A short and efficient synthesis of (±)-β-cuparenone

Article abstract of DOI:10.1016/j.tetlet.2006.03.012

A Wittig olefination-Claisen rearrangement strategy has been applied to achieve one of the shortest and efficient synthesis of (±)-β-cuparenone.

Full text of DOI:10.1016/j.tetlet.2006.03.012

Tetrahedron Letters 47 (2006) 3027–3029
A short and efficient synthesis of ( )-b-cuparenone
Mukund G. Kulkarni,* Saryu I. Davawala, Mahadev P. Shinde, Attrimuni P. Dhondge,
Ajit S. Borhade, Sanjay W. Chavhan and Dnyaneshwar D. Gaikwad
Department of Chemistry, University of Pune, Ganeshkhind, Pune 411 007, Maharashtra, India
Received 20 December 2005; revised 18 February 2006; accepted 2 March 2006
Abstract—A Wittig olefination–Claisen rearrangement strategy has been applied to achieve one of the shortest and efficient synthesis
of ( )-b-cuparenone.
Ó 2006 Elsevier Ltd. All rights reserved.
The essential oils of Thuja orientalis L.,1 Biota orientalis2
and Marchantia polymorpha3 have been a rich source of
sesquiterpenes of the cuparene family. All the members
characteristically have two contiguous quaternary cen-
ters in the cyclopentane ring, the construction of which
has always been a synthetic challenge.
chain intermediate5,7,10 having at least one of the quater-
nary centers. Using these diverse strategies several syn-
theses of a-cuparenone and b-cuparenone have been
reported. However, most of these syntheses either are
somewhat lengthy and/or result in a low overall yield.
We report herein (Scheme 1), one of the shortest and
O
O
CHO
CHO
ii
i
4
6
5
7
1
2
3
Several strategies have been developed for the syntheses
of various members of this family, such as a-cuparenone
1,4,5 b-cuparenone 26,7 and cuparene 38–10 in racemic
as well as in optically pure form. The methodologies
employed include, construction of the quaternary cen-
ter/s onto a cyclopentane ring4,6,8 which was effected
either by adding a methyl group to a cyclopentane deriv-
ative containing the aromatic ring or by adding an
appropriate p-tolyl moiety to a cyclopentane derivative.
A route involving the addition of an aromatic ring onto
an existing five-membered ring9 has also been devel-
oped. Alternatively, the synthesis of these compounds
was achieved through cyclopentannulation of an open
iii
iv
O
OH
v
2
8
Scheme 1. Reagents and conditions: (i) (a) MOMCl, PPh3, t-BuOÀK+,
t-BuOH, THF, 0 °C, 6 h, 77%; (b) 30% HCl, rt, 4 h, 90%; (ii) CH3I,
PPh3, t-BuOÀK+, BuOH, 0 °C, 6 h, 88%; (iii) Grubbs’ catalyst (first
generation), DCM, rt, 3 h, 96%; (iv) (a) 9-BBN, THF, rt, 1.5 h; (b) 30%
H2O2, 10 N NaOH, rt, 30 min, 85%; (v) PDC, DCM, 0 °C to rt, 2 h,
85%.
*
Corresponding author. Tel.: +91 020 2560 1225; fax: +91 020 2569
1728; e-mail addresses: mgkulkarni@chem.unipune.ernet.in; ochem@
chem.unipune.ernet.in
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.012

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M. G. Kulkarni et al. / Tetrahedron Letters 47 (2006) 3027–3029
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most efficient syntheses of ( )-b-cuparenone 2 to date
using simple starting materials.
The synthesis commenced with the 4-pentenal 411 which
has the required two contiguous quaternary centers,
properly disposed. A one-carbon homologation of this
unsaturated aldehyde 4 was achieved via Wittig olefin-
ation with methoxymethylenetriphenylphosphorane in
THF to yield the corresponding enol ether in 77% yield.
Acid hydrolysis of this enol ether resulted in the forma-
tion of the one carbon homologated 5-hexenal 5 in
nearly quantitative yield. Reaction of aldehyde 5 with
methylenetriphenylphosphorane in THF yielded the
Wittig olefination product 1,6-heptadiene product 6.
Ring closing metathesis of diene 6 using Grubbs’ cata-
lyst12 [PhCH@RuCl2(PCy3)2] furnished the substituted
cyclopentene 7 in 96% yield. Subjecting the cyclopentene
7 to a hydroboration–oxidation sequence using 9-BBN13
yielded b-cuparenol 8 in good yield. Finally, PDC oxida-
tion of the alcohol 8 afforded b-cuparenone 2 in good
yield. Thus, one of the shortest and most efficient syn-
thesis of b-cuparenone has been achieved in five steps.
Acknowledgements
The authors M.P.S., A.P.D., A.S.B., S.W.C. and
D.D.G. thank CSIR, New Delhi, for fellowships.
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