Organocatalytic Enantioselective Desymmetrization of ... · (ESI) m/z : 353 [M+Na]+; Melting point: 137-138°C. (2E,6E)-2,6-dibenzylidene-4-phenylcyclohexanone 1d. Method A was employed

1

Organocatalytic Enantioselective Desymmetrization of Cyclic

Enones via Phosphine Promoted [3+2] Annulations

Nathalie Pinto, Pascal Retailleau, Arnaud Voituriez and Angela Marinetti*

Institut de Chimie des Substances Naturelles

CNRS UPR 2301, Centre de Recherche de Gif

1 av. de la Terrasse, 91198 Gif sur Yvette, France

[email protected]

Table of Contents :

1) General methods

2) Substrates

3) Phosphine promoted [3+2] cyclisations on enones 1.

4) NMRspectra and HPLC analysis

Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010

2

1) General methods

All reactions were run under argon by using standard techniques for manipulating air-

sensitive compounds. Anhydrous solvents were obtained by filtration through drying columns

(THF, Et2O, CH2Cl2). All reagents were of commercial quality and were used without further

purification. Flash column chromatography was performed using 40-63 mesh silica. Nuclear

magnetic resonance spectra (1H, 13C, 31P) were recorded either on Brucker AV 500 or AV 300

spectrometers. IR spectra were recorded with a Perkin-Elmer FT-IR spectrophotometer. High

resolution mass spectra (HRMS-ESI) were obtained on LCT Waters equipment. Optical

rotations were determined with a JASCO P-1010 polarimeter. HPLC was performed at a

column temperature of 30°C on a Waters 2695 Separations Module equipped with a diode

array UV detector. Data are reported as follows: column type, eluent, flow rate, retention

time.

2) Substrates

4-methylcyclohexanone, 4-tert-butylcyclohexanone, 4-phenylcyclohexanone and 4-

isopropylcyclohexanone are commercially available. The diarylidenecyclohexanones

1a,c,d,f,e are known compounds. 1 , 2 They have been prepared as shown hereafter. 2,4-

dibenzylidenebicyclo[3.1.0]hexan-3-one 4a and 2,4-dibenzylidene-6-

methylbicyclo[3.1.0]hexan-3-one 4b were prepared according to literature procedure.3

(2E,6E)-2,6-dibenzylidene-4-methylcyclohexanone 1a. Method

A: 4-methylcyclohexanone (10 mmol, 1.12 g) was dissolved in

a mixture of ethanol (20 mL) and water (10 mL).

Benzaldehyde (20 mmol, 2 mL) and NaOH [1M] (10 mL) were

then added at 0°C. The mixture was stirred at room temperature overnight. The yellow

precipitate was filtrated and the desired compound was obtained as a yellow solid (2.27 g,

79%). 1H NMR (500 MHz, CDCl3) δ 7.81 (bs, 2H, C=CHC6H5), 7.50-7.25 (m, 10H), 3.07

1 Frey, H. Synthesis 1992, 387-390. 2 Dimmock, J. R.; Padmanilayam, M. P.; Zello, G. A.; Nienaber, K. H.; Allen, T. M.; Santos, C. L.; De Clercq, E.; Balzarini, J.; Manavathu E. K. ; Stables, J. P. Eur. J. Med. Chem., 2003, 38, 169-177 3 Kearley, M. L.; Lahti, P. M. Tetrahedron Lett.1991, 32, 5869-5872 ; Kearley, M. L.; Ichimura, A. S.; Lahti, P. M. J. Am. Chem. Soc. 1995, 117, 5235-5244; Flaugh, M. E.; Crowell, T. A.; Farlow, D. S. J. Org. Chem. 1980, 45, 5399-5400.

O


3

(dd, 2JAB = 16.0, 3J = 3.5 Hz, 2H, CHH), 2.52 (m, 2H, 2CHH), 1.89 (m, 1H, CHCH3), 1.08 (d, 3J = 6.5 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 190.3 (Cq), 137.3 (C=CHC6H5),

136.1 (Cq), 135.5 (Cq), 130.5 (CH), 128.7 (CH), 128.5 (CH), 36.6 (CH2), 29.6 (CHCH3), 21.8

(CHCH3); IR: νmax= 2957, 1660, 1603, 1568, 1444, 1288, 1240, 1142, 931, 770, 755, 692 cm-

1; MS (ESI) m/z : 289 [M+H]+; Melting point: 96-97°C.

(2E,6E)-2,6-dibenzylidene-4-isopropylcyclohexanone 1b.

Method A was employed, starting from 4-isopropyl-

cyclohexanone (1.6 mmol, 0.25 mL) and benzaldehyde (3.2

mmol, 0.35 mL). The product was obtained as a yellow solid

(330 mg, 65%). 1H NMR (500 MHz, CDCl3) δ 7.8 (br, 2H), 7.50-7.30 (m, 10H), 3.06 (dd, J =

15.5, 3.0 Hz, 2H, CH2), 2.60-2.55 (m, 2H, CH2), 1.64 (m, J = 6.5 Hz, 1H, CH), 1.60-1.50 (m,

1H, CH), 0.91 (d, 3J = 7.0 Hz, 6H, CH3); 13C NMR (75 MHz, CDCl3) δ 190.7 (Cq), 137.3

(C6H5CH=C), 136.2 (Cq), 135.8 (Cq), 130.5 (CH), 128.7 (CH), 128.6 (CH), 40.4 (CH), 31.7

(CH), 31.6 (CH2), 19.9 (CH3); IR: νmax= 1661, 1570, 1444, 1291, 1154, 775, 693 cm-1; MS

(ESI) m/z : 339 [M+Na]+; Melting point: 102-103°C.

(2E,6E)-2,6-dibenzylidene-4-tert-butylcyclohexanone 1c. Method

A: 4-tert-butylcyclohexanone (10 mmol, 1.54 g), was dissolved

in a mixture of ethanol (20 mL) and water (10 mL).

Benzaldehyde (20 mmol, 2 mL) and NaOH [1M] (10 mL) were

then added and the resulting mixture was heated at 50°C and stirred overnight. The yellow

precipitate was filtrated and the desired compound was obtained as a yellow solid after

crystallization in ethanol (1.79 g, 54%). 1H NMR (500 MHz, CDCl3) δ 7.80-7.75 (m, 2H),

7.50-7.30 (m, 10H), 3.17 (dd, J = 15.5, 2.0 Hz, 2H, CH2), 2.50-2.40 (m, 2H, CH2), 1.49 (m,

1H, CH), 0.95 (s, 9H, CH3); 13C NMR (75 MHz, CDCl3) δ 190.8 (Cq), 137.0 (CH), 136.3

(Cq), 136.2 (Cq), 130.4 (CH), 128.7 (CH), 128.6 (CH), 44.5 (CH), 32.7 (Cq), 29.7 (CH2),

27.4 (CH3); IR: νmax= 2959, 1660, 1603, 1445, 1244, 1157, 983, 776, 693 cm-1; MS

(ESI) m/z : 353 [M+Na]+; Melting point: 137-138°C.

(2E,6E)-2,6-dibenzylidene-4-phenylcyclohexanone 1d.

Method A was employed starting from 4-phenylcyclohexanone

(2.87 mmol, 500 mg) and benzaldehyde (5.74 mmol, 0.9 mL).

The product was obtained as a yellow solid from the crude

O

O

O


4

reaction mixture by filtration (958 mg, 96%). 1H NMR (500 MHz, CDCl3) δ 7.90-7.85 (m,

2H), 7.45-7.25 (m, 15H), 3.35-3.30 (m, 2H), 3.10-3.00 (m, 3H); 13C NMR (75 MHz, CDCl3)

δ 189.7 (Cq), 144.8 (Cq), 138.0 (CH), 135.9 (Cq), 135.2 (Cq), 130.6 (CH), 128.89 (CH),

128.87 (CH), 128.6 (CH), 126.99 (CH), 126.97 (CH), 41.0 (CH), 36.1 (CH2); IR: νmax= 1733,

1660, 1598, 1443, 1288, 1146, 983, 750 691 cm-1; MS (ESI) m/z : 373 [M+Na]+;Melting

point: 134-135°C.

(2E,6E)-4-tert-butyl-2,6-bis(4-methoxybenzylidene)

cyclohexanone 1e. Method A was employed starting

from 4-tert-butylcyclohexanone (10 mmol, 1.54 g)

and 4-methoxybenzaldehyde (20 mmol, 2.4 mL).

The product was obtained as a yellow solid (2.42 g,

62%). 1H NMR (500 MHz, CDCl3) δ 7.73 (m, 2H), 7.45 (d, J = 8.5 Hz, 4H), 6.95 (d, J = 8.5

Hz, 4H), 3.85 (s, 6H, OMe), 3.15 (dd, J = 15.5, 2.5 Hz, 2H, CH2), 2.44 (t, J ~ 14 Hz, 2H),

1.48 (tt, J = 13.0, 3.0 Hz, 1H), 0.97 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 190.5 (Cq), 160.0

(2Cq), 136.5 (CH), 134.4 (Cq), 132.3 (CH), 128.9 (Cq), 114.1 (CH), 55.4 (OCH3), 44.5 (Cq),

32.6 (Cq), 29.7 (CH2), 27.5 (CH3); IR: νmax= 2951, 1664, 1507, 1291, 1254, 1169, 1029, 830,

770 cm-1; MS (ESI) m/z : 413 [M+Na]+; Melting point: 171-172°C.

