10.1002/adsc.201800956
Advanced Synthesis & Catalysis
3345, 3192, 1732, 1667 cm-1; HRMS (FT-MS-ESI): m/z
calcd. for C19H21NO3Na: 334.1414 [M+Na]+; Found:
334.1415.
obtained from HPLC analysis using columns coated with
chiral stationary phases.
Benzyl (R)-3-benzyl-4-carbamoylbutanoate (4a): white
o
Benzyl (R)-3-(2-bromophenyl)-4-carbamoylbutanoate
solid (522 mg, 84%); mp: 87 - 88 C; [α]25 -11.2o (c 1.3,
D
(2g): white solid (346 mg, 92%); mp: 88 - 89 C; [α]25
CHCl3); ee > 99.5%; 1H NMR (400 MHz, CDCl3) 7.35 -
7.33 (m, 5H), 7.29 - 7.25 (m, 2H), 7.22 - 7.14 (m, 3H),
5.49 (brs, 1H), 5.22 (brs, 1H), 5.15 - 5.08 (m, 2H), 2.74 -
2.60 (m, 3H), 2.44 (d, J = 6.4 Hz, 2H), 2.26 - 2.24 (m, 2H);
13C NMR (75MHz, CDCl3) 174.2, 172.6, 139.3, 135.8,
129.3, 128.6, 128.44, 128.38, 126.4, 66.3, 40.0, 39.2, 37.4,
34.6; IR (KBr) 3391, 3210, 1730, 1639, 1613 cm-1;
HRMS (FT-MS-ESI): m/z calcd. for C19H21NO3Na:
334.1414 [M+Na]+; Found: 334.1418. In the scaled-up
biocatalytic reaction, 1579 mg 9a was obtained in 85%
yield and >99% ee (entry 2, Table 2).
o
D
+11.8o (c 0.9, CHCl3); ee > 99.5%; H NMR (400 MHz,
1
CDCl3) 7.53 (d, J = 8.0 Hz, 1H), 7.30 - 7.28 (m, 3H),
7.22 - 7.18 (m, 4H), 7.07 - 7.05 (m, 1H), 5.80 - 5.65 (m,
2H), 5.05 - 4.98 (m, 2H), 4.15 - 4.08 (m, 1H), 2.94 - 2.78
(m, 2H), 2.60 - 2.58 (m, 2H); 13C NMR (100 MHz, CDCl3)
173.0, 171.4, 141.2, 135.7, 133.4, 128.50, 128.45, 128.18,
128.16, 127.8, 124.5, 66.4, 40.5, 38.5, 37.6; IR (KBr)
3345, 3193, 1732, 1668 cm-1; HRMS (FT-MS-ESI): m/z
calcd. for C18H18BrNO3Na: 398.0362 [M+Na]+ (79Br);
Found: 398.0363.
Benzyl (R)-4-carbamoyl-3-(2-chlorophenyl)butanoate
Benzyl (R)-3-(2-bromobenzyl)-4-carbamoylbutanoate
o
(2h): white solid (315 mg, 95%); mp: 104 - 105 C; [α]25
(4b): white solid (686 mg, 88%); mp: 100 - 101 oC; [α]25
-
D
D
+10.8o (c 2.4, CHCl3); ee > 99.5%; H NMR (400 MHz,
6.7o (c 0.9, CHCl3); ee > 99.5%; H NMR (300 MHz,
CDCl3) 7.51 (d, J = 7.9 Hz, 1H), 7.36 - 7.28 (m, 5H),
7.22 - 7.17 (m, 2H), 7.10 - 7.03 (m, 1H), 5.59 (brs, 2H),
5.14 - 5.06 (m, 2H), 2.93- 2.65 (m, 3H), 2.55 - 2.42 (m,
2H), 2.38 - 2.22 (m, 2H); 13C NMR (75MHz, CDCl3)
173.9, 172.5, 138.9, 135.8, 133.0, 131.6, 128.6, 128.39,
128.35, 128.16, 127.4, 125.0, 66.4, 39.9, 39.0, 37.4, 33.4;
IR (KBr) 3380, 3187, 1720, 1655 cm-1; MS (ESI) m/z
414 [M+Na]+ (81Br); Anal. Calcd. for C19H20NO3Br: C,
58.47; H, 5.17; N, 3.59. Found: C, 58.73; H, 5.20; N, 3.50.
1
1
CDCl3) 7.36 - 7.29 (m, 4H), 7.24 - 7.14 (m, 5H), 5.59
(brs, 2H), 5.05 - 4.99 (m, 2H), 4.17 - 4.10 (m, 1H), 2.95 -
2.80 (m, 2H), 2.62 (d, J = 7.2 Hz, 2H); 13C NMR (100
MHz, CDCl3) 173.0, 171.5, 139.5, 135.7, 133.7, 130.1,
128.5, 128.20, 128.18, 128.0, 127.2, 66.4, 40.2, 38.4, 35.2;
IR (KBr) 3402, 3191, 1729, 1653 cm-1; HRMS (FT-MS-
ESI): m/z calcd. for C18H18ClNO3Na: 354.0867 [M+Na]+;
Found: 354.0869.
