S. Ma and B. Ni
FULL PAPER
5.66 (s, 2H), 4.04 (t, J=1.8 Hz, 2H), 2.92 (d, J=14.7 Hz, 2H), 2.49 (d,
J=14.7 Hz, 2H), 1.37 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d=
171.5, 141.8, 129.2, 128.3, 62.2, 51.9, 44.8, 24.9 ppm; IR (neat): n˜ =3398,
2884, 1629, 1408, 1355, 1283, 1217, 1158, 971, 794 cmꢀ1; MS (EI): m/z
(%): 163 [M +] (3.5), 80 (100.0); HRMS (EI): m/z: calcd for C10H13NO:
163.09971; found: 163.10095. 7k: 1H NMR (300 MHz, CDCl3): d=6.41
(dd, J=16.5, 9.8 Hz, 1H), 6.29 (dd, J=16.5, 2.4 Hz, 1H), 6.00 5.85 (m,
1H), 5.65 5.50 (m, 3H), 5.34 5.14 (m, 2H), 4.00 3.82 (m, 2H), 2.80 (d,
J=15.3 Hz, 2H), 2.55 (d, J=15.3 Hz, 2H), 1.36 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): d=168.1, 135.8, 130.8, 128.5, 127.6, 117.1, 66.9, 48.8,
46.1, 25.1 ppm; IR (neat): n˜ =1657, 1617 cmꢀ1; MS (EI): m/z (%): 191
[M +] (1.4), 150 [M +ꢀC3H5] (19.8), 55 (100.0); HRMS (EI): calcd for
C12H17NO: 191.13101; found: 191.13110.
3H)ppm; 13C NMR (75 MHz, CDCl3): d=167.9, 146.6, 130.6, 128.3,
127.3, 111.3, 66.7, 51.1, 45.6, 33.8, 29.8, 24.8, 22.5, 13.9 ppm; IR (neat):
n˜ =2930, 1660, 1614, 1416 cmꢀ1; MS (ESI): m/z: 248.2 [M ++H]; HRMS
(ESI): m/z: calcd for C16H25NONa: 270.18339; found: 270.18342.
Preparation of 6h and 8h: Following GP F, a solution of 2h (135 mg,
0.579 mmol)and 3 (26 mg, 5 mol%)in CH Cl2 (20 mL)was stirred under
2
reflux conditions for 11.5 h to afford 6h (71 mg, 69.2%)and 8h (8 mg,
7.8%)as liquids. 6h: 1H NMR (300 MHz, CDCl3): d=6.22 (dt, J=
11.6 Hz, 5.5 Hz, 1H), 6.00 (d, J=11.6 Hz, 1H), 5.80 5.69 (m, 1H), 5.68
5.50 (m, 1H), 4.43 (dd, J=16.5, 6.7 Hz, 1H), 3.92 3.75 (m, 2H), 2.50
1.70 (m, 8H)ppm; 13C NMR (75 MHz, CDCl3): d=168.9, 137.2, 131.0,
128.0, 126.9, 58.8, 39.0, 34.7, 30.3, 29.1, 25.3 ppm; IR (neat): n˜ =2936,
1642, 1601, 1419, 1286, 1180, 822, 640 cmꢀ1; MS (EI): m/z (%): 177 [M +
]
(100.0), 176 [M +ꢀH] (17.4); HRMS (EI): m/z: calcd for C11H15NO:
177.11536; found: 177.11318. 8h: 1H NMR (300 MHz, CDCl3): d=6.99
(dt, J=5.8 Hz, 1.2 Hz, 1H), 6.11 (dt, J=5.8 Hz, 2.5 Hz, 1H), 5.90 5.70
(m, 2H), 4.25 4.10 (m, 1H), 3.89 (s, 2H), 2.30 2.00 (m, 4H), 1.90 1.70
