Auxiliaries for Cu-Catalyzed Asymmetric Michael Reactions
1014±1027
(3CH3), 28.12 (CH2), 29.01 (CH2), 31.71 (CH2), 35.87 (CH3), 39.91 (CH),
7.2 Hz, 3H), 1.78 (s, 3H), 3.19 (s, 3H), 2.00 ± 2.10 (m, 1H), 3.15 ± 3.24 (m,
1H), 3.26 ± 3.36 (m, 1H), 3.38 ± 3.47 (m, 1H), 3.51 ± 3.61 (m, 1H), 4.10 (dd,
J 8.8, 6.3 Hz, 1H), 4.10 ± 4.17 (m, 2H), 9.59 (brd, J 8.9 Hz, 1H);
13CNMR (50 MHz, CDCl3): d 12.83 (CH3), 12.95 (CH3), 14.52 (CH3),
14.65 (CH3), 15.84 (CH3), 18.10 (CH3), 19.89 (CH3), 32.34 (CH), 40.26
(CH2), 41.45 (CH2), 58.78 (CH2), 59.78 (CH), 88.37 (C), 157.34 (C), 170.74
37.84 (CH3), 50.55 (CH3), 59.41 (CH), 95.50 (C), 164.98 (C), 160.72 (C O),
1
171.44 (C O); IR (ATR): nÄ 1636, 1580, 1276, 1261, 1206, 1096, 1085 cm
;
MS (EI, 70 eV): m/z (%): 310 (26) [M] , 279 (8), 253 (38), 238 (85), 221
(73), 206 (100), 193 (38), 150 (20), 120 (10), 95 (42), 93 (23), 91 (26), 81 (21),
72 (72), 69 (38); HR-MS: C17H30N2O3: calcd: 310.2256; found: 310.2253;
elemental analysis calcd (%) for C17H30N2O3 (310.44): C 65.77, H 9.74, N
9.02; found: C 65.41, H 10.07, N 9.08.
(C O), 170.83 (C O); IR (ATR): nÄ 1646, 1590, 1247, 1105 cm 1; MS (EI,
70 eV): m/z (%): 299 (1) [MH] , 209 (7), 198 (19), 181 (5), 152 (100), 124
(8), 110 (6), 96 (6), 70 (7); HR-MS: C16H30N2O3 (298.43): calcd: 298.2256;
found: 298.2255.
N-(2-Methoxycarbonyl-1-cycloheptenyl)-l-tert-leucine
diethylamide
(3 fg): Oxoester 1 f (503 mg, 2.95 mmol), auxiliary 2g (550 mg, 2.95 mmol),
and molecular sieves (2 g) in toluene (5 mL) were converted according to
GP2 to yield 3 fg after chromatography (MTB/PE 2:1, Rf 0.45) as a
colorless solid (252 mg, 0.744 mmol, 25%). M.p. 978C; [a]2D3 120 (c
5.8 in CHCl3); 1HNMR (200 MHz, CDCl3): d 1.03 (s, 9H), 1.11 (t, J
7.1 Hz, 3H), 1.17 (t, J 7.1 Hz, 3H), 1.30 ± 1.78 (m, 6H), 2.36 (ddd, J 15.3,
9.2, 1.9 Hz, 1H), 2.40 ± 2.48 (m, 2H), 2.58 (ddd, J 15.3, 8.0, 2.0 Hz, 1H),
2.93 ± 3.11 (m, 1H), 3.15 ± 3.34 (m, 1H), 3.50 ± 3.86 (m, 2H), 3.67 (s, 3H),
4.26 (d, J 9.6 Hz, 1H), 9.86 (brd, J 9.0 Hz, 1H); 13CNMR (50 MHz,
CDCl3): d 12.82 (CH3), 14.42 (CH3), 25.52 (CH2), 26.17 (CH2), 26.82
(3CH3), 28.17 (CH2), 28.71 (CH2), 31.79 (CH2), 36.32 (C), 40.05 (CH2),
N-(2-Ethoxycarbonyl-1-methyl-1-propenyl)-l-tert-leucine
diethylamide
(3hg): Oxoester 1h (542 mg, 3.76 mmol), auxiliary 2g (700 mg, 3.76 mmol),
and molecular sieves (2.5 g) in toluene (5 mL) were converted according to
GP2 to yield 3hg after chromatography (MTB/PE 2:1, Rf 0.56) as a
colorless solid (717 mg, 2.29 mmol, 61%). M.p. 818C; [a]2D3 136 (c 5.7
in CHCl3); 1HNMR (400 MHz, CDCl3): d 1.03 (s, 9H), 1.11 (t, J 7.0 Hz,
3H), 1.19 (t, J 7.1 Hz, 3H), 1.26 (t, J 7.2 Hz, 3H), 1.78 (s, 3H), 1.92 (s,
3H) 3.00 ± 3.09 (m, 1H), 3.22 ± 3.32 (m, 1H), 3.54 ± 3.64 (m, 1H), 3.69 ± 3.79
(m, 1H), 4.10 ± 4.19 (m, 2H), 4.21 (d, J 9.8 Hz, 1H), 9.75 (d, J 9.7 Hz,
1H); 13CNMR (50 MHz, CDCl3): d 12.78 (CH3), 13.07 (CH3), 14.51
(CH3), 14.66 (CH3), 15.73 (CH3), 26.82 (3CH3), 36.41 (C), 39.87 (CH2),
42.16 (CH2), 50.50 (CH3), 59.19 (CH), 95.01 (C), 164.81 (C), 170.06 (C O),
170.51 (C O); IR (ATR): nÄ 1642, 1585, 1253 cm 1; MS (EI, 70 eV): m/z
42.12 (CH2), 58.80 (CH2), 59.45 (CH), 88.13 (C), 156.35 (C), 170.13 (C O),
170.50 (C O); IR (ATR): nÄ 1635, 1580, 1250, 1096 cm 1; MS (EI, 70 eV):
(%): 338 (9) [M] , 281 (11), 249 (21), 238 (100), 221 (8), 206 (87); HR-MS:
C19H34N2O3: calcd: 338.2569; found: 338.2569; elemental analysis calcd
(%) for C19H34N2O3 (338.49): C 67.42, H 10.12, N 8.28; found: C 67.38, H
10.03, N 8.38.
m/z (%): 312 (8) [M] , 267 (9), 255 (22), 212 (100), 209 (43), 181 (9), 166
(91), 110 (7), 100 (16), 86 (10), 72 (15); HR-MS: C17H32N2O3: calcd:
312.2413; found: 312.2420; elemental analysis calcd (%) for C17H32N2O3
(312.45): C 65.35, H 10.32, N 8.97; found: C 65.32, H 10.49, N 8.96.
N-(2-Methoxycarbonyl-1-cycloheptenyl)-l-valine piperidide (3 fi): Oxo-
ester 1 f (508 mg, 2.99 mmol), auxiliary 2i (550 mg, 2.99 mmol), and molecular
sieves (2 g) in toluene (5 mL) were converted according to GP2 to yield 3 fi
N-(2-Isobutoxycarbonyl-1-methyl-1-propenyl)-l-valine
diethylamide
(3 ib): Oxoester 1i (720 mg, 4.18 mmol), auxiliary 2b (600 mg, 3.48 mmol),
and molecular sieves (2.5 g) in toluene (5 mL) were converted according to
GP2 to yield 3ib after chromatography (MTB/PE 1:1, Rf 0.43) as a
colorless solid (702 mg, 2.15 mmol, 62%). M.p. 398C; [a]2D3 123 (c 6.1
after chromatography (MTB/PE 2:1, Rf 0.36) as
a colorless solid
(328 mg, 0.975 mmol, 33%). M.p. 72 ± 738C; [a]2D3 252 (c 6.6 in
1
CHCl3); HNMR (400 MHz, CDCl3): d 1.00 (d, J 6.7 Hz, 3H), 1.04 (d,
1
J 6.7 Hz, 3H), 1.35 ± 1.74 (m, 12H), 2.01 ± 2.10 (m, 1H), 2.35 ± 2.43 (m,
3H), 2.53 (ddd, J 15.3, 8.5, 1.8 Hz, 1H), 3.42 ± 3.55 (m, 3H), 3.56 ± 3.65 (m,
1H), 3.66 (s, 3H), 4.18 (t, J 7.6 Hz, 1H), 9.64 (brd, J 7.9 Hz, 1H);
13CNMR (50 MHz, CDCl3): d 18.71 (CH3), 19.83 (CH3), 24.53 (CH2),
25.12 (CH2), 25.67 (CH2), 25.96 (CH2), 26.60 (CH2), 28.18 (CH2), 29.17
(CH2), 31.78 (CH2), 31.88 (CH), 43.34 (CH2), 46.48 (CH2), 50.48 (CH3),
in CHCl3); HNMR (500 MHz, CDCl3): d 0.92 (d, J 6.7 Hz, 6H), 0.99
