A catalytic highly enantioselective direct synthesis of 2 … Lower-energy conformation for anti-4a Lower-energy conformation for syn-4a Conformational energies were minimized using

1

A catalytic highly enantioselective direct synthesis of 2-bromo-2-

nitroalkan-1-ols through a Henry reaction

Gonzalo Blay, * Victor Hernández-Olmos and José R. Pedro*

Departament de Química Orgànica, Facultat de Química, Universitat de València, Dr.

Moliner 50, E-46100-Burjassot (València), Spain

General Experimental Methods: Commercial reagents were used as purchased.

Glassware was oven-dried overnight at 120 °C. Reactions were monitored by TLC

analysis using Merck Silica Gel 60 F-254 thin layer plates. Flash column

chromatography was performed on Merck silica gel 60, 0.040-0.063 mm. Specific

optical rotations were recorded on a Perkin-Elmer 241 polarimeter using sodium light

(D line 589 nm). 1H NMR were run at 300 MHz for 1H and at 75 MHz for 13C NMR

spectra were recorded on Bruker Advance spectrometers in the deuterated solvents as

stated, using residual non-deuterated solvent as internal standard. J values are given in

Hz. The carbon type was determined by DEPT experiments. Mass spectra were

recorded on a Fisons Instruments VG Autospec GC 8000 series. Mass spectra (EI) were

run at 70 eV. Mass spectra (FAB) were carried out at 30 kV in a MNBA matrix. Chiral

HPLC analyses were performed in a Hitachi Elite Lachrom instrument equipped with a

Hitachi UV diode-array L-4500 detector using chiral stationary columns from Daicel.

IMPORTANT: Throughout this supporting information, for the stereochemical

description of compounds 4, i. e. (1S, 2R), 1 always refers to the C-OH carbon and 2

always refers to the C-NO2 carbon, regardless of the numbering of these carbons in the

systematic name of the compound.

General procedure for the enantioselective addition of bromonitromethane to

aldehydes. A solution of amino pyridine 1 (6.7 mg, 0.025 mmol) in absolute ethanol (2

mL) was added to Cu(OAc)2·H2O (5.0 mg, 0.025 mmol) contained in a Schlenk tube

under nitrogen. The mixture was stirred for 1 h at room temperature until the formation

of a deep blue solution. The aldehyde 2 (0.5 mmol) was added and the reaction flask

introduced in a bath at the reaction temperature. After 5 min, 90% pure technical

2

bromonitromethane (3, 0.39 mL, 5 mmol) was added and the reaction mixture was

stirred until completion (TLC). The mixture was treated with 1M aqueous HCl (15 mL)

and extracted with dichloromethane (3 × 15 mL). The organic layer was washed with

brine (20 mL), dried over MgSO4 and concentrated under reduced pressure to give

product 4. For the reactions with additional base, the same procedure was followed, the

base being added just after the addition of bromonitromethane.

General procedure for the synthesis of racemic bromonitroalkanols 4. In a test tube

were successively added ethanol (1 mL), aldehyde 2 (0.25 mmol), 90% pure technical

bromonitromethane (3, 0.195 mL, 2.5 mmol) and DIPEA (87.1 µL, 0.5 mmol). The

reaction mixture was stirred at room temperature. The racemic products were isolated

following the usual work up.

Determination of the absolute configuration of compound 4a.

NO2

OHNO2

OH

Br

4aanti/sin 65:35eeanti 79%eesin 80%

(S)-5ee 80%

Bu3SnH (1.2 eq)

Bz, hν, quartz

AIBN (20 mol %)

98%

A solution of a 65:35 anti/syn mixture of 4a (50 mg, 0.2 mmol, 79% ee for the anti

isomer, 80% ee for the syn isomer), Bu3SnH (65 µL, 0.24 mmol) and AIBN (6.7 mg,

0.04 mmol) in dry benzene (1.5 mL) contained in a quartz tube was deoxygenated by

bubbling nitrogen for 5 min. The solution was then irradiated with a UV lamp under

nitrogen for 7 h. The solvent was removed under reduced pressure and the residue

chromatographed on silica gel eluting with hexane:diethyl ether (from 95:5 to 85:15) to

give 33.9 mg (99%) of (S)-5. Compound 5 was obtained in 80% ee as determined by

HPLC (Chiralcel OD-H), hexane:i-PrOH 90:10, 1 mL/min, major enantiomer (S) tr =

15.8, minor enantiomer (R) tr = 13.5. The absolute stereochemistry of (S)-5 was assigned

by comparison of its spectral features, optical rotation sign and retention times in HPLC

with those of an authentical sample of (S)-5.1

3

Lower-energy conformation for anti-4a

Lower-energy conformation for syn-4a Conformational energies were minimized using the MM2 force field implemented in the Chem3D Pro program

2-Bromo-2-nitro-1-phenylethanol (4a)2

NO2

Br

OH

Purified according to the general procedure. Diastereomeric ratios (anti/syn, 60:40)

were determined by 1H NMR. Enantiomeric excesses were determined by chiral HPLC

(Chiralcel OD-H), hexane:i-PrOH 90:10, 1 mL/min, antimajor(1S, 2S) tr = 11.7 min,

antiminor(1R, 2R) tr = 10.4 min, synmajor(1S, 2R) tr = 17.4 min, synminor(1R, 2S) tr = 12.7

min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 7.43 (5 H, s, CH aromatic), 5.95 (1 H,

d, J = 9.0, CHBr), 5.31 (1 H, d, J = 9.0, CHOH) and 2.21 (1 H, br s, OH); δC (75.5

MHz, CDCl3) 136.0 (C), 129.8 (CH), 128.9 (2 x CH), 127.3 (2x CH), 81.0 (CH) and

76.3 (CH); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.40 (5 H, s, CH aromatic), 6.07

4

(1 H, d, J = 4.9, CHBr), 5.36 (1 H, d, J = 4.9, CHOH) and 2.21 (1 H, br s, OH); δC

(75.5 MHz, CDCl3) 135.8 (C), 129.5 (CH), 128.9 (2 x CH), 126.4 (2 x CH), 85.5 (CH)

and 74.6 (CH); m/z (EI) 247 (0.8 %), 245 (M+, 0.8), 107 (91), 106 (93), 105 (96) and 77

(100); HRMS 244.9686 (M+), C8H8BrNO3 requires 244.9688.