(2E,6E)-4-tert-butyl-2,6-bis(4-methylbenzylidene)cyclo-

hexanone 1f. Method A was employed with 4-tert-

butylcyclohexanone (10 mmol, 1.54 g) and 4-

methylbenzaldehyde (20 mmol, 2.35 mL)). The product

was obtained as a yellow solid (3.10 g, 87%). 1H NMR (500 MHz, CDCl3) δ 7.78 (m, 2H),

7.41 (d, J = 7.5 Hz, 4H), 7.25 (d, J = 7.5 Hz, 4H), 3.19 (d, J = 15.0 Hz, 2H), 2.46 (t, J ~ 14

Hz, 2H), 2.41 (s, 6H), 1.51 (t, J = 12.5 Hz, 1H), 0.99 (s, 9H); 13C NMR (75 MHz, CDCl3) δ

190.7 (Cq), 138.9 (Cq), 136.9 (CH), 135.6 (Cq), 133.4 (Cq), 130.5 (CH), 129.3 (CH), 44.5

(CH), 32.7 (Cq), 29.7 (CH2), 27.4 (C(CH3)3), 21.5 (CH3); IR: νmax= 2961, 2358, 1663, 1573,

1315, 1174, 930, 817, 666 cm-1; MS (ESI) m/z : 381 [M+Na]+; Melting point: 156-157°C.

(2E,6E)-4-tert-butyl-2,6-bis(4-chlorobenzylidene)cyclo-

hexanone 1g. Method A was employed starting from 4-

tert-butylcyclohexanone (10 mmol, 1.54 g) and 4-

chlorobenzaldehyde (20 mmol, 2.8 g). The product was

obtained as a yellow solid (3.25 g, 82%). 1H NMR (500 MHz, CDCl3) δ 7.65 (bs, 2H), 7.39

O

O

MeO OMe


5

(bs, 8H), 3.09 (m, 2H), 2.41 (m, 2H), 1.47 (m, 1H), 0.94 (s, 9H); 13C NMR (75 MHz, CDCl3)

δ 190.2 (Cq), 136.6 (Cq), 135.8 (CH), 134.7 (Cq), 134.5 (Cq), 131.6 (CH), 128.9 (CH), 44.5

(CH), 32.7 (Cq), 29.6 (CH2), 27.4 (CH3); IR: νmax= 2958, 1663, 1577, 1558, 1404, 1241,

1092, 983, 928, 823, 704 cm-1; MS (ESI) m/z : 421 [M+Na]+; Melting point: 177-178°C.

(2E,6E)-4-tert-butyl-2,6-bis(naphthalen-1-ylmethylene)-

cyclohexanone 1h. Method A was employed starting from 4-

tert-butylcyclohexanone (10 mmol, 1.54 g) and 1-

naphthaldehyde (20 mmol, 2.7 mL). The product was

obtained as a yellow solid (1.98 g, 46%). 1H NMR (300

MHz, CDCl3) δ 8.43 (m, 2H), 8.10-8.05 (m, 2H), 7.95-7.85 (m, 4H), 7.60-7.45 (m, 8H), 3.06

(dd, J = 15.0, 2.4 Hz, 2H), 2.38 (m, 2H), 1.53 (tt, J = 12.6, 3.3 Hz, 1H), 0.78 (s, 9H); 13C

NMR (75 MHz, CDCl3) δ 190.5 (Cq), 138.3 (Cq), 135.4 (CH), 133.7 (Cq), 133.3 (Cq), 132.2

(Cq), 129.0 (CH), 128.7 (CH), 126.9 (CH), 126.6 (CH), 126.3 (CH), 125.2 (CH), 124.9 (CH),

45.1 (CH), 32.7 (Cq), 29.9 (CH2), 27.2 (CH3); IR: νmax= 2955, 1593, 1231, 1196, 1156, 968,

861, 778 cm-1; MS (ESI) m/z : 453 [M+Na]+; Melting point: 146-148°C.

(2E,6E)-4-tert-butyl-2,6-bis(naphthalen-2-

ylmethylene)cyclohexanone 1i. Method A was

employed with 4-tert-butylcyclohexanone (5 mmol,

770 mg) and 2-naphthaldehyde (10 mmol, 1.56 g).

The product was obtained as a yellow solid (1.79 g,

83%). 1H NMR (500 MHz, CDCl3) δ 7.96 (bs, 4H), 7.90-7.80 (m, 6H), 7.60 (d, J = 8.5 Hz,

2H), 7.55-7.45 (m, 4H), 3.31 (d, J = 15.5 Hz, 2H), 2.58 (t, J ~14 Hz, 2H), 1.55-1.50 (m, 1H),

0.97 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 190.7 (Cq), 137.1 (CH), 136.6 (Cq), 133.8 (2Cq),

133.3 (Cq), 133.2 (Cq), 130.4 (CH), 128.6 (CH), 128.2 (CH), 127.8 (CH), 127.7 (CH), 127.0

(CH), 126.6 (CH), 44.7 (CH), 32.7 (Cq), 29.8 (CH2), 27.4 (CH3): IR: νmax= 2356, 1692, 1595,

1563, 1429, 1297, 992, 747, 724 cm-1; MS (ESI) m/z : 453 [M+Na]+; Melting point: 191-

193°C.

(2E,6E)-4-tert-butyl-2,6-bis(furan-2-ylmethylene)cyclohexanone

1j. Method A was employed starting from 4-tert-

butylcyclohexanone (10 mmol, 1.54 g) and 2-furaldehyde (20

mmol, 1.65 mL). The product (2.45g, 79%) was obtained as a

yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.58 (d, J = 1.8 Hz, 2H), 7.53 (d, J = 2.4 Hz,

OO

O

O

O


6

2H), 6.67 (d, J = 3.4 Hz, 2H), 6.53 (dd, J = 3.4, 1.8 Hz, 2H), 3.38 (dd, J = 16.5, 3.0 Hz, 2H),

2.41 (m, 2H), 1.65-1.55 (tt, J = 12.9, 3.6 Hz, 1H), 1.06 (s, 9H); 13C NMR (75 MHz, CDCl3) δ

189.5 (Cq), 152.9 (Cq), 144.7 (CH), 133.3 (Cq), 123.4 (CH), 116.2 (CH), 112.4 (CH), 43.3

(CH), 32.2 (Cq), 29.4 (CH2), 27.5 (CH3); IR: νmax= 2959, 1596, 1477, 1307, 1239, 730 cm-1;

MS (ESI) m/z : 333 [M+Na]+; Melting point: 136-138°C.

3) Phosphine promoted [3+2] cyclisations on enones 1.

Procedure a: Ethyl 2,3 butadienoate (0,40 mmol) was added to a mixture of enones 1 (0.20

mmol) and cyclohexyldiphenyl phosphine (10 mol %, 0.020 mmol, 5.4 mg) in degazed

toluene (0.7 mL) under argon atmosphere. The solution was stirred at 40°C until completion.

The crude mixture was concentrated in vacuo. Diastereomeric ratios were measured by NMR

on the crude mixture, based on integration of the C=CHPh signals at about 7.5 ppm. The final

product was purified by flash chromatography on silica gel (5% EtOAc / heptanes).

Procedure b: Ethyl 2,3 butadienoate (0,30 mmol) was added to a mixture of enones 1 (0.15

mmol) and either FerroPHANE, A, or t-Bu-Binepine, B (10 mol %, 0.015 mmol) in degazed

toluene (0.5 mL) under argon atmosphere. The solution was stirred at 80°C until completion.

The crude mixture was concentrated in vacuo. Diastereomeric ratios were measured by NMR

on the crude mixture, based on integration of the C=CHPh signals at about 7.5 ppm. The final

product was purified by flash chromatography on silica gel (5% EtOAc / heptanes).

