Divergent Kinetic Control of Classical versus Ozonolytic Lactonization:Mechanism-Based Diastereoselection

摘要

As part of a program with the ultimate goal of a synthesis of peloruside A,we have developed selective and complementary lactonization reactions of substrates 1 and 2(Scheme 1).Each contains diastereotopic terminal R groups that can be differentiated by engaging the hydroxy group on the chirotopic but nonstereo-genic2 C5(peloruside numbering,throughout).This would lead to the 3,5-trans-monolactone ester 3-trans [from cyclization to pro-R C1] or to the 5,7-cis-monolactone ester 3-cis [to pro-5 C9].As we report below,diester 1 gives lactone 3-cis;diene 2 gives 3-trans.This unexpected complementarity originates from the mechanistically orthogonal pathways that govern the classical(acid-or base-catalyzed)cyclization of 1 versus the ozonolytic lactonization of 2.