Tandem Allylboration-Prins Reaction for the Rapid Construction of Substituted Tetrahydropyrans: Application to the Total Synthesis of (-)-Clavosolide A

Abstract

Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three-component allylboration-Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (-)-clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation-borylation reaction to attach the cyclopropyl-containing side chain. Growing complexity: A highly efficient and diasteroselective three-component allylboration-Prins reaction serves to construct the highly functionalised THP-ring of (-)-clavosolide A from simple starting materials. An early stage diasteroselective glycosidation and a late stage lithiation-borylation are used to complete the synthesis of this complex natural product in just 13 steps from ethanol in 14 % overall yield.