(E)-ethyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-

carboxylate 2a. Procedure a (catalyst CyPPh2): 95% yield, 90/10 dr;

Procedure b (catalyst (S,S)-FerroPHANE): 91% yield, 76% ee, 80/20 dr;

Pale yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.57 (bs, 1H,

C6H5CH=C), 7.35-7.10 (m, 10H), 6.91 (m, 1H, CH2CH=C), 4.15-4.00

(m, 3H, CH2CH3, CH2CHC6H5), 2.88 (ddd, 2JAB = 18.0 Hz, 3J = 10,2, 1.8 Hz, 1H,

CH2CH=C), 2.75-2.65 (m, 2H, CH2CH=C, CH2CHCH3), 2.13 (ddd, 2JAB = 15.3 Hz, 3J = 12.6,

3.0 Hz, 1H, CH2CHCH3), 1.85 (dt, 2JAB = 13.8, 3J ≈ 4J = 3.0 Hz, 1H, CH2CHCH3), 1.60 (t, 2J

≈ 3J = 13 Hz, 1H, CH2CHCH3), 1.18 (t, 3J = 6.9 Hz, 3H, CH2CH3), 0.54 (d, 3J = 6.6 Hz, 3H,

CHCH3), 0.40-0.25 (m, 1H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 205.2 (Cq), 163.8 (Cq),

143.4 (Cq), 143.3 (CH2CH=C), 139.1 (Cq), 136.7 (Cq), 136.1 (Cq), 136.0 (C6H5CH=C),

130.5 (2CH), 128.6 (2CH), 128.5 (CH), 128.4 (2CH), 128.4 (2CH), 127.5 (CH), 62.9 (Cq),

60.7 (CH2CH3), 56.1 (CH2CHC6H5), 37.5 (CH2), 36.6 (CH2), 35.7 (CH2), 26.5 (CHCH3), 22.0

(CHCH3), 14.3 (CH2CH3); IR: νmax= 2924, 1706, 1592, 1491, 1445, 1242, 1075, 1026, 904,

O

Ph

Ph

EtOOC


7

750, 696 cm-1; HRMS (ESI) calcd. For C27H28NaO3 [M+Na]+: 423.1936, found: 423.1921;

HPLC Analysis: 76% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane, 1mL/min, 300 nm,

retention times: 19.8 min (major) and 34.8 min (minor)]. Minor diastereoisomer: selected 1H

NMR data (300 MHz, CDCl3) δ 7.67 (bs), 6.99 (dd, J = 3.0, 2.0 Hz), 4.21 (dd, J = 11.1, 7.5

Hz), 1.40 (t, J = 13.0 Hz), 0.75 (d, J = 6.6 Hz).

(E)-ethyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-

1-carboxylate 2b. Procedure a (catalyst CyPPh2): 93% yield, 85/15 dr;

Procedure b (catalyst (S,S)-FerroPHANE): 44% yield, 82% ee, 80/20 dr;

Pale yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 2.5 Hz, 1H),

7.40-7.15 (m, 10H), 7.00 (t, J = 2.0 Hz, 1H), 4.25-4.10 (m, 3H), 2.96

(ddd, J = 18.0, 10.0, 2.0 Hz, 1H), 2.80-2.75 (m, 2H), 2.24 (ddd, J = 15.5, 12.2, 3.0 Hz, 1H),

1.93 (dt, J = 13.5, 3.0 Hz, 1H), 1.69 (t, J = 13.0 Hz, 1H), 1.25 (t, J = 7.0 Hz, 3H), 1.20-1.10

(m, 1H), 0.57 (d, J = 6.5 Hz, 3H), 0.54 (d, J = 6.5 Hz, 3H), 0.30-0.20 (m, 1H); 13C NMR (75

MHz, CDCl3) δ 205.4 (Cq), 163.8 (Cq), 143.5 (CH), 143.3 (Cq), 139.1 (Cq), 136.9 (Cq),

136.2 (Cq), 136.1 (CH), 130.4 (2CH), 128.9 (2CH), 128.5 (2CH), 128.4 (3CH), 127.4 (CH),

62.8 (Cq), 60.6 (CH2), 55.9 (CH), 36.6 (CH), 35.8 (CH2), 32.3 (CH), 31.8 (CH2), 31.7 (CH2),

19.6 (CH3), 18.9 (CH3), 14.2 (CH3); IR: νmax= 2956, 2360, 1708, 1592, 1446, 1326, 1244,

1091, 1027, 911, 865 cm-1; HRMS (ESI) calcd. For C29H32NaO3 [M+Na]+: 451.2249, found:

451.2259; HPLC Analysis: 82% ee [Daicel CHIRACEL IA, 10% iPrOH/n-heptane,

1mL/min, 300 nm, retention times: 7.7 min (minor) and 10.2 min (major)]; Minor

diastereoisomer: selected 1H NMR data (500 MHz, CDCl3) δ 7.68 (br), 7.04 (dd, J = 2.9, 1.95

Hz), 0.73 (dd, J = 7.0, 5.5 Hz).

(E)-ethyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-

1-carboxylate 2c. Procedure a (catalyst CyPPh2): 92% yield, >95/5 dr;

Procedure b (catalyst (S,S)-FerroPHANE): 98% yield, 92% ee, >95/5 dr;

White solid; 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J = 2.4 Hz, 1H), 7.30-

7.10 (m, 10H), 6.95 (t, J = 2.7 Hz, 1H), 4.15-4.00 (m, 3H), 2.90 (ddd, J =

18.3, 9.6, 2.1 Hz, 1H), 2.83 (dt, J = 14.4, 3.0 Hz, 1H), 2.71 (ddd, J = 18.3, 8.1, 3.0 Hz, 1H),

2.15 (td, J = 15.0, 2.7 Hz, 1H), 1.92 (dt, J = 13.8, 2.7 Hz, 1H), 1.65 (t, J = 13.2 Hz, 1H), 1.18

(t, J = 6.9 Hz, 3H), 0.49 (s, 9H), 0.27 (tt, J = 13.0, 3.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ

205.4 (Cq), 163.8 (Cq), 143.6 (CH), 143.3 (Cq), 139.0 (Cq), 137.4 (Cq), 136.2 (Cq), 135.9

(CH), 130.2 (2CH), 129.1 (2CH), 128.5 (2CH), 128.4 (2CH), 128.3 (CH), 127.4 (CH), 63.0

(Cq), 60.6 (CH2), 55.8 (CH), 40.2 (CH), 35.8 (CH2), 32.2 (Cq), 29.9 (CH2), 29.2 (CH2), 27.0

O

Ph

Ph

EtOOC

O

PhPh

COOEt


8

(3CH3), 14.2 (CH3); IR: νmax= 2946, 1697, 1667, 1588, 1370, 1327, 1243, 1232, 1162, 1095,

1027, 754, 697 cm-1; HRMS (ESI) calcd. For C30H34NaO3 [M+Na]+: 465.2406, found:

465.2397; HPLC Analysis: 92% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane,

1mL/min, 300 nm, retention times: 16.4 min (major) and 40.0 min (minor)]; [α]D24 = + 290 (c

= 0.91, CHCl3); Melting point: 128-130°C.

(E)-ethyl 7-benzylidene-6-oxo-1,9-diphenylspiro[4.5]dec-1-ene-2-

carboxylate 2d. Procedure a (catalyst CyPPh2): 86% yield, 90/10 dr;

Procedure b (catalyst (S,S)-FerroPHANE): 98% yield, 92% ee, 85/15

dr; White solid; 1H NMR (500 MHz, CDCl3) δ 7.79 (bs, 1H), 7.40-7.15

(m, 13H), 7.02 (bs, 1H), 6.80 (d, J = 7.5 Hz, 2H), 4.30-4.20 (m, 3H),

3.05-2.90 (m, 2H), 2.85-2.75 (m, 2H), 2.24 (dd, J = 14.0, 13.0 Hz, 1H), 2.18 (d, J = 13.0 Hz,

1H), 1.65-1.60 (m, 1H), 1.33 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 204.7 (Cq),

163.8 (Cq), 145.1 (Cq), 143.4 (Cq), 143.1 (CH), 138.9 (Cq), 136.9 (CH), 136.4 (Cq), 135.8

(Cq), 130.5 (2CH), 128.9 (2CH), 128.8 (2CH), 128.6 (2CH), 128.5 (3CH), 127.7 (CH), 126.8

(2CH), 126.5 (CH), 63.3 (Cq), 60.8 (CH2), 56.2 (CH), 37.8 (CH), 37.2 (CH2), 35.5 (CH2),

35.2 (CH2), 14.3 (CH3); IR: νmax= 2932, 1697, 1592, 1371, 1327, 1240, 1151, 760, 747, 693

cm-1; HRMS (ESI) calcd. For C32H30NaO3 [M+Na]+: 485.2093, found: 485.2073; HPLC

Analysis: 92% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1ml/min, 270 nm, retention

times: 13.8 min (minor) and 18.4 min (major)]; Melting point: 165-166°C.

(E)-tert-butyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-

1-ene-1-carboxylate 3a. Procedure a (catalyst CyPPh2): 90% yield,

85/15 dr; Procedure b (catalyst (S,S)-FerroPHANE): 86% yield,

90% ee, 80/20 dr; White solid; 1H NMR (300 MHz, CDCl3) δ 7.57

(d, J = 2.4 Hz, 1H), 7.35-7.05 (m, 10H), 6.85 (t, J = 2.4 Hz, 1H),

3.98 (m, 1H), 2.86 (ddd, J = 17.7, 10.2, 2.1 Hz, 1H), 2.70-2.60 (m,

1H), 2.08 (ddd, J = 15.3, 12.6, 3.0 Hz, 1H), 1.83 (dt, J = 13.8, 3.0 Hz, 1H), 1.59 (t, J = 12.6

Hz, 2H), 1.37 (s, 9 H), 0.54 (d, J = 6.6 Hz, 3H), 0.35-0.25 (m, 1H); 13C NMR (75 MHz,

CDCl3) δ 205.1 (Cq), 163.1 (Cq), 144.6 (Cq), 142.8 (CH), 139.3 (Cq), 136.8 (Cq), 136.2 (Cq),

135.9 (CH), 130.4 (2CH), 128.6 (2CH), 128.44 (CH), 128.41 (4CH), 127.43 (CH), 81.2 (Cq),

62.9 (Cq), 56.5 (CH), 37.5 (CH2), 36.7 (CH2), 35.4 (CH2), 28.2 (CH3), 26.3 (CH), 22.0 (CH3);

IR: νmax= 2919, 1693, 1671, 1590, 1445, 1332, 1244, 1148, 1076, 1022, 847 cm-1; Melting

point: 142-144°C; HRMS (ESI) calcd. For C29H32NaO3 [M+Na]+: 451.2249, found:

OCOOtBu

Ph

O

PhPh

COOEt


9


1mL/min, 300 nm, retention times: 7.4 min (minor) and 12.1 min (major)].

