Y. Kita et al.
FULL PAPER
1774, 1713, 1624 cmÀ1; HRMS: calcd for C13H16O4 [M ]: 236.1048; found:
236.1007.
24 h followed by flash column chromatography (hexane/Et2O/Et3N
100:10:1 ! 100:30:1) to give (S)-3i (53 mg, 48%, 82% ee) and (2R)-syn-
5n (53 mg, 34%, ꢀ99% ee).
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3h with 2b: Similarly to the typical procedure, a mixture of 2b (1.13 mmol),
(Æ)-3h (154 mg, 0.75 mmol), and lipase LIP (0.30 g) was stirred at 308C for
6 d followed by flash column chromatography (hexane/Et2O/Et3N 93:2:5
(1R,2R,5S,6S,7S)-6-Acetyl-9-bromo-2-ethyl-7-methyl-3,10-dioxa-4-oxotri-
cyclo[5.2.1.01,5]dec-8-ene (syn-5n): Pale yellow oil (ꢀ99% ee); [a]2D0
20.7 (c 1.4, MeOH); 1H NMR (500 MHz, [D6]acetone): d 1.02 (t,
J 7.5 Hz, 3H), 1.65 1.76 (m, 1H), 1.77 (s, 3H), 1.80 1.89 (m, 1H), 2.25 (s,
3H), 3.36 (d, J 4.0 Hz, 1H), 3.39 (d, J 4.0 Hz, 1H), 4.93 (t, J 7.5 Hz,
1H), 6.49 (s, 1H); 13C NMR (125 MHz, [D6]acetone) d 9.8, 18.9, 23.0,
26.4, 53.3, 63.2, 80.1, 91.7, 95.5, 123.9, 138.9, 174.2, 204.5; IR (KBr): nÄ 1778,
1713 cmÀ1; elemental analysis calcd (%) for C13H15BrO4 (315.2): C 49.54, H
4.80; found: C 49.72, H 4.80.
!
85:10:5) to give (S)-3h (58 mg, 38%, ꢀ99% ee) and (2R)-syn-5j
(106 mg, 43%, 96% ee).
(S)-3h (ꢀ99% ee): Pale yellow oil; [a]2D4 À1.6 (c 1.0, CHCl3).
Ethyl
(1R,2R,5S,6S,7S)-9-bromo-2-ethyl-3,10-dioxa-4-oxotricyclo-
[5.2.1.01,5]dec-8-ene-6-carboxylate (syn-5j): Pale yellow oil (96% ee);
[a]2D4 À42.7 (c 1.2, MeOH); 1H NMR (300 MHz, [D6]acetone): d
1.04 (t, J 7.5 Hz, 3H), 1.24 (t, J 7.0 Hz, 3H), 1.64 1.95 (m, 2H), 3.36
(d, J 3.5 Hz, 1H), 3.50 (dd, J 3.5, 4.5 Hz, 1H), 4.14 (q, J 7.0 Hz, 2H),
5.03 (t, J 7.5 Hz, 1H), 5.41 (dd, J 2.0, 4.5 Hz, 1H), 6.64 (d, J 2.0 Hz,
1H); 13C NMR (75 MHz, [D6]acetone): d 9.7, 14.3, 22.9, 50.0, 50.8, 62.0,
79.7, 82.5, 96.6, 125.0, 135.4, 169.9, 173.6; IR (KBr): nÄ 1788, 1730,
1570 cmÀ1; elemental analysis calcd (%) for C13H15BrO5 (331.2): C 47.15, H
4.57; found: C 47.32, H 4.62.
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3j with 2a: Similarly to the typical procedure, a mixture of 2a (0.75 mmol),
(Æ)-3j (125 mg, 0.50 mmol), and lipase LIP (0.20 g) was stirred at 308C for
4.5 days followed by flash column chromatography (hexane/Et2O/Et3N
93:2:5 ! 85:10:5) to give (S)-3j (55 mg, 44%, ꢀ99% ee) and (2R)-syn-5o
(78 mg, 43%, 94% ee).
(S)-3j (ꢀ99% ee): Pale yellow oil. [a]2D5 À4.6 (c 1.0, CHCl3).
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3h with 2c: Similarly to the typical procedure, a mixture of 2c (1.13 mmol),
(Æ)-3h (154 mg, 0.75 mmol), and lipase LIP (0.15 g) was stirred at 308C for
5 d followed by flash column chromatography (hexane/Et2O/Et3N 92:3:5
Methyl (1R,2R,5S,6S,7R)-9-bromo-2-ethyl-7-methoxymethyl-3,10-dioxa-
4-oxotricyclo[5.2.1.01,5]dec-8-ene-6-carboxylate (syn-5o): Pale yellow oil
(94% ee); [a]2D4 7.8 (c 1.0, MeOH); 1H NMR (300 MHz, [D6]acetone):
d 1.05 (t, J 7.5 Hz, 3H), 1.65 1.95 (m, 2H), 3.39 (s, 3H), 3.45 3.48 (m,
2H), 3.70 (s, 3H), 3.99 (d, J 12.0 Hz, 1H), 4.04 (d, J 12.0 Hz, 1H), 5.01
(t, J 7.5 Hz, 1H), 6.57 (s, 1H); 13C NMR (75 MHz, [D6]acetone): d 9.8,
22.9, 49.6, 52.8, 52.9, 59.6, 70.6, 79.8, 94.9, 96.1, 124.9, 135.9, 170.5, 173.5; IR
!
20:75:5) to give (S)-3h (74 mg, 48%, ꢀ99% ee) and (2R)-syn-5k
(90 mg, 40%, ꢀ99% ee).
(1R,2R,5S,6S,7S)-6-Acetyl-9-bromo-2-ethyl-3,10-dioxa-4-oxotricyclo-
[5.2.1.01,5]dec-8-ene (syn-5k): Pale yellow oil (ꢀ99% ee); [a]2D5 À14.4
(c 1.1, MeOH); 1H NMR (300 MHz, [D6]acetone): d 1.04 (t, J 7.5 Hz,
3H), 1.64 1.97 (m, 2H), 2.27 (s, 3H), 3.39 (d, J 4.0 Hz, 1H), 3.69 3.71
(m, 1H), 5.01 (t, J 7.5 Hz, 1H), 5.56 (dd, J 2.0, 4.5 Hz, 1H), 6.62 (d, J
2.0 Hz, 1H); 13C NMR (75 MHz, [D6]acetone): d 9.7, 22.9, 49.3, 58.6, 79.8,
(KBr): nÄ 1788, 1738, 1574 cmÀ1
; elemental analysis calcd (%) for
C14H17BrO6 (361.2): C 46.56, H 4.74; found: C 46.56, H 4.72.
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3j with 2b: Similarly to the typical procedure, a mixture of 2b (0.75 mmol),
(Æ)-3j (125 mg, 0.50 mmol), and lipase LIP (0.20 g) was stirred at 308C for
4.5 d followed by flash column chromatography (hexane/Et2O/Et3N 93:2:5
! 85:10:5) to give (S)-3j (55 mg, 44%, 98% ee) and syn-5p (84 mg, 45%,
96% ee).
82.5, 96.8, 124.7, 134.9, 174.2, 203.1; IR (KBr): nÄ 1778, 1713, 1570 cmÀ1
;
elemental analysis calcd (%) for C12H13BrO4 (301.1): C 47.86, H 4.35;
found: C 47.85, H 4.35.
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3i with 2a: Similarly to the typical procedure, a mixture of 2a (0.75 mmol),
(Æ)-3i (110 mg, 0.50 mmol), and lipase LIP (0.10 g) was stirred at 308C for
2.5 d followed by flash column chromatography (hexane/Et2O/Et3N
100:10:1 ! 100:30:1) to give (S)-3i (59 mg, 54%, 82% ee) and (2R)-syn-
5l (61 mg, 35%, 95% ee).
Ethyl (1R,2R,5S,6S,7R)-9-bromo-2-ethyl-7-methoxymethyl-3,10-dioxa-4-
oxotricyclo[5.2.1.01,5]dec-8-ene-6-carboxylate (syn-5p): Pale yellow oil
(96% ee); [a]2D5 0.8 (c 1.3, MeOH); 1H NMR (300 MHz, [D6]ace-
tone): d 1.05 (t, J 7.5 Hz, 3H), 1.26 (t, J 7.0 Hz, 3H), 1.65 1.92 (m,
2H), 3.39 (s, 3H), 3.44 3.45 (m, 2H), 3.99 (d, J 12.0 Hz, 1H), 4.05 (d, J
12.0 Hz, 1H), 4.15 (q, J 7.0 Hz, 2H), 5.01 (t, J 7.5 Hz, 1H), 6.57 (s, 1H);
13C NMR (75 MHz, [D6]acetone): d 9.8, 14.3, 22.9, 49.8, 52.8, 59.6, 62.1,
70.7, 79.8, 94.9, 96.1, 124.9, 135.9, 169.9, 173.5; IR (KBr): nÄ 1782, 1730,
1574 cmÀ1; elemental analysis calcd (%) for C15H19BrO6 (375.2): C 48.02, H
5.10; found: C 48.05, H 5.08.
(S)-3i (82% ee): Colorless oil; [a]2D0 À5.8 (c 1.0, CHCl3).
Methyl (1R,2R,5S,6S,7S)-9-bromo-2-ethyl-7-methyl-3,10-dioxa-4-oxotricy-
clo[5.2.1.01,5]dec-8-ene-6-carboxylate (syn-5l): Colorless crystals (95% ee);
m.p. 64 66 8C (AcOEt); [a]2D0 À6.8 (c 0.81, MeOH); 1H NMR
(300 MHz, [D6]acetone): d 1.03 (t, J 7.5 Hz, 3H), 1.65 1.74 (m, 1H),
1.77 (s, 3H), 1.80 1.90 (m, 1H), 3.14 (d, J 4.0 Hz, 1H), 3.45 (d, J 4.0 Hz,
1H), 3.69 (s, 3H), 4.97 (t, J 7.0 Hz, 1H), 6.50 (s, 1H); 13C NMR (125 MHz,
[D6]acetone): d 9.8, 18.6, 23.0, 52.7, 53.9, 54.8, 80.0, 92.1, 95.8, 124.9, 138.3,
170.7, 173.6; IR (KBr): nÄ 1782, 1732 cmÀ1; elemental analysis calcd (%)
for C13H15BrO5 (331.2): C 47.15, H 4.57; found: C 47.33, H 4.57.
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3j with 2c: Similarly to the typical procedure, a mixture of 2c (0.75 mmol),
(Æ)-3j (125 mg, 0.50 mmol), and lipase LIP (0.20 g) was stirred at 308C for
4.5 d followed by flash column chromatography (hexane/Et2O/Et3N 93:2:5
! 85:10:5) to give (S)-3j (55 mg, 44%, 93% ee) and (2R)-syn-5q (62 mg,
36%, 93% ee).
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3i with 2b: Similarly to the typical procedure, a mixture of 2b (0.75 mmol),
(Æ)-3i (110 mg, 0.50 mmol), and lipase LIP (0.10 g) was stirred at 308C for
2.5 d followed by flash column chromatography (hexane/Et2O/Et3N
100:30:1 ! 100:100:1) to give (S)-3i (50 mg, 45%, ꢀ99% ee) and (2R)-
syn-5m (50 mg, 30%, 95% ee).
(1R,2R,5S,6S,7R)-6-Acetyl-9-bromo-2-ethyl-7-methoxymethyl-3,10-dioxa-
4-oxotricyclo[5.2.1.01,5]dec-8-ene (syn-5q): Pale yellow oil (93% ee);
[a]2D5 21.7 (c 1.2, MeOH); 1H NMR (300 MHz, [D6]acetone): d
1.04 (t, J 7.5 Hz, 3H), 1.67 1.92 (m, 2H), 2.25 (s, 3H), 3.40 (d, J
4.0 Hz, 1H), 3.41 (s, 3H), 3.66 (d, J 4.0 Hz, 1H), 3.95 (d, J 12.0 Hz,
1H), 4.00 (d, J 12.0 Hz, 1H), 4.97 (t, J 7.5 Hz, 1H), 6.74 (s, 1H);
13C NMR (75 MHz, [D6]acetone): d 9.8, 22.9, 52.5, 57.9, 59.6, 71.0, 79.9,
Ethyl (1R,2R,5S,6S,7S)-9-bromo-2-ethyl-7-methyl-3,10-dioxa-4-oxotricy-
clo[5.2.1.01,5]dec-8-ene-6-carboxylate (syn-5m) (95% ee): Colorless oil
(95% ee); [a]2D0 À9.3 (c 1.7, MeOH); 1H NMR (500 MHz, [D6]acetone):
d 1.03 (t, J 7.5 Hz, 3H), 1.25 (t, J 7.5 Hz, 3H), 1.66 1.74 (m, 1H), 1.78
(s, 3H), 1.81 1.91 (m, 1H), 3.12 (d, J 4.0 Hz, 1H), 3.44 (d, J 4.0 Hz,
1H), 4.10 4.17 (m, 2H), 4.97 (t, J 7.5 Hz, 1H), 6.50 (s, 1H); 13C NMR
(125 MHz, [D6]acetone): d 9.8, 14.4, 18.8, 23.0, 53.8, 55.0, 62.0, 80.0, 92.2,
95.8, 124.9, 138.2, 170.0, 173.7; IR (KBr): nÄ 1784, 1736 cmÀ1; elemental
analysis calcd (%) for C14H17BrO5 (345.2): C 48.71, H 4.96; found: C 49.00,
H 4.98.
94.6, 96.0, 124.1, 136.2, 174.0, 204.5; IR (KBr): nÄ 1778, 1713, 1574 cmÀ1
;
elemental analysis calcd (%) for C14H17BrO5 (345.2): C 48.71, H 4.96;
found: C 48.80, H 4.96.
Methyl
(1R,2R,5S,6S,7S)-2-ethyl-7-methyl-3,10-dioxa-4-oxotricyclo-
[5.2.1.01,5]decane-6-carboxylate (syn-6e): Similarly to the hydrogenation
of 5d, (2R)-syn-6e (6.0 mg, 79%) was obtained from (2R)-syn-5l (95% ee,
10 mg, 0.030 mmol) after flash column chromatography (hexane/Et2O
1:1 ! 1:2) as colorless crystals. M.p. 74 76 8C; [a]2D5 12.8 (c 0.42,
CHCl3); 1H NMR (300 MHz, CDCl3) d 1.11 (t, J 7.0 Hz, 3H), 1.57 (s,
3H), 1.74 1.90 (m, 6H), 3.05 (m, 1H), 3.36 (d, J 4.5 Hz, 1H), 3.73 (s,
3H), 4.47 (dd, J 4.5, 9.0 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 10.6,
20.5, 21.9, 28.8, 31.8, 52.4, 54.3, 57.0, 82.0, 87.3, 91.0, 171.0, 175.8; IR (KBr):
Lipase-catalyzed domino kinetic resolution/Diels Alder reaction of( Æ)-
3i with 2c: Similarly to the typical procedure, a mixture of (Æ)-3i (110 mg,
0.50 mmol), 2c (0.75 mmol), and lipase LIP (0.10 g) was stirred at 108C for
4262
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Chem. Eur. J. 2002, 8, No. 18