2-Bromo-2-nitro-1-o-tolylethanol (4b)

NO2

Br

OH

CH3 Purified according to the general procedure. Diastereomeric ratios (anti/syn, 16:84)


(Chiralpak IC), hexane:i-PrOH 98:2, 1 mL/min. antimajor(1S, 2S) tr = 15.3 min,


min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 7.39-7.37 (1 H, m, CH aromatic), 7.21-

7.16 (3 H, m, CH aromatic), 6.03 (1 H, d, J = 9.0, CHBr), 5.63 (1 H, d, J = 9.0, CHOH),

2.96 (1 H, br s, OH) and 2.50 (3 H s, CH3); δC (75.5 MHz, CDCl3) 136.6 (C), 134.6

(C), 131.1 (CH), 129.5 (CH), 126.9 (CH), 126.1 (CH), 80.7 (CH), 72.1 (CH) and 19.7

(CH3); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.55-7.49 (1 H, m, CH aromatic),

7.31-7.25 (3 H, m, CH aromatic), 6.11 (1 H, d, J = 4.8, CHBr), 5.58 (1 H, d, J = 4.8,

CHOH), 2.96 (1 H, br s, OH) and 2.39 (3 H, s, CH3); δC (75.5 MHz, CDCl3) 135.0 (C),

134.1 (C), 131.0 (CH), 129.3 (CH), 126.7 (CH), 126.6 (CH), 84.7 (CH), 71.4 (CH) and

19.0 (CH3); m/z (EI) 261 (7.9 %), 259 (M+, 7.9), 121 (67), 120 (100), 119 (95) and 91


2-Bromo-1-(2-methoxyphenyl)-2-nitroethanol (4c)

NO2

Br

OH

OMe Purified according to the general procedure. Diastereomeric ratios (anti/syn, 21:79)


(Chiralpak AD-H), hexane:i-PrOH 95:5, 1 mL/min. antimajor(1S, 2S) tr = 28.0 min,


5


6.90 (2 H, m, CH aromatic), 6.31 (1 H, d, J = 8.7, CHBr), 5.26 (1 H, t, J = 8.7, CHOH),

3.94 (3 H, s, OMe) and 3.43 (1 H, br s, OH); δC (75.5 MHz, CDCl3) δ 156.8 (C), 130.8

(CH), 128.6 (CH), 123.2 (C), 121.3 (CH), 111.0 (CH), 79.6 (CH), 76.1 (CH) and 55.5

(CH3); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.44-7.30 (2 H, m, CH aromatic),

7.05-6.90 (2 H, m, CH aromatic), 6.40 (1 H, d, J = 3.9, CHBr), 5.54 (1 H, unresolved t,

CHOH), 3.90 (3 H, s, OMe) and 3.43 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 155.7 (C),

130.3 (CH), 128.5 (CH), 124.0 (C), 121.1 (CH), 110.5 (CH), 84.3 (CH), 71.5 (CH) and

55.5 (CH3); m/z (EI) 277 (2.6 %), 275 (M+, 2.8), 137 (59), 136 (100), 135 (54) and 77


2-Bromo-1-(2-chlorophenyl)-2-nitroethanol (4d)3

NO2

Br

OH

Cl Purified according to the general procedure. Diastereomeric ratios (anti/syn, 13:87)


(Chiralpak AS-H), hexane:i-PrOH 95:5, 1 mL/min. antimajor(1S, 2S) tr = 17.2 min,



7.30 (3 H, m, CH aromatic), 6.22 (1 H, d, J = 7.5, CHBr), 5.76 (1 H, d, J = 7.5, CHOH)

and 3.53 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 133.7 (C), 133.0 (C), 130.6 (CH),

130.0 (CH), 128.5 (CH), 127.6 (CH), 80.0 (CH) and 72.8 (CH); syn isomer (1S, 2R): δH

(300 MHz, CDCl3) 7.70-7.67 (1 H m, CH aromatic), 7.42-7.30 (3 H, m, CH aromatic),

6.38 (1 H, d, J = 2.4, CHBr), 5.84 (1 H, d, J = 2.4, CHOH) and 3.53 (1 H, br s, OH). δC

(75.5 MHz, CDCl3) 133.9 (C), 131.3 (C), 130.3 (CH), 129.5 (CH), 127.3 (CH), 84.4

(CH) and 70.6 (CH); m/z (EI) 281 (1.0 %), 279 (M+, 0.8), 141 (74), 140 (72), 139

(100) and 111 (36). HRMS 278.9291 (M+), C8H7BrClNO3 requires 278.9298.

6

2-Bromo-2-nitro-1-(2-nitrophenyl)ethanol (4e)

NO2

Br

OH

NO2 Purified according to the general procedure. Diastereomeric ratios (anti/syn, 21:79)




min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 8.11-7.56 (4 H, m, CH aromatic), 6.35

(1 H d, J = 6.3, CHBr), 5.96 (1 H, d, J = 6.3, CHOH) and 3.75 (1 H, br s, OH); δC (75.5

MHz, CDCl3) 147.9 (C), 134.1 (CH), 131.4 (C), 130.4 (CH), 129.5 (CH), 125.3 (CH),

81.0 (CH) and 72.1 (CH); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 8.11 (1 H, dd, J =

8.4, 1.2, CH aromatic), 8.03 (1 H, d, J = 8.4, CH aromatic), 7.78 (1 H, td, J = 8.4, 1.2,

CH aromatic), 7.59 (1 H, td, J = 8.4, 1.2, CH aroamtic), 6.55 (1 H, d, J = 2.1, CHBr),

6.10 (1 H, d, J = 2.1, CHOH) and 3.64 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 146.8

(C), 134.2 (CH), 132.3 (C), 130.5 (CH), 130.1 (CH), 125.0 (CH), 84.7 (CH) and 69.1

(CH); m/z (EI) 246 (1.7 %), 244 ([M-NO2]+, 2.1), 152 (100), 121 (48), 104 (36), 65

(36); HRMS 243.9614 [M-NO2]+, C8H7BrNO3 requires 243.9610.

2-Bromo-2-nitro-1-m-tolylethanol (4f)

NO2

Br

OH

CH3 Purified according to the general procedure. Diastereomeric ratios (anti/syn, 32:68)





(1 H, d, J = 9.0, CHBr) 5.24 (1 H, d, J = 9.0, CHOH), 3.07 (1 H, br s, OH) and 2.38 (3

H, s, CH3); δC (75.5 MHz, CDCl3) 138.8 (C), 136.0 (C), 130.5 (CH), 128.8 (CH), 127.8

(CH), 124.5 (CH), 81.0 (CH), 76.3 (CH) and 21.4 (CH3); syn isomer (1S, 2R): δH (300

MHz, CDCl3) 7.33-7.16 (4 H, m, CH aromatic), 6.06 (1 H, d, J = 5.1, CHBr) 5.30 (1 H,

7

d, J = 5.1, CHOH), 3.07 (1 H, br s, OH) and 2.36 (3 H, s, CH3); δC (75.5 MHz, CDCl3)

138.8 (C), 135.8 (C), 130.3 (CH), 128.8 (CH), 127.0 (CH), 123.5 (CH), 85.5 (CH), 74.7

(CH) and 21.4 (CH3); m/z (EI) 261 (3.2 %), 259 (M+, 3.5), 121 (77), 119 (58), 91 (100).

HRMS 258.9839 (M+), C9H10BrNO3 requires 258.9844.

2-Bromo-1-(3-methoxyphenyl)-2-nitroethanol (4g)

NO2

Br

OH

OMe Purified according to the general procedure. Diastereomeric ratios (anti/syn, 61:39)




min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 7.33 (1 H, t, J = 8.1, CH aromatic),


CHOH), 3.82 (3 H, s, OMe) and 3.23 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 159.8 (C),

137.5 (C), 130.0 (CH), 119.6 (CH), 115.1 (CH), 112.9 (CH), 80.9 (CH), 76.2 (CH) and

55.3 (CH3); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.30 (1 H, t, J = 8.1, CH

aromatic), 7.01-6.88 (3 H, m, CH aromatic), 6.07 (1 H, d, J = 4.8, CHBr) 5.32 (1 H, d, J

= 4.8, CHOH), 3.80 (3 H, s, OMe) and 3.23 (1 H, br s, OH); δC (75.5 MHz, CDCl3)

159.8 (C), 137.5 (C), 118.6 (CH), 114.9 (CH), 112.1 (CH), 85.5 (CH), 74.5 (CH) and

55.3 (CH3); m/z (EI) 277 (3.7 %), 275 (M+, 3.7), 136 (100), 135 (89), 107 (29) and 77

(35). HRMS 274.9804 (M+), C9H10BrNO4 requires 274.9793.

2-Bromo-1-(3-chlorophenyl)-2-nitroethanol (4h)

NO2

Br

OH




antiminor(1R, 2R) tr = 17.8 min, synmajor(both enantiomers) tr = 23.1 min. anti isomer (1S,

8

2S): δH (300 MHz, CDCl3) 7.44-7.25 (4 H, m, CH aromatic), 5.90 (1 H, d, J = 9.0,

CHBr), 5.29 (1 H, d, J = 9.0, CHOH) and 3.22 (1 H, br s, OH); δC (75.5 MHz, CDCl3)

137.9 (C), 134.8 (C), 130.2 (CH), 129.9 (CH), 127.5 (CH), 125.7 (CH), 80.6 (CH) and

75.6 (CH); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.44-7.25 (4 H, m, CH aromatic),

6.05 (1 H, d, J = 4.5, CHBr) 5.36 (1 H, d, J = 4.5, CHOH), 3.22 (1 H, br s, OH); δC


(CH), 85.3 (CH) and 73.8 (CH); m/z (EI) 281 (5.1 %), 279 (M+, 4.4), 141 (100), 140

(69), 139 (91), 125 (39), 111 (48) and 77 (44); HRMS 278.9293 (M+), C8H7BrClNO3

requires 278.9298.

2-Bromo-2-nitro-1-(3-nitrophenyl)ethanol (4i)4

NO2

Br

OH

NO2 Purified according to the general procedure. Diastereomeric ratios (anti/syn, 40:60)




min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 8.32 (1H, m, CH aromatic), 8.22 (1H,

m, CH aromatic), 7.78 (1H, dd, J = 8.1, 3.0, CH aromatic), 7.61 (1H, m, CH aromatic),

5.96 (1 H, d, J = 8.7, CHBr), 5.48 (1 H, d, J = 8.7, CHOH) and 3.87 (1 H, br s, OH); δC


(CH), 80.5 (CH) and 75.1 (CH); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 8.32 (1H,

m, CH aromatic), 8.22 (1H, m, CH aromatic), 7.78 (1H, dd, J = 8.1, 3.0, CH aromatic),

7.61 (1H, m, CH aromatic), 6.16 (1 H, d, J = 4.2, CHBr), 5.58 (1 H, d, J = 4.2, CHOH)

and 3.76 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 148.3 (C), 138.4 (C), 132.6 (CH),

129.9 (CH), 124.2 (CH), 121.7 (CH), 85.2 (CH) and 73.3 (CH); m/z (EI) 272 ([M-

H2O]+, 0.5 %), 151 (100), 150 (80), 105 (42), 95 (40), 93 (43) and 77 (58); HRMS

271.9438 [M-H2O]+, C8H5BrN2O3 requires 271.9433.

9

2-Bromo-2-nitro-1-p-tolylethanol (4j)

NO2

Br

OH

H3C Purified according to the general procedure. Diastereomeric ratios (anti/syn, 70:30)


(Chiralcel OD-H), hexane:i-PrOH 95:5, 0.5 mL/min. antimajor(1S, 2S) tr = 33.7 min,



(1 H, d, J = 9.0, CHBr), 5.24 (1 H, d, J = 9.0, CHOH), 3.20 (1 H, br s, OH) and 2.37 (3

H, s, CH3); δC (75.5 MHz, CDCl3) 139.7 (C), 133.1 (C), 129.6 (2 x CH), 127.2 (2 x

CH), 81.1 (CH), 76.1 (CH) and 21.2 (CH3); syn isomer (1S, 2R): δH (300 MHz, CDCl3)


CHOH), 3.20 (1 H, br s, OH) and 2.34 (3 H, s, CH3); δC (75.5 MHz, CDCl3) 139.5 (C),

132.9 (C), 129.6 (2 x CH), 126.4 (2 x CH), 85.4 (CH), 74.6 (CH) and 21.2 (CH3); m/z

(EI) 261 (1.2 %), 259 (M+, 1.2), 120 (84), 119 (100) and 91 (99); HRMS 258.9849

(M+), C9H10BrNO3 requires 258.9844.

