32(2) 22(2) -2(1) 4(1) 3(1)

C(1) 24(1) 29(1) 25(2) 2(1) -1(1) 0(1)

C(2) 28(2) 32(2) 25(2) 1(1) 1(1) 5(1)

C(3) 34(2) 30(1) 24(2) -1(1) 0(1) 3(1)

C(4) 29(2) 29(2) 25(2) 2(1) -3(1) 0(1)

C(5) 28(1) 31(2) 23(2) 2(1) 1(1) 2(1)

C(6) 28(1) 27(1) 22(2) 2(1) -1(1) 2(1)

C(7) 31(2) 41(2) 38(2) -7(2) -5(1) -3(1)

C(8) 41(3) 41(3) 39(3) -6(2) 10(2) 6(2)

C(8B) 41(3) 41(3) 39(3) -6(2) 10(2) 6(2)

C(9) 36(3) 43(3) 52(5) -11(3) -3(3) 8(2)

C(9B) 36(3) 43(3) 52(5) -11(3) -3(3) 8(2)

C(10) 45(3) 26(3) 34(2) -6(2) 2(2) -4(2)

C(10B) 37(8) 42(8) 26(8) -6(7) -8(6) 5(6)

C(11) 40(3) 47(3) 48(3) -15(2) -2(2) 1(2)

C(11B) 45(3) 26(3) 34(2) -6(2) 2(2) -4(2)

______________________________________________________________________________

52




Table S5. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 10 3)for CCDC # 863213.

________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________

H(2) 12185 2435 -179 34

H(3) 9824 1889 -1191 35

H(5) 7140 3550 606 33

H(7A) 5795 2453 -522 56

H(7B) 6825 1731 -1054 56

H(7C) 6546 2500 -1984 56

H(8A) 7201 5681 4458 48

H(8B) 6166 5030 3603 48

H(8BA) 6510 5195 4734 48

H(8BB) 5706 4782 3391 48

H(9A) 6558 6619 2733 66

H(9B) 4930 6265 3282 66

H(9C) 5548 5969 1856 66

H(9BA) 5607 6013 2256 66

H(9BB) 6394 6424 3610 66

H(9BC) 4624 6045 3607 66

H(10A) 9221 6376 2824 42

H(10B) 10003 5803 1752 42

H(10C) 10350 5120 3942 42

H(10D) 9240 5774 4591 42

H(11A) 11498 5155 3581 68

H(11B) 10717 5729 4652 68

H(11C) 11921 6074 3588 68

H(11D) 10140 5805 1847 53

H(11E) 10943 6342 3050 53

H(11F) 9086 6468 2534 53

53





Me

Me

OTs

33

CCDC #863214Table S6. Crystal data and structure refinement for CCDC #863214.

Identification code CCDC #863214

Empirical formula C17 H24 O3 S




Crystal system Orthorhombic

Space group P2(1)2(1)2(1)

Unit cell dimensions a = 5.9123(3) Å α= 90°

b = 15.7609(7) Å β= 90°

c = 17.3746(7) Å γ = 90°

Volume 1619.02(13) Å3

Z 4

Density (calculated) 1.265 g/cm3


F(000) 664


Crystal color, habit Colorless rod

Theta range for data collection 1.74 to 25.40°

Index ranges -7<=h<=6, -19<=k<=13, -20<=l<=20




Absorption correction Multi-scan



54








Absolute structure parameter 0.05(7)

Largest diff. peak and hole 0.227 and -0.248 e Å-3

Table S7. Atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2x 103)for CCDC

#863214. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ S(1) -2070(1) 3948(1) 2488(1) 21(1)

O(1) -4486(2) 3998(1) 2472(1) 29(1)

O(2) -778(2) 4370(1) 1909(1) 27(1)

O(3) -1570(2) 2967(1) 2473(1) 21(1)

C(1) -1252(3) 1482(1) 3952(1) 30(1)

C(2) 458(3) 1929(1) 3666(1) 24(1)

C(3) 1923(4) 2467(1) 4164(1) 29(1)

C(4) 1052(3) 1852(1) 2819(1) 20(1)

C(5) 3496(3) 1534(1) 2701(1) 24(1)

C(6) 4038(3) 1396(1) 1852(1) 25(1)

C(7) 3612(3) 2189(1) 1368(1) 22(1)

C(8) 1215(3) 2530(1) 1508(1) 22(1)

C(9) 803(3) 2679(1) 2361(1) 19(1)

C(10) 3999(3) 2004(1) 515(1) 28(1)

C(11) -1125(3) 4299(1) 3398(1) 21(1)

C(12) -2530(3) 4189(1) 4034(1) 25(1)

C(13) -1873(3) 4525(1) 4739(1) 26(1)

C(14) 155(3) 4968(1) 4818(1) 24(1)

C(15) 1559(3) 5044(1) 4176(1) 24(1)

C(16) 932(3) 4717(1) 3462(1) 22(1)

C(17) 777(4) 5381(1) 5571(1) 33(1)

________________________________________________________________________________

55




Table S8. Bond lengths [Å] and angles [°] for CCDC #863214.

_____________________________________________________

S(1)-O(2) 1.4273(12)

S(1)-O(1) 1.4307(12)

S(1)-O(3) 1.5756(10)

S(1)-C(11) 1.7648(15)

O(3)-C(9) 1.4871(17)

C(1)-C(2) 1.329(3)

C(2)-C(3) 1.489(2)

C(2)-C(4) 1.519(2)

C(4)-C(9) 1.534(2)

C(4)-C(5) 1.543(2)

C(5)-C(6) 1.526(2)

C(6)-C(7) 1.528(2)

C(7)-C(10) 1.529(2)

C(7)-C(8) 1.535(2)

C(8)-C(9) 1.521(2)

C(11)-C(16) 1.387(2)

C(11)-C(12) 1.394(2)

C(12)-C(13) 1.389(2)

C(13)-C(14) 1.394(2)

C(14)-C(15) 1.395(2)

C(14)-C(17) 1.507(2)

C(15)-C(16) 1.394(2)

O(2)-S(1)-O(1) 119.71(7)

O(2)-S(1)-O(3) 110.14(6)

O(1)-S(1)-O(3) 103.93(6)

O(2)-S(1)-C(11) 108.41(7)

O(1)-S(1)-C(11) 108.46(8)

O(3)-S(1)-C(11) 105.24(6)

C(9)-O(3)-S(1) 118.60(8)

C(1)-C(2)-C(3) 121.81(16)

C(1)-C(2)-C(4) 119.71(15)

C(3)-C(2)-C(4) 118.35(15)

C(2)-C(4)-C(9) 114.30(12)

C(2)-C(4)-C(5) 111.77(13)

C(9)-C(4)-C(5) 107.28(12)

C(6)-C(5)-C(4) 111.81(13)

C(5)-C(6)-C(7) 112.31(12)

C(6)-C(7)-C(10) 110.64(12)

C(6)-C(7)-C(8) 110.60(13)

C(10)-C(7)-C(8) 110.98(14)

C(9)-C(8)-C(7) 110.84(13)

O(3)-C(9)-C(8) 109.00(12)

O(3)-C(9)-C(4) 106.36(12)

C(8)-C(9)-C(4) 110.99(11)

