Facile Synthesis of Housanes by an Unexpected Strategy
Yanyao Liu, Somanea Tranin, Yu‐Che Chang, Evan B. Piper, Thomas C. Fessard, Ryan Van Hoveln, Christophe Salomé, M. Kevin Brown
Abstract
Rigid bicyclic hydrocarbons have emerged as important building blocks in the drug discovery industry. Despite progress in this general area, bicyclo[2.1.0]pentanes (housanes) are an understudied class of molecules. Herein we report an unconventional synthesis of borylated housanes. Our method features a broad scