I. Asymmetric conjugate addition of allylstannanes. II. Synthetic approaches to the stereotriad of hydroxydictyolactone.

摘要

A major objective in the area of natural product synthesis deals with the chemist's ability to impart stereoselectivity in carbon-carbon bond-forming reactions. The utility of 1,3-oxazolidinones as chiral auxiliaries has been well-documented for this purpose. Coupled with the use of Lewis acids to enhance electrophilicity, developments of stereoselective 1,3-dipolar cycloaddition, Diels-Alder, ene and organocopper conjugate addition reactions have been enabled by the use of nonracemic alpha,beta-unsaturated N-enoyl-1,3-oxazolidinones. Recent efforts in the Williams group have illustrated the use of Yamamoto organocopper reagents for asymmetric conjugate additions directed toward several natural product syntheses. More recently, this reaction manifold has been generalized for the efficient preparation of syn- and anti-1,3- and 1,2-dimethyl arrays. One area which has received relatively little attention is the 1,4-conjugate addition reactions of allylstannanes.;Using either zirconium(IV) chloride or scandium(III) triflate, the reactions of allylstannanes with nonracemic alpha,beta-unsaturated N-enoyl-1,3-oxazolidinones were found to proceed with high diastereoselectivity and in good yield. Surprisingly, the stereochemical outcome of these reactions was opposite to that which was expected based on the widely accepted model for the role played by the chiral auxiliary. The methodology described herein offers significant flexibility for the coupling of larger, more complex fragments in comparison to related organocopper conjugate addition reactions. Additionally, terminally substituted allylstannanes allow for the efficient preparation of 2 stereocenters in a single reaction.;During the course of these methodology studies, a useful model for proving the stereochemistry of products of these and other conjugate addition reactions has emerged. Studies directed toward elucidating the mechanism of the reversal in stereoselectivity offer some insight into the qualitative nature of interactions which direct facial bias in this system. Finally, the application of this methodology toward the synthesis of the novel xenicane natural product, hydroxydictyolactone will be described. The synthetic results achieved demonstrate the generality and flexibility of this reaction for the purpose of natural product synthesis.