[3 + 2] Annulation of Allylic Silanes in Acyclic Stereocontrol: Total Synthesis of (9S)-Dihydroerythronolide A

Abstract

The [3 + 2] annulation reactions of allylic silanes can be utilized to achieve acyclic stereocontrol. This method was employed as a key step in an enantioselective total synthesis of (9S)-dihydroerythronolide A. The key annulation reaction served to establish most of the stereochemistry of the target, including the two tetrasubstituted carbon stereocenters. The symmetry of the target molecule allowed it to be disconnected into two equally sized fragments, both of which were generated from the same annulation reaction. The two fragments were coupled using a tin(II)-mediated chelation-controlled aldol reaction of an alpha-benzyloxy ethyl ketone. This convergent total synthesis of (9S)-dihydroerythronolide A was accomplished with the longest linear sequence of 29 steps and in 5.4% overall yield.