2-Bromo-1-(4-methoxyphenyl)-2-nitroethanol (4k)

NO2

Br

OH

MeO Purified according to the general procedure. Diastereomeric ratios (anti/syn, 63:37)


(Chiralcel OD-H), hexane:i-PrOH 90:10, 1 mL/min. antimajor(1S, 2S) tr = 14.5 min,

antiminor(1R, 2R) tr = 16.2 min, syn (both enantiomers) tr = 18.5 min. (Chiralpak IC),

hexane:i-PrOH 90:10, 1 mL/min. anti(both enantiomers) tr = 14.1 min, synminor(1R, 2S)

tr = 11.6 min, synmajor (1S, 2R) tr = 12.9 min. anti isomer (1S, 2S): δH (300 MHz, CDCl3)

7.35-7.29 (2 H, m, CH aromatic), 6.94-6.88 (2 H, m, CH aromatic), 5.92 (1 H, d, J =

8.7, CHBr), 5.26 (1 H, d, J = 8.7, CHOH), 3.82 (3 H, s, OMe) and 3.04 (1 H, br s, OH);

δC (75.5 MHz, CDCl3) 160.5 (C), 128.6 (2 x CH), 128.1 (C), 114.3 (2 x CH), 81.3 (CH),

75.9 (CH) and 55.3 (CH3); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.35-7.29 (2 H,

m, CH aromatic), 6.94-6.88 (2 H, m, CH aromatic), 6.01 (1 H, d, J = 5.7, CHBr), 5.26

10

(1 H, d, J = 5.7, CHOH), 3.80 (3 H, s, OMe) and 3.04 (1 H, br s, OH); δC (75.5 MHz,

CDCl3) 160.4 (C), 127.9 (2 x CH), 127.7 (C), 114.3 (2 x CH), 85.2 (CH), 74.5 (CH) and

55.3 (CH3); m/z (EI) 277 (2.3 %), 275 (M+, 2.6), 137 (69), 136 (70), 135 (100) and 77


2-Bromo-1-(4-chlorophenyl)-2-nitroethanol (4l)

NO2

Br

OH



(Chiralcel OD-H), hexane:i-PrOH 95:5, 1 mL/min. antimajor(1S, 2S) tr = 18.9 min,



(1 H, d, J = 8.7, CHBr), 5.30 (1 H, d, J = 8.7, CHOH) and 3.13 (1 H, br s, OH); δC (75.5

MHz, CDCl3) 135.7 (C), 134.4 (C), 129.1 (2 x CH), 128.7 (2 x CH), 80.8 (CH) and 75.6

(CH); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.42-7.33 (4 H, m, CH aromatic), 6.02

(1 H, d, J = 4.8, CHBr), 5.35 (1 H, d, J = 4.8, CHOH) and 3.13 (1 H, br s, OH); δC (75.5


(CH); m/z (EI) 281 (5.0 %), 279 (M+, 4.0), 141 (72), 140 (70), 139 (100), 111 (32);

HRMS 278.9286 (M+), C8H7BrClNO3 requires 278.9298.

2-Bromo-2-nitro-1-(4-nitrophenyl)etanol (4m)

NO2

Br

OH

O2N Purified according to the general procedure. Diastereomeric ratios (anti/syn, 64:36)




min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 8.26 (2 H, d, J = 8.7, CH aromatic),

7.66 (2 H, d, J = 8.7 CH aromtic), 5.94 (1 H, d, J = 8.7, CHBr) 5.47 (1 H, d, J = 8.7,

CHOH) and 3.51 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 148.5 (C), 142.8 (C), 128.6 (2

11

x CH), 123.9 (2 x CH), 80.3 (CH) and 75.1 (CH); syn isomer (1S, 2R): δH (300 MHz,

CDCl3) 8.25 (2 H, d, J = 8.7, CH aromatic), 7.63 (2 H, d, J = 8.7, CH aromatic), 6.12 (1

H, d, J = 4.2, CHBr), 5.56 (1 H, d, J = 4.2, CHOH) and 3.56 (1 H, br s, OH); δC (75.5


(CH); m/z (EI) 292 (0.1 %), 290 (M+, 0.1), 141 (72), 151 (100), 150 (86) and 77 (47).

HRMS 289.9532 (M+), C8H7BrN2O5 requires 289.9538.

2-Bromo-2-nitro-1-(thiophen-2-yl)ethanol (4n)

NO2

Br

OH

S Purified according to the general procedure. Diastereomeric ratios (anti/syn, 36:64)




min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 7.40 (1H, dd, J = 5.1, 1.2, CH

aromatic), 7.19 (1 H, dd, J = 3.6, 0.6, CH aromatic), 7.05 (1 H, dd, J = 5.1, 3.6, CH

aromatic), 5.99 (1 H, d, J = 9.0, CHBr) 5.59 (1 H, d, J = 9.0, CHOH), 3.27 (1 H, br s,

OH); δC (75.5 MHz, CDCl3) 138.6 (C), 127.7 (CH), 127.1 (CH), 126.7 (CH), 80.9 (CH),

72.3 (CH); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.37 (1H, dd, J = 5.1, 1.2, CH

aromatic), 7.08 (1 H, dt, J = 3.6, 0.8, CH aromatic), 7.01 (1 H, dd, J = 5.1, 3.9, CH

aromatic), 6.09 (1 H, d, J = 5.1, CHBr), 5.61 (1 H, d, J = 5.1, CHOH), 3.27 (1 H, br s,

OH); δC (75.5 MHz, CDCl3) 138.5 (C), 127.2 (CH), 127.0 (CH), 126.7 (CH), 84.6 (CH)

and 71.5 (CH); m/z (EI) 253 (2.7 %), 251 (M+, 2.8), 113 (69), 111 (100), 95 (49) and 93

(55); HRMS 250.9258 (M+), C6H6BrNO3S requires 250.9252.

