Aldol Reactions by Lipase From Rhizopus niveus, an Example of Unspecific Protein Catalysis
(1H, m), 1.31–1.71 (4H, m). Enantiomeric excess was
determined by HPLC with a Chiralpak AD-H column
(9:1 hexane:2-propanol), 30°C, 225 nm, 1.0 mL min−1;
rac‑syn enantiomers tr=13.9 and 15.2 min; anti major
(S,R)-enantiomer tr=16.7 min, minor (R,S)-enanti-
omer tr=20.6 min.
2.3.6 (S)‑2‑[(R)‑Hydroxy(2,4‑dichlorophenyl)methyl]
White powder, [ꢀ ]=+10.0 (c 1.5, CHCl3) 1H NMR
25
D
(400 MHz, CDCl3): δ 7.50 (1H, d, J=8.4 Hz), 7.35 (1H,
s), 7.29 (1H, d, J=8.4 Hz), 5.29 (1H, dd, J=7.5, 3.3 Hz),
4.10 (1H, d, J=3.9 Hz), 2.70–2.55 (1H, m), 2.50–2.25 (2H,
m), 2.15–2.05 (1H, m), 1.90–1.78 (1H, m), 1.75–1.50 (4 H,
m). Enantiomeric excess was determined by HPLC with a
Chiralcell AS-H column (90:10 hexane:2-propanol), 30°C,
254 nm, 0.5 mL min−1; rac‑syn enantiomers tr=9.5 and
10.5 min; anti minor (R,S)-enantiomer tr=12.1 min, major
(S,R)-enantiomer tr=13.2 min.
2.3.3 (S)‑2‑[(R)‑Hydroxy(2‑nitrophenyl)methyl]
Yellow powder, [ꢀ ]= +5.3 (c 1.5, CHCl3) 1H NMR
25
D
(400 MHz, CDCl3): δ 7.84 (1H, d, J = 8.1 Hz), 7.77
(1H, d, J = 8.0 Hz), 7.63 (1H, t, J = 8.1 Hz), 7.43 (1H,
t, J = 8.1 Hz), 5.45 (1H, d, J = 6.6 Hz), 4.10 (1H, br),
2.82–2.70 (1H, m), 2.50–2.30 (2H, m), 2.15-2.00 (1H,
m), 1.90–1.50 (5 H, m). Enantiomeric excess was deter-
mined by HPLC with a Chiralcell OD-H column (95:5
hexane:2-propanol), 30 °C, 225 nm, 1.0 mL min−1;
rac‑syn enantiomers tr = 10.6 and 12.3 min; anti major
(S,R)-enantiomer tr = 15.0 min, minor (R,S)-enantiomer
tr = 17.1 min.
2.3.7 (S)‑2‑[(R)‑Hydroxy(phenyl)methyl]cyclohexanone
White powder, [ꢀ ]=+11.0 (c 1.0, CHCl3) 1H NMR
25
D
(400 MHz, CDCl3): δ 7.45–7.20 (5 H, m), 4.80 (1H, d,
J=9.0 Hz), 4.00 (1H, m), 2.70–2.50 (1H, m), 2.55–2.42
(1H, m), 2.34 (1H, td, J=12.3, 5.4 Hz), 2.15–2.02 (1H,
m), 1.88–1.70 (1H, m), 1.75–1.50 (3H, m), 1.40–1.20 (1H,
m). Enantiomeric excess was determined by HPLC with a
Chiralcell OD-H column (90:10 hexane:2-propanol), 30°C,
254 nm, 0.5 mL min−1; rac‑syn enantiomers tr=12.7 and
13.9 min; anti major (S,R)-enantiomer tr=15.1 min, (R,S)-
minor enantiomer tr=17.8 min.
2.3.4 (S)‑2‑[(R)‑Hydroxy(4‑cyanophenyl)methyl]
White powder, [ꢀ ]= +14.0 (c 1.5, CHCl3) 1H NMR
25
(400 MHz, CDClD3): δ 7.65 (2H, d, J = 8.1 Hz), 7.45
(2H, d, J = 8.1 Hz), 4.85 (1H, dd, J = 8.1, 3.0 Hz), 4.13
(1H, d, J = 3.0 Hz), 2.60–2.40 (2H, m), 2.37 (1H, m),
2.17–2.06 (1H, m), 1.88–1.77 (1H, m), 1.72–1.47 (3H,
m), 1.44–1.31 (1H, m). Enantiomeric excess was deter-
mined by HPLC with a Chiralpak AD-H column (80:20
hexane:2-propanol), 30 °C, 225 nm, 0.5 mL min−1;
rac‑syn enantiomers tr = 15.8 and 17.8 min; anti minor
(R,S)-enantiomer tr = 19.5 min, major (S,R)-enantiomer
tr = 23.9 min.
2.3.8 (R)‑2‑[(S)‑Hydroxy(4‑methoxyphenyl)methyl]
White powder, [ꢀ ]=−10.0 (c 1.0, CHCl3) 1H NMR
25
D
(400 MHz, CDCl3): δ 7.22 (2H, d, J=8.4 Hz), 6.88 (2H,
d, J=8.7 Hz), 4.74 (1H, dd, J=8.8, 2.5 Hz), 3.92 (1H, d,
J=2.7 Hz), 3.80 (3H, s), 2.65–2.49 (1H, m), 2.52–2.43
(1H, m), 2.35 (1H, td, J=12.9, 5.4 Hz), 2.18–2.03 (1H,
m), 1.84–1.73 (1H, m), 1.70–1.45 (3H, m), 1.35–1.23 (1H,
m). Enantiomeric excess was determined by HPLC with a
Chiralpak AD-H column (95:5 hexane:2-propanol), 30°C,
254 nm, 1.0 mL min−1; rac‑syn enantiomers tr=17.6 and
20.8 min; anti minor (S,R)-enantiomer tr=29.8 min, (R,S)-
major enantiomer tr=31.5 min.
2.3.5 (S)‑2‑[(R)‑Hydroxy(4‑chlorophenyl)methyl]
White powder, [ꢀ ]=+10.6 (c 1.5, CHCl3) 1H NMR
2.4 Yield, Enantioselectivity and Diastereoselectivity
Determination
25
(400 MHz, CDCl3)D: δ 7.29 (4H, dd, J=20.2, 8.4 Hz), 4.75
(1H, dd, J=8.7, 2.7 Hz), 4.00 (1H, d, J=3.0 Hz), 2.60–2.40
(2H, m), 2.35 (1H, td, J=12.9, 5.4 Hz), 2.15–2.05 (1H, m),
1.85–1.75 (1H, m), 1.70–1.50 (3H, m), 1.35–1.20 (1H, m).
Enantiomeric excess was determined by HPLC with a Chi-
ralpak AD-H column (90:10 hexane:2-propanol), 30°C,
254 nm, 0.5 mL min−1; rac‑syn enantiomers tr=15.8 and
18.4 min; anti minor (R,S)-enantiomer tr=23.1 min, major
(S,R)-enantiomer tr=26.8 min.
NMR analyses: the reaction product was dissolved in
25 mL of ethyl acetate. Subsequently, 3 mL of this solu-
tion were evaporated under reduced pressure, dissolved in
1
CDCl3 and employed in H-NMR analyses recorded on
an Agilent Technologies 400/54 Premium Shielded spec-
trometer, with TMS as internal standard. The anti and syn
ratio was determined by 1H-NMR for the aldol products of
1 3