A. Srikrishna, V. Gowri / Tetrahedron: Asymmetry 22 (2011) 1553–1559
1557
(c 7.0, CHCl3); IR (neat):
m
max/cmꢂ1 1736 (OC@O), 1661, 1368,
C-11), 55.1 (CH3, OCH3), 49.0 (C), 47.3 (C), 46.9 (CH2, C-9), 35.3
(CH2, C-3), 34.8 (CH, C-4), 31.1 (CH3), and 23.0 (CH3) [2 ꢃ tert-
CH3], 16.5 (CH2, C-2), 12.6 (CH3, olefinic-CH3); HRMS: m/z calcd
for C17H24O3Na (M+Na): 299.1624; found: 299.1631.
Further elution of the column with ethyl acetate–hexane (1:9)
furnished the minor tetracyclic ketone 24 (5 mg, 11%) as an oil.
1338, 1174, 1150, 1120, 1097, 1050, 999, 918, 894; 1H NMR
(300 MHz): d 5.15 (1H, s, H-20), 5.06, and 4.88 (2H, 2 ꢃ d, J
2.4 Hz, C@CH2), 4.71 and 4.68 (2H, 2 ꢃ d, J 6.6 Hz, OCH2O), 4.50–
4.35 (1H, m, H-70), 4.07 (2H, q, J 7.2 Hz, OCH2CH3), 3.36 (3H, s,
OCH3), 2.64, and 2.44 (2H, 2 ꢃ d, J 15.3 Hz, H-2), 2.35 (1H, dd, J
8.1, and 7.5 Hz), 2.15 (1H, dt, J 11.7, and 6.9 Hz), 1.56 (3H, s, ole-
finic-CH3), 1.39 (1H, q, J 11.1 Hz), 1.24 (3H, t, J 6.9 Hz, OCH2CH3),
1.11 (3H, s), and 0.96 (3H, s) [2 ꢃ tert-CH3]; 13C NMR (75 MHz): d
171.0 (C, OC@O), 156.6 (C, C@CH2), 144.3 (C, C-3), 129.3 (CH, C-
20), 105.3 (CH2, C@CH2), 95.9 (CH2, OCH2O), 79.6 (CH, C-70), 59.7
(CH2, OCH2CH3), 55.9 (C, C-10), 55.1 (CH3, OCH3), 52.8 (CH, C-50),
47.4 (C, C-40), 45.2 (CH2, C-2), 34.6 (CH2, C-60), 29.6 (CH3), and
21.8 (CH3) [2 ꢃ tert-CH3], 14.2 (CH3, OCH2CH3), 12.1 (CH3, ole-
finic-CH3); HRMS: m/z calcd for C18H28O4Na (M+Na): 331.1886;
found: 331.1897.
½
a 2D2
ꢄ
¼ ꢂ8:6 (c 0.7, CHCl3); IR (neat):
m
max/cmꢂ1 3032, 1719
(C@O), 1370, 1212, 1151, 1118, 1044, 1012, 917, 899, 885; 1H
NMR (300 MHz): d 5.25 (1H, d, J 2.4 Hz) and 5.15 (1H, d, J 3.0 Hz)
[C@CH2], 4.77 and 4.71 (2H, 2 ꢃ d, J 6.6 Hz, OCH2O), 4.40–4.25
(1H, m, H-10), 3.41 (3H, s, OCH3), 2.71 (1H, dd, J 18.0, and 1.5 Hz,
H-2A), 2.57 (1H, d, J 5.1 Hz, H-4), 2.27 (1H, d, J 18.0 Hz, H-2B),
2.17 (1H, quintet, J 5.7 Hz), 1.85–1.55 (3H, m), 1.10 (6H, s), and
1.07 (3H, s) [3 ꢃ tert-CH3]; 13C NMR (100 MHz): d 213.5 (C, C@O),
156.2 (C, C-11), 107.7 (CH2, C@CH2), 96.1 (CH2, OCH2O), 79.6 (CH,
C-10), 63.2 (CH), 56.3 (C, C-1), 55.4 (CH3, OCH3), 55.2 (CH2, C-2),
54.5 (CH), 50.4 (C, C-6), 47.9 (CH), 44.7 (C, C-7), 35.5 (CH2, C-9),
29.2 (CH3), 25.4 (CH3), and 19.5 (CH3) [3 ꢃ tert-CH3]; HRMS: m/z
calcd for C17H24O3Na (M+Na): 299.1624; found: 299.1612.