(d, J 6.9 Hz, 3H), 1.01 (d, J 6.9 Hz, 3H), 1.10 (t, J 7.1 Hz, 3H), 1.17 (t,
J 7.1 Hz, 3H), 1.78 (s, 3H), 1.89 (s, 3H), 1.87 ± 1.96 (m, 1H), 2.01 ± 2.08 (m,
1H), 3.14 ± 3.23 (m, 1H), 3.26 ± 3.35 (m, 1H), 3.37 ± 3.46 (m, 1H), 3.50 ± 3.58
(m, 1H), 3.83 (dd, J 10.5, 6.6 Hz, 1H), 3.86 (dd, J 10.6, 6.7 Hz, 1H), 4.08
(dd, J 8.7, 6.4 Hz, 1H), 9.60 (brd, J 8.5 Hz, 1H); 13CNMR (125 MHz,
CDCl3): d 12.80 (CH3), 12.82 (CH3), 14.48 (CH3), 15.77 (CH3), 18.07
(CH3), 19.26 (2CH3), 19.88 (CH3), 27.87 (CH), 32.25 (CH), 40.23 (CH2),
60.14 (CH), 95.37 (C), 165.87 (C), 170.21 (C O), 170.80 (C O); IR (ATR):
nÄ 1640, 1591, 1438, 1251, 1205 cm 1; MS (EI, 70 eV): m/z (%): 336 (9)
[M] , 256 (5), 224 (92), 192 (100), 164 (5), 137 (6), 129 (23), 101 (8), 95 (14),
41.40 (CH2), 59.82 (CH), 69.19 (CH2), 88.43 (C), 157.37 (C), 170.79 (C O),
170.80 (C O); IR (ATR): nÄ 1645, 1591, 1244, 1106, 1088 cm 1; MS (EI,
86 (67), 81 (18), 69 (45); HR-MS: C19H32N2O3: calcd: 336.2413; found:
336.2420; elemental analysis calcd (%) for C19H32N2O3 (336.47): C 67.82, H
9.59, N 8.33; found: C 67.85, H 9.48, N 8.50.
70 eV): m/z (%): 326 (9) [M] , 253 (11), 226 (100), 209 (6), 170 (19), 152
(88), 100 (8), 72 (9); HR-MS: C18H34N2O3: calcd: 326.2569; found:
326.2630; elemental analysis calcd (%) for C18H34N2O3 (326.50): C 66.22,
H 10.50, N 8.58; found: C 66.00, H 10.21, N 8.72.
N-(2-Isobutoxycarbonyl-1-cycloheptenyl)-l-valine diethylamide (3gb):
Oxoester 1g (863 mg, 4.06 mmol), auxiliary 2b (500 mg, 2.90 mmol), and
molecular sieves (2.5 g) in toluene (6 mL) were converted according to
GP2 to yield 3gb after chromatography (MTB/PE 1:2, Rf 0.43) as a
colorless solid (410 mg, 1.12 mmol, 39%). M.p. 103 ± 1048C; [a]2D3 140
(c 10.0 in CHCl3); 1HNMR (400 MHz, CDCl3): d 0.93 (d, J 6.6 Hz,
6H), 0.99 (d, J 6.8 Hz, 3H), 1.02 (d, J 6.8 Hz, 3H), 1.11 (t, J 7.1 Hz,
3H), 1.17 (t, J 7.1 Hz, 3H), 1.36 ± 1.75 (m, 6H), 1.85 ± 2.00 (m, 1H), 2.01 ±
2.10 (m, 1H), 2.38 ± 2.45 (m, 3H), 2.57 (ddd, J 15.1, 8.5, 1.7 Hz, 1H),
3.16 ± 3.25 (m, 1H), 3.27 ± 3.37 (m, 1H), 3.37 ± 3.47 (m, 1H), 3.48 ± 3.57 (m,
1H), 3.83 (dd, J 10.6, 6.7 Hz, 1H), 3.87 (dd, J 10.6, 6.6 Hz, 1H), 4.11
(dd, J 8.2, 6.8 Hz, 1H), 9.64 (brd, J 8.3 Hz, 1H); 13CNMR (50 MHz,
CDCl3): d 12.83 (CH3), 14.42 (CH3), 18.46 (CH3), 19.28 (2CH3), 19.82
(CH3), 25.22 (CH2), 26.03 (CH2), 27.90 (CH), 28.11 (CH2), 29.06 (CH2),
31.78 (CH2), 32.30 (CH), 40.36 (CH2), 41.42 (CH2), 60.11 (CH), 69.13
N-(1,2-Dimethyl-3-oxo-3-phenyl-1-propenyl)-l-valine diethylamide (3jb):
Diketone 1j (640 mg, 3.63 mmol), auxiliary 2b (626 mg, 3.63 mmol), and