(E)-tert-butyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]-

dec-1-ene-1-carboxylate 3b. Procedure a (catalyst CyPPh2): 91%

yield, 70/30 dr; Procedure b (catalyst (S,S)-FerroPHANE): 43%

yield, 86% ee, 70/30 dr; Pale yellow oil; Selected data from the

mixture of two diastereoisomers: 1H NMR (300 MHz, CDCl3) δ

7.67 (d, J = 2.5 Hz, 1H), 7.45-7.15 (m, 10H), 6.98 (m, 1H), 4.09 (dd, J = 9.0, 8.5 Hz, 1H),

3.00-2.90 (m, 1H), 2.80-2.70 (m, 2H), 2.24 (td, J = 15.5, 2.5 Hz, 1H), 1.95 (broad d, J = 13.5

Hz, 1H), 1.73 (t, J = 13.5 Hz, 1H), 1.46 (s, 9H), 1.25-1.15 (m, 1H), 0.62 (d, J = 7.0 Hz, 3H),

0.58 (d, J = 6.5 Hz, 3H), 0.30-0.20 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 205.4 (Cq), 163.1

(Cq), 144.5 (Cq), 142.9 (CH), 137.1 (Cq), 136.3 (Cq), 135.9 (CH), 130.3 (2CH), 129.0

(2CH), 128.4 (4CH), 128.3 (CH), 127.3 (CH), 81.1 (Cq), 62.8 (Cq), 56.4 (CH), 36.3 (CH2),

35.5 (CH), 32.3 (CH2), 31.85 (CH), 31.78 (CH), 28.2 (CH3), 19.6 (CH3), 18.9 (CH3); IR:

νmax= 2927, 1702, 1674, 1591, 1366, 1161, 935, 754, 696 cm-1; HRMS (ESI) calcd. For

C31H36NaO3 [M+Na]+: 479.2562, found: 479.2581; HPLC Analysis: 86% ee [Daicel

CHIRACEL IA, 2% EtOH/n-heptane, 1mL/min, 300 nm, retention times: 11.3 min (minor)

and 15.4 min (major)].

(E)-tert-butyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]-

dec-1-ene-1-carboxylate 3c. Procedure a (catalyst CyPPh2): 87%

yield, 90/10 dr; Procedure b (catalyst (S,S)-FerroPHANE): 71%

yield, 95% ee, 90/10 dr; Pale yellow solid; 1H NMR (500 MHz,

CDCl3) δ 7.65 (d, J = 1.5 Hz, 1H), 7.45-7.15 (m, 10H), 6.99 (br, 1H), 4.06 (t, J = 9.0 Hz, 1H),

2.95 (ddd, J = 18.0, 9.5, 2.0 Hz, 1H), 2.91 (m, 1H), 2.78 (ddd, J = 18.0, 8.0, 3.0 Hz, 1H), 2.21

(m, 1H), 1.99 (m, 1H), 1.75 (t, J = 13.0 Hz, 1H), 1.47 (s, 9H), 0.60 (s, 9H), 0.33 (m, 1H); 13C

NMR (75 MHz, CDCl3) δ 205.4 (Cq), 163.2 (Cq), 144.6 (Cq), 143.0 (CH), 139.3 (Cq), 137.6

(Cq), 136.3 (Cq), 135.8 (CH), 130.2 (2CH), 129.2 (2CH), 128.5 (4CH), 128.4 (CH), 127.4

(CH), 81.2 (Cq), 62.9 (Cq), 56.3 (CH), 39.9 (CH), 35.6 (CH2), 32.3 (Cq), 29.9 (CH2), 29.2

(CH2), 28.3 (CH3), 27.0 (CH3); IR: νmax= 2965, 1701, 1586, 1365, 1253, 1161, 1105, 758, 691

cm-1; Melting point: 123-126°C; HRMS (ESI) calcd. For C32H38NaO3 [M+Na]+: 493.2719,

found: 493.2713; HPLC Analysis: 95% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane,

1ml/min, 300 nm, retention times: 6.5 min (minor) and 8.4 min (major)].

OCOOtBu

OCOOtBu


10

(E)-tert-butyl 7-benzylidene-6-oxo-4,9-diphenylspiro[4.5]dec-1-ene-1-

carboxylate 3d. Procedure a (catalyst CyPPh2): 64% yield, 85/15 dr;

White solid; 1H NMR (500 MHz, CDCl3) δ 7.79 (m, 1H), 7.40-6.95 (m,

15H), 6.82 (d, J = 7.5 Hz, 1H), 4.23 (dd, J = 10.0, 8.0 Hz, 1H), 3.00-

2.90 (m, 2H), 2.90-2.70 (m, 2H), 2.25 (t, J = 13.5 Hz, 1H), 2.15-2.10

(m, 1H), 1.65-1.55 (m, 1H), 1.53 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 204.6 (Cq), 163.0

(Cq), 145.2 (Cq), 144.4 (Cq), 142.9 (CH), 139.1 (Cq), 136.8 (CH), 136.5 (Cq), 135.9 (Cq),

130.4 (CH), 128.9 (CH), 128.8 (CH), 128.6 (CH), 128.5 (CH), 127.7 (CH), 126.7 (CH), 126.5

(CH), 81.3 (Cq), 63.2 (Cq), 56.6 (CH), 37.6 (CH), 37.1 (CH2), 35.3 (CH2), 35.2 (CH2), 28.3

(CH3); IR: νmax= 3060, 2979, 1695, 1591, 1338, 1243, 1157, 1122, 945, 750, 692 cm-1;

HRMS (ESI) calcd. For C34H34NaO3 [M+Na]+: 513.2406, found: 513.2406; HPLC Analysis:

90% ee [Daicel CHIRACEL IA, 5% EtOH/n-heptane, 1mL/min, 300 nm, retention times: 6.3

min and 7.3 min]; Melting point: 130-131°C.

(E)-ethyl 9-tert-butyl-7-(4-methoxybenzylidene)-4-(4-

methoxyphenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2e.

Procedure b (catalyst (S,S)-FerroPHANE): 91% yield, 93%

ee, >95/5 dr; Colorless oil; 1H NMR (300 MHz, CDCl3) δ

7.63 (d, J = 2.1 Hz, 1H), 7.38 (d, J = 8.7 Hz, 2H), 7.12 (d, J

= 8.4 Hz, 2H), 6.99 (t, J = 2.4 Hz, 1H), 6.92 (d, J = 6.9 Hz,

2H), 6.78 (d, J = 8.7 Hz, 2H), 4.20-4.05 (m, 3H), 3.83 (s, 3H), 3.75 (s, 3H), 2.95-2.85 (m,

2H), 2.76 (ddd, J = 18.3, 8.1, 3.0 Hz, 1H), 2.30-2.20 (m, 1H), 1.96 (dt, J = 13.5, 3.0 Hz, 1H),

1.70 (t, J = 13.2 Hz, 1H), 1 .24 (t, J = 6.9 Hz, 3H), 0.61 (s, 9H), 0.43 (tt, J = 12.6, 3.0 Hz,

1H); 13C NMR (75 MHz, CDCl3) δ 205.2 (Cq), 163.9 (Cq), 159.9 (Cq), 158.9 (Cq), 143.5

(CH), 143.4 (Cq), 136.1 (CH), 135.2 (Cq), 132.2 (2CH), 131.3 (Cq), 130.1 (2CH), 128.8

(Cq), 114.0 (2CH), 113.9 (2CH), 62.7 (Cq), 60.5 (CH2), 55.5 (CH3), 55.4 (CH3), 55.0 (CH),

40.0 (CH), 36.1 (CH2), 32.2 (Cq), 29.8 (CH2), 29.3 (CH2), 27.2 (3CH3), 14.2 (CH3); IR:

νmax= 2953, 2358, 1709, 1604, 1509, 1366, 1248, 1162, 1030, 830, 730 cm-1; HRMS (ESI)

calcd. For C32H38NaO5 [M+Na]+: 525.2617, found: 555.2601; HPLC Analysis: 94% ee

[Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm, retention times: 22.4 min

(minor) and 43.8 min major)]; [α]D24 = +355 (c = 1.23, CHCl3).

OEtOOC

MeO

OMe

Ph

O

PhPh

COOtBu


11

(E)-ethyl 9-tert-butyl-7-(4-methylbenzylidene)-6-oxo-4-p-tolyl-

spiro[4.5]dec-1-ene-1-carboxylate 2f. Procedure b (catalyst (S,S)-

FerroPHANE): 77% yield, 90% ee, 95/5 dr; White solid; 1H NMR (300 MHz, CDCl3) δ 7.62 (d, J = 2.1 Hz, 1H), 7.30 (d, J

= 8.1 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H),

7.04 (d, J = 8.4 Hz, 2H), 7.01 (t, J = 2.4 Hz, 1H), 4.30-4.00 (m, 3H), 3.00-2.85 (m, 2H),

2.76(ddd, J = 18.0, 7.8, 3.0 Hz, 1H), 2.37 (s, 3H), 2.29 (s, 3H), 2.25-2.15 (m, 1H), 1.97 (dt, J

= 13.5, 3.0 Hz, 1H), 1.70 (t, J = 13.2 Hz, 1H), 1.24 (t, J = 7.2 Hz, 3H), 0.58 (s, 9H), 0.37 (tt, J

= 12.9, 3.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 205.5 (Cq), 163.9 (Cq), 143.5 (CH), 143.4

(Cq), 138.6 (Cq), 137.0 (Cq), 136.5 (Cq), 136.1 (CH), 136.0 (Cq), 133.4 (Cq), 130.4 (2CH),

129.2 (2CH), 129.1 (2CH), 129.0 (2CH), 62.8 (Cq), 60.6 (CH2), 55.5 (CH), 40.0 (CH), 35.9

(CH2), 32.3 (Cq), 29.9 (CH2), 29.3 (CH2), 27.1 (3CH3), 21.5 (CH3), 21.1 (CH3), 14.2 (CH3);

IR: νmax= 2945, 1701, 1670, 1597, 1435, 1367, 1233, 1160, 1093, 1029, 813, 755 cm-1;

Melting point: 172-173°C; HRMS (ESI) calcd. For C32H38NaO3 [M+Na]+: 493.2719, found:


1mL/min, 300 nm, retention times: 11.5 min (minor) and 17.9 min major)]; [α]D24 = +320 (c =

0.87, CHCl3).

(E)-ethyl 9-tert-butyl-7-(4-chlorobenzylidene)-4-(4-chloro

phenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2g. Procedure b

(catalyst (S,S)-FerroPHANE): 86% yield, 86% ee, >95/5 dr;

White solid; 1H NMR (300 MHz, CDCl3) δ 7.57 (d, J = 2.4 Hz,

1H), 7.36 (d, J = 8.7 Hz, 2H), 7.30 (d, J = 8.7 Hz, 2H), 7.23 (d, J

= 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 7.00 (t, 3J = 2.5 Hz, 1H,

CH2CH=C), 4.20-4.00 (m, 3H), 2.95-2.75 (m, 3H), 2.25 (m, 1H), 1.95 (dt, J = 13.8, 2.7 Hz,

1H), 1.72 (t, J = 13.2 Hz, 1H), 1.25 (t, J = 7.2 Hz, 3H), 0.59 (s, 9H), 0.29 (tt, J = 12.9, 2.7 Hz,

1H); 13C NMR (75 MHz, CDCl3) δ 204.8 (Cq), 163.7 (Cq), 143.3 (CH, Cq), 137.7 (Cq),

137.5 (Cq), 134.9 (CH), 134.5 (Cq), 134.4 (Cq), 133.2 (Cq), 131.5 (2CH), 130.4 (2CH), 128.8

(2CH), 128.6 (2CH), 62.8 (Cq), 60.7 (CH2), 54.9 (CH), 40.5 (CH), 35.9 (CH2), 32.3 (Cq),

29.8 (CH2), 29.2 (CH2), 27.1 (CH3), 14.3 (CH3); IR: νmax= 2942, 1704, 1587, 1491, 1369,

1235, 1163, 1089, 1013, 831, 760 cm-1; Melting point: 145-147°C; HRMS (ESI) calcd. For

C30H32NaCl2O3 [M+Na]+: 533.1626, found: 533.1608; HPLC Analysis: 86% ee [Daicel

CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm, retention times: 11.6 min (minor)

and 15.8 min major)]; [α]D24 = +280 (c = 1.0, CHCl3).

OEtOOC

OEtOOC

Cl

Cl


12

(E)-ethyl 9-tert-butyl-4-(naphthalen-1-yl)-7-(naphthalen-1-

ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2h


ee, 95/5 dr; Pale yellow oil; 1H NMR (500 MHz, CDCl3) δ

8.14 (d, J = 8.5 Hz, 1H), 7.95 (br, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.79 (dd, J = 12.5, 8.5 Hz,

2H), 7.72 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 7.0 Hz, 1H), 7.55-7.20 (m, 7H), 7.13 (t, J = 2.5 Hz,

1H), 6.95 (d, J = 7.0 Hz, 1H), 5.02 (t, J = 9.0 Hz, 1H), 4.30-4.20 (m, 2H), 3.22 (ddd, J = 18.5,

10.0, 2.0 Hz, 1H), 2.96 (ddd, J = 18.0, 7.5, 3.0 Hz, 1H), 2.28 (dt, J = 14.5, 2.8 Hz, 1H), 2.19

(dt, J = 14.0, 2.5 Hz, 1H), 1.97 (m, 1H), 1.75 (t, J = 13.0 Hz, 1H), 1.33 (t, J = 7.0 Hz, 3H),

0.37 (s, 9H), -0.1 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 206.4 (Cq), 163.9 (Cq), 143.5 (Cq),

143.2 (CH), 139.4 (Cq), 135.4 (Cq), 134.9 (CH), 134.1 (Cq), 133.6 (Cq), 133.4 (Cq), 132.7

(Cq), 131.6 (Cq), 128.9 (CH), 128.3 (CH), 128.2 (CH), 126.7 (CH), 126.3 (CH), 126.2 (CH),

126.1 (CH), 126.0 (CH), 125.9 (CH), 125.4 (CH), 125.3 (CH), 125.0 (CH), 124.5 (CH), 63.5

(Cq), 60.7 (CH2), 50.0 (CH), 40.9 (CH), 37.8 (CH2), 32.2 (Cq), 31.0 (CH2), 29.1 (CH2), 26.9

(CH3), 14.4 (CH3); IR: νmax= 2954, 1704, 1597, 1440, 1366, 1246, 1160, 1046, 907, 777, 728

cm-1; HRMS (ESI) calcd. For C38H38KO3 [M+K]+: 581.2458, found: 581.2482; HPLC

Analysis: 81% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm,

retention times: 10.9 min (minor) and 18.4 min major)]; [α]D24 = -20 (c = 1.2, CHCl3).

(E)-ethyl 9-tert-butyl-4-(naphthalen-2-yl)-7-(naphthalen-2-

ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2i.


ee, 95/5 dr; White solid; 1H NMR (300 MHz, CDCl3) δ

7.90-7.70 (m, 9H), 7.55-7.40 (m, 5H), 7.31 (dd, J = 8.1, 1.5

Hz, 1H), 7.10 (t, J = 2.7 Hz, 1H), 4.35-4.15 (m, 3H), 3.14

(ddd, J = 18.0, 9.6, 2.1 Hz, 1H), 2.98 (m, 1H), 2.90 (ddd, J =18.3, 7.8, 3.0 Hz, 1H), 2.40-2.30

(m, 1H), 2.11 (dt, J = 13.8, 2.7 Hz, 1H), 1.80 (t, J = 12.9 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H),

0.41 (s, 9H), 0.31 (dt, J = 12.9, 3.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 205.4 (Cq), 163.9

(Cq), 143.6 (CH), 143.4 (Cq), 137.7 (Cq), 136.6 (Cq), 136.2 (CH), 133.7 (Cq), 133.4 (Cq),

133.2 (Cq), 133.1 (Cq), 132.8 (Cq), 130.1 (CH), 128.4 (CH), 128.0 (3CH), 127.79 (CH),

127.75 (CH), 127.62 (CH), 127.59 (CH), 127.3 (CH), 126.8 (CH), 126.5 (CH), 126.3 (CH),

125.9 (CH), 63.2 (Cq), 60.7 (CH2), 56.0 (CH), 40.3 (CH), 36.0 (CH2), 32.1 (Cq), 30.1 (CH2),

29.4 (CH2), 26.9 (CH3), 14.3 (CH3); IR: νmax= 2956, 2359, 1706, 1585, 1366, 1241, 1162,

1097, 855, 818, 746, 668 cm-1; Melting point: 165-166°C; HRMS (ESI) calcd. For

C38H38NaO3 [M+Na]+: 565.2719, found: 565.2736; HPLC Analysis: 90% ee [Daicel

OEtOOC

OEtOOC


13

CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm, retention times: 14.8 min (minor)

and 27.8 min (major)]; [α]D24 = +343 (c = 0.88, CHCl3).

