Acid-catalysed formation of compounds 7, 8 and 9. A solution
of 6 (7.5 mg, 0.0240 mmol) in deuterochloroform (1 mL, Cam-
bridge Isotopes, Ag stabilised) was monitored by 1H NMR
spectroscopy at 0.08, 0.25, 1.5, 4.5, 8.5 and 24 h intervals.
After 0.25 h 1H NMR spectroscopic analysis revealed the near
complete consumption of starting material and the formation
of three new products, which had chemical shifts correspond-
ing to 7, 8 and 9 (ca. 5:5:1 ratio). These products were con-
verted over 24 h into 7. In a control experiment, a solution
of 6 (7.5 mg, 0.0240 mmol) in deuterochloroform (1 mL, Cam-
bridge Isotopes, Ag stabilised) that had been filtered through
basic alumina was monitored by 1H NMR spectroscopic meth-
ods and showed no change after 24 h.
oil; [a]D +37.2 (c 0.7, CHCl3); Rf 0.22 (25% ethyl acetate–
petroleum ether); nmax 3331 (br, s) cmꢀ1; dH (300 MHz, CDCl3)
4.24 (1H, app t, J 5.9 Hz), 2.97 (1H, d, J 6.0 Hz), 2.89 (1H, s),
2.21 (1H, m), 2.10–1.60 (9H, m), 1.50 (1H, m), 1.26–1.18
(1H, m), 1.08 (3H, d, J 7.8 Hz), 1.08 (3H, s), 0.91 (3H, s); dC
(75 MHz, CDCl3) 88.4, 76.6, 61.6, 51.6, 46.0, 40.1, 33.8,
31.2, 28.1, 25.6, 25.2, 24.4, 21.7, 19.4; m/z 224 (M+, 13%),
206 (46), 194 (50), 191 (40), 179 (24), 173 (27), 163 (42), 150
(45), 137 (49), 135 (43), 125 (73), 122 (61), 111 (100). Found
(HRMS): M+ 224.1772; C14H24O2 requires 224.1776.
A second fraction afforded 11 (35.5 mg, 59%) as a colourless
oil; [a]D ꢀ21.4 (c 0.6, CHCl3); Rf 0.27 (25% ethyl acetate–
petroleum ether); nmax 3312 (br s) cmꢀ1; dH (300 MHz, CDCl3)
4.19 (1H, app t, J 6.4 Hz), 3.01 (1H, d, J 6.8 Hz), 2.44 (1H, s),
2.09–1.40 (12H, m), 1.11 (3H, d, J 6.8 Hz), 0.92 (6H, s);
dC (75 MHz, CDCl3) 90.0, 75.4, 61.0, 52.0, 45.6, 40.5, 34.4,
28.1, 27.9, 27.2, 26.9, 22.8, 20.8, 18.5; m/z 224 (M+, 6%),
206 (27), 194 (20), 191 (16), 163 (14), 150 (19), 137 (18), 135
(22), 125 (100), 122 (40), 111 (80). Found (HRMS): M+
224.1777; C14H24O2 requires 224.1776.
Photochemical synthesis of (3aS,4R,7S,8S,8aR)-hexahydro-
4,9,9-trimethyl-8-(phenylmethoxy)-1H-3a,7-methanoazulene-
4,8a-oxide (8). A solution of 6 (21 mg, 0.0672 mmol) in deuter-
oacetonitrile (1 mL) was placed in a Rayonet reactor and irra-
diated at 254 nm for 0.5 h after which time no starting material
was observable by 1H NMR techniques. The mixture was con-
centrated under reduced pressure and subject to flash chroma-
tography (8% ethyl acetate–petroleum ether) to afford 8 (10.9
mg, 52%) as a colourless oil, [a]D ꢀ36.3 (c 0.5, CHCl3); Rf
0.36 (15% ethyl acetate–petroleum ether); nmax 1456, 1370,
1125 cmꢀ1; dH (300 MHz, CDCl3) 7.38–7.25 (5H, m), 4.60
(1H, d, J 12.2 Hz), 4.48 (1H, d, J 12.2 Hz), 3.93 (1H, d, J
5.6 Hz), 2.47–2.39 (2H, m), 2.26 (1H, m), 2.17 (1H, m),
1.96–1.52 (6H, m), 1.29 (1H, m), 1.23 (3H, s), 0.96 (3H, s),
0.82 (3H, s); dC (75 MHz, CDCl3) 139.0, 128.2, 127.5, 127.3,
94.5, 85.4, 81.0, 71.1, 62.9, 53.6, 37.8, 36.5, 33.3, 31.9, 27.9,
23.8, 23.2, 20.9, 17.4; m/z 312 (M+, 4%), 221 (39), 204 (50),
188 (30), 175 (17), 163 (36), 145 (46), 135 (43), 119 (24), 109
(39), 91 (100). Found (HRMS): M+ 312.2094; C21H28O2
requires 312.2089.