C(16)-C(11)-C(12) 121.20(14)

C(16)-C(11)-S(1) 119.87(12)

C(12)-C(11)-S(1) 118.84(13)

C(13)-C(12)-C(11) 119.01(15)

C(12)-C(13)-C(14) 121.22(15)

C(13)-C(14)-C(15) 118.41(15)

C(13)-C(14)-C(17) 120.78(16)

C(15)-C(14)-C(17) 120.77(16)

C(16)-C(15)-C(14) 121.44(15)

C(11)-C(16)-C(15) 118.67(14)

_____________________________________________________

56




Table S9. Anisotropic displacement parameters (Å2x 103) for CCDC #863214. The anisotropic displacement factor

exponent takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12]______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

S(1) 20(1) 21(1) 23(1) -1(1) -1(1) 3(1)

O(1) 21(1) 32(1) 34(1) -5(1) -4(1) 5(1)

O(2) 30(1) 24(1) 26(1) 3(1) 0(1) 3(1)

O(3) 18(1) 21(1) 25(1) -2(1) -1(1) -1(1)

C(1) 30(1) 37(1) 24(1) 2(1) 3(1) 1(1)

C(2) 28(1) 22(1) 21(1) 0(1) -1(1) 4(1)

C(3) 37(1) 28(1) 23(1) -2(1) -2(1) 1(1)

C(4) 23(1) 19(1) 19(1) -1(1) -1(1) -3(1)

C(5) 26(1) 21(1) 24(1) 2(1) -2(1) 4(1)

C(6) 26(1) 22(1) 28(1) -2(1) 3(1) 5(1)

C(7) 22(1) 22(1) 23(1) -2(1) 2(1) 0(1)

C(8) 24(1) 22(1) 19(1) 0(1) -1(1) 0(1)

C(9) 15(1) 20(1) 22(1) -2(1) -1(1) 1(1)

C(10) 31(1) 29(1) 24(1) 0(1) 5(1) 3(1)

C(11) 21(1) 16(1) 24(1) -1(1) -1(1) 2(1)

C(12) 21(1) 23(1) 31(1) 2(1) 1(1) -2(1)

C(13) 30(1) 24(1) 25(1) 2(1) 6(1) 1(1)

C(14) 29(1) 17(1) 26(1) 1(1) -1(1) 4(1)

C(15) 24(1) 20(1) 30(1) 0(1) -3(1) -3(1)

C(16) 22(1) 20(1) 25(1) -1(1) 3(1) 1(1)

C(17) 44(1) 28(1) 26(1) -2(1) -4(1) 1(1)

______________________________________________________________________________

57




Table S10. Hydrogen coordinates (x 104) and isotropic displacement parameters (Å2 x 10 3) for CCDC #863214.________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ H(4A) 9 1423 2585 24

H(5A) 4564 1955 2918 28

H(5B) 3704 994 2983 28

H(6A) 3097 925 1652 30

H(6B) 5644 1227 1800 30

H(7A) 4716 2635 1532 27

H(8A) 1012 3070 1224 26

H(8B) 94 2118 1310 26

H(9A) 1878 3116 2562 23

H(10A) 5536 1786 440 42

H(10B) 3807 2528 217 42

H(10C) 2902 1580 339 42

H(12A) -3916 3889 3987 30

H(13A) -2823 4451 5175 31

H(15A) 2973 5324 4227 29

H(16A) 1893 4780 3027 27

H(17A) 84 5065 5996 49

H(17B) 226 5967 5575 49

H(17C) 2425 5378 5631 49

H(1A) -2120(40) 1122(12) 3639(12) 33(5)

H(3A) 1960(40) 3037(15) 3984(13) 54(7)

H(1B) -1560(30) 1522(12) 4486(12) 35(5)

H(3B) 1240(40) 2511(14) 4674(14) 51(6)

H(3C) 3440(40) 2213(14) 4160(14) 49(6)

________________________________________________________________________________

58




X-ray crystallographic data for (–)-39:

NHTs

Me

(–)-39



Empirical formula C15 H21 N O2 S





Space group P2(1)


b = 9.5301(10) Å β= 96.0140(10)°

c = 9.8131(11) Å γ = 90°

Volume 752.83(14) Å3

Z 2



F(000) 300



Index ranges -7<=h<=9, -11<=k<=11, -9<=l<=11







Goodness-of-fit on F2 1.048Final R indices [I>2sigma(I)] R1 = 0.0391, wR2 = 0.1010


59







#863215. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________

S(1) -689(1) 778(1) 9825(1) 22(1)

O(1) -800(2) -650(2) 10281(2) 28(1)

O(2) -1829(2) 1797(2) 10253(2) 30(1)

N(1) 1157(3) 1343(2) 10367(2) 25(1)

C(1) 4031(8) 1093(5) 6043(4) 89(2)

C(2) 3963(5) -354(4) 6573(4) 53(1)

C(3) 3407(4) -412(3) 7989(3) 37(1)

C(4) 3259(3) 697(3) 8765(2) 27(1)

C(5) 2671(3) 517(2) 10183(3) 26(1)

C(6) -922(3) 764(3) 8012(2) 23(1)

C(7) -1056(4) -488(3) 7288(3) 30(1)

C(8) -1260(4) -458(3) 5865(3) 35(1)

C(9) -1322(3) 809(4) 5156(2) 31(1)

C(10) -1525(4) 830(5) 3609(3) 47(1)

C(11) 4293(6) 2226(4) 6954(4) 65(1)

C(12) 3641(5) 2160(3) 8304(4) 43(1)

C(13) -989(3) 2045(3) 7336(3) 26(1)

C(14) -1187(4) 2051(3) 5904(3) 30(1)

C(15) 4000(3) 946(4) 11333(3) 41(1)

________________________________________________________________________________

60





_____________________________________________________

S(1)-O(2) 1.4333(19)

S(1)-O(1) 1.4384(18)

S(1)-N(1) 1.625(2)

S(1)-C(6) 1.769(2)

N(1)-C(5) 1.483(3)

C(1)-C(11) 1.404(6)

C(1)-C(2) 1.477(6)

C(2)-C(3) 1.506(5)

C(3)-C(4) 1.316(4)

C(4)-C(12) 1.508(4)

C(4)-C(5) 1.526(3)

C(5)-C(15) 1.532(4)

C(6)-C(13) 1.388(4)

C(6)-C(7) 1.387(4)

C(7)-C(8) 1.389(4)

C(8)-C(9) 1.392(5)

C(9)-C(14) 1.391(5)

C(9)-C(10) 1.509(3)

C(11)-C(12) 1.478(5)

C(13)-C(14) 1.397(4)

O(2)-S(1)-O(1) 119.11(11)

O(2)-S(1)-N(1) 106.13(12)

O(1)-S(1)-N(1) 107.29(11)

O(2)-S(1)-C(6) 107.20(12)

O(1)-S(1)-C(6) 107.61(13)

N(1)-S(1)-C(6) 109.25(11)

C(5)-N(1)-S(1) 121.80(17)

C(11)-C(1)-C(2) 120.2(4)

C(1)-C(2)-C(3) 112.6(3)

C(4)-C(3)-C(2) 124.0(3)

C(3)-C(4)-C(12) 122.3(2)

C(3)-C(4)-C(5) 119.6(3)