(E)-ethyl 9-tert-butyl-4-(furan-2-yl)-7-(furan-2-ylmethylene)-6-

oxospiro[4.5]dec-1-ene-1-carboxylate 2j. Procedure b (catalyst

(S,S)-FerroPHANE): 57% yield, 92% ee, 75/25 dr; Yellow oil; 1H

NMR (300 MHz, CDCl3) δ 7.54 (d, J = 1.5 Hz, 1H), 7.49 (d, J = 2.4

Hz, 1H), 7.29 (dd, J = 1.5, 0.6 Hz, 1H), 6.91 (t, J = 2.4 Hz, 1H), 6.62

(d, J = 3.3 Hz, 1H), 6.49 (dd, J = 3.3, 1.8 Hz, 1H), 6.28 (dd, J = 3.0, 1.8 Hz, 1H), 6.11 (d, J =

3.0 Hz, 1H), 4.20-4.00 (m, 3H), 3.18 (dt, J = 16.5, 3.0 Hz, 1H), 2.88 (ddd, J = 18.0, 10.5, 3.0

Hz, 1H), 2.77 (ddd, J = 18.0, 8.1, 3.0 Hz, 1H), 2.31 (ddd, J = 15.9, 13.2, 2.7 Hz, 1H), 2.03 (dt,

J = 13.8, 2.7 Hz, 1H), 1.65 (t, J = 13.2 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H), 0.76 (s, 9H), 0.44 (tt,

J = 12.9, 3.6 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 203.6 (Cq), 163.5 (Cq), 153.5 (Cq),

152.9 (Cq), 144.6 (CH), 143.8 (Cq), 142.6 (CH), 141.4 (CH), 133.1 (Cq), 123.5 (CH), 116.2

(CH), 112.4 (CH), 110.6 (CH), 108.1 (CH), 62.2 (Cq), 60.6 (CH2), 49.0 (CH), 39.4 (CH),

34.7 (CH2), 32.3 (Cq), 30.0 (CH2), 29.4 (CH2), 27.2 (CH3), 14.1 (CH3); IR: νmax= 2960,

1709, 1670, 1591, 1243, 1103, 735 cm-1; HRMS (ESI) calcd. For C26H30NaO5 [M+Na]+:

423.2171, found: 423.2176; HPLC Analysis: 92% ee [Daicel CHIRACEL IA, 5% iPrOH/n-

heptane, 1mL/min, 330 nm, retention times: 22.3 min (minor) and 35.8 min (major)]; [α]D24 =

+166 (c = 0.62, CHCl3).

(E)-ethyl 4-benzylidene-3-oxo-5'-phenylspiro[bicyclo[3.1.0]hexane-2,1'-

cyclopent[2]ene]-2'-carboxylate 5a. Procedure b (catalyst (S,S)-

FerroPHANE): 63% yield, 83% ee, 95/5 dr; Orange oil; 1H NMR (500

MHz, CDCl3) δ 7.91 (m, 2H), 7.65-7.45 (m, 9H), 7.38 (t, J = 2.7 Hz, 1H),

4.33 (m, 2H), 4.08 (dd, J = 8.4, 6.0 Hz, 1H), 3.46 (ddd, J = 18.6, 8.4, 2.7 Hz, 1H), 3.06 (ddd,

J = 18.9, 6.3, 2.7 Hz, 1H), 2.75-2.60 (m, 1H), 1.85-1.75 (m, 1H), 1.39 (t, J = 6.9 Hz, 3H),

1.17-1.10 (m, 1H), 0.03 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 209.1 (Cq), 163.9 (Cq), 146.2

(CH), 142.6 (Cq), 140.4 (Cq), 139.3 (Cq), 135.9 (Cq), 131.1 (CH), 130.1 (2CH), 129.1 (CH),

128.8 (2CH), 128.7 (2CH), 128.4 (2CH), 126.9 (CH), 67.0 (Cq), 60.6 (CH2), 52.5 (CH), 40.0

(CH2), 22.3 (CH), 20.2 (CH), 15.9 (CH2), 14.1 (CH3); IR: νmax= 2928, 1708, 1625, 1493,

1325, 1263, 1177, 1112, 1028, 755, 692 cm-1; HRMS (ESI) calcd. For C26H24NaO3

[M+Na]+: 407.1623, found: 407.1634; HPLC Analysis: 86% ee [Daicel CHIRACEL IA,

10% iPrOH/ n-heptane, 1mL/min, 300 nm, retention times: 6.8 min (major) and 7.8 min

(minor)]; [α]D24 = +11 (c = 1.6, CHCl3).

OEtOOC

O

O

O

Ph

Ph

COOEt


14

(E)-ethyl 4-benzylidene-6-methyl-3-oxo-5'-phenylspiro[bicyclo[3.1.0]

hexane-2,1'-cyclopent[2]ene]-2'-carboxylate 5b. Procedure b (catalyst

(S,S)-FerroPHANE): 66% yield, 83% ee, 95/5 dr; Orange oil; 1H NMR

(500 MHz, CDCl3) δ 7.63 (d, J = 7.5 Hz, 2H), 7.40-7.20 (m, 9H), 7.11 (t,

J = 2.5 Hz, 1H), 4.08 (m, 2H), 3.77 (dd, J = 9.0, 5.5 Hz, 1H), 3.24 (ddd, J = 19.0, 9.0, 2.5 Hz,

1H), 2.79 (ddd, J = 19.0, 5.5, 2.5 Hz, 1H), 2.23 (m, 1H), 1.25 (m, 1H), 1.14 (t, J = 7.0 Hz,

3H), 0.69 (d, J = 6.0 Hz, 3H), 0.13 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 209.8 (Cq), 163.9

(Cq), 146.0 (CH), 143.5 (Cq), 140.3 (Cq), 138.9 (Cq), 135.9 (Cq), 130.7 (CH), 130.1 (2CH),

129.1 (CH), 128.7 (4CH), 128.4 (2CH), 126.9 (CH), 67.9 (Cq), 60.6 (CH2), 52.4 (CH), 40.5

(CH2), 30.9 (CH), 29.0 (CH), 25.1 (CH) 16 9 (CH3), 14.1 (CH3); IR: νmax= 2924, 1711, 1627,

1448, 1264, 1176, 1102, 1027, 732 cm-1; HRMS (ESI) calcd. For C27H26NaO3 [M+Na]+:

421.1780, found: 421.1786; HPLC Analysis: 83% ee [Daicel CHIRACEL IA, 10% iPrOH/

n-heptane, 1mL/min, 270 nm, retention times: 7.9 min (major) and 10.9 min (minor)]; [α]D24

= +16 (c = 1.5, CHCl3).

O

Ph

Ph

COOEt


15

4) NMR spectra and HPLC analysis

(E)-ethyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 2a 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5 ppm

0.634

0.647

0.845

0.858

1.256

1.264

1.270

1.278

1.293

1.669

1.696

1.721

1.924

1.930

1.936

1.958

1.963

2.222

2.227

2.232

2.258

2.735

2.741

2.771

2.777

2.782

2.792

2.798

2.813

2.819

2.828

2.834

2.952

2.956

2.972

2.976

4.143

4.159

4.163

4.173

4.178

4.187

4.192

4.201

4.206

7.006

7.011

7.016

7.231

7.237

7.241

7.251

7.255

7.265

7.270

7.282

7.314

7.327

7.333

7.340

7.344

7.378

7.381

7.394

7.404

7.407

7.419

7.671

7.676

0.84

2.74

3.12

1.10

1.00

0.92

2.16

1.02

2.62

0.62

8.80

0.57

13C NMR (75 MHz, CDCl3):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.255

21.969

26.497

35.725

36.575

37.467

56.086

60.664

62.942

76.750

77.173

77.596

127.492

128.419

128.460

128.500

128.601

130.489

136.071

136.136

136.673

139.094

143.318

143.348

163.837

205.219

OCOOEt

OCOOEt


16

HPLC Analysis: Table 2, entry 1: 76% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane, 1 mL/min, 300 nm]:

OCOOEt

OCOOEt


17

(E)-ethyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 2b 1H NMR (300 MHz, CDCl3):

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

0.242

0.246

0.537

0.551

0.564

0.577

1.159

1.171

1.231

1.245

1.259

1.661

1.688

1.714

1.913

1.919

1.925

1.946

2.246

2.760

2.766

2.776

2.782

2.790

2.796

2.802

2.812

2.818

2.929

2.933

2.949

2.953

4.099

4.115

4.120

4.127

4.135

4.141

4.149

4.155

4.163

4.170

4.177

4.184

4.191

4.199

6.995

7.000

7.004

7.167

7.196

7.202

7.211

7.222

7.233

7.250

7.275

7.286

7.292

7.298

7.304

7.310

7.315

7.353

7.369

7.376

7.380

7.644

7.649

1.00

5.96

1.17

3.74

1.26

1.01

1.00

2.36

1.18

3.62

1.01

14.11

1.13


OCOOEt


18

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.238

18.929

19.639

31.747

31.822

32.290

35.812

36.641

55.859

60.598

62.817

76.732

77.155

77.579

127.372

128.424

128.464

128.931

130.396

136.095

136.155

136.979

139.074

143.286

143.469

163.813

205.428

HPLC Analysis: Table 2, entry 2: 82% ee [Daicel CHIRACEL IA, 10% iPrOH/n-heptane, 1 mL/min, 300 nm]:

OCOOEt

OCOOEt


19

OCOOEt


20

(E)-ethyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 2c

1H NMR (300 MHz, CDCl3):

