Iterative synthesis of stereodefined polyacetals and their domino-Coates–Claisen rearrangement

Abstract

We report a fully stereocontrolled synthesis of previously unknown unsaturated polyacetals through an iteration of two steps: (1) Pd-catalyzed hydroalkoxylation of alkoxyallenes; and (2) base-mediated isomerization of propargyl ethers into alkoxyallenes. Site- and stereoselective alkene isomerization of the capping allyl group initiates a domino-Coates–Claisen rearrangement, which completely rearranges the iteratively assembled backbone with the stereochemistry of the newly formed stereocentres controlled by the configuration of the acetal centres in the starting materials. The resulting products feature multiple stereocentres in a 1,3-relationship, which map onto a broad range of bioactive natural products, including deoxypropionates.