Benzyl (R)-4-carbamoyl-3-(2-methylphenyl)butanoate
o
(2i): white solid (280 mg, 90%); mp: 73 - 74 C; [α]25
Benzyl (R)-3-(3-bromobenzyl)-4-carbamoylbutanoate
D
+16.7o (c 1.5, CHCl3); ee > 99.5%; H NMR (400 MHz,
(4c): white solid (655 mg, 84%); mp: 65 - 66 C; [α]25
-
1
o
D
1
CDCl3) 7.29 - 7.27 (m, 3H), 7.15 - 7.09 (m, 6H), 5.66
(brs, 1H), 5.43 (brs, 1H), 5.01 - 4.95 (m, 2H), 3.98 - 3.90
(m, 1H), 2.83 - 2.68 (m, 2H), 2.57 - 2.44 (m, 2H), 2.35 (s,
3H); 13C NMR (100 MHz, CDCl3) 173.5, 171.7, 140.9,
136.2, 135.7, 130.8, 128.5, 128.15, 128.12, 126.7, 126.4,
125.3, 66.3, 41.9, 40.1, 33.6, 19.6; IR (KBr) 3338, 3191,
1731, 1666 cm-1; HRMS (FT-MS-ESI): m/z calcd. for
C19H21NO3Na: 334.1414 [M+Na]+; Found: 334.1416.
10.0o (c 1.2, CHCl3); ee > 99.5%; H NMR (300 MHz,
CDCl3) 7.37 - 7.32 (m, 7H), 7.16 - 7.07 (m, 2H), 5.55
(brs, 2H), 5.16 - 5.07 (m, 2H), 2.75- 2.55 (m, 3H), 2.43 -
2.41 (m, 2H), 2.31 - 2.17 (m, 2H); 13C NMR (75MHz,
CDCl3) 173.7, 172.3, 141.7, 135.8, 132.3, 130.0, 129.6,
128.6, 128.4, 128.0, 122.5, 66.4, 39.5, 38.9, 37.2, 34.5; IR
(KBr) 3449, 3206, 1718, 1651 cm-1; MS (ESI) m/z 390
[M+H]+ (79Br); Anal. Calcd. for C19H20NO3Br: C, 58.47;
H, 5.17; N, 3.59. Found: C, 58.49; H, 5.20; N, 3.47.
Benzyl 4-carbamoyl-3-(2-methoxyphenyl)butanoate (2j):
o
white solid (98 mg, 30%); mp: 121 - 122 C; [α]25 0o (c
Benzyl (R)-3-(4-bromobenzyl)-4-carbamoylbutanoate
D
1
o
2.6, CHCl3); ee = 5%; H NMR (400 MHz, CDCl3) 7.32
(4d): white solid (663 mg, 85%); mp: 96 - 97 C; [α]25
-
D
1
- 7.29 (m, 3H), 7.23 - 7.19 (m, 3H), 7.16 - 7.13 (m, 1H),
6.90 - 6.85 (m, 2H), 5.61 (brs, 1H), 5.34 (brs, 1H), 5.05 -
4.99 (m, 2H), 3.97 - 3.89 (m, 1H), 3.81 (s, 3H), 2.85 - 2.82
(m, 2H), 2.67 - 2.65 (m, 2H); 13C NMR (100 MHz, CDCl3)
173.8, 172.1, 157.0, 135.9, 130.2, 128.48, 128.38, 128.14,
128.11, 120.9, 110.9, 66.2, 55.4, 40.5, 38.7, 33.8; IR (KBr)
3351, 3191, 1730, 1665 cm-1; HRMS (FT-MS-ESI): m/z
calcd. for C19H21NO4K: 350.1363 [M+Na]+; Found:
350.1365.
6.0o (c 1.0, CHCl3); ee > 99.5%; H NMR (400 MHz,
CDCl3) 7.39 - 7.36 (m, 7H), 7.03 (d, J = 8.4 Hz, 2H),
5.48 (brs, 1H), 5.24 (brs, 1H), 5.14 - 5.07 (m, 2H), 2.72 -
2.54 (m, 3H), 2.42 (d, J = 6.0 Hz, 2H), 2.29 - 2.18 (m, 2H);
13C NMR (75MHz, CDCl3) 173.8, 172.3, 138.3, 135.8,
131.5, 131.1, 128.6, 128.4, 120.2, 66.4, 39.3, 38.9, 37.2,
34.4; IR (KBr) 3390, 3196, 1732, 1652 cm-1; MS (ESI)
m/z 392 [M+H]+ (81Br); Anal. Calcd. for C19H20NO3Br: C,
58.47; H, 5.17; N, 3.59. Found: C, 57.98; H, 5.09; N, 3.50.
General procedure for the biotransformations of 3-
arylmethylglutaramides 3a-j.
Benzyl (R)-4-carbamoyl-3-(4-chlorobenzyl)butanoate
o
(4e): white solid (615 mg, 89%); mp: 81 - 82 C; [α]25
-
D
1
10.0o (c 0.8, CHCl3); ee > 99.5%; H NMR (400 MHz,
CDCl3) 7.37 - 7.34 (m, 5H), 7.24 - 7.24 (m, 2H), 7.09 -
7.07 (m, 3H), 5.49 (brs, 1H), 5.31 (brs, 1H), 5.14 - 5.07 (m,
2H), 2.70 - 2.58 (m, 3H), 2.42 (d, J = 6.4 Hz, 2H), 2.25 -
2.22 (m, 2H); 13C NMR (125MHz, CDCl3) 174.1, 172.4,
137.8, 135.7, 132.1, 130.6, 128.60, 128.50, 128.37, 128.36,
3-arylmethylglutaramide 3 was treated following the
aforementioned biotransformations procedure and gave
product 4. All products were fully characterized by means
of spectroscopic data. Enantiomeric excess values were
7
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