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

0.270

0.493

0.537

0.641

1.156

1.180

1.194

1.203

1.649

1.693

1.895

2.807

2.848

2.855

4.005

4.038

4.063

4.086

4.101

4.125

6.938

6.945

6.954

7.123

7.149

7.155

7.170

7.181

7.224

7.240

7.252

7.295

7.309

7.563

7.571

1.21

8.48

4.80

1.36

1.05

1.03

1.17

2.00

3.61

1.19

11.07

1.07


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.248

27.028

29.166

29.937

32.223

35.799

40.214

55.782

60.580

62.950

76.740

77.163

77.587

127.362

128.358

128.433

128.459

129.131

130.214

135.926

136.177

137.407

139.043

143.268

143.558

163.810

205.437

OCOOEt

OCOOEt


21

HPLC Analysis: Table 2, entry 3: 92% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane, 1 mL/min, 300 nm]:

OCOOEt

OCOOEt


22

(E)-ethyl 7-benzylidene-6-oxo-1,9-diphenylspiro[4.5]dec-1-ene-2-carboxylate 2d 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

1.321

1.335

1.346

1.360

1.564

1.570

1.590

1.596

1.609

1.616

2.122

2.128

2.150

2.200

2.226

2.253

2.787

2.793

2.802

2.808

2.823

2.828

2.838

2.845

2.852

2.878

2.883

2.957

2.974

2.977

2.989

3.010

3.013

4.182

4.197

4.204

4.211

4.218

4.223

4.232

4.237

4.247

4.252

4.259

4.266

4.274

4.280

4.296

6.782

6.796

7.016

7.030

7.143

7.158

7.172

7.198

7.213

7.282

7.340

7.354

7.365

7.368

7.397

7.412

7.780

7.784

3.80

1.22

1.24

1.16

2.34

2.36

3.25

1.86

1.00

13.43

0.74


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.312

35.180

35.474

37.171

37.847

56.175

60.753

63.295

76.738

77.161

77.584

126.527

126.755

127.692

128.461

128.643

128.797

128.909

130.494

135.823

136.440

136.940

138.929

143.148

143.448

145.080

163.788

204.692

OCOOEt

OCOOEt


23


OCOOEt

OCOOEt


24

(E)-tert-butyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 3a

1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

0.379

0.385

0.391

0.398

0.404

0.637

0.650

0.851

0.864

0.893

0.908

0.921

1.283

1.290

1.310

1.464

1.470

1.490

1.498

1.517

1.667

1.693

1.719

1.913

1.918

1.941

1.946

2.154

2.160

2.185

2.210

2.215

2.733

2.739

2.749

2.755

2.761

2.769

2.785

2.791

2.916

2.919

2.937

2.940

2.952

2.955

2.972

4.088

4.104

4.107

4.123

6.950

6.954

7.173

7.188

7.210

7.215

7.245

7.248

7.282

7.306

7.320

7.391

7.400

7.414

7.425

7.670

7.674

7.693

1.03

3.07

0.81

0.74

11.96

1.32

0.24

1.09

1.24

2.24

1.05

1.00

0.19

0.84

0.17

13.24

1.01

0.20


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.243

14.327

21.160

22.003

22.818

26.314

28.238

35.429

36.706

37.508

56.548

60.505

62.890

76.741

77.164

77.588

81.197

127.429

128.416

128.443

128.597

130.416

135.891

136.161

136.789

139.267

142.792

144.566

163.080

171.244

205.114

OCOOtBu

OCOOtBu


25


OCOOtBu

OCOOtBu


26

(E)-tert-butyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 3b 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

0.582

0.596

0.609

0.623

0.759

0.774

0.788

1.194

1.207

1.268

1.280

1.460

1.465

1.500

1.512

1.621

1.679

1.696

1.723

1.750

1.785

1.809

1.939

1.967

2.235

2.751

2.757

2.767

2.773

2.782

2.787

2.792

2.805

2.809

2.924

2.928

2.944

2.948

2.960

4.072

4.090

4.107

6.976

6.980

6.990

7.176

7.192

7.227

7.237

7.246

7.257

7.270

7.272

7.281

7.296

7.322

7.325

7.333

7.337

7.341

7.349

7.395

7.402

7.405

7.417

7.419

7.673

7.678

7.688

1.07

7.22

3.38

1.44

15.64

2.84

1.24

1.17

3.54

1.73

1.00

0.46

1.30

15.33

1.20


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

18.929

19.550

19.591

19.643

28.231

28.259

31.662

31.775

31.854

32.040

32.334

32.488

33.025

34.483

35.556

36.373

36.687

56.351

57.101

61.718

62.773

76.741

77.164

77.588

81.131

81.165

127.218

127.340

128.164

128.353

128.403

128.445

128.545

128.962

128.983

130.337

130.635

135.958

136.201

136.290

136.481

137.087

139.248

142.929

143.078

144.551

146.372

163.111

163.841

203.959

205.391

OCOOtBu

OCOOtBu


27

HPLC Analysis: Table 2, entry 6: 86% ee [Daicel CHIRACEL IA, 2% EtOH/n-heptane, 1 mL/min, 300 nm]:

OCOOtBu

OCOOtBu


28

(E)-tert-butyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 3c 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

0.094

0.307

0.333

0.358

0.422

0.467

0.604

0.641

0.753

0.890

0.905

0.918

0.964

1.262

1.267

1.287

1.307

1.324

1.338

1.467

1.512

1.619

1.726

1.753

1.779

1.986

2.013

2.176

2.181

2.206

2.232

2.237

2.753

2.759

2.769

2.775

2.789

2.795

2.805

2.811

2.896

2.926

2.945

2.949

2.962

2.981

2.985

4.045

4.062

4.080

6.988

7.193

7.226

7.239

7.245

7.251

7.261

7.282

7.291

7.329

7.343

7.369

7.383

7.390

7.405

7.415

7.420

7.651

7.654

0.97

8.89

10.44

1.24

1.01

1.00

1.28

2.11

0.84

0.81

9.93

0.73


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

27.023

28.267

29.216

29.967

32.310

35.624

39.923

56.302

57.201

62.967

76.743

77.166

77.590

81.189

127.276

127.366

128.352

128.479

129.051

129.209

130.182

130.633

135.801

136.267

137.571

139.261

143.027

144.552

163.163

205.436

OCOOtBu

OCOOtBu


29

HPLC Analysis: Table 2, entry 7: 95% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 300 nm]:

OCOOtBu

OCOOtBu


30

(E)-ethyl 9-tert-butyl-7-(4-methoxybenzylidene)-4-(4-methoxyphenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2e 1H NMR (300 MHz, CDCl3):

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

0.429

0.435

0.605

0.643

0.748

1.222

1.236

1.251

1.598

1.681

1.708

1.734

1.948

1.975

2.257

2.282

2.759

2.773

2.779

2.789

2.795

2.864

2.868

2.888

2.900

2.904

2.920

3.753

3.776

3.819

3.830

4.069

4.087

4.097

4.104

4.111

4.119

4.133

4.147

4.150

4.165

4.179

4.187

4.194

4.201

6.772

6.790

6.907

6.924

6.993

6.998

7.002

7.108

7.125

7.257

7.371

7.388

7.622

7.625

1.12

9.43

4.41

1.25

0.99

1.03

1.20

2.12

3.05

3.28

3.32

2.11

2.16

1.05

2.06

2.15

1.00


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.256

27.173

29.359

29.778

32.257

36.113

40.065

54.987

55.431

55.513

60.536

62.722

76.744

77.167

77.591

113.885

113.999

128.828

130.072

131.343

132.240

135.241

136.100

143.463

143.565

158.968

159.880

163.898

205.222

OEtOOC

MeO

OMe

OEtOOC

MeO

OMe


31


OEtOOC

MeO

OMe

OEtOOC

MeO

OMe


32

(E)-ethyl 9-tert-butyl-7-(4-methylbenzylidene)-6-oxo-4-p-tolylspiro[4.5]dec-1-ene-1-carboxylate 2f 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

1.261

1.270

1.284

1.304

1.310

1.702

1.728

1.754

1.979

2.006

2.224

2.229

2.254

2.280

2.285

2.311

2.337

2.372

2.392

2.762

2.768

2.778

2.784

2.799

2.804

2.814

2.820

2.918

2.924

2.947

2.961

2.980

2.984

4.079

4.096

4.114

4.130

4.137

4.144

4.151

4.180

4.199

4.207

4.214

4.221

4.228

4.235

7.031

7.059

7.075

7.105

7.121

7.208

7.224

7.282

7.316

7.332

7.645

0.84

7.28

3.31

1.06

0.83

0.96

2.69

2.76

1.00

1.69

2.76

0.85

3.59

1.69

1.68

0.85


OEtOOC


33

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.259

21.087

21.499

27.107

29.305

29.895

32.253

35.914

40.015

55.467

60.559

62.847

76.740

77.163

77.587

129.013

129.063

129.207

130.448

130.754

133.385

136.022

136.137

136.530

136.965

138.565

143.362

143.643

163.894

205.470


OEtOOC


34

OEtOOC

OEtOOC


35

(E)-ethyl 9-tert-butyl-7-(4-chlorobenzylidene)-4-(4-chlorophenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2g 1H NMR (300 MHz, CDCl3):