2-Bromo-2-nitro-1-(thiophen-3-yl)ethanol (4o)

NO2

Br

OH

S Purified according to the general procedure. Diastereomeric ratios (anti/syn, 32:68)


12



min. anti isomer (1S, 2S): δH (300 MHz, CDCl3) 7.43 (1 H, dd, J = 3.0, 1.1, CH

aromatic), 7.36 (1 H, d, J = 3.0, CH aromatic), 7.14 (1 H, dd, J = 5.1, 1.2, CH aromatic),

5.96 (1 H, d, J = 9.0, CHBr), 5.42 (1 H, d, J = 9.0, CHOH) and 3.11 (1 H, br s, OH); δC

(75.5 MHz, CDCl3) 137.0 (C), 127.2 (CH), 125.5 (CH), 125.0 (CH), 80.7 (CH) and 72.2


(1 H, dd, J = 4.8, 1.5, CH aromatic), 6.08 (1 H, d, J = 5.1, CHBr), 5.45 (1 H, d, J = 5.1,

CHOH) and 3.11 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 137.0 (C), 127.2 (CH), 125.0

(CH), 124.2 (CH), 84.7 (CH) and 71.5 (CH); m/z (EI) 253 (11.2 %), 251 (M+, 11.3),

113 (100), 111 (45), 97 (39); HRMS 250.9245 (M+), C6H6BrNO3S requires 250.9252.

1-Bromo-1-nitroundecan-2-ol (4p)

CH3(CH2)8NO2

Br

OH



(Chiralpak AD-H), hexane:i-PrOH 99:1, 1 mL/min. (CAUTION, for the stereochemical

notation, see page 1 of SI) antimajor(1S, 2S) tr = 27.9 min, antiminor(1R, 2R) tr = 18.4 min,

synmajor(1S, 2R) tr = 20.8 min, synminor(1R, 2S) tr = 18.9 min. anti isomer (1S, 2S): δH

(300 MHz, CDCl3) 5.75 (1 H, d, J = 8.1, CHBr), 4.26-4.17 (1 H, m, CHOH), 2.61 (1 H,

br s, OH), 1.66-1.48 (2 H, m, CH2CHOH), 1.26 (14 H, m, 7 x CH2) and 0.88 (3 H, t, J =

6.6, CH3); δC (75.5 MHz, CDCl3) 81.6 (CH), 73.3 (CH), 33.7 (CH2), 31.8 (CH2), 29.4

(CH2), 29.3 (CH2), 29.2 (CH2), 29.1 (CH2), 25.1 (CH2), 22.6 (CH2) and 14.1 (CH3); syn

isomer (1S, 2R): δH (300 MHz, CDCl3) 5.98 (1 H, d, J = 3.3, CHBr), 4.26-4.17 (1 H, m,

CHOH), 2.73 (1 H, br s, OH), 1.66-1.48 (2 H, m, CH2CHOH), 1.26 (14 H, m, 7 x CH2)

and 0.87 (3 H, t, J = 6.6, CH3); δC (75.5 MHz, CDCl3) 86.3 (CH), 72.6 (CH), 32.0

(CH2), 31.8 (CH2), 29.4 (CH2), 29.3 (CH2), 29.2 (CH2), 29.1 (CH2), 24.9 (CH2), 22.6

(CH2) and 14.1 (CH3); m/z (EI) 216 ([M-Br]+, 2.5 %), 95 (67), 82 (73), 81 (66), 69 (81),

57 (80), 55 (100); HRMS 216.1593 [M-Br]+, C11H22NO3 requires 216.1600.

13

1-Bromo-1-nitro-4-phenylbutan-2-ol (4q)5

NO2

Br

OH






(300 MHz, CDCl3) 7.24-7.18 (5 H, m, CH aromatic), 5.76 (1 H, d, J = 7.8, CHBr), 4.26-

4.19 (1 H, m, CHOH) 2.98-1.78 (5 H, m, 2 x CH2 + OH); δC (75.5 MHz, CDCl3) 140.3

(C), 128.7 (2 x CH), 128.4 (2 x CH), 126.4 (CH), 81.4 (CH), 72.6 (CH), 33.5 (CH2) and

31.1 (CH2); syn isomer (1S, 2R): δH (300 MHz, CDCl3) 7.34-7.31 (5 H, m, CH

aromatic), 5.94 (1 H, d, J = 3.3, CHBr), 4.26-4.19 (1 H, m, CHOH) and 2.98-1.78 (5 H,

m, 2 x CH2 + OH); δC (75.5 MHz, CDCl3) 140.1 (C), 128.7 (2 x CH), 128.4 (2 x CH),

126.4 (CH), 85.9 (CH), 71.6 (CH), 35.1 (CH2) and 31.2 (CH2); m/z (EI) 275 (0.2 %),

273 (M+, 0.3), 134 (36), 92 (39), 91 (100); HRMS 272.9997 (M+), C10H12BrNO3

requires 273.0001.

1-Bromo-4-methyl-1-nitropentan-2-ol (4r)1

NO2

Br

OH






(300 MHz, CDCl3) 5.73 (1 H, d, J = 7.8, CHBr), 4.31-4.25 (1 H, m, CHOH), 2.50 (1 H,

br s, OH), 1.96-1.77 (1 H, m, CH(CH3)2), 1.63-1.42 (1 H, m, CH2), 1.35-1.25 (1 H, m,

CH2) and 0.97 (6 H, t, J = 6.9, 2 x CH3); δC (75.5 MHz, CDCl3) 82.1(CH), 71.9 (CH),

40.8 (CH2), 24.4 (CH), 23.5 (CH3) and 21.2 (CH3); syn isomer (1S, 2R): δH (300 MHz,

CDCl3) 5.96 (1 H, d, J = 3.3, CHBr), 4.31-4.25 (1 H, m, CHOH), 2.60 (1 H, br s, OH),

14

1.96-1.77 (1 H, m, CH(CH3)2), 1.63-1.42 (2 H, m, CH2), 0.97 (6 H, t, J = 6.9, 2 x CH3);

δC (75.5 MHz, CDCl3) 86.5 (CH), 71.0 (CH), 42.4 (CH2), 24.4 (CH), 23.0 (CH3) and

21.7 (CH3); m/z (EI) 146 ([M-Br]+, 0.9 %), 87 (77), 81 (76), 69 (100); HRMS 146.0818

[M-Br]+, C6H12NO3 requires 146.0817.

