A general enantioselective route to the chamigrene natural product family

Type
Article

Authors
White, David E.
Stewart, Ian C.
Seashore-Ludlow, Brinton A.
Grubbs, Robert H.
Stoltz, Brian M.

KAUST Grant Number
KUS-11-006-02

Date
2010-06

Abstract
Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.

Citation
White DE, Stewart IC, Seashore-Ludlow BA, Grubbs RH, Stoltz BM (2010) A general enantioselective route to the chamigrene natural product family. Tetrahedron 66: 4668–4686. Available: http://dx.doi.org/10.1016/j.tet.2010.04.128.

Acknowledgements
This publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). Additionally, the authors wish to thank the NIH-NIGMS (R01 GM080269-01, postdoctoral fellowships to D.E.W. and I.C.S.), Abbott, Amgen, Bristol-Myers Squibb, Merck, and Caltech for generous funding; Materia, Inc. for their kind donation of catalyst 49 used in these studies; Professors Mercedes Cueto and Karen L. Erickson for their kind donation of natural samples of elatol (1); Professor Adusumilli Srikrishna for copies of 1H and 13C NMR spectra of synthetic (+/-)-laurencenone C ((+/-)-8) and (+/-)-alpha-chamigrene ((+/-)-5): and Professor Peter B. Dervan and David M. Chenoweth for use of their HPLC. Finally, B.M.S. thanks all of his current and former co-workers and colleagues who have made working at Caltech over the past 10 years such an enjoyable experience. As evidenced by the collaborative nature of this project, the spectacular environment at Caltech is one-of-a-kind and second-to-none.

Publisher
Elsevier BV

Journal
Tetrahedron

DOI
10.1016/j.tet.2010.04.128

PubMed ID
20798895

PubMed Central ID
PMC2925317

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