(m, 2H), 1.50 1.30 (m, 2H) ppm; IR (neat): n˜ =2925, 2852, 1673, 1447,
Preparation of 6n, 7n, and 8n: Following GP F, a solution of 2n (105 mg,
0.425 mmol)and 3 (19 mg, 5 mol%)in CH 2Cl2 (8.5 mL)was stirred
under reflux conditions for 14.5 h to afford a mixture of 6n and 8a
(33 mg, 41%)and 7n (33 mg, 35%)as liquids. 6n: 1H NMR (300 MHz,
CDCl3): d=6.98 6.80 (m, 1H), 6.10 5.98 (m, 1H), 5.61 (s, 2H), 4.00 (s,
2H), 2.80 (d, J=15.9 Hz, 2H), 2.54 (d, J=15.9 Hz, 2H), 1.30 1.00 (m,
4H), 0.95 0.70 (m, 3H) ppm. 8n: 1H NMR (300 MHz, CDCl3): d=6.40
6.30 (m, 1H), 5.83 (d, J=9.8 Hz, 1H), 5.75 5.50 (m, 2H), 4.49 (d, J=
19.6 Hz, 1H), 3.47 (d, J=19.6 Hz, 1H), 2.38 1.95 (m, 4H), 1.50 1.00 (m,
4H), 0.95 0.70 (m, 3H) ppm; IR (neat): n˜ =2958, 2931, 1677, 1616, 1439,
1234, 805 cmꢀ1; MS (EI): m/z (%): 176 [M +ꢀCH3] (7.6), 162 [M +ꢀC2H5]
1401, 1243, 801 cmꢀ1; MS (EI): m/z (%): 178 [M ++H] (14.0), 177 [M +
]
(42.6), 84 (100.0); HRMS (EI): m/z: calcd for C11H15NO: 177.11536;
found: 177.11768.
Preparation of 6j: Following GP F, a solution of 2j (75 mg, 0.304 mmol)
and 4 (13 mg, 5 mol%)in CH 2Cl2 (6 mL)was stirred under reflux condi-
tions for 3.5 h to afford 6j (45 mg, 78%)as a colorless oil. 1H NMR
(300 MHz, CDCl3): d=6.25 6.15 (m, 1H), 5.98 (d, J=11.3 Hz, 1H),
5.35 5.27 (m, 1H), 4.18 (d, J=16.3 Hz, 1H), 3.95 (d, J=16.4 Hz, 1H),
3.85 3.70 (m, 1H), 2.38 2.63 (m, 11H) ppm; 13C NMR (75 MHz, CDCl3):
d=168.6, 136.9, 134.5, 127.7, 123.9, 58.3, 43.7, 33.9, 29.9, 27.7, 25.1,
23.7 ppm; IR (neat): n˜ =2933, 1644, 1603, 1417 cmꢀ1; MS (EI): m/z (%):
192 [M ++H] (18.0), 191 [M +] (100.0); HRMS (EI): m/z: calcd for
C12H17NO: 191.13102; found: 191.13200.
1
(14.4), 148 [M +ꢀC3H7] (100.0). 7n: H NMR (300 MHz, CDCl3): d=6.43
(dd, J=16.7, 10.2 Hz, 1H), 6.31 (dd, J=16.4, 2.4 Hz, 1H), 6.02 5.87 (m,
1H), 5.62 5.56 (m, 3H), 5.35 5.15 (m, 2H), 4.00 3.90 (m, 2H), 2.85 2.63
(m, 4H), 1.90 1.80 (m, 2H), 1.30 1.15 (m, 2H), 0.88 (t, J=7.1 Hz,
3H)ppm; 13C NMR (75 MHz, CDCl3): d=167.7, 135.6, 130.5, 128.4,
127.4, 117.0, 70.0, 50.0, 44.0, 40.4, 17.8, 14.5 ppm; IR (neat): n˜ =1656,
1613 cmꢀ1; MS (ESI): m/z: 220.1 [M ++H]; HRMS (ESI): m/z: calcd for
C14H21NONa: 242.15209; found: 242.15247.
