Prev. Article Next Article Table of Contents

Article

Highly Selective Diels-Alder Reactions of Directly Connected Enyne Dienophiles

Supporting Info

Mingji Dai,^† David Sarlah,^† Maolin Yu,^† Samuel J. Danishefsky,*^†^‡ Gavin O. Jones,^§ and K. N. Houk*^§;

Contribution from the Department of Chemistry, Columbia University, Havemeyer Hall, New York, New York 10027, Laboratory for Bioorganic Chemistry, The Sloan-Kettering Institute for Cancer Research Center,1275 York Avenue, Room RRL 1301, New York, New York 10021, and Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569

J. Am. Chem. Soc., 2007, 129 (3), pp 645–657

DOI: 10.1021/ja065762u

Publication Date (Web): December 29, 2006

†

Columbia University.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

‡

The Sloan-Kettering Institute for Cancer Research Center.

University of California.

, s-danishefsky@ski.mskcc.org, ; , houk@chem.ucla.edu

Abstract

The paper describes the course of cycloadditions of Diels−Alder dienophiles containing linked enyne sites, each substituted with activating groups. Consistently, it was found that in the enyne cases the Diels−Alder reaction occurred specifically at the acetylenic center. Furthermore, it was found that the regiochemical sense of the cycloaddition was apparently determined by the remote activating group bound to the olefinic site. This remote acrylyl group totally dominated the course of the cycloaddition, relative to the activating group bound directly on the acetylene site. Explanations for these findings at the computational level are provided. The computations also rationalize the strong preference for cycloaddition to occur at the acetylene linkage and encompass the otherwise surprising regiochemical dominance by the remote ester on the olefinic site. The high selectivities available through such reactions provide important new opportunities in the synthesis of orsenillate type substructures that are found in a variety of natural products of contemporary interest.

View: Full Text HTML | Hi-Res PDF