A novel and stereospecific synthesis of (+)-exo-brevicomin

Article abstract of DOI:10.1016/j.tetlet.2003.09.082

A novel and stereospecific synthesis of (+)-exo-brevicomin is disclosed. The key step of the reaction sequence employs the sulfinyl moiety as an intramolecular nucleophile to functionalize an alkene π-complexed to a bromonium ion.

Full text of DOI:10.1016/j.tetlet.2003.09.082

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8237–8239
A novel and stereospecific synthesis of (+)-exo-brevicominꢀ
Sadagopan Raghavan* and Suju C. Joseph
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 22 July 2003; revised 2 September 2003; accepted 11 September 2003
Abstract—A novel and stereospecific synthesis of (+)-exo-brevicomin is disclosed. The key step of the reaction sequence employs
the sulfinyl moiety as an intramolecular nucleophile to functionalize an alkene p-complexed to a bromonium ion.
© 2003 Elsevier Ltd. All rights reserved.
exo-Brevicomin1 1 is an aggregation pheromone pro-
duced by Dendroctonus brevicomis, the western pine
beetle, which is a principal pest in the timber regions on
the western coast of North America. The pheromone
attracts other beetles of the same species to the host tree
which is inoculated with a pathogenic fungus leading to
the tree’s death. exo-Brevicomin was first synthesized in
racemic form2 and since then several syntheses of the
racemic substance as well as the optically active isomers
have been reported,3 perhaps more as a test for the
efficacy and versatility of new synthetic strategies. In
spite of the large number of reported syntheses, they are
not satisfactory in terms of the simplicity of the process
and the enantiomeric and/or diastereomeric excess of the
products. The design of a highly successful strategy still
remains a synthetic challenge. We have been interested
in the regio- and stereoselective heterofunctionalization
of olefins by 1,2/1,3-asymmetric induction using the
sulfinyl moiety as an internal nucleophile.4 We illustrate
the potential of this methodology by the stereospecific
synthesis of (+)-exo-brevicomin using a straightforward
sequence of reactions. Our approach to (+)-1 is illustrated
retrosynthetically in Scheme 1.
We envisioned that 1 would be obtained from the diketal
2 by reduction followed by ketal exchange and that 2
would be derived from the diol 3 which in turn would
be derived from olefin 4.
The synthesis began with the allyl alcohol 45 which was
transformed into the bromohydrin
5 regio- and
stereospecifically.5 Treatment of 5 with dimethylcuprite
afforded diol 3 cleanly in 72% yield. Subjecting diol 3 to
treatment with 2,2-dimethoxypropane in the presence of
catalytic amounts of camphor-10-sulfonic acid afforded
the acetonide 6. Subjecting
6 to rearrangement
Scheme 1.
Keywords: exo-brevicomin; sulfinyl moiety; internal nucleophile.
ꢀ IICT Communication No. 030712.
* Corresponding author. E-mail: purush101@yahoo.com
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.082

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S. Ragha6an, S. C. Joseph / Tetrahedron Letters 44 (2003) 8237–8239
Scheme 2. Reaction conditions: (a) NBS, H2O, toluene, rt, 30 min, 81%; (b) Me2CuLi, THF, −78°C to rt, 2 h, 72%; (c) 2,2-DMP,
cat. CSA, acetone, rt, 1 h, 92%; (d) TFAA, Et3N, CH2Cl2, 0°C, 15 min, then aq. NaHCO3, 0°C–rt, 15 min, 64% overall yield;
(e) LiHMDS, THF, −78°C to rt, 3 h, 68%; (f) Pt/C, H2, EtOAc, 4 h, rt, 91%; (g) PTSA, CH2Cl2, rt, 88%.
under Pummerer reaction conditions6 with trifluoro-
acetic anhydride in the presence of Et3N afforded inter-
mediate 7 which without isolation was subjected to
hydrolysis by treatment with aq. saturated NaHCO3 to
yield the aldehyde 8. Condensation of 8 with the sul-
fone 97 using the modified Julia olefination conditions8
afforded the trans olefin 2 as the only isolated product.
Reduction of the double-bond by treatment with Pt/C
under an atmosphere of hydrogen in ethyl acetate as
the solvent yielded diketal 10 (Scheme 2).
Acknowledgements
S.R. is thankful to Dr. J. S. Yadav, Head, Org. Div. I,
Dr. K. V. Raghavan, Director, I. I. C. T, for constant
support and encouragement. S.C.J. is thankful to
CSIR, New Delhi for a fellowship. Financial assistance
from DST (New Delhi) is gratefully acknowledged. We
thank Dr. A. C. Kunwar for the NMR spectra and Dr.
Vairamani for the mass spectra.
Treatment of 10 with catalytic amounts of p-toluenesul-
fonic acid9 in dichloromethane as the solvent afforded
(+)-exo-brevicomin 1 with physical characteristics in
excellent agreement with those reported in the
literature.3
References
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using DIBAH/ZnCl2 (Eq. (1)).11 Following the same
sequence of reactions as detailed above, (−)-exo-brevi-
comin can be elaborated from 12.
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(1)
In summary, we have disclosed herein an efficient,
stereospecific synthesis of (+)-exo-brevicomin. The key
steps of the reaction sequence include diastereoselective
reduction of b-ketosulfoxide 11 to yield allyl alcohol 4
or 12 (>95% d.e.) and use of the sulfinyl moiety as the
internal nucleophile for the regio- and stereospecific
functionalization of the alkene.

S. Ragha6an, S. C. Joseph / Tetrahedron Letters 44 (2003) 8237–8239
8239
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10. 12: 1H NMR (200 MHz, CDCl3) l 7.55 (d, J=8.0 Hz,
2H), 7.32 (d, J=8.0 Hz, 2H), 5.83 (ddd, J=17.0, 11.0,