C(12)-C(4)-C(5) 118.1(2)

N(1)-C(5)-C(4) 113.1(2)

N(1)-C(5)-C(15) 107.1(2)

C(4)-C(5)-C(15) 112.3(2)

C(13)-C(6)-C(7) 120.95(19)

C(13)-C(6)-S(1) 118.0(2)

C(7)-C(6)-S(1) 121.1(2)

C(6)-C(7)-C(8) 119.5(3)

C(7)-C(8)-C(9) 121.0(3)

C(14)-C(9)-C(8) 118.5(2)

C(14)-C(9)-C(10) 120.9(3)

C(8)-C(9)-C(10) 120.6(3)

C(1)-C(11)-C(12) 119.6(3)

C(11)-C(12)-C(4) 114.4(3)

C(6)-C(13)-C(14) 118.6(2)

C(9)-C(14)-C(13) 121.4(3)

___________________________________________

61




Table S14. Anisotropic displacement parameters (Å2x 103) for CCDC #863215. The anisotropic displacement

factor exponent takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12]______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

S(1) 27(1) 21(1) 18(1) 0(1) 4(1) 0(1)

O(1) 37(1) 24(1) 23(1) 2(1) 4(1) -1(1)

O(2) 37(1) 29(1) 24(1) -1(1) 8(1) 2(1)

N(1) 33(1) 19(1) 23(1) 0(1) 1(1) 0(1)

C(1) 154(5) 75(4) 47(2) -2(2) 54(3) -23(3)

C(2) 71(3) 54(2) 38(2) -9(2) 21(2) 5(2)

C(3) 40(2) 30(1) 42(2) -1(1) 9(1) -1(1)

C(4) 21(1) 31(1) 29(1) 4(1) 0(1) -2(1)

C(5) 32(1) 21(2) 26(1) 3(1) 1(1) 2(1)

C(6) 21(1) 30(1) 17(1) 1(1) 2(1) 2(1)

C(7) 40(2) 26(1) 23(2) -2(1) 5(1) 2(1)

C(8) 42(2) 36(2) 27(2) -8(1) 6(1) 2(1)

C(9) 28(1) 47(1) 19(1) -1(2) 2(1) -2(2)

C(10) 57(2) 62(2) 20(1) -4(2) -1(1) -3(2)

C(11) 91(3) 53(2) 58(2) 14(2) 34(2) -3(2)

C(12) 54(2) 36(2) 42(2) 4(1) 17(2) -10(1)

C(13) 23(2) 29(2) 26(2) -1(1) 1(1) -1(1)

C(14) 31(2) 36(2) 22(2) 7(1) -1(1) -1(1)

C(15) 38(1) 48(2) 34(1) 3(2) -7(1) 5(2)

______________________________________________________________________________

62




Table S15. Hydrogen coordinates (x 104) and isotropic displacement parameters (Å2 x 10 3) for CCDC #863215.

63





MeMe

MeTsO

41



Empirical formula C22 H32 O3 S





Space group P2(1)


b = 6.1623(6) Å β= 100.004(2)°

c = 17.1390(17) Å γ = 90°

Volume 1021.61(18) Å3

Z 2



F(000) 408


Crystal color, habit Pale yellow plate


Index ranges -10<=h<=11, -7<=k<=7, -20<=l<=20







64







Absolute structure parameter -0.01(7)




________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ S(1) 7605(1) 7174(1) 8530(1) 22(1)

O(1) 7505(2) 9409(2) 8079(1) 23(1)

O(2) 6984(2) 7491(3) 9212(1) 32(1)

O(3) 7119(2) 5460(3) 7988(1) 30(1)

C(1) 3910(3) 10387(6) 8072(2) 50(1)

C(2) 4484(2) 9438(4) 7504(1) 33(1)

C(3) 3972(2) 7357(5) 7142(2) 44(1)

C(4) 5547(2) 10702(4) 7140(1) 26(1)

C(5) 5000(2) 11234(4) 6267(1) 33(1)

C(6) 6047(2) 12559(4) 5903(1) 35(1)

C(7) 7449(2) 11419(4) 5966(1) 26(1)

C(8) 8462(2) 12975(4) 5661(1) 33(1)

C(9) 9969(2) 12224(5) 5835(1) 35(1)

C(10) 10439(2) 11819(4) 6716(1) 30(1)

C(11) 9495(2) 10216(4) 7054(1) 29(1)

C(12) 7993(2) 10990(4) 6861(1) 20(1)

C(13) 7283(3) 9348(4) 5457(1) 34(1)

C(14) 9825(2) 7907(4) 6904(1) 30(1)

C(15) 6962(2) 9589(4) 7220(1) 20(1)

C(16) 9399(2) 6879(4) 8842(1) 22(1)

C(17) 10155(2) 8517(4) 9273(1) 26(1)

C(18) 11563(2) 8255(4) 9519(1) 29(1)

C(19) 12228(2) 6360(4) 9348(1) 29(1)

65




C(20) 11445(2) 4721(4) 8934(1) 30(1)

C(21) 10030(2) 4955(4) 8680(1) 25(1)

C(22) 13769(2) 6084(5) 9609(2) 41(1)

________________________________________________________________________________


_____________________________________________________

S(1)-O(2) 1.4226(15)

S(1)-O(3) 1.4329(16)

S(1)-O(1) 1.5739(16)

S(1)-C(16) 1.759(2)

O(1)-C(15) 1.480(2)

C(1)-C(2) 1.341(4)

C(2)-C(3) 1.475(4)

C(2)-C(4) 1.521(3)

C(4)-C(15) 1.535(3)

C(4)-C(5) 1.535(3)

C(5)-C(6) 1.529(3)

C(6)-C(7) 1.533(3)

C(7)-C(8) 1.537(3)

C(7)-C(13) 1.538(3)

C(7)-C(12) 1.558(3)

C(8)-C(9) 1.530(3)

C(9)-C(10) 1.521(3)

C(10)-C(11) 1.535(3)

C(11)-C(14) 1.491(3)

C(11)-C(12) 1.531(3)

C(12)-C(15) 1.538(3)

C(16)-C(21) 1.388(3)

C(16)-C(17) 1.388(3)

C(17)-C(18) 1.383(3)

C(18)-C(19) 1.393(3)

C(19)-C(20) 1.388(3)

C(19)-C(22) 1.512(3)

C(20)-C(21) 1.390(3)

O(2)-S(1)-O(3) 119.42(10)

O(2)-S(1)-O(1) 106.54(10)

O(3)-S(1)-O(1) 109.95(8)

O(2)-S(1)-C(16) 108.35(9)

O(3)-S(1)-C(16) 108.90(10)

O(1)-S(1)-C(16) 102.32(9)

C(15)-O(1)-S(1) 122.36(13)

C(1)-C(2)-C(3) 122.0(3)

C(1)-C(2)-C(4) 118.7(3)

C(3)-C(2)-C(4) 118.7(2)

C(2)-C(4)-C(15) 114.25(18)

C(2)-C(4)-C(5) 111.08(19)

C(15)-C(4)-C(5) 109.95(17)

C(6)-C(5)-C(4) 111.42(18)

C(5)-C(6)-C(7) 112.7(2)

C(6)-C(7)-C(8) 108.45(19)

