K. Piwowarczyk et al. / Tetrahedron: Asymmetry 19 (2008) 309–317
315
4.4. Reaction of (2S,3S)-5 with racemic benzoin
4.5.2. (S)-(+)-Benzoin. The title compound was obtained
from ester 14 in 91% yield.
(2S,3S)-1-Methyl-5-oxo-2-phenyltetrahydro-1H-pyrrolidine-
3-carboxylic acid 5 (219 mg, 1 mmol), rac-benzoin (212 mg,
1 mmol) and DMAP (30.5 mg, 0.25 mmol) were dissolved
in dry CH2Cl2 (10 mL) under argon and the mixture was
stirred for 10 min. After cooling to 0 °C, DCC (309 mg,
1.5 mmol) was added and the reaction mixture was stirred
for 12 h at room temperature. The DCU precipitate was fil-
tered off and the solvent was evaporated under vacuum.
The residue was taken up in CH2Cl2 and washed twice with
0.5 N HCl, then dried over MgSO4. The solvent was evap-
orated and the residue was subjected to column chroma-
tography using CH2Cl2/CH3OH (99:1, v/v) as eluent to
afford two diastereomeric esters 13 and 14.
22
Mp 133–134 °C, ½aꢂD ¼ þ109:2 (c 1.3, acetone); lit.39: mp
22
135–137 °C, ½aꢂD ¼ þ115 (c 1.5, acetone).
4.6. Reaction of (2S,3S)-5 with racemic 1-(2,3,4-trichloro-
phenyl)ethanol 15
A mixture of 243 mg (1.1 mmol) of acid (2S,3S)-5 and
250 mg (1.1 mmol) of racemic 1-(2,3,4-trichlorophenyl)eth-
anol 1529 and 34 mg (0.28 mmol) of DMAP in 10 mL of
dry CH2Cl2 was stirred under argon for 10 min at room
temperature. After cooling to 0 °C, a sample of 343 mg
(1.7 mmol) of DCC was introduced in one portion and
the mixture was stirred at 0 °C for 2 h. The precipitate of
DCU was then filtered off and the solution was washed
twice with 1% HClaq and brine, and dried over anhydrous
MgSO4. After evaporation of the solvent, the residue was
subjected to column chromatography on silica-gel using
cyclohexane/ethyl acetate (9:1, v/v) as eluent.
4.4.1. (1R)-2-Oxo-1,2-diphenyl-ethyl (2S,3S)-1-methyl-5-
oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylate 13.
22
Yield of 161 mg (39%). ½aꢂD ¼ ꢀ34:2 (c 1.1, CHCl3);
1H NMR (500 MHz, CDCl3) d = 7.90 (m, 2H, Harom),
7.51 (m, 1H, Harom), 7.36 (m, 10H, Harom), 7.23 (m, 2H,
Harom), 6.85 (s, 1H, PhCHC@O), 4.86 (d, 1H, J = 6.0 Hz,
H-2), 3.21 (m, 1H, H-3), 2.96 (m, 2H, H-4), 2.68 (s, 3H,
NCH3); 13C NMR (125 MHz, CDCl3) d = 193.0, 172.7,
171.8, 139.2, 134.4, 133.7, 132.9, 129.6, 129.2, 129.1, 128.8,
128.7, 128.7, 128.5, 126.7, 78.4, 66.2, 46.1, 33.6, 28.3; ESI
MS (positive) m/z: 436 (M+Na)+, 849 (2M+Na)+; HR
MS: calcd for C26H23NO4 413.4651, found 413.4647.
4.6.1. (1R)-1-(2,3,4-Trichlorophenyl)ethyl (2S,3S)-1-methyl-
5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylate 16.
A less polar diastereomer was isolated in 38% yield in the
form of oil.
22
1
½aꢂD ¼ þ36:7 (c 1.0, CHCl3); H NMR (200 MHz, CDCl3)
d = 7.33–7.45 (m, 4H, Harom), 7.13–7.27 (m, 2H, Harom),
7.08 (d, 1H, J = 8.3 Hz, CHCCl), 6.19 (q, 1H,
J = 6.5 Hz, PhCHC@O), 4.76 (d, 1H, J = 6.0 Hz, H-2),
3.13 (m, 1H, H-3), 2.80 (dd, 2H, 1J = 14.0 Hz,
2J = 8.2 Hz, H-4), 2.67 (s, 3H, NCH3), 1.49 (d, 3H,
J=6.5 Hz, CH3); 13C NMR (50 MHz, CDCl3) d = 175.2,
171.2, 139.8, 139.3, 133.8, 132.3, 129.5, 128.9, 126.9,
126.9, 124.6, 70.7, 66.6, 46.4, 33.6, 25.1, 21.0; ESI MS (po-
sitive) m/z: 448 (M+Na)+.