2-Bromo-1-cyclohexyl-2-nitroethanol (4s)1

NO2

Br

OH






(300 MHz, CDCl3) 5.85 (1 H, d, J = 8.4, CHBr), 4.07 (1 H, dd, J = 8.4, 3.3, CHOH),

2.58 (1 H, br s, OH) and 2.07-1.05 (11 H, m, Cy); δC (75.5 MHz, CDCl3) 79.8 (CH),

76.8 (CH), 38.5 (CH), 29.9 (CH2), 26.0 (CH2), 25.9 (CH2), 25.6 (CH2) and 24.9 (CH2);

syn isomer (1S, 2R): δH (300 MHz, CDCl3) 6.14 (1 H, d, J = 3.0, CHBr), 3.92 (1 H, dd,

J = 7.8, 2.7, CHOH ), 2.58 (1 H, br s, OH) and 2.07-1.05 (10 H, m, Cy); δC (75.5 MHz,

CDCl3) 86.0 (CH), 76.7 (CH), 41.4 (CH), 28.6 (CH2), 28.3 (CH2), 25.9 (CH2), 25.5

(CH2) and 25.4 (CH2); m/z (EI) 172 ([M-Br]+, 3.4 %), 95 (43), 83 (100), 55 (27); HRMS

172.0981 [M-Br]+, C8H14NO3 requires 172.0970.

(E)-1-Bromo-1-nitro-4-phenylbut-3-en-2-ol (4t)

NO2

Br

OH



(Chiralpak AS-H), hexane:i-PrOH 95:5, 1 mL/min. (CAUTION, for the stereochemical



(300 MHz, CDCl3) 7.42-7.27 (5 H, m, CH aromatic), 6.83 (1 H, d, J = 15.9, CH

15

olephinic), 6.17 (1 H, dd, J = 15.9, 6.9, CH olephinic), 5.84 (1 H, d, J = 8.1, CHBr),

4.97-4.92 (1 H, m, CHOH), 2.94 (1 H, br s, OH); δC (75.5 MHz, CDCl3) 136.2 (CH),

135.2 (C), 128.8 (CH), 128.7 (2 x CH), 126.9 (2 x CH), 122.6 (CH), 80.8 (CH), 74.4


(1 H, d, J = 15.9, CH olephinic), 6.12 (1 H, dd, J = 15.9, 6.6, CH olephinic), 6.03 (1 H,

d, J = 4.2, CHBr), 4.97-4.92 (1 H, m, CHOH), 2.94 (1 H, br s, OH); δC (75.5 MHz,

CDCl3) 135.7 (CH), 135.1 (C), 128.8 (CH), 128.7 (2 x CH), 126.9 (2 x CH), 123.0

(CH), 84.6 (CH), 73.9 (CH); m/z (EI) 273 (0.4 %), 271 (M+, 0.4), 132 (71), 131 (100),

103 (58) and 77 (48). HRMS 278.9841 (M+), C10H10BrNO3 requires 270.9844.

REFERENCES 1. G. Blay, L. R. Domingo, V. Hernández-Olmos, J. R. Pedro, Chem. Eur. J., 2008, 14, 4725.

2. J. M. Concellon, H. Rodriguez-Solla, C. Concellon, S. Garcia-Granda, M. R.; Diaz, Org. Lett., 2006, 8,

5979.

3. Jpn. pat., JP 54141738, 1979.

4. Jpn. pat., JP 50117933, 1975.

5. R. Ballini, G. Bosica, P. Forconi, Tetrahedron, 1996, 52, 1677.

6. Jpn. pat., JP 60048903, 1985

16

ppm (t1)1.502.002.503.003.504.004.505.005.506.006.507.007.50

7.43

17.

405

7.26

0

6.07

86.

061

5.96

75.

938

5.37

45.

357

5.33

05.

300

2.21

0

1.01.6

1.51.0

5.37.5

4.2

jr05-326, cdcl3, 300 MHz

ppm (t1)60.065.070.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0

135.

98

129.

7612

9.53

128.

9312

7.34

126.

45

85.4

7

80.9

6

77.4

2

77.0

0

76.5

876

.25

74.6

3

NO2

Br

OH

4a

17

ppm (t1)1.502.002.503.003.504.004.505.005.506.006.507.007.508.00

7.54

87.

536

7.52

37.

517

7.50

57.

493

7.39

27.

307

7.29

47.

283

7.27

57.

264

7.25

47.

205

7.19

27.

180

7.17

57.

162

6.11

96.

104

6.04

36.

012

5.64

0

5.61

05.

584

5.56

8

2.95

9

2.49

62.

389

1.04.8

1.04.9

5.113.31.15.1

4.4

2.915.2

ppm (t1)255075100125150

136.

64

134.

9813

4.56

134.

1413

1.09

130.

9912

9.46

129.

3212

6.85

126.

7012

6.58

126.

07

84.7

2

80.7

277

.42

77.0

076

.58

72.1

0

71.3

7

19.6

7

18.9

6

NO2

Br

OHMe

4b

18

ppm (t1)2.503.003.504.004.505.005.506.006.507.007.508.00

7.43

97.

434

7.41

47.

410

7.39

07.

385

7.36

47.

359

7.33

87.

332

7.30

67.

301

7.26

07.

049

7.02

4

6.99

66.

976

6.94

86.

927

6.90

06.

404

6.39

1

6.32

1

6.29

2

5.54

2

5.28

2

5.25

5

5.22

7

3.93

73.

898

3.44

63.

427

1.04.4

4.66.11.4

11.5

4.7

1.1

3.914.4

4.5

ppm (t1)5075100125150

156.

7515

5.71

130.

8113

0.75

130.

3312

8.56

128.

4912

4.01

123.

1512

1.25

121.

12

110.

98

110.

46

84.3

2

79.6

477

.42

77.0

076

.58

76.1

171

.50

55.5

1

NO2

Br

OHOMe

4c

19

ppm (t1)3.003.504.004.505.005.506.006.507.007.508.00

7.70

17.

696

7.67

77.

669

7.54

17.

535

7.51

77.

511

7.36

97.

355

7.34

87.

259

6.37

96.

371

6.23

16.

206

5.83

95.

832

5.77

75.

752

1.0

0.1

1.0

0.1

3.4

1.00.2

ppm (t1)70.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0

133.

8713

3.66

132.

9513

1.25

130.

6413

0.31

129.

9912

9.49

129.

0312

8.46

127.

5812

7.28

84.3

6

79.9

7

77.4

2

77.0

0

76.5

7

72.8

2

70.6

3

NO2

Br

OHCl

4d

20

ppm (t1)3.504.004.505.005.506.006.507.007.508.008.50

8.12

18.

097

8.07

1

8.04

1

8.01

37.

804

7.80

07.

778

7.77

57.

753

7.74

97.

728

7.71

4

7.61

6

7.58

8

7.56

0

7.26

0

6.55

46.

547

6.35

76.

336

6.09

5

5.96

95.

