Total Synthesis of (-)-Sarain A

J. Am. Chem. Soc., 129 (39), 11987 -12002, 2007. 10.1021/ja074300t S0002-7863(07)04300-4
Web Release Date: September 12, 2007

Total Synthesis of (-)-Sarain A

Michael H. Becker,¹^a Peter Chua,¹^b Robert Downham,¹^c Christopher J. Douglas,¹^d Neil K. Garg,¹^e Sheldon Hiebert,¹^f Stefan Jaroch,¹^g Richard T. Matsuoka,¹^h Joy A. Middleton,¹ⁱ Fay W. Ng,¹^j and Larry E. Overman*

Contribution from the Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025

leoverma@uci.edu

Received June 13, 2007

Abstract:

This article describes the details of our synthetic studies toward the complex marine alkaloid sarain A. Various strategies were conceived, setbacks encountered, and solutions developed, ultimately leading to a successful enantioselective total synthesis. Our route to (-)-sarain A features a number of key steps, including an asymmetric Michael addition to install the C4'-C3'-C7' stereotriad, an enoxysilane-N-sulfonyliminium ion cyclization to set the C3 quaternary carbon stereocenter, and assemble the diazatricycloundecane core, a ring-closing metathesis to construct the 13-membered ring, an intramolecular Stille coupling to fashion the unsaturated 14-membered macrocycle, and a late-stage installation of the tertiary amine-aldehyde proximity interaction.

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