C(6)-C(7)-C(13) 109.61(18)

C(8)-C(7)-C(13) 109.66(17)

C(6)-C(7)-C(12) 107.28(16)

C(8)-C(7)-C(12) 107.97(17)

C(13)-C(7)-C(12) 113.71(18)

C(9)-C(8)-C(7) 114.0(2)

C(10)-C(9)-C(8) 111.09(17)

66




C(9)-C(10)-C(11) 112.42(19)

C(14)-C(11)-C(12) 119.3(2)

C(14)-C(11)-C(10) 112.68(19)

C(12)-C(11)-C(10) 109.89(18)

C(11)-C(12)-C(15) 114.54(17)

C(11)-C(12)-C(7) 114.76(16)

C(15)-C(12)-C(7) 110.63(16)

O(1)-C(15)-C(4) 106.67(15)

O(1)-C(15)-C(12) 106.94(15)

C(4)-C(15)-C(12) 111.24(17)

C(21)-C(16)-C(17) 120.72(19)

C(21)-C(16)-S(1) 119.10(17)

C(17)-C(16)-S(1) 120.12(17)

C(18)-C(17)-C(16) 119.4(2)

C(17)-C(18)-C(19) 121.0(2)

C(20)-C(19)-C(18) 118.6(2)

C(20)-C(19)-C(22) 120.4(2)

C(18)-C(19)-C(22) 121.0(2)

C(19)-C(20)-C(21) 121.3(2)

C(16)-C(21)-C(20) 118.9(2)

67




Table S19. Anisotropic displacement parameters (Å2x 103) for CCDC #863216. The anisotropic displacement factor

exponent takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12]______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

S(1) 25(1) 20(1) 23(1) 3(1) 8(1) -1(1)

O(1) 31(1) 19(1) 19(1) 1(1) 5(1) -1(1)

O(2) 30(1) 39(1) 29(1) 9(1) 13(1) 6(1)

O(3) 29(1) 23(1) 35(1) 1(1) 2(1) -6(1)

C(1) 46(2) 71(2) 36(1) 2(2) 18(1) -11(2)

C(2) 24(1) 33(1) 45(1) 4(1) 12(1) 4(1)

C(3) 27(1) 39(2) 66(2) 8(2) 6(1) -3(1)

C(4) 26(1) 22(1) 31(1) -1(1) 9(1) 3(1)

C(5) 27(1) 39(2) 34(1) 3(1) 4(1) 4(1)

C(6) 37(1) 36(2) 29(1) 10(1) 0(1) 5(1)

C(7) 33(1) 26(1) 21(1) 1(1) 8(1) -2(1)

C(8) 46(1) 28(1) 25(1) 5(1) 9(1) -6(1)

C(9) 40(1) 33(1) 38(1) -3(1) 24(1) -7(1)

C(10) 28(1) 22(1) 43(1) 1(1) 15(1) -2(1)

C(11) 26(1) 25(1) 37(1) 6(1) 11(1) 2(1)

C(12) 24(1) 17(1) 21(1) -2(1) 7(1) 0(1)

C(13) 40(1) 39(2) 24(1) -3(1) 10(1) -9(1)

C(14) 30(1) 22(1) 42(1) -1(1) 16(1) 1(1)

C(15) 24(1) 20(1) 16(1) -1(1) 6(1) 1(1)

C(16) 24(1) 24(1) 20(1) 2(1) 8(1) -1(1)

C(17) 32(1) 23(1) 24(1) -1(1) 11(1) -2(1)

C(18) 34(1) 30(1) 24(1) -1(1) 8(1) -10(1)

C(19) 27(1) 33(1) 29(1) 8(1) 11(1) -2(1)

C(20) 31(1) 29(1) 33(1) 3(1) 11(1) 5(1)

C(21) 30(1) 21(1) 26(1) -3(1) 8(1) -1(1)

C(22) 27(1) 51(2) 46(1) 12(1) 5(1) -5(1)

______________________________________________________________________________

68





x y z U(eq)

________________________________________________________________________________ H(1A) 3190(40) 9570(60) 8271(18) 69(10)

H(1B) 4250(30) 11450(50) 8372(18) 53(10)

H(3A) 3313 6746 7433 66

H(3C) 4733 6373 7154 66

H(3D) 3537 7597 6602 66

H(4A) 5693 12086 7423 31

H(5A) 4800 9894 5972 40

H(5B) 4145 12047 6227 40

H(6A) 6181 13952 6169 42

H(6B) 5677 12829 5349 42

H(8A) 8185 13144 5093 39

H(8B) 8397 14388 5902 39

H(9A) 10066 10900 5544 42

H(9B) 10553 13323 5657 42

H(10A) 10453 13186 6998 36

H(10B) 11374 11251 6803 36

H(11A) 9747 10383 7630 34

H(12A) 7985 12409 7118 24

H(13B) 6948 9725 4914 50

H(13C) 6636 8391 5642 50

H(13D) 8162 8635 5498 50

H(14A) 9208 6973 7125 45

H(14B) 10761 7600 7147 45

H(14C) 9718 7662 6344 45

H(15A) 6871 8150 6973 24

H(17A) 9719 9780 9396 31

H(18A) 12073 9359 9802 35

H(20A) 11876 3442 8823 36

H(21A) 9515 3840 8407 30

H(22A) 14146 7365 9884 62

H(22B) 14197 5859 9153 62

H(22C) 13943 4853 9955 62

69





x y z U(eq)

________________________________________________________________________________ H(1A) 3190(40) 9570(60) 8271(18) 69(10)

H(1B) 4250(30) 11450(50) 8372(18) 53(10)

H(3A) 3313 6746 7433 66

H(3C) 4733 6373 7154 66

H(3D) 3537 7597 6602 66

H(4A) 5693 12086 7423 31

H(5A) 4800 9894 5972 40

H(5B) 4145 12047 6227 40

H(6A) 6181 13952 6169 42

H(6B) 5677 12829 5349 42

H(8A) 8185 13144 5093 39

H(8B) 8397 14388 5902 39

H(9A) 10066 10900 5544 42

H(9B) 10553 13323 5657 42

H(10A) 10453 13186 6998 36

H(10B) 11374 11251 6803 36

H(11A) 9747 10383 7630 34

H(12A) 7985 12409 7118 24

H(13B) 6948 9725 4914 50

H(13C) 6636 8391 5642 50

H(13D) 8162 8635 5498 50

H(14A) 9208 6973 7125 45

H(14B) 10761 7600 7147 45

H(14C) 9718 7662 6344 45

H(15A) 6871 8150 6973 24

H(17A) 9719 9780 9396 31

H(18A) 12073 9359 9802 35

H(20A) 11876 3442 8823 36

H(21A) 9515 3840 8407 30

H(22A) 14146 7365 9884 62

H(22B) 14197 5859 9153 62

H(22C) 13943 4853 9955 62

70





iPrTsN

MeMe

43

CCDC #863217

Table S22. Crystal data and structure refinement for CCDC #863217.








Unit cell dimensions a = 8.724(3) Å α= 90°.

b = 11.713(4) Å β= 90°.

c = 22.823(7) Å γ = 90°.