948

3.75

2

3.64

3

1.0

3.1

1.0

2.9

4.02.03.3

3.63.4

1.0

3.0

ppm (t1)65.070.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0145.0150.0

147.

94

146.

83

134.

2113

4.13

132.

2613

1.38

130.

5413

0.37

130.

1012

9.48

125.

3012

5.02

84.6

9

80.9

5

77.4

2

77.0

0

76.5

8

72.1

1

69.0

9

NO2

Br

OHNO2

4e

21

ppm (t1)2.002.503.003.504.004.505.005.506.006.507.007.50

7.32

87.

304

7.27

77.

252

7.22

4

7.19

47.

187

7.15

8

6.06

56.

048

5.95

9

5.92

9

5.30

55.

288

5.25

3

5.22

3

3.06

7

2.38

12.

364

1.01.9

12.2

1.91.1

2.6

3.05.9

ppm (t1)255075100125150

138.

8213

8.77

135.

9513

5.80

130.

5213

0.28

128.

7912

7.84

127.

0112

4.47

123.

50

85.5

0

80.9

877

.42

77.0

076

.58

76.2

9

74.6

7

21.3

8

NO2

Br

OHMe

4f

22

ppm (t1)2.503.003.504.004.505.005.506.006.507.007.50

7.35

27.

327

7.30

0

7.27

37.

260

7.00

86.

982

6.94

76.

944

6.93

56.

921

6.91

86.

913

6.07

66.

059

5.95

7

5.92

7

5.33

05.

313

5.26

0

5.23

0

3.81

73.

804

3.23

0

1.0

1.6

1.01.7

8.4

2.3

2.6

8.3

ppm (t1)5075100125150

159.

8315

9.78

137.

53

129.

99

119.

6111

8.57

115.

1011

4.88

112.

91

112.

08

85.5

1

80.8

9

77.4

277

.00

76.5

876

.17

74.4

5

55.3

2

NO2

Br

OHMeO

4g

23

ppm (t1)3.003.504.004.505.005.506.006.507.007.508.00

7.44

47.

436

7.43

07.

385

7.37

97.

371

7.36

27.

356

7.34

97.

332

7.31

87.

307

7.28

27.

277

7.27

07.

260

7.25

4

6.06

06.

045

5.91

9

5.88

9

5.36

75.

352

5.30

15.

296

5.27

2

3.21

9

1.01.4

1.3

0.9

8.9

2.1

ppm (t1)60.065.070.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0145.0

137.

90

134.

9213

4.81

130.

1712

9.89

129.

6512

7.53

126.

6712

5.66

124.

60

85.2

5

80.5

9

77.4

277

.00

76.5

775

.57

73.7

8

NO2

Br

OHCl

4h

24

ppm (t1)3.003.504.004.505.005.506.006.507.007.508.008.509.00

8.33

78.

331

8.32

18.

314

8.30

88.

246

8.24

28.

236

8.23

28.

224

8.22

18.

216

8.21

28.

208

8.20

58.

201

7.79

87.

788

7.77

17.

762

7.74

57.

640

7.62

77.

613

7.60

07.

574

7.25

9

6.16

56.

151

5.97

45.

945

5.58

55.

572

5.49

55.

466

3.87

23.

755

1.0

0.4

1.00.4

1.3

1.41.4

1.4

1.4

ppm (t1)65.070.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0145.0150.0

148.

2714

8.16

138.

3913

8.23

133.

6713

2.63

129.

9212

9.86

124.

3912

4.19

122.

5112

1.66

85.1

6

80.5

2

77.4

277

.00

76.5

775

.06

73.2

5

NO2

Br

OHO2N

4i

25

ppm (t1)2.002.503.003.504.004.505.005.506.006.507.007.50

7.30

47.

276

7.24

67.

222

7.19

7

6.03

76.

019

5.94

25.

912

5.29

15.

273

5.25

15.

221

3.19

5

2.36

52.

343

1.01.7

2.8

12.7

2.6

8.0

ppm (t1)255075100125

139.

7213

9.49

133.

1013

2.89

129.

5512

7.21

126.

36

85.4

381

.13

77.4

277

.00

76.5

776

.07

74.6

1

21.2

021

.17

NO2

Br

OH

Me

4j

26

ppm (t1)3.003.504.004.505.005.506.006.507.007.50

7.34

7

7.31

8

7.28

9

7.26

0

6.93

9

6.91

0

6.88

4

6.01

65.

997

5.93

0

5.90

1

5.27

45.

255

5.22

5

3.81

83.

801

3.03

5

1.01.7

5.5

5.6

2.7

4.33.5

2.6

ppm (t1)5075100125150

160.

4816

0.36

128.

6112

8.06

127.

8812

7.70

114.

26

85.1

8

81.2

7

77.4

277

.00

76.5

8

75.8

774

.50

55.3

155

.29

NO2

Br

OH

MeO

4k

27

ppm (t1)2.503.003.504.004.505.005.506.006.507.007.50

7.39

97.

390

7.38

47.

369

7.35

57.

346

7.32

67.

261

6.03

16.

015

5.90

7

5.87

8

5.35

65.

340

5.31

4

5.28

5

3.13

0

1.0

1.4

2.5

9.5

2.1

ppm (t1)70.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0

135.

6913

5.49

134.

4313

4.30

129.

13

128.

7412

7.87

85.1

7

80.7

7

77.4

2

77.0

0

76.5

8

75.5

5

73.9

4

NO2

Br

OH

Cl

4l

28

ppm (t1)3.003.504.004.505.005.506.006.507.007.508.008.50

8.27

08.

263

8.24

08.

233

7.67

37.

644

7.61

5

7.25

9

6.12

36.

110

5.94

95.

921

5.56

55.

553

5.47

95.

450

3.55

6

3.51

3

1.0

1.2

1.11.3

4.4

4.7

2.2

ppm (t1)65.070.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0145.0150.0155.0

148.

4814

8.31

142.

9714

2.82

128.

6012

7.57

123.

9912

3.91

84.9

7

80.2

9

77.4

277

.00

76.5

875

.12

73.3

9

NO2

Br

OH

O2N

4m

29

ppm (t1)3.003.504.004.505.005.506.006.507.007.50

7.40

97.

405

7.39

27.

385

7.38

17.

368

7.36

47.

260

7.19

37.

183

7.08

97.

077

7.06

17.

049

7.04

47.

029

7.01

67.

012

7.00

0

6.10

36.