Double RCM reaction of 2g
Preparation of 7l and 8l: Following GP F, a solution of 2l (80 mg,
0.343 mmol)and 4 (15 mg, 5 mol%)in CH 2Cl2 (8 mL)was stirred under
reflux conditions for 3.5 h to afford 8l (4 mg, 7%)and 7l (62 mg, 88%)
as liquids. 8l: 1H NMR (300 MHz, CDCl3): d=5.78 (q, J=1.5 Hz, 1H),
5.67 (s, 2H), 3.90 (s, 2H), 2.92 (d, J=15.0 Hz, 2H), 2.50 (brd, J=
16.5 Hz, 2H), 2.02 (d, J=1.5 Hz, 3H), 1.37 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): d=172.5, 154.1, 128.6, 124.5, 62.3, 55.0, 45.2, 25.1,
15.1 ppm; IR (neat): n˜ =2916, 1675, 1390 cmꢀ1; MS (EI): m/z (%): 178
[M ++H] (21.2), 98 (100.0); HRMS (EI): m/z: calcd for C11H15NO:
177.11536; found: 177.11635. 7l: 1H NMR (500 MHz, CDCl3): d=6.35
6.25 (m, 2H), 5.60 (brs, 2H), 5.56 (dd, J=8.4, 4.1 Hz, 1H), 5.00 (s, 1H),
4.91 (s, 1H), 3.71 (s, 2H), 2.81 (d, J=14.9 Hz, 2H), 2.56 (d, J=14.9 Hz,
2H), 1.73 (s, 3H), 1.38 (s, 3H)6ppm; 13C NMR (75 MHz, CDCl3): d=
167.8, 142.4, 130.5, 128.2, 127.4, 112.3, 66.6, 51.9, 45.6, 24.8, 20.1 ppm; IR
(neat): n˜ =1660, 1611, 1415, 1208 cmꢀ1; MS (ESI): m/z: 206.1 [M ++H];
HRMS (ESI): m/z: calcd for C13H19NONa: 228.13644; found: 228.13548.
Preparation of 6A, 6B, 8g, and 5g: Following GP F, a solution of 2g
(105 mg, 0.479 mmol)and 3 (21 mg, 5 mol%)in CH 2Cl2 (9 mL)was stir-
red under reflux conditions for 8 h to afford a mixture of 6A and 6B
(30 mg, 6A/6B 1.3:1, 38%), 8g (10 mg, 13%)as a liquid, and 5g (40 mg,
44%). 8g: 1H NMR (300 MHz, CDCl3): d=7.04 (dt, J=5.8 Hz, 1.8 Hz,
1H), 6.13 (dt, J=5.8 Hz, 1.8 Hz, 1H), 5.70 5.45 (m, 2H), 4.37 4.18 (m,
1H), 4.00 3.75 (m, 2H), 2.38 1.85 (m, 4H), 1.85 1.50 (m, 2H) ppm;
13C NMR (75 MHz, CDCl3): d=171.3, 142.8, 128.4, 127.1, 125.1, 49.3,
47.1, 30.0, 27.9, 25.5 ppm; IR (neat): n˜ =3456, 2919, 1666, 1587 cmꢀ1; MS
(EI): m/z (%): 163 [M +] (13.9), 80 (100.0); HRMS (EI): m/z: calcd for
C10H13NO: 163.09971; found: 163.09933. 5g was used for the next step
without further characterization.
Preparation of 6A: Following GP F, a solution of 5g (34 mg, 0.178 mmol)
and 4 (5 mg, 3 mol%)in CH 2Cl2 (5 mL)was stirred under reflux condi-
tions for 2.5 h to afford 6A (25 mg, 86%)as a colorless oil. 1H NMR
(300 MHz, CDCl3): d=6.18 (dt, J=11.7 Hz, 5.9 Hz, 1H), 5.95 (d, J=
11.7 Hz, 1H), 5.90 5.70 (m, 2H), 4.20 4.05 (m, 1H), 3.96 3.75 (m, 2H),
2.45 1.70 (m, 6H)ppm; 13C NMR (75 MHz, CDCl3): d=168.8, 137.8,
127.8, 125.2, 124.7, 51.8, 42.0, 34.6, 28.9, 25.6 ppm; IR (neat): n˜ =1652,
RCM reaction of 14aA with 4 as the catalyst: Following GP F, a solution
of 14aA (179 mg, 1.0 mmol)and 4 (9 mg, 1 mol%)in CH 2Cl2 (20 mL)
was stirred under reflux conditions for 3 h to afford 16l (129 mg, 85%)
as a colorless oil. 1H NMR (300 MHz, CDCl3): d=6.16 (dd, J=17.1,
1.8 Hz, 1H), 5.95 (dd, J=17.1, 9.8 Hz, 1H), 5.75 5.40 (m, 4H), 2.67 (d,
J=15.1 Hz, 2H), 2.36 (d, J=15.0 Hz, 2H), 1.40 (s, 3H) ppm; IR (neat):
n˜ =1674, 1657, 1556, 1625 cmꢀ1; MS (EI): m/z (%): 151 [M +] (1.0), 80
(100.0); elemental analysis calcd for C9H13NO: C 71.49, H 8.67, N 9.26;
found: C 71.25, H 8.44, N 9.05.