Volume 2332.3(12) Å3

Z 4

Density (calculated) 1.246 Mg/m3


F(000) 944


Crystal color, habit Colorless Rod

Theta range for data collection 1.95 to 25.45°.

Index ranges -10<=h<=10, -14<=k<=12, -27<=l<=22




Absorption correction multi-scan



71









Largest diff. peak and hole 0.315 and -0.427 e.Å-3

Table S23. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103)

for CCDC #863217. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ S(1) 6651(1) 6954(1) 4093(1) 24(1)O(1) 5756(3) 7955(3) 4210(1) 29(1)

O(2) 8285(3) 7034(3) 4044(1) 28(1)N(1) 6233(4) 6059(3) 4602(2) 24(1)

C(1) 4683(5) 6114(4) 4875(2) 25(1)C(2) 4654(5) 5074(4) 5277(2) 24(1)

C(3) 5666(5) 4205(4) 4937(2) 23(1)C(4) 7069(5) 4967(4) 4778(2) 21(1)

C(5) 7989(5) 5261(4) 5336(2) 27(1)C(6) 7025(5) 5891(4) 5789(2) 30(1)

C(7) 5427(5) 5380(4) 5865(2) 30(1)C(8) 4874(5) 3827(4) 4367(2) 24(1)

C(9) 5910(4) 3094(4) 3996(2) 26(1)C(10) 7522(5) 3563(4) 3942(2) 24(1)

C(11) 8064(5) 4436(4) 4299(2) 23(1)C(12) 9578(5) 4804(4) 4209(2) 25(1)

C(13) 10494(5) 4322(4) 3783(2) 29(1)C(14) 9962(5) 3453(4) 3422(2) 28(1)

C(15) 8479(5) 3084(4) 3522(2) 24(1)C(16) 3010(5) 4675(4) 5392(2) 29(1)

C(17) 6094(5) 3142(4) 5285(2) 27(1)C(18) 10892(5) 2935(5) 2931(2) 31(1)

C(19) 10437(6) 3444(6) 2351(2) 47(2)C(20) 12603(5) 2987(5) 3030(2) 34(1)

72




C(21) 5954(5) 6401(4) 3426(2) 27(1)C(22) 4448(5) 6635(4) 3259(2) 28(1)

C(23) 3895(5) 6177(4) 2739(2) 29(1)C(24) 4783(6) 5490(4) 2385(2) 31(1)

C(25) 6284(6) 5267(5) 2562(2) 32(1)C(26) 6869(5) 5710(4) 3073(2) 27(1)

C(27) 4184(7) 5014(5) 1819(2) 42(1)________________________________________________________________________________


_____________________________________________________

S(1)-O(2) 1.433(3)

S(1)-O(1) 1.434(3)

S(1)-N(1) 1.606(4)

S(1)-C(21) 1.762(5)

N(1)-C(1) 1.491(5)

N(1)-C(4) 1.526(5)

C(1)-C(2) 1.526(7)

C(1)-H(1A) 0.9900

C(1)-H(1B) 0.9900

C(2)-C(16) 1.531(6)

C(2)-C(7) 1.543(7)

C(2)-C(3) 1.555(6)

C(3)-C(17) 1.524(6)

C(3)-C(8) 1.538(6)

C(3)-C(4) 1.558(6)

C(4)-C(11) 1.529(6)

C(4)-C(5) 1.544(6)

C(5)-C(6) 1.523(6)

C(5)-H(5A) 0.9900

C(5)-H(5B) 0.9900

C(6)-C(7) 1.527(6)

C(6)-H(6A) 0.9900

C(6)-H(6B) 0.9900

C(7)-H(7A) 0.9900

C(7)-H(7B) 0.9900

C(8)-C(9) 1.507(6)

C(8)-H(8A) 0.9900

C(8)-H(8B) 0.9900

C(9)-C(10) 1.514(6)

C(9)-H(9A) 0.9900

C(9)-H(9B) 0.9900

C(10)-C(15) 1.390(6)

C(10)-C(11) 1.390(6)

C(11)-C(12) 1.405(6)

C(12)-C(13) 1.380(7)

C(12)-H(12) 0.9500

C(13)-C(14) 1.388(7)

C(13)-H(13) 0.9500

C(14)-C(15) 1.383(6)

C(14)-C(18) 1.512(7)

C(15)-H(15) 0.9500

C(16)-H(16A) 0.9800

C(16)-H(16B) 0.9800

C(16)-H(16C) 0.9800

C(17)-H(17A) 0.9800

C(17)-H(17B) 0.9800

73




C(17)-H(17C) 0.9800

C(18)-C(19) 1.504(7)

C(18)-C(20) 1.511(6)

C(18)-H(18) 1.0000

C(19)-H(19A) 0.9800

C(19)-H(19B) 0.9800

C(19)-H(19C) 0.9800

C(20)-H(20A) 0.9800

C(20)-H(20B) 0.9800

C(20)-H(20C) 0.9800

C(21)-C(26) 1.394(6)

C(21)-C(22) 1.395(6)

C(22)-C(23) 1.390(7)

C(22)-H(22) 0.9500

C(23)-C(24) 1.378(7)

C(23)-H(23) 0.9500

C(24)-C(25) 1.394(7)

C(24)-C(27) 1.501(7)

C(25)-C(26) 1.374(7)

C(25)-H(25) 0.9500

C(26)-H(26) 0.9500

C(27)-H(27A) 0.9800

C(27)-H(27B) 0.9800

C(27)-H(27C) 0.9800

O(2)-S(1)-O(1) 120.2(2)

O(2)-S(1)-N(1) 108.9(2)

O(1)-S(1)-N(1) 106.00(19)

O(2)-S(1)-C(21) 107.5(2)

O(1)-S(1)-C(21) 105.9(2)

N(1)-S(1)-C(21) 107.8(2)

C(1)-N(1)-C(4) 111.0(3)

C(1)-N(1)-S(1) 118.7(3)

C(4)-N(1)-S(1) 129.0(3)

N(1)-C(1)-C(2) 103.5(3)

N(1)-C(1)-H(1A) 111.1

C(2)-C(1)-H(1A) 111.1

N(1)-C(1)-H(1B) 111.1

C(2)-C(1)-H(1B) 111.1

H(1A)-C(1)-H(1B) 109.0

C(1)-C(2)-C(16) 111.3(4)

C(1)-C(2)-C(7) 109.3(4)

C(16)-C(2)-C(7) 109.4(4)

C(1)-C(2)-C(3) 102.2(4)

C(16)-C(2)-C(3) 114.7(4)

C(7)-C(2)-C(3) 109.8(4)

C(17)-C(3)-C(8) 108.4(4)

C(17)-C(3)-C(2) 114.4(4)

C(8)-C(3)-C(2) 110.9(4)

C(17)-C(3)-C(4) 113.4(3)

C(8)-C(3)-C(4) 108.7(4)

C(2)-C(3)-C(4) 100.8(3)

N(1)-C(4)-C(11) 115.1(4)

N(1)-C(4)-C(5) 106.2(4)

C(11)-C(4)-C(5) 112.6(4)

N(1)-C(4)-C(3) 99.6(3)

C(11)-C(4)-C(3) 112.3(4)

C(5)-C(4)-C(3) 110.1(4)

C(6)-C(5)-C(4) 112.3(4)