084

6.00

2

5.97

2

5.61

95.

602

5.57

3

3.27

1

1.01.8

1.01.81.01.8

0.81.7

2.8

1.71.1

ppm (t1)65.070.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0

138.

6113

8.50

127.

6812

7.17

127.

1412

6.96

126.

66

84.5

7

80.9

1

77.4

2

77.0

0

76.5

8

72.2

871

.45

NO2

Br

OHS

4n

30

ppm (t1)2.503.003.504.004.505.005.506.006.507.007.50

7.43

77.

433

7.42

77.

424

7.40

07.

382

7.36

57.

355

7.26

07.

154

7.15

07.

137

7.13

3

7.10

57.

100

7.08

97.

084

6.08

86.

071

5.97

6

5.94

7

5.45

75.

439

5.40

8

3.11

2

1.02.2

2.11.0

0.94.11.2

2.01.1

3.1

ppm (t1)70.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0

136.

99

127.

1912

5.49

125.

0112

4.96

124.

22

84.7

0

80.7

0

77.4

2

77.0

0

76.5

8

72.2

171

.50

NO2

Br

OH

S4o

31

ppm (t1)0.501.001.502.002.503.003.504.004.505.005.506.006.50

5.98

85.

977

5.76

45.

738

4.26

34.

254

4.23

54.

225

4.21

04.

199

4.18

34.

172

1.84

31.

835

1.82

31.

814

1.79

01.

556

1.26

4

0.89

80.

876

0.85

31.0

1.1

2.1

1.0

1.2

42.7

8.4

ppm (t1)10.015.020.025.030.035.040.045.050.055.060.065.070.075.080.085.090.0

86.2

7

81.5

6

77.4

2

77.0

0

76.5

8

73.3

372

.64

33.7

032

.01

31.8

229

.43

29.4

029

.36

29.3

329

.22

29.2

129

.15

25.1

424

.85

22.6

3

14.0

6

CH3(CH2)8NO2

Br

OH

4p

32

ppm (t1)1.502.002.503.003.504.004.505.005.506.006.507.007.50

7.33

77.

333

7.30

77.

283

7.24

27.

218

7.17

8

5.94

85.

937

5.76

85.

742

4.25

7

4.22

44.

197

4.15

5

2.97

92.

928

2.89

72.

838

2.79

92.

753

2.72

72.

670

2.64

62.

234

2.17

82.

122

2.00

7

1.93

1

1.86

0

1.82

81.

781

1.0

1.1

4.87.4

2.1

2.8

4.5

1.3

3.7

ppm (t1)5075100125

140.

2614

0.11

128.

6612

8.65

128.

3812

6.43

126.

38

85.8

8

81.3

8

77.4

277

.00

76.5

872

.58

71.6

4

35.1

133

.54

31.2

231

.08

NO2

Br

OH

Ph

4q

33

ppm (t1)0.501.001.502.002.503.003.504.004.505.005.506.00

5.96

45.

953

5.74

65.

720

4.31

34.

305

4.28

84.

280

4.26

24.

254

2.59

52.

500

1.96

41.

887

1.85

21.

769

1.63

41.

588

1.55

51.

465

1.41

81.

353

1.31

11.

246

0.99

10.

968

0.94

50.

941

1.0

1.2

2.2

2.1

2.5

3.6

1.4

13.6

ppm (t1)20.025.030.035.040.045.050.055.060.065.070.075.080.085.0

86.5

40

82.0

75

77.4

24

77.0

00

76.5

77

71.9

1571

.005

42.3

79

40.8

27

24.3

77

23.4

76

23.0

40

21.7

3821

.184

NO2

Br

OH

4r

34

ppm (t1)0.501.001.502.002.503.003.504.004.505.005.506.00

6.14

26.

132

5.86

45.

836

4.09

04.

079

4.06

24.

051

3.94

03.

931

3.91

43.

905

2.07

3

2.03

0

1.80

91.

794

1.78

5

1.66

41.

231

1.22

41.

219

1.20

71.

200

1.19

3

1.0

1.6

1.6

1.0

2.1

1.0

33.7

ppm (t1)20.025.030.035.040.045.050.055.060.065.070.075.080.085.090.0

86.0

3

79.7

677

.42

77.0

076

.77

76.7

176

.58

41.4

1

38.5

3

29.8

5

28.5

528

.27

26.0

425

.90

25.8

525

.64

25.5

225

.38

24.8

8

NO2

Br

OH

4s

35

ppm (t1)2.503.003.504.004.505.005.506.006.507.007.50

7.41

77.

371

7.33

8

7.31

37.

270

7.24

2

6.85

46.

811

6.80

26.

758

6.21

16.

188

6.15

66.

134

6.10

36.

081

6.03

56.

021

5.85

5

5.82

8

4.96

64.

945

4.93

14.

918

2.94

2

1.8

3.91.92.91.0

5.7

6.0

31.6

5.8

ppm (t1)70.075.080.085.090.095.0100.0105.0110.0115.0120.0125.0130.0135.0140.0

137.

49

136.

2313

5.74

135.

1813

5.11

128.

8012

8.71

126.

89

123.

01

122.

60

84.5

6

80.8

079

.82

77.4

2

77.0

0

76.5

874

.44

73.8

7

NO2

Br

OH

Ph

4t

36

NO2

Br

OH

4a

37

NO2

Br

OH

4b

Me

38

NO2

Br

OH

4c

OMe

39

NO2

Br

OH

4d

Cl

40

NO2

Br

OH

4e

NO2

41

NO2

Br

OH

4f

Me

42

NO2

Br

OH

4g

MeO

43

NO2

Br

OH

4h

Cl

44

NO2

Br

OH

4i

O2N

45

NO2

Br

OH

4jMe

46

NO2

Br

OH

4kOD-H

MeO

47

NO2

Br

OH

4kIC

MeO

48

NO2

Br

OH

4lCl

49

NO2

Br

OH

4mO2N

50

NO2

Br

OH

4n

S

51

NO2

Br

OH

4oS

52

CH3(CH2)8NO2

Br

OH

4p

53

NO2

Br

OH

4q

Ph

54

NO2

Br

OH

4r

55

NO2

Br

OH

4s

56

NO2

Br

OH

4t

Ph

Documents

A catalytic highly enantioselective direct synthesis of 2 … Lower-energy conformation for anti-4a Lower-energy conformation for syn-4a Conformational energies were minimized using