1589 cmꢀ1; MS (70 eV, EI): m/z (%): 164 [M ++H] (100.0), 163 [M +
]
(4.25); HRMS (EI): m/z: calcd for C10H13NO: 163.09971; found:
163.10183.
Characterization of 6A by bromination: Following GP G, a solution of
6A (25 mg, 0.15 mmol)in CCl
(3 mL)was treated with bromine
4
(0.79 mL, 0.389m in CCl4, 0.31 mmol)to afford 15g (30 mg, 40%)as a
white solid. M.p. 90 928C (recrystallized from dichloromethane/petrole-
um ether); 1H NMR (300 MHz, CDCl3): d=5.19 (d, J=5.4 Hz, 1H), 4.56
(dd, J=9.7, 5.1 Hz, 1H), 4.49 4.35 (m, 2H), 4.30 4.20 (m, 1H), 4.19 4.05
(m, 1H), 3.79 (dd, J=14.0, 7.6 Hz, 1H), 2.66 (ddd, J=14.4, 6.5, 3.5 Hz,
1H), 2.30 2.10 (m, 4H), 2.10 2.00 (m, 1H) ppm; IR (KBr): n˜ =
1657 cmꢀ1; MS (EI): m/z (%): 488 [M ++H] with 4î81Br (1.9), 486 [M +
+H] with 3î81Br, 1î79Br (7.8), 484 [M ++H] with 2î81Br, 2î79Br (12.8),
482 [M ++H] with 1î81Br, 3î79Br (9.5), 480 [M ++H] with 4î79Br (3.8),
402 (100.0).
Preparation of 7m and 8m: Following GP F, a solution of 2m (87 mg,
0.316 mmol)and 4 (13 mg, 5 mol%)in CH 2Cl2 (8 mL)was stirred under
reflux conditions for 11 h to afford 8m (5 mg, 7%)and 7m (70 mg, 90%)
as liquids. 8m: 1H NMR (300 MHz, CDCl3): d=5.77 (t, J=1.4 Hz, 1H),
5.67 (s, 2H), 3.90 (d, J=1.1 Hz, 2H), 2.92 (d, J=14.7 Hz, 2H), 2.49 (d,
J=14.7 Hz, 2H), 2.31 (t, J=8.0 Hz, 2H), 1.60 1.42 (m, 2H), 1.42 1.26
(m, 5H), 0.92 (t, J=7.4 Hz, 3H)ppm; 13C NMR (75 MHz, CDCl3): d=
172.5, 158.9, 128.6, 123.3, 62.3, 53.9, 45.2, 29.8, 29.2, 25.1, 22.4, 13.8 ppm;
IR (neat): n˜ =2929, 1678 cmꢀ1; MS (EI): m/z (%): 220 [M ++H] (1.8),
219 [M +] (2.6), 140 (100.0); HRMS (EI): m/z: calcd for C14H21NO:
219.16232; found: 219.15824. 7m: 1H NMR (300 MHz, CDCl3): d=6.31
(s, 1H), 6.29 (s, 1H), 5.60 (s, 2H), 5.54 (t, J=6.0 Hz, 1H), 5.03 (s, 1H),
4.91 (s, 1H), 3.73 (s, 2H), 2.80 (d, J=14.7 Hz, 2H), 2.54 (d, J=15.3 Hz,
2H), 2.00 (t, J=7.0 Hz, 2H), 1.50 1.20 (m, 7H), 0.90 (t, J=7.6 Hz,
Total synthesis of four stereoisomers of lupinine and its derivatives
General procedure H–Synthesis of (2S,3S)-21: Anhydrous powdered
4 ä molecular sieves (1.2 g)and anhydrous CH Cl2 (110 mL)were placed
2
in a 250 mL round-bottomed flask under Ar. After cooling the flask to
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2004, 10, 3286 3300