C(6)-C(5)-H(5A) 109.1

C(4)-C(5)-H(5A) 109.1

C(6)-C(5)-H(5B) 109.1

C(4)-C(5)-H(5B) 109.1

H(5A)-C(5)-H(5B) 107.9

C(5)-C(6)-C(7) 113.1(4)

C(5)-C(6)-H(6A) 109.0

C(7)-C(6)-H(6A) 109.0

C(5)-C(6)-H(6B) 109.0

C(7)-C(6)-H(6B) 109.0

H(6A)-C(6)-H(6B) 107.8

C(6)-C(7)-C(2) 113.0(4)

C(6)-C(7)-H(7A) 109.0

74




C(2)-C(7)-H(7A) 109.0

C(6)-C(7)-H(7B) 109.0

C(2)-C(7)-H(7B) 109.0

H(7A)-C(7)-H(7B) 107.8

C(9)-C(8)-C(3) 111.7(4)

C(9)-C(8)-H(8A) 109.3

C(3)-C(8)-H(8A) 109.3

C(9)-C(8)-H(8B) 109.3

C(3)-C(8)-H(8B) 109.3

H(8A)-C(8)-H(8B) 107.9

C(8)-C(9)-C(10) 113.3(4)

C(8)-C(9)-H(9A) 108.9

C(10)-C(9)-H(9A) 108.9

C(8)-C(9)-H(9B) 108.9

C(10)-C(9)-H(9B) 108.9

H(9A)-C(9)-H(9B) 107.7

C(15)-C(10)-C(11) 119.8(4)

C(15)-C(10)-C(9) 117.8(4)

C(11)-C(10)-C(9) 122.4(4)

C(10)-C(11)-C(12) 117.4(4)

C(10)-C(11)-C(4) 121.7(4)

C(12)-C(11)-C(4) 120.9(4)

C(13)-C(12)-C(11) 121.4(4)

C(13)-C(12)-H(12) 119.3

C(11)-C(12)-H(12) 119.3

C(12)-C(13)-C(14) 121.7(4)

C(12)-C(13)-H(13) 119.2

C(14)-C(13)-H(13) 119.2

C(15)-C(14)-C(13) 116.4(4)

C(15)-C(14)-C(18) 119.9(5)

C(13)-C(14)-C(18) 123.7(4)

C(14)-C(15)-C(10) 123.3(4)

C(14)-C(15)-H(15) 118.3

C(10)-C(15)-H(15) 118.3

C(2)-C(16)-H(16A) 109.5

C(2)-C(16)-H(16B) 109.5

H(16A)-C(16)-H(16B) 109.5

C(2)-C(16)-H(16C) 109.5

H(16A)-C(16)-H(16C) 109.5

H(16B)-C(16)-H(16C) 109.5

C(3)-C(17)-H(17A) 109.5

C(3)-C(17)-H(17B) 109.5

H(17A)-C(17)-H(17B) 109.5

C(3)-C(17)-H(17C) 109.5

H(17A)-C(17)-H(17C) 109.5

H(17B)-C(17)-H(17C) 109.5

C(19)-C(18)-C(20) 112.2(4)

C(19)-C(18)-C(14) 110.6(4)

C(20)-C(18)-C(14) 113.7(4)

C(19)-C(18)-H(18) 106.6

C(20)-C(18)-H(18) 106.6

C(14)-C(18)-H(18) 106.6

C(18)-C(19)-H(19A) 109.5

C(18)-C(19)-H(19B) 109.5

H(19A)-C(19)-H(19B) 109.5

C(18)-C(19)-H(19C) 109.5

H(19A)-C(19)-H(19C) 109.5

H(19B)-C(19)-H(19C) 109.5

C(18)-C(20)-H(20A) 109.5

C(18)-C(20)-H(20B) 109.5

H(20A)-C(20)-H(20B) 109.5

C(18)-C(20)-H(20C) 109.5

H(20A)-C(20)-H(20C) 109.5

H(20B)-C(20)-H(20C) 109.5

C(26)-C(21)-C(22) 119.7(4)

C(26)-C(21)-S(1) 121.0(4)

C(22)-C(21)-S(1) 119.2(4)

C(23)-C(22)-C(21) 118.9(4)

C(23)-C(22)-H(22) 120.5

C(21)-C(22)-H(22) 120.5

C(24)-C(23)-C(22) 122.0(5)

C(24)-C(23)-H(23) 119.0

75




C(22)-C(23)-H(23) 119.0

C(23)-C(24)-C(25) 117.9(5)

C(23)-C(24)-C(27) 121.6(5)

C(25)-C(24)-C(27) 120.4(5)

C(26)-C(25)-C(24) 121.6(5)

C(26)-C(25)-H(25) 119.2

C(24)-C(25)-H(25) 119.2

C(25)-C(26)-C(21) 119.8(4)

C(25)-C(26)-H(26) 120.1

C(21)-C(26)-H(26) 120.1

C(24)-C(27)-H(27A) 109.5

C(24)-C(27)-H(27B) 109.5

H(27A)-C(27)-H(27B) 109.5

C(24)-C(27)-H(27C) 109.5

H(27A)-C(27)-H(27C) 109.5

H(27B)-C(27)-H(27C) 109.5

76




Table S25. Anisotropic displacement parameters (Å2x 103) for CCDC #863217. The anisotropic

displacement factor exponent takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12 ]______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

S(1) 31(1) 22(1) 20(1) 0(1) 0(1) -2(1)O(1) 40(2) 21(2) 26(2) 2(2) 2(1) -1(2)

O(2) 29(2) 29(2) 26(2) 0(2) 2(2) -5(2)N(1) 28(2) 19(2) 24(2) 2(2) 2(2) -1(2)

C(1) 27(2) 23(3) 26(3) -2(2) 7(2) 4(2)C(2) 25(2) 25(3) 22(3) -1(2) 4(2) 1(2)

C(3) 24(2) 21(3) 24(3) 5(2) 3(2) -3(2)C(4) 24(2) 21(2) 19(3) 2(2) 3(2) 1(2)

C(5) 33(3) 30(3) 18(3) 1(2) -3(2) 0(2)C(6) 33(2) 33(3) 23(3) -4(2) -3(2) 1(2)

C(7) 36(2) 37(3) 17(3) -3(2) 3(2) 0(2)C(8) 23(2) 22(3) 28(3) -3(2) 4(2) -1(2)

C(9) 22(2) 32(3) 24(3) -8(2) -1(2) -1(2)C(10) 25(2) 25(2) 22(3) -1(2) -3(2) 1(2)

C(11) 28(2) 20(3) 21(3) 2(2) -1(2) 2(2)C(12) 26(2) 24(3) 24(3) 1(2) 1(2) 1(2)

C(13) 20(2) 35(3) 32(3) 0(2) 0(2) 1(2)C(14) 28(2) 34(3) 22(3) 6(2) 1(2) 2(2)

C(15) 25(2) 26(3) 21(2) -5(2) -6(2) 3(2)C(16) 28(2) 28(3) 32(3) -3(2) 7(2) 0(2)

C(17) 28(2) 26(3) 28(3) 2(2) 3(2) 2(2)C(18) 26(2) 42(3) 24(3) -3(3) 2(2) 1(2)

C(19) 41(3) 80(5) 21(3) 3(3) 3(2) 18(3)C(20) 28(2) 46(3) 27(3) -5(3) 4(2) 6(3)

C(21) 33(2) 27(3) 20(3) 1(2) 3(2) -5(2)C(22) 32(2) 27(3) 25(3) 1(2) 7(2) -2(2)

C(23) 31(2) 28(3) 26(3) 0(2) -5(2) 3(2)C(24) 41(3) 32(3) 20(3) 3(2) 2(2) -3(2)

C(25) 37(3) 34(3) 24(3) -2(2) 1(2) 1(2)C(26) 33(2) 24(3) 24(3) 1(2) -1(2) 1(2)

C(27) 43(3) 46(4) 36(3) -3(3) -9(3) 0(3)______________________________________________________________________________

77




Table S26. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 10 3)

for CCDC #863217.