4.4.2. (1S)-2-Oxo-1,2-diphenyl-ethyl (2S,3S)-1-methyl-5-
oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylate 14.
22
Yield of 153 mg (37%). ½aꢂD ¼ þ150:8 (c 1.0, CHCl3);
1H NMR (500 MHz, CDCl3) d = 7.93 (m, 2H, Harom),
7.53 (m, 1H, Harom), 7.38 (m, 12H, Harom), 6.88 (s, 1H,
PhCHC@O), 4.99 (d, 1H, J = 5.0 Hz, H-2), 3.21 (m, 1H,
H-3), 2.87 and 2.86 (2ꢁ m, 2H, H-4), 2.71 (s, 3H, NCH3);
13C NMR (125 MHz, CDCl3) d = 193.5, 173.1, 172.2,
139.8, 134.5, 133.9, 133.0, 129.7, 129.4, 129.3, 129.0,
128.9, 128.9, 128.7, 126.9, 78.6, 66.7, 45.7, 33.0, 28.6; ESI
MS (positive) m/z: 436 (M+Na)+, 849 (2M+Na)+; HR
MS: calcd for C26H23NO4 413.4651, found 413.4654.
4.6.2. (1S)-1-(2,3,4-Trichlorophenyl)ethyl (2S,3S)-1-methyl-
5-oxo-2-phenyltetrahydro-1H-pyrrolidine-3-carboxylate 17.
A more polar diastereomer was isolated in 42% yield in the
22
form of an amorphous solid. ½aꢂD ¼ þ49:5 (c 1.0, CHCl3);
1H NMR (200 MHz, CDCl3) d = 7.33–7.46 (m, 3H,
Harom), 7.12–7.22 (m, 2H, Harom), 7.31 (dAB, 1H, J =
8.4 Hz, CHCHCCl), 6.98 (dAB, 1H, J = 8.4 Hz, CHCCl),
6.21 (q, 1H, J = 6.4 Hz, PhCHC@O), 4.68 (d, 1H, J =
4.5. Hydrolysis of esters 13 and 14
To a solution of 100 mg (0.24 mmol) of ester 13 or 14 in
10 mL of methanol, 0.25 mL of NH3aq was added and
the reaction mixture was stirred at room temperature until
all substrates were consumed (TLC, approx. 1 h). After
subsequent addition of 0.1 mL of glacial acetic acid, the
solvent was evaporated and the residue was taken up into
benzene (10 mL) and the organic layer was washed with
brine (3 ꢁ 10 mL). After drying over anhydrous Na2SO4
and evaporation of the solvent, the residue was chromato-
graphed on silica-gel (CH2Cl2) to afford optically active
benzoin.
1
2
6.0 Hz, H-2), 3.12 (td, 1H, J = 8.8 Hz, J = 6.0 Hz, H-3),
1
2
2.85 (dd, 2H, J = 8.8 Hz, J = 5.0 Hz, H-4), 2.66 (s, 3H,
NCH3), 1.49 (d, 3H, J = 6.4 Hz, CH3); 13C NMR
(50 MHz, CDCl3) d = 172.7, 171.5, 139.7, 139.1, 133.7,
132.1, 129.5, 129.0, 128.8, 126.9, 124.8, 70.8, 66.8, 46.6,
34.0, 28.5, 20.9; ESI MS (positive) m/z: 448 (M+Na)+.
4.7. (1R)-1-(2,3,4-Trichlorophenyl)ethanol (R)-(+)-15
To a solution of 75 mg (0.176 mmol) of ester 16 in 10 mL
of methanol, a solution of 20% KOHaq (0.2 mL) was added
and the mixture was stirred for 30 min at room tempera-
ture. The solvent was then evaporated and the mixture
was quenched with 10 mL of CH2Cl2 and 10 mL of water.
The organic layer was washed with water (2 ꢁ 2 mL), dried
and evaporated to leave (R)-(+)-15 as an amorphous solid
4.5.1. (R)-(ꢀ)-Benzoin. The title compound was obtained
from ester 13 in 95% yield.
22
Mp 132–134 °C, ½aꢂD ¼ ꢀ110:4 (c 1.3, acetone); lit.39: mp
22
135–137 °C, ½aꢂD ¼ ꢀ115 (c 1.5, acetone).