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

0.251

0.284

0.294

0.303

0.327

0.337

0.525

1.158

1.181

1.205

1.612

1.657

1.701

1.850

1.860

1.869

1.896

1.906

1.915

2.126

2.136

2.177

2.185

2.219

2.229

2.666

2.675

2.692

2.702

2.726

2.736

2.752

2.762

2.784

2.791

2.815

2.822

3.981

4.011

4.028

4.040

4.052

4.064

4.070

4.088

4.094

4.107

4.111

4.118

4.131

4.142

4.154

6.916

6.924

6.932

7.052

7.080

7.141

7.149

7.171

7.177

7.190

7.220

7.249

7.276

7.298

7.305

7.504

7.512

1.19

8.45

4.68

1.13

0.96

0.97

3.05

3.41

0.95

8.57

1.00


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.276

27.084

29.221

29.792

32.316

35.983

40.502

54.949

60.717

62.791

76.738

77.161

77.585

128.594

128.789

130.404

131.540

133.205

134.446

134.497

134.947

137.513

137.656

143.321

163.690

204.767

OEtOOC

Cl

Cl

OEtOOC

Cl

Cl


36


OEtOOC

Cl

Cl

OEtOOC

Cl

Cl


37

(E)-ethyl 9-tert-butyl-4-(naphthalen-1-yl)-7-(naphthalen-1-ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2h 1H NMR (300 MHz, CDCl3):

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

-0.091

0.311

0.370

0.520

1.311

1.325

1.339

1.720

1.747

1.773

1.966

2.184

2.212

2.276

2.305

2.963

4.206

4.221

4.228

4.242

4.263

4.277

4.284

5.008

5.024

5.043

6.947

6.961

7.127

7.132

7.137

7.247

7.260

7.296

7.299

7.310

7.312

7.319

7.327

7.329

7.335

7.349

7.410

7.424

7.440

7.454

7.456

7.462

7.478

7.487

7.489

7.493

7.504

7.506

7.520

7.653

7.667

7.709

7.725

7.775

7.791

7.799

7.816

7.841

7.857

7.954

7.957

8.135

8.152

1.00

8.98

3.53

1.16

0.98

2.12

1.09

1.03

2.23

1.01

0.94

1.02

7.95

5.42

1.02

1.06


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.336

26.931

29.077

30.946

32.184

37.771

40.896

49.955

60.705

63.469

76.728

77.152

77.575

124.496

125.060

125.250

125.375

125.884

125.971

126.125

126.195

126.274

126.409

126.722

128.009

128.228

128.312

128.861

131.592

132.655

133.378

133.592

134.079

134.905

135.409

139.374

143.223

143.497

163.914

206.335

OEtOOC

OEtOOC


38


OEtOOC

OEtOOC


39

(E)-ethyl 9-tert-butyl-4-(naphthalen-2-yl)-7-(naphthalen-2-ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2i 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

0.312

0.338

0.364

0.423

0.490

0.701

1.298

1.312

1.326

1.781

1.807

1.834

2.102

2.129

2.337

2.901

2.906

2.916

2.922

2.937

2.942

2.952

2.958

2.977

3.006

3.125

3.144

3.158

3.161

4.180

4.194

4.201

4.216

4.231

4.246

4.260

4.268

4.282

4.314

4.332

4.348

7.115

7.281

7.320

7.337

7.444

7.452

7.460

7.462

7.493

7.505

7.513

7.520

7.523

7.527

7.530

7.723

7.745

7.761

7.769

7.781

7.788

7.799

7.811

7.818

7.830

7.841

7.857

7.880

1.46

9.02

3.30

1.11

1.04

0.96

2.08

1.00

2.84

0.77

1.22

4.37

8.13


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.246

14.304

22.818

26.889

29.359

29.486

29.785

29.827

30.105

32.053

32.134

35.976

40.343

56.001

60.665

63.165

76.738

77.161

77.584

125.878

126.343

126.467

126.801

127.319

127.589

127.620

127.754

127.799

127.965

128.432

130.089

132.777

133.051

133.239

133.382

133.708

136.161

136.618

137.663

143.439

143.589

163.881

205.384

OEtOOC

OEtOOC


40


OEtOOC

OEtOOC


41

(E)-ethyl 9-tert-butyl-4-(furan-2-yl)-7-(furan-2-ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2j 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

0.432

0.442

0.453

0.761

1.167

1.190

1.214

1.602

1.647

1.691

2.000

2.009

2.019

2.045

2.055

2.254

2.264

2.298

2.308

2.317

2.779

2.789

2.806

2.816

2.829

2.836

2.864

2.871

3.147

3.156

3.211

4.050

4.062

4.074

4.086

4.098

4.110

4.112

4.127

4.136

4.149

4.160

4.172

6.104

6.114

6.274

6.280

6.284

6.290

6.486

6.492

6.497

6.503

6.619

6.630

6.906

6.914

6.922

7.262

7.272

7.281

7.284

7.287

7.289

7.486

7.494

7.538

7.543

7.552

1.13

8.12

3.93

0.94

0.94

1.01

1.24

1.07

1.00

3.13

0.87

1.11

0.99

0.94

0.86

0.96

1.94


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.161

27.199

29.352

30.028

32.254

34.699

39.385

48.961

60.621

62.158

76.742

77.165

77.589

108.069

110.574

112.356

116.211

123.467

133.146

141.387

142.579

143.792

144.563

152.909

153.464

163.521

203.580

OEtOOC

O

O

OEtOOC

O

O


42


OEtOOC

O

O

OEtOOC

O

O


43

(E)-ethyl 4-benzylidene-3-oxo-5'-phenylspiro[bicyclo[3.1.0]hexane-2,1'-cyclopent[2]ene]-2'-carboxylate 5a 1H NMR (300 MHz, CDCl3):

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

0.000

0.017

1.096

1.115

1.123

1.142

1.149

1.169

1.363

1.387

1.410

1.502

1.508

1.525

1.762

1.778

1.785

1.789

1.801

1.805

1.812

2.724

2.737

3.027

3.039

3.081

3.089

3.101

3.110

3.410

3.419

3.439

3.448

3.501

3.510

4.054

4.075

4.083

4.103

4.299

4.307

4.323

4.331

4.347

4.355

4.370

4.378

7.369

7.378

7.387

7.463

7.470

7.476

7.486

7.498

7.507

7.516

7.528

7.542

7.556

7.575

7.580

7.590

7.615

7.637

7.644

7.897

7.920

7.925

1.00

1.19

3.03

1.07

1.00

1.03

1.01

1.02

2.02

1.01

9.39

2.09


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.114

15.916

20.215

22.270

40.023

52.533

60.611

66.968

76.739

77.162

77.585

126.909

128.366

128.676

128.787

129.091

130.147

131.112

135.864

139.341

140.406

142.634

146.157

163.855

209.115

O

Ph

Ph

COOEt

O

Ph

Ph

COOEt


44

HPLC Analysis: product 5a: 86% ee [Daicel CHIRACEL IA, 10% iPrOH /n-heptane, 1 mL/min, 300 nm]:

O

Ph

Ph

COOEt

O

Ph

Ph

COOEt


45

(E)-ethyl 4-benzylidene-6-methyl-3-oxo-5'-phenylspiro[bicyclo[3.1.0]hexane-2,1'-cyclopent[2]ene]-2'-carboxylate 5b 1H NMR (300 MHz, CDCl3):

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

0.106

0.113

0.117

0.120

0.125

0.133

0.685

0.697

1.122

1.136

1.150

1.237

1.246

1.251

1.259

2.223

2.230

2.237

2.242

2.767

2.772

2.778

2.783

2.805

2.810

2.816

2.821

3.211

3.216

3.229

3.234

3.249

3.254

3.267

3.272

3.755

3.766

3.773

3.784

4.051

4.059

4.068

4.073

4.082

4.087

4.096

4.101

4.111

4.118

7.102

7.107

7.112

7.203

7.206

7.217

7.232

7.253

7.259

7.267

7.275

7.289

7.305

7.310

7.325

7.350

7.366

7.380

7.621

7.636

1.00

3.05

3.18

1.59

1.02

1.06

1.03

1.00

2.14

0.93

10.27

1.97


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.128

16.987

25.051

29.047

30.952

40.539

52.421

60.618

67.862

76.744

77.167

77.590

126.873

128.404

128.703

129.057

130.066

130.675

135.992

138.976

140.261

143.487

146.001

163.914

209.758

O

Ph

Ph

COOEt

O

Ph

Ph

COOEt


46

HPLC Analysis: product 5b: 83% ee [Daicel CHIRACEL IA, 10% iPrOH /n-heptane, 1 mL/min, 270 nm]:

O

Ph

Ph

COOEt

O

Ph

Ph

COOEt


Documents

Organocatalytic Enantioselective Desymmetrization of ... · (ESI) m/z : 353 [M+Na]+; Melting point: 137-138°C. (2E,6E)-2,6-dibenzylidene-4-phenylcyclohexanone 1d. Method A was employed