Transannular Cyclization of Epoxycaryophyllenes Catalyzed by TiIII
FULL PAPER
(100 MHz, CDCl3): δ = 150.4 (C-8), 112.8 (C-15), 64.7 (C-14), 64.0 (3 mL), and TMSCl (9.09 mmol) were added, and the solution was
(C-4), 61.1 (C-5), 50.9 (C-1), 44.3 (C-9), 40.7 (C-10), 34.6 (C-11), stirred for 40 min. The reaction was then quenched with HCl (2 )
29.9 (C-13), 29.5 (C-3), 29.0 (C-6), 25.0 (C-7), 24.2 (C-2), 21.6 (C- and extracted with MeOtBu. The organic phase was washed with
12) ppm. FAB HRMS: calcd. for C15H24O2Na [M+Na]+ 259.1674;
found 259.1669.
brine, dried (anhydrous Na2SO4), and the solvent was removed.
Products obtained were isolated by column chromatography of the
crude residue on silica gel (H/E).
General Procedure for the Protection of Epoxyalcohols 19 and 20
(1R,2S,5R,8S,9R)-1,4,4,8-Tetramethyltricyclo[6.3.0.02,5]undecan-
9α-ol (8): According to the general procedure, the resulting crude
product was purified by column chromatography (H/E, 97:3) on
silica gel to afford 8 [297 mg (65%) from 2, 233 mg (51%) from
2+3, and 137 mg (30%) from 4+5]. [α]2D0 = –4.2 (c = 1, CHCl3). IR
Imidazole (77.2 mg, 1.13 mmol) was added to a solution of the
epoxyalcohol (0.48 mmol) in anhydrous DMF (4 mL) at room tem-
perature, and the mixture was stirred for 20 min, TBDMSCl
(148 mg, 0.98 mmol) was then added. After 15 min, MeOtBu
(10 mL) was added. The solution was successively washed with HCl
(2 ) and brine. The organic phase was dried with anhydrous
Na2SO4 and concentrated to give a crude residue.
(film): ν = 3338, 2957, 2921, 2862, 1452, 1380, 1256, 1048 cm–1. 1H
˜
NMR (400 MHz, CDCl3): δ = see Table 1. 13C NMR (100 MHz,
CDCl3): δ = see Table 1. EI HRMS: calcd. for C14H21 [M–H2O–
CH3]+ 189.1643; found 189.1642.
14-tert-Butyldimethylsilyloxymethyl-4α,5α-epoxy-4,5-dihydrocaryo-
phyllene (6): According to the general procedure from epoxyalcohol
19, the resulting crude product was purified by column chromatog-
(1R,2S,5R,8S,9R)-1,4,4,8-Tetramethyltricyclo[6.3.0.02,5]undecan-
9α-yl Acetate (8a): [α]2D0 = –5.4 (c = 1, CHCl ). IR (film): ν = 2956,
˜
3
raphy (H/E, 96:4) on silica gel to afford 237 mg (86%) of 6. [α]2D0
=
2925, 2863, 1738, 1455, 1363, 1240, 1039, 1019 cm–1
.
1H NMR
+14.4 (c = 1, CH Cl ). IR (film): ν = 3070, 2951, 2928, 2857, 1633,
˜
2
2
(400 MHz, CDCl3): δ = 4.88 (dd, J = 3.3, 8.0 Hz, 1 H, 9-H), 2.20
(m, 2 H), 2.06 (s, 3 H, COCH3) 1.71–1.21 (m, 10 H), 1.04 (s, 3 H,
13-H), 1.01 (s, 3 H, 12-H), 0.87 (s, 3 H, 15-H), 0.76 (s, 3 H, 14-
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.7 (COCH3), 86.1
(C-9), 48.2 (C-1), 44.8 (C-5), 44.6 (C-8), 38.6 (C-2), 36.2 (C-4), 35.9
(C-3), 34.3 (C-11), 32.4 (C-7), 30.4 (C-12), 30.2 (C-10), 25.2 (C-
14), 24.4 (C-6), 21.6 (COCH3), 21.1 (C-13), 16.9 (C-15) ppm. FAB
HRMS: calcd. for C17H28O2Na [M + Na]+ 287.1987; found
287.1984.
