142
C. M. Marson et al. / Tetrahedron Letters 44 (2003) 141–143
steroidal10–12 and non-steroidal13–15 cases. The observed
migration often proceeds through a chair transition
state,13,16 and can involve migration of a group that is
either the more substituted13 or the less substituted14 at
the a-position. Migration involving the less substituted
(methylene) a-carbon atom of 6 can proceed through a
chair transition state, leading to the a-ketol 7, after
hydrolytic work-up. A more detailed study of such
processes and the scope of related reactions is
warranted.
Reaction of cis-jasmone with dimethylcopperlithium in
diethyl ether, generated from methyllithium (2.0 equiv.)
and CuI (1.0 equiv.) at 0°C, and BF3·OEt2 (1.78 equiv.)
at −78°C with subsequent warming to 20°C over 4 h
afforded the gem-dimethyl ketone 1 in 63% yield.4
Addition of vinylmagnesium bromide (1.3 equiv.) in
THF to 1 in THF at −78°C with subsequent warming
to 20°C over 20 h afforded 2 as the major diastereoiso-
mer (15:1; total yield 98%). Reaction of the epimeric
mixture of 2 with tert-butyl hydroperoxide5 (1.4 equiv.,
70% aqueous solution, CAUTION) and VO(acac)2 (0.5
mol%) in benzene at reflux for 24 h gave the 2,3-epoxy
alcohol 3 as the major diastereoisomer (6:1, total yield
74%). Treatment of this epimeric mixture 3 with SnBr4
(2.0 mol. equiv.) in dichloromethane at 0°C for 1 h
afforded, after column chromatography, the cyclo-
propyl a-ketol 7 (65%), isolated as a single diastereoiso-
mer.6 The structure of 7 was confirmed by X-ray
crystallography (Fig. 1) on a single crystal of the p-bro-
mobenzenesulfonate derivative 8, mp 96°C7 (obtained
in 75% yield by reaction of 7 with p-bromobenzenesul-
fonyl chloride in pyridine at 0°C).
Acknowledgements
Financial support from Glaxo SmithKline, Tonbridge
and the Engineering and Physical Sciences Research
Council (CASE award to C.A.O. and studentship to
J.M.) is gratefully acknowledged.
References
The transformation of 3 into 7 demonstrates that a
2,3-epoxy alcohol can undergo the formalism of cyclo-
propanation of an alkene; we are aware of one other
formation of a cyclopropane ring from a 2,3-epoxy
alcohol.8 Consistent with Sharpless’ observations8 and
our previous work on cyclizations to give seven-mem-
bered rings,1–3 an indirect route seems likely, probably
via a chelation-controlled conversion of 4 into a seven-
membered ring intermediate such as 5 that subsequently
undergoes collapse, with formation of the cyclopropane
ring.9 Ring expansions of 1-hydroxycyclopentanecar-
boxaldehyde systems to a-ketols under Brønsted–
Lowry or Lewis acidic conditions are known in both
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6. Spectral data for 7: IR: umax 3435 (OH), 1710 (CꢁO)
cm−1 1H NMR lH (250 MHz, CDCl3) 4.20 (1H, t,
;
J=3.5, 11.0 Hz, CHOH), 3.68 (1H, d, J=3.5 Hz,
CHOH), 2.30 (1H, m, C(CH3)2CHCꢁO), 2.10–0.80 (8H,
m, OꢁCCHCH2, CH(OH)(CH2)2, CH2CH3), 1.18 (3H, s,
C(CH3)CH3), 1.00 (3H, t, J=7.5 Hz, CH2CH3), 0.71 (3H,
s, CCH3(CH3)), 0.70–0.50 (2H, cyclopropyl-CH), 0.25
(2H, m, cyclopropyl-CH2); 13C NMR lC (63 MHz,
CDCl3) 212.5 (s), 75.1 (d), 59.3 (d), 40.9 (s), 38.0 (t), 33.0
(t), 29.7 (d), 22.2 (t), 21.6 (t), 20.3 (d), 17.8 (q), 15.2 (q),
14.6 (q), 10.9 (t); EI (m/z, %) 224 (5, M+), 209 (40), 127
(40), 109 (30), 95 (30), 81 (35), 60 (40), 55 (90), 41 (100).
HRMS found 224.1783, C14H24O2 requires 224.1776.
7. X-Ray data for 8 have been deposited at the Cam-
bridge Crystallographic Data Centre, deposition num-
ber 195063.
8. Morgans, D. J., Jr.; Sharpless, K. B.; Traynor, S. G. J.
Am. Chem. Soc. 1981, 103, 462.
9. Models suggest that a colinear alignment of the partial
epoxide CꢀO bond and the p-orbital from the alkenic
carbon atom, at the requisite distance for carbonꢀcarbon
bond formation, is more readily achievable in a transition
state that leads to the seven-membered ring than in one
that results in a six-membered ring.
Figure 1. ORTEP representation of 8.
10. Miller, T. C. J. Org. Chem. 1969, 34, 3829.