molecular sieves (2.5 g) in toluene (5 mL) were converted according to
GP2 to yield 3jb after chromatography (MTB/PE 1:1, Rf 0.11) as a
colorless solid (550 mg, 1.66 mmol, 50%). M.p. 128 ± 1298C; [a]2D3 257
(c 6.3 in CHCl3); 1HNMR (500 MHz, CDCl3): d 1.05 (d, J 6.8 Hz,
3H), 1.09 (d, J 6.8 Hz, 3H), 1.12 (t, J 7.0 Hz, 3H), 1.19 (t, J 7.0 Hz,
3H), 1.81 (s, 3H), 1.99 (s, 3H), 2.12 ± 2.19 (m, 1H), 3.21 ± 3.28 (m, 1H),
3.34 ± 3.46 (m, 2H), 3.48 ± 3.56 (m, 1H), 4.23 (t, J 7.2 Hz, 1H), 7.27 ± 7.34
(m, 3H), 7.38 ± 7.42 (m, 2H), 12.74 (brd, J 7.3 Hz, 1 H) ; 13CNMR
(125 MHz, CDCl3): d 12.76 (CH3), 14.37 (CH3), 16.25 (CH3), 16.57
(CH3), 18.16 (CH3), 19.92 (CH3), 31.81 (CH), 40.36 (CH2), 41.47 (CH2),
61.21 (CH), 98.24 (C), 127.10 (2CH), 127.61 (2CH), 128.30 (CH), 143.14
(CH2), 95.62 (C), 165.21 (C), 170.44 (C O), 170.83 (C O); IR (ATR): nÄ
(C), 163.66 (C), 169.78 (C O), 193.34 (C O); IR (ATR): nÄ 1644, 1590,
1635, 1581, 1251 cm 1; MS (EI, 70 eV): m/z (%): 366 (8) [M] , 293 (5), 266
1576, 1546, 1227, 1003 cm 1; MS (EI, 70 eV): m/z (%): 330 (3) [M] , 230
(97), 252 (9), 210 (8), 192 (100), 178 (11), 165 (8), 150 (13), 138 (7), 95 (15),
81 (13), 69 (17); HR-MS: C21H38N2O3 (366.54): calcd: 366.2882; found:
366.2881.
(100), 186 (6), 105 (95), 100 (7), 77 (16), 72 (9); HR-MS: C20H30N2O2
(330.47): calcd: 330.2307; found: 330.2306.
rac-Isobutyl 2-acetyl-2-methyl-5-oxohexanoate (5i): MVK (4, 0.50 mg,
0.70 mmol) was added to a mixture of donor 1i (60 mg, 0.35 mmol) and
FeCl3 ´ 6H2O (7.1 mg, 0.026 mmol) in CH2Cl2 (1 mL). After the mixture had
been stirred for 12 h at 238C, all volatile materials were removed in vacuo
and the residue was chromatographed on SiO2 (MTB/PE 1:4, Rf 0.12)
to afford 5i as a colorless oil (71 mg, 0.29 mmol, 84%). 1HNMR (200 MHz,
CDCl3): d 0.92 (d, J 6.7 Hz, 6H), 1.34 (s, 3H), 2.83 ± 2.25 (m, 3H), 2.13
(s, 3H), 2.16 (s, 3H), 2.39 (dd, J 6.3, 2.2 Hz, 1H), 2.44 (dd, J 6.6, 3.5 Hz,
N-(2-Ethoxycarbonyl-1-methyl-1-propenyl)-l-valine diethylamide (3hb):
Oxoester 1h (502 mg, 3.48 mmol), auxiliary 2b (600 mg, 3.48 mmol), and
molecular sieves (2.5 g) in toluene (5 mL) were converted according to
GP2 to yield 3hb after chromatography (MTB/PE 1:1, Rf 0.35) as a
colorless resin (444 mg, 1.49 mmol, 43%). [a]2D3 167 (c 5.40 in
1
CHCl3); HNMR (400 MHz, CDCl3): d 1.00 (d, J 6.9 Hz, 3H), 1.02 (d,
J 7.0 Hz, 3H), 1.11 (t, J 7.0 Hz, 3H), 1.19 (t, J 7.1 Hz, 3H), 1.26 (t, J
Chem. Eur. J. 2001, 7, No. 5
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0705-1023 $ 17.50+.50/0
1023