________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________

H(1A) 3867 6066 4575 31

H(1B) 4552 6828 5101 31

H(5A) 8386 4546 5511 33

H(5B) 8879 5740 5227 33

H(6A) 6924 6699 5669 36

H(6B) 7564 5873 6171 36

H(7A) 4773 5934 6077 36

H(7B) 5504 4683 6108 36

H(8A) 3934 3393 4464 29

H(8B) 4566 4511 4140 29

H(9A) 5461 3024 3599 31

H(9B) 5959 2320 4168 31

H(12) 9981 5398 4447 29

H(13) 11513 4591 3735 35

H(15) 8096 2471 3292 29

H(16A) 3030 3966 5621 44

H(16B) 2491 4539 5018 44

H(16C) 2458 5264 5612 44

H(17A) 6511 3369 5666 41

H(17B) 6866 2704 5069 41

H(17C) 5179 2670 5344 41

H(18) 10612 2108 2914 37

H(19A) 9320 3407 2308 71

H(19B) 10923 3013 2033 71

H(19C) 10771 4242 2334 71

H(20A) 12926 3786 3064 51

H(20B) 13134 2629 2699 51

H(20C) 12860 2580 3392 51

H(22) 3810 7100 3498 33

H(23) 2873 6343 2623 34

78




H(25) 6916 4798 2324 38

H(26) 7895 5546 3184 32

H(27A) 3079 5153 1793 63

H(27B) 4381 4191 1804 63

H(27C) 4702 5389 1490 63

________________________________________________________________________________


iPrMe

Me NHTs44










b = 9.7183(3) Å β= 90°

c = 32.9845(12) Å γ = 90°

Volume 2403.61(15) Å3

Z 4



F(000) 944

79






Index ranges -5<=h<=8, -11<=k<=11, -35<=l<=38













Table S28. Atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2x 103) for CCDC


________________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ S(1) 140(1) 5117(1) 7655(1) 19(1)

O(1) 1053(2) 3819(1) 7621(1) 24(1)

O(2) -1755(2) 5143(1) 7610(1) 25(1)

N(1) 935(2) 6140(2) 7313(1) 21(1)

C(1) 1957(3) 7431(2) 9311(1) 32(1)

C(2) 1524(3) 6856(2) 8899(1) 25(1)

C(3) 1833(3) 5470(2) 8808(1) 25(1)

C(4) 1445(2) 4938(2) 8429(1) 23(1)

C(5) 724(2) 5800(2) 8136(1) 20(1)

C(6) 2858(3) 6458(2) 7319(1) 23(1)

C(7) 3685(3) 6576(2) 6890(1) 22(1)

C(8) 3577(2) 5153(2) 6674(1) 20(1)

C(9) 3614(2) 5236(2) 6202(1) 22(1)

80




C(10) 3469(2) 3770(2) 6027(1) 21(1)

C(11) 2994(3) 3597(2) 5619(1) 23(1)

C(12) 2883(3) 2315(2) 5443(1) 25(1)

C(13) 3240(3) 1123(2) 5667(1) 24(1)

C(14) 3185(3) -296(2) 5471(1) 28(1)

C(15) 1374(3) -599(2) 5283(1) 38(1)

C(16) 418(3) 7181(2) 8216(1) 23(1)

C(17) 822(3) 7691(2) 8595(1) 25(1)

C(18) 5591(3) 7093(2) 6966(1) 27(1)

C(19) 1998(3) 6105(2) 6069(1) 24(1)

C(20) 1854(3) 7428(2) 6305(1) 25(1)

C(21) 2635(3) 7642(2) 6658(1) 24(1)

C(22) 5317(3) 5897(2) 6027(1) 26(1)

C(23) 4670(3) -448(2) 5155(1) 38(1)

C(24) 3707(2) 1289(2) 6072(1) 22(1)

C(25) 3845(2) 2584(2) 6255(1) 20(1)

C(26) 4399(3) 2658(2) 6697(1) 22(1)

C(27) 4945(3) 4106(2) 6828(1) 22(1)


_____________________________________________________

S(1)-O(2) 1.4290(14)

S(1)-O(1) 1.4398(14)

S(1)-N(1) 1.6176(16)

S(1)-C(5) 1.7737(18)

N(1)-C(6) 1.475(2)

C(1)-C(2) 1.506(3)

C(2)-C(17) 1.392(3)

C(2)-C(3) 1.398(3)

C(3)-C(4) 1.385(3)

C(4)-C(5) 1.389(3)

C(5)-C(16) 1.387(3)

C(6)-C(7) 1.549(3)

C(7)-C(21) 1.509(3)

C(7)-C(18) 1.536(3)

C(7)-C(8) 1.558(2)

C(8)-C(27) 1.531(3)

C(8)-C(9) 1.559(2)

C(9)-C(10) 1.541(3)

C(9)-C(19) 1.542(3)

C(9)-C(22) 1.543(3)

C(10)-C(11) 1.404(3)

C(10)-C(25) 1.405(3)

C(11)-C(12) 1.377(3)

C(12)-C(13) 1.400(3)

81




C(13)-C(24) 1.389(3)

C(13)-C(14) 1.524(3)

C(14)-C(15) 1.521(3)

C(14)-C(23) 1.531(3)

C(16)-C(17) 1.380(3)

C(19)-C(20) 1.506(3)

C(20)-C(21) 1.321(3)

C(24)-C(25) 1.400(3)

C(25)-C(26) 1.518(2)

C(26)-C(27) 1.528(2)

O(2)-S(1)-O(1) 118.67(8)

O(2)-S(1)-N(1) 106.47(8)

O(1)-S(1)-N(1) 107.98(8)

O(2)-S(1)-C(5) 109.33(8)

O(1)-S(1)-C(5) 106.34(8)

N(1)-S(1)-C(5) 107.62(8)

C(6)-N(1)-S(1) 118.62(12)

C(17)-C(2)-C(3) 118.05(18)

C(17)-C(2)-C(1) 120.95(19)

C(3)-C(2)-C(1) 121.00(19)

C(4)-C(3)-C(2) 121.22(18)

C(3)-C(4)-C(5) 119.02(18)

C(16)-C(5)-C(4) 121.01(17)

C(16)-C(5)-S(1) 119.47(15)

C(4)-C(5)-S(1) 119.50(14)

N(1)-C(6)-C(7) 113.21(15)

C(21)-C(7)-C(18) 110.08(16)