1
1459, 1364, 1253, 1123, 1100, 837, 777 cm–1. H NMR (400 MHz,
CDCl3): δ = 4.79 (br. s, 1 H, 15a-H), 4.76 (br. s, 1 H, 15b-H), 3.85
(d, J = 11.7 Hz, 1 H, 14a-H), 3.24 (d, J = 11.7 Hz, 1 H, 14b-H),
2.69 (dd, J = 2.9, 11.3 Hz, 1 H, 5-H), 2.42 (q, J = 8.8 Hz, 1 H, 9-H),
2.19 (m, 3 H, 3a-H, 3b-H, 6a-H), 2.04 (ddd, J = 2.5, 5.0, 13.4 Hz, 1
H, 7a-H), 1.83 (m, 1 H, 1-H), 1.79 (dd, J = 8.7, 10.9, 1 H, 10a-H),
1.56–1.19 (m, 5 H, 2a-H, 2b-H, 6b-H, 7b-H, 10b-H), 0.99 (s, 3 H,
13-H), 0.92 (s, 3 H, 12-H), 0.83 [s, 9 H, SiC(CH3)3], 0.00 (s, 3 H,
SiCH3), –0.01 (s, 3 H, SiCH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 154.4 (C-8), 110.8 (C-15), 66.3 (C-14), 63.6 (C-4), 60.3 (C-5), (1S,2S,5R,8R,9R)-1,4,4,8-Tetramethyltricyclo[6.3.0.02,5]undecan-
49.3 (C-1), 40.9 (C-10), 37.7 (C-9), 33.5 (C-11), 30.9 (C-3), 30.1 (C- 9α-ol (9): According to the general procedure, the resulting crude
13), 26.7 (C-6), 25.9 [SiC(CH3)3], 23.9 (C-7), 23.5 (C-2), 22.9 (C-
product was purified by column chromatography (H/E, 95:5) on
12), 18.4 [SiC(CH3)3], –5.2 (SiCH3), –5.4 (SiCH3) ppm. FAB silica gel to afford 9 [137 mg (30%) from 2, 100 mg (22%) from
HRMS: calcd. for C21H38O2SiNa [M + Na]+ 373.2539; found
373.2535.
2+3, and 55 mg (12%) from 4+5]. [α]2D0 = +10.8 (c = 1, CHCl3). IR
(film): ν = 3395, 2996, 2930, 2862, 1457, 1365, 1255, 1020 cm–1. 1H
˜
NMR (400 MHz, CDCl3): δ = see Table 1. 13C NMR (100 MHz,
CDCl3): δ = see Table 1. EI HRMS: calcd. for C14H21 [M–H2O–
CH3]+ 189.1643; found 189.1647.
14-tert-Butyldimethylsilyloxymethyl-4β,5β-epoxy-4,5-dihydrocaryo-
phyllene (7): According to the general procedure from epoxyalcohol
20, the resulting crude product was purified by column chromatog-
raphy (H/E, 96:4) on silica gel to afford 12 mg (80%) of 7. [α]2D0 = –
(1S,2S,5R,8R,9R)-1,4,4,8-Tetramethyltricyclo[6.3.0.02,5]undecan-
2.0 (c = 1, CH Cl ). IR (film): ν = 3069, 2951, 2929, 2858, 1631, 9α-yl Acetate (9a): [α]2D0 = +11.3 (c = 1, CHCl ). IR (film): ν =
˜
˜
2
2
3
1461, 1364, 1253, 1125, 1099, 1056, 837, 777 cm–1
.
1H NMR 2950, 2927, 2861, 1737, 1457, 1366, 1246, 1021 cm–1
.
1H NMR
(400 MHz, CDCl3): δ = 4.79 (d, J = 2.2 Hz, 1 H, 15a-H), 4.68 (d, (400 MHz, CDCl3): δ = 4.69 (dd, J = 2.5, 7.4 Hz, 1 H, 9-H), 2.30
J = 2.2 Hz, 1 H, 15b-H), 3.94 (d, J = 11.8 Hz, 1 H, 14a-H), 3.31
(d, J = 11.8 Hz, 1 H, 14b-H), 2.81 (dd, J = 2.7, 11.6 Hz, 1 H, 5-
H), 2.64 (q, J = 9.7 Hz, 1 H, 9-H), 2.57 (m, 1 H, 3a-H), 2.34 (m,
(m, 1 H), 2.02 (s, 3 H, COCH3), 2.01 (m, 1 H), 1.67 (m, 2 H), 1.51
(m, 2 H), 1.26 (m, 6 H), 1.06 (s, 3 H, 13-H), 1.01 (s, 3 H, 12-H),
0.90 (s, 3 H, 14-H), 0.87 (s, 3 H, 15-H) ppm. 13C NMR (100 MHz,
1 H, 3b-H), 2.12 (m, 2 H, 2a-H, 6a-H), 1.82 (m, 1 H, 1-H), 1.73 CDCl3,): δ = 170.8 (COCH3), 84.0 (C-9), 49.2 (C-1), 46.2 (C-5),
(m, 1 H, 10a-H), 1.56 (m, 2 H, 7a-H, 10b-H), 1.42 (dt, J = 2.8, 45.6 (C-8), 42.0 (C-2), 41.2 (C-4), 37.6 (C-3), 36.9 (C-7), 30.4 (C-
11.2 Hz, 1 H, 7b-H), 1.14 (dt, J = 2.8, 13.7 Hz, 1 H, 6b-H), 1.01
(s, 3 H, 13-H), 1.00 (s, 3 H, 12-H), 0.91 [s, 9 H, SiC(CH3)3], 0.07
(s, 3 H, SiCH3), 0.06 (s, 3 H, SiCH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 150.2 (C-8), 112.5 (C-15), 66.4 (C-14), 64.2 (C-4), 60.5
(C-5), 50.5 (C-1), 44.3 (C-9), 40.4 (C-10), 34.5 (C-11), 29.8 (C-13),
29.3 (C-3), 28.1 (C-6), 25.8 [SiC(CH3)3], 25.1 (C-7), 23.9 (C-2), 21.5
(C-12), 18.3 [SiC(CH3)3], –5.2 (SiCH3), –5.5 (SiCH3) ppm. FAB
HRMS: calcd. for C21H38O2SiNa [M + Na]+ 373.2539; found
373.2535.
11, C-12), 30.1 (C-10), 23.6 (C-6), 22.9 (C-15), 21.4 (COCH3), 20.8
(C-13), 16.0 (C-14) ppm. FAB HRMS: calcd. for C17H28O2Na
[M+Na]+ 287.1987; found 287.1989.
(1R,2S,5R,8S,9S)-1,4,4,8-Tetramethyltricyclo[6.3.0.02,5]undecan-9β-
ol (10): According to the general procedure, the resulting crude
product was purified by column chromatography (H/E, 95:5) on
silica gel to afford 10 [55 mg (12%) from 2+3 and 137 mg (30%)
from 4+5]. [α]2D0 = +38.8 (c = 1, CHCl ). IR (film): ν = 3406, 2952,
˜
3
2923, 2864, 1455, 1259, 1097, 1044 cm–1
.
1H NMR (400 MHz,
General Procedure for the Transannular Cyclization of Epoxy-
caryophyllenes (8–15)
CDCl3): δ = see Table 1. 13C NMR (100 MHz, CDCl3): δ = see
Table 1. EI HRMS: calcd. for C14H21 [M–H2O–CH3]+ 189.1643;
found 189.1645.
Strictly deoxygenated THF (30 mL) was added to a mixture of
Cp2TiCl2 (0.41 mmol) and Mn dust (16.5 mmol) under an argon
atmosphere, and the suspension was stirred at room temperature
until it turned lime green (after about 15 min.). Then, a solution of
epoxide (2.06 mmol) and 2,4,6-collidine (15.9 mmol) in THF
(1R,2S,5R,8S,9S)-1,4,4,8-Tetramethyltricyclo[6.3.0.02,5]undecan-9β-
yl Acetate (10a): [α]2D0 = +39.5 (c = 1, CHCl ). IR (film): ν = 2952,
˜
3
2925, 2868, 1735, 1458, 1363, 1246, 1024 cm–1
.
1H NMR
(400 MHz, CDCl3): δ = 5.45 (dd, J = 7.0, 9.2 Hz, 1 H, 9-H), 2.25
Eur. J. Org. Chem. 2006, 3434–3441
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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