Non-felkin diastereoselectivity in aldol couplings of thiopyran-based polypropionate synthons

Abstract

Polypropionates represent a large family of natural products and several strategies have been developed for their synthesis. The aldol reaction is one of the most important tools for the construction of polypropionate natural products. The Ward group has developed an approach to polypropionate natural products based on sequential aldol reactions of thiopyran building blocks. The Thiopyran Route to Polypropionates (TR2P) involves the stepwise aldol reactions of 15 and 16 to rapidly access stereochemically complex tetrapropionate and hexapropionate synthons in a few steps. The current work describes the effort to prepare enantioenriched 17-AA and/or 17-SA through chiral transition metal based Lewis acids (176) and chiral organocatalysts (48, 179) with chelating Lewis acids. The preparation of non-Felkin tetrapropionate and hexapropionate synthons through the use of a weak base in conjunction with a Lewis acid was developed.