4.6. (1S,2S,4S,8R,11S)-2-(Methoxymethoxy)-5,5,6-trimethyl-
tetracyclo[6.4.0.01,11.04,8]dodec-6-en-10-one 23 and (1S,4R,
5S,6R,8S,10S)-10-(methoxymethoxy)-6,7,7-trimethyl-11-
methylenetetracyclo[6.3.0.01,5.04,6]undecan-3-one 24
4.7. (1R,5S,6S,8S)-6-(Methoxymethoxy)-5,9,9,10-tetramethyl-
tricyclo[6.3.0.01,5]undec-10-en-3-one 25 and (1R,3R,5S,6S,8S)-
6-(methoxymethoxy)-5,9,9,10-tetramethyltricyclo[6.3.0.01,5]-
undec-10-en-3-ol 26
To a magnetically stirred solution of the ester 20 (98 mg,
0.32 mmol) in methanol (2 mL) was added 10% aq. NaOH (2 mL)
and then refluxed for 5 h. The reaction mixture was cooled to rt
and washed with CH2Cl2 (1 mL). The aqueous layer was then acid-
ified with 3 M HCl (3 mL) and extracted with CH2Cl2 (3 ꢃ 5 mL).
The organic extract was washed with brine (5 mL) and dried
(Na2SO4). Evaporation of the solvent furnished the acid 22
To magnetically stirred, freshly distilled (over sodium and ferric
chloride) ammonia (50 mL) in a two-necked RB flask equipped
with a Dewar condenser was added a solution of the tetracyclic ke-
t
tone 23 (23 mg, 0.08 mmol) in THF (2 mL) and anhydrous BuOH
(90 mg, 100%) as an oil. IR (neat):
m
max/cmꢂ1 3081 (br, OH), 3029,
(0.3 mL) followed by the addition of freshly cut lithium (33 mg,
4.71 mmol). The resulting blue colored solution was stirred for
15 min at ꢂ30 °C and then the reaction was quenched carefully
with solid NH4Cl. After evaporation of ammonia, the residue was
taken in water (5 mL) and extracted with ether (3 ꢃ 4 mL). The
combined ether extract was washed with brine (3 mL) and dried
(Na2SO4). Evaporation of the solvent and purification of the residue
on a silica gel column using ethyl acetate–hexane (1:9) as eluent
first furnished the triquinane ketone 25 (10 mg, 43%) as an oil.
1709 (C@O), 1662, 1150, 1120, 1049, 999, 918, 896, 849, 828.
To a magnetically stirred solution of the acid 22 (66 mg,
0.24 mmol) in dry benzene (2 mL) was added oxalyl chloride
(0.1 mL, 1.16 mmol) and then stirred for 3 h at rt. Evaporation of
the excess oxalyl chloride and solvent under reduced pressure gave
the acid chloride, which was taken in dry ether (2 mL), added to a
cold (0–5 °C), magnetically stirred ethereal solution of diazometh-
ane [excess, prepared from N-nitroso-N-methylurea (700 mg,
6.80 mmol), 5 mL of 60% aqueous KOH solution and 6 mL of ether]
and the reaction mixture was stirred at 0 °C for 30 min and at rt for
2.5 h. Careful evaporation of the excess diazomethane and solvent
on a hot water bath and purification of the residue on a silica gel
column using ethyl acetate–hexane (1:9) as eluent furnished the
½
a 2D2
ꢄ
¼ ꢂ5:0 (c 1.2, CHCl3); IR (neat):
m
max/cmꢂ1 1742 (C@O),
1377, 1361, 1221, 1180, 1146, 1119, 1096, 1042, 995, 918, 848;
1H NMR (300 MHz): d 5.13 (1H, s, H-11), 4.65, and 4.56 (2H,
2 ꢃ d, J 6.6 Hz OCH2O), 3.60 (1H, dd, J 8.7, and 5.1 Hz, H-6), 3.34
(3H, s, OCH3), 2.44 and 2.35 (2H, 2 ꢃ dd, J 19.2, and 1.5 Hz), 2.35
and 2.15 (2H, 2 ꢃ dd, J 18.3, and 1.2 Hz), 2.07–1.91 (2H, m, H-7),
1.70–1.50 (1H, m, H-8), 1.62 (3H, d, J 1.5 Hz, olefinic-CH3), 1.05
(3H, s), 1.02 (3H, s), and 0.98 (3H, s) [3 ꢃ tert-CH3]; 13C NMR
(75 MHz): d 217.3 (C, C@O), 146.8 (C, C-10), 126.5 (CH, C-11),
95.7 (CH2, OCH2O), 84.7 (CH, C-6), 61.1 (C, C-1), 58.4 (CH, C-8),
55.3 (CH3, OCH3), 52.4 (CH2), and 51.2 (CH2) [C-2 and C-4], 50.3
(C, C-5), 47.4 (C, C-9), 32.2 (CH2, C-7), 30.5 (CH3), 22.3 (CH3), and
18.7 (CH3) [3 ꢃ tert-CH3], 12.4 (CH3, olefinic CH3); HRMS: m/z calcd
for C17H26O3Na (M+Na): 301.1781; found: 301.1784.
