Studies toward the total synthesis of (+)-neopeltolide using N-heterocyclic carbene-catalyzed oxo-acyloxylation/reductive oxa-Michael addition strategy

This article describes a concise synthesis of two important fragments (tetrahydropyran [THP] and ketone moieties) of the cytotoxic macrolide (+)-neopeltolide in 10 long linear steps in enantiomerically pure form. Asymmetric Keck allylation to install the required C11 and C13 stereocenters, N-heterocyclic carbene (NHC)-catalyzed oxoacyloxylation to functionalize alkenes, and reductive oxa-Michael addition to construct 2,6-difunctionalized THP unit intramolecularly are the important steps in synthetic efforts. Finally, Keck asymmetric allylation and Lewis acid-catalyzed diastereoselective allylation of the aldehyde were sequentially employed to establish the stereocenters at C11 and C13 positions, respectively.

Automated summary

This article describes a concise synthesis of two important fragments (tetrahydropyran [THP] and ketone moieties) of the cytotoxic macrolide (+)-neopeltolide in 10 long linear steps in enantiomerically pure form. Asymmetric Keck allylation, N-heterocyclic carbene (NHC)-catalyzed oxoacyloxylation, and reductive oxa-Michael addition are the key steps in the synthetic efforts. The stereocenters at C11 and C13 positions are established through Keck asymmetric allylation and Lewis acid-catalyzed diastereoselective allylation, respectively.