C(21)-C(7)-C(6) 107.78(15)

C(18)-C(7)-C(6) 104.36(15)

C(21)-C(7)-C(8) 110.53(15)

C(18)-C(7)-C(8) 114.39(15)

C(6)-C(7)-C(8) 109.33(15)

C(27)-C(8)-C(7) 113.79(14)

C(27)-C(8)-C(9) 110.73(14)

C(7)-C(8)-C(9) 114.18(15)

C(10)-C(9)-C(19) 110.16(15)

C(10)-C(9)-C(22) 107.64(15)

C(19)-C(9)-C(22) 108.39(15)

C(10)-C(9)-C(8) 108.94(15)

C(19)-C(9)-C(8) 107.37(15)

C(22)-C(9)-C(8) 114.31(15)

C(11)-C(10)-C(25) 117.81(17)

C(11)-C(10)-C(9) 119.18(16)

C(25)-C(10)-C(9) 122.98(16)

C(12)-C(11)-C(10) 121.85(18)

C(11)-C(12)-C(13) 121.01(17)

C(24)-C(13)-C(12) 117.31(18)

C(24)-C(13)-C(14) 121.36(18)

C(12)-C(13)-C(14) 121.29(17)

C(15)-C(14)-C(13) 111.88(18)

C(15)-C(14)-C(23) 110.70(18)

C(13)-C(14)-C(23) 110.90(17)

C(17)-C(16)-C(5) 118.98(18)

C(16)-C(17)-C(2) 121.70(18)

C(20)-C(19)-C(9) 112.16(16)

C(21)-C(20)-C(19) 123.94(18)

C(20)-C(21)-C(7) 124.77(18)

C(13)-C(24)-C(25) 122.60(18)

C(24)-C(25)-C(10) 119.40(16)

C(24)-C(25)-C(26) 118.61(16)

C(10)-C(25)-C(26) 121.99(17)

C(25)-C(26)-C(27) 112.87(15)

C(26)-C(27)-C(8) 109.80(15

82




Table S30. Anisotropic displacement parameters (Å2x 103) for CCDC #863218. The anisotropic displacement factor exponent

takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12]______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

S(1) 23(1) 17(1) 16(1) 0(1) -1(1) -1(1)

O(1) 32(1) 18(1) 21(1) -1(1) -3(1) -2(1)

O(2) 27(1) 27(1) 22(1) 3(1) -2(1) -3(1)

N(1) 26(1) 21(1) 15(1) 2(1) -2(1) 1(1)

C(1) 29(1) 44(1) 22(1) -9(1) 0(1) -3(1)

C(2) 19(1) 36(1) 20(1) -5(1) 2(1) -3(1)

C(3) 24(1) 32(1) 20(1) 4(1) -1(1) -1(1)

C(4) 23(1) 24(1) 21(1) 1(1) 1(1) -2(1)

C(5) 20(1) 23(1) 16(1) -1(1) 2(1) -2(1)

C(6) 26(1) 21(1) 21(1) -3(1) -1(1) -1(1)

C(7) 25(1) 22(1) 19(1) 0(1) 2(1) -1(1)

C(8) 20(1) 20(1) 18(1) 1(1) 2(1) 0(1)

C(9) 25(1) 21(1) 19(1) 0(1) 0(1) 0(1)

C(10) 21(1) 22(1) 20(1) 2(1) 3(1) 1(1)

C(11) 26(1) 24(1) 20(1) 4(1) 2(1) 1(1)

C(12) 29(1) 29(1) 17(1) -1(1) 1(1) -1(1)

C(13) 24(1) 25(1) 24(1) -1(1) 4(1) -1(1)

C(14) 39(1) 23(1) 22(1) 0(1) 2(1) 0(1)

C(15) 47(1) 33(1) 34(1) -8(1) -2(1) -6(1)

C(16) 23(1) 23(1) 23(1) 1(1) 1(1) 1(1)

C(17) 23(1) 25(1) 26(1) -4(1) 4(1) -2(1)

C(18) 29(1) 26(1) 27(1) -3(1) 1(1) -5(1)

C(19) 30(1) 21(1) 20(1) 3(1) 0(1) 2(1)

C(20) 30(1) 21(1) 23(1) 5(1) 5(1) 3(1)

C(21) 29(1) 19(1) 24(1) 2(1) 8(1) 1(1)

C(22) 33(1) 24(1) 22(1) 0(1) 6(1) -3(1)

C(23) 53(1) 30(1) 31(1) -5(1) 9(1) 7(1)

C(24) 22(1) 21(1) 21(1) 3(1) 2(1) 0(1)

C(25) 20(1) 23(1) 18(1) 1(1) 3(1) 0(1)

C(26) 23(1) 22(1) 20(1) 1(1) -1(1) 4(1)

C(27) 25(1) 23(1) 19(1) 0(1) -1(1) 0(1)

83





x y z U(eq)

________________________________________________________________________________ H(1) 234 6500 7127 25

H(1A) 3248 7387 9356 48

H(1B) 1344 6890 9520 48

H(1C) 1561 8391 9326 48

H(3) 2318 4884 9010 30

H(4) 1668 3997 8370 27

H(6A) 3490 5727 7471 27

H(6B) 3044 7336 7465 27

H(8) 2382 4766 6746 23

H(11) 2742 4387 5459 28

H(12) 2559 2238 5166 30

H(14) 3400 -994 5688 34

H(15A) 444 -501 5489 57

H(15B) 1364 -1541 5177 57

H(15C) 1149 50 5061 57

H(16) -62 7766 8013 28

H(17) 616 8637 8651 29

H(18A) 6253 7101 6710 41

H(18B) 6189 6481 7159 41

H(18C) 5548 8027 7078 41

H(19A) 2106 6321 5777 28

H(19B) 894 5562 6108 28

H(20) 1159 8152 6193 30

H(21) 2529 8532 6775 29

H(22A) 6369 5462 6148 40

H(22B) 5324 6883 6088 40

H(22C) 5341 5765 5732 40

H(23A) 4612 -1368 5034 57

H(23B) 5831 -322 5286 57

H(23C) 4517 248 4943 57

H(24) 3941 492 6230 26

H(26A) 5411 2023 6743 26

84




H(26B) 3394 2345 6869 26

H(27A) 6137 4327 6717 26

H(27B) 5015 4151 7128 26

________________________________________________________________________________

References

85

1 Procedure adapted from: Gross, M. L.; Blank, D. H.; Welch, W. M. J. Org. Chem. 1993, 58, 2104.

2 When the amine•HCl salt is used, 4 equiv of DMAP are used.

3 Schopohl, M.C.; Bergander, K.; Kataeva, O.; Fröhlich, R.; Waldvogel, S. R. Synthesis 2003, (17), 2689.

4 Chen, K.; Baran, P. S. Nature 2009, 459, 824.

5 Bang, E.K-.; Kim, B. H. Tetrahedron Lett. 2009, 50, 2545.

6 Belleau, B.; Gulini, U.; Gour-Salin, B. Can. J. Chem. 1985, 63, 1268.

7 Ordóñez, M.; De la Cruz-Cordero, R.; Fernández-Zertuche, M.; Muñoz-Hernández, M. A.; García-Barradas, O. Tetrahedron: Asymmetry 2004, 15, 3035.


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