Samarium(II) iodide mediated formation of (3aR,7S,8S,8aR)-
hexahydro-9,9-dimethyl-4-methylene-8-(phenyl-methoxy)-1H-
3a,7-methanoazulene-8a(4H)-ol (9) and (3aR,4R,7S,8S,8aR)-
hexahydro-4,9,9-trimethyl-8-(phenylmethoxy)-1H-3a,7-metha-
noazulene-8a(4H)-ol (12). A magnetically stirred solution of
ketone 6 (20.0 mg, 0.0640 mmol) and hexamethylphosphor-
amide (0.8 mL) in THF (2.4 mL) maintained at 0 ꢂC was treated
dropwise with samarium(II) iodide (1.00 mL of a 0.1 M solu-
tion in THF, 0.100 mmol). The completion of the reaction
was indicated by the appearance of a moderately persistent
purple colour. The reaction mixture was then poured into
water (10 mL) and extracted with diethyl ether (3 ꢁ 10
mL). The combined organic extract was washed with brine
(1 ꢁ 10 mL), dried over magnesium sulfate and concentrated
under reduced pressure to give a colourless oil. Subjection of
this material to flash chromatography (12% ether–petroleum
ether, 2 elutions) gave 9 (10.8 mg, 54%) as a colourless oil;
[a]D +65 (c 0.4, CHCl3); Rf 0.35 (10% ethyl acetate–petro-
leum ether); nmax 3530 (m), 3331 (m), 1635 (s), 1606 (w)
cmꢀ1; dH (300 MHz, CDCl3) 7.40–7.31 (5H, m), 4.78 (1H,
s), 4.68 (1H, m), 4.64 (2H, m), 4.05 (1H, d, J 6.1 Hz),
3.26 (1H, s), 2.57 (1H, m), 2.24–1.53 (10H, m), 0.96 (3H,
s), 0.83 (3H, s); dC (75 MHz, CDCl3) 151.4, 138.1, 128.4,
127.7, 127.4, 107.5, 87.4, 84.3, 72.7, 67.4, 50.3, 46.0, 40.4,
29.7, 26.8, 26.7, 24.8, 23.3, 21.6; m/z 312 (M+, 3%), 294
(39), 221 (24), 204 (71), 203 (68), 185 (37), 175 (41), 161
(39), 147 (23), 135 (37), 133 (40), 119 (32), 105 (36), 91
(100). Found (HRMS): M+ 312.2096; C21H28O2 requires
312.2089.
Tin(II) chloride catalysed transformation of 8 into 7. A solu-
tion of 8 (2.1 mg, 0.0067 mmol) in chloroform was treated with
tin(II) chloride (cat.) and the resulting mixture stirred for 3 h at
18 ꢂC, at which point thin layer chromatography revealed the
complete conversion of 8 into 7. Accordingly, the reaction mix-
ture was quenched with sodium bicarbonate (10 mL of a satu-
rated aqueous solution) and extracted with diethyl ether
(3 ꢁ 10 mL). The combined organic extract was washed with
brine (1 ꢁ 10 mL), dried over magnesium sulfate and concen-
trated under reduced pressure to give 7 as a colourless oil.
Tin(II) chloride catalysed transformation of 9 into 7. A solu-
tion of 9 (8.0 mg, 0.0256 mmol) in chloroform (1 mL) was trea-
ted with tin(II) chloride (1.2 mg, 0.0064 mmol) and the
resulting mixture stirred for 48 h at 18 ꢂC. The reaction mix-
ture was quenched with sodium bicarbonate solution (10 mL
of a saturated aqueous solution) and extracted with diethyl
ether (3 ꢁ 10 mL). The combined organic extract was washed
with brine (1 ꢁ 10 mL), dried over magnesium sulfate and con-
centrated under reduced pressure to give a colourless oil. Sub-
jection of this material to flash chromatography (10% ethyl
acetate–petroleum ether) afforded 7 (7.2 mg, 90%) as a colour-
less oil.
The second fraction afforded 12 (7.8 mg, 39%), mp 53–54 ꢂC;
[a]D +17.9 (c 0.9, CHCl3); Rf 0.48 (10% ethyl acetate–petro-
leum ether); nmax 3549 (s), 1605 (m) cmꢀ1; dH (300 MHz,
CDCl3) 7.37–7.29 (5H, m), 4.60 (2H, m), 3.95 (1H, d, J 5.9
Hz), 3.32 (1H, s), 2.08–1.33 (12H, m), 1.14 (3H, d, J 6.8 Hz),
0.93 (3H, s), 0.91 (3H, s); dC (75 MHz, CDCl3) 138.2, 128.4,
127.7, 127.4, 89.4, 83.1, 72.6, 60.9, 50.5, 45.7, 40.6, 34.7,
28.2, 28.1, 27.1, 27.0, 22.8, 21.5, 18.4; m/z 223 (M+ ꢀ C7H7 ,
100%), 205 (22) 149 (13), 135 (35), 125 (15), 121 (12), 111
(18), 109 (16), 91 (71). Found (HRMS): M+ ꢀ C7H7
223.1699; C14H23O2 requires 223.1698.
(3aR,4S,7S,8S,8aR)-Hexahydro-4,9,9-trimethyl-1H-3a,7-
methanoazulene-8,8a(4H)-diol (10) and (3aR,4R,7S,8S,8aR)-
hexahydro-4,9,9-trimethyl-1H-3a,7-methanoazulene-8,8a(4H)-
diol (11). Compound 7 (83.8 mg, 0.263 mmol) was dissolved in
methanol (3.0 mL) containing 10% palladium on carbon (28.0
mg) and the resulting mixture placed in a Parr hydrogenator
under a hydrogen atmosphere (60 psi) and rocked for 48 h
at 18 ꢂC. The mixture was then filtered to remove the catalyst
and concentrated under reduced pressure. Subjection of the
residue to column chromatography (25% ethyl acetate–petro-
leum ether, 2 elutions) gave 10 (12.6 mg, 21%) as a colourless
Samarium(II) iodide–thiophenol mediated synthesis of (12). A
magnetically stirred solution of ketone 6 (10.0 mg, 0.0320
mmol) and hexamethylphosphoramide (0.32 mL) in THF
(0.96 mL) maintained at 0 ꢂC was treated dropwise with thio-
phenol (0.131 mL, 1.28 mmol), followed by samarium(II)
iodide (0.96 mL of a 0.1 M solution in THF, 0.096 mmol).
The completion of the reaction was indicated by the appear-
ance of a persistent purple colour. The reaction mixture
54
New J. Chem., 2003, 27, 50–59