diazoketone 21 (48 mg, 67%) as a yellow oil. IR (neat): m
max/cmꢂ1
3086, 2101 (N@N), 1635 (C@O), 1362, 1314, 1215, 1149, 1119,
1048, 998, 917, 893, 846, 831.
To a magnetically stirred, refluxing (by placing two 100 W tung-
sten lamps near the reaction flask) suspension of copper powder
(107 mg, 1.68 mmol) and anhydrous copper sulfate (80 mg,
0.50 mmol) in dry cyclohexane (7 mL) was added drop wise, a solu-
tion of the diazoketone 21 (48 mg, 0.16 mmol) in dry cyclohexane
(4 mL) over a period of 20 min and the reaction mixture was re-
fluxed for 3.5 h. It was then cooled to rt, copper and copper sulfate
were filtered off using a sintered funnel. Evaporation of the solvent
under reduced pressure and purification of the residue on a silver
nitrate impregnated silica gel column using ethyl acetate–hexane
(1:19) as eluent first furnished the major tetracyclic ketone 23
Further elution of the column with ethyl acetate–hexane (1:4)
furnished the alcohol 26 (9 mg, 39%) as an oil. ½a D23
¼ ꢂ6:7 (c 0.9,
ꢄ
CHCl3); IR (neat): m
max/cmꢂ1 3397 (OH), 3029, 1376, 1361, 1229,
1217, 1146, 1109, 1042, 998, 918, 851; 1H NMR (300 MHz): d
5.07 (1H, s, H-11), 4.61, and 4.56 (2H, 2 ꢃ d, J 6.6 Hz, OCH2O),
4.13 (1H, tt, J 9.9, and 6.0 Hz, H-3), 3.51 (1H, dd, J 11.7, and
5.0 Hz, H-6), 3.32 (3H, s, OCH3), 2.03 (1H, dd, J 11.3, and 6.0 Hz),
1.93 (1H, dd, J 12.0, and 6.0 Hz), 1.85–1.67 (2H, m), 1.64 (1H, br
s, OH), 1.55 (3H, s, olefinic-CH3), 1.50–1.15 (3H, m), 1.02 (3H, s),
0.90 (3H, s), and 0.88 (3H, s) [3 ꢃ tert-CH3]; 13C NMR (75 MHz): d
144.8 (C, C-10), 128.2 (CH, C-11), 95.7 (CH2, OCH2O), 84.8 (CH,
C-6), 71.5 (CH, C-3), 62.5 (C, C-1), 56.4 (CH, C-8), 55.1 (CH3,
OCH3), 50.3 (C, C-5), 48.5 (CH2), 48.4 (CH2), 46.8 (C, C-9), 32.8
(CH2), 30.0 (CH3), 21.8 (CH3), and 19.3 (CH3) [3 ꢃ tert-CH3], 12.4
(23 mg, 52%) as an oil. ½a D22
¼ þ80:0 (c 1.4, CHCl3); IR (neat):
ꢄ
m
max/cmꢂ1 3027, 1725 (C@O), 1359, 1249, 1220, 1197, 1147,
1101, 1048, 916, 778; 1H NMR (300 MHz): d 5.12 (1H, s, H-7),
4.60 and 4.50 (2H, 2 ꢃ d, J 6.9 Hz, OCH2O), 3.80–3.75 (1H, m, H-
2), 3.29 (3H, s, OCH3), 2.30–2.00 (5H, m), 1.70 (1H, dd, J 9.1, and
5.4 Hz), 1.62–1.58 (1H, m), 1.60 (3H, s, olefinic-CH3), 1.46 (1H,
dd, J 4.7 and 3.3 Hz), 1.08 (3H, s) and 1.04 (3H, s) [2 ꢃ tert-CH3];
13C NMR (75 MHz): d 211.4 (C, C@O), 147.3 (C, C-6), 126.3 (CH,
C-7), 94.6 (CH2, OCH2O), 81.1 (CH, C-2), 59.6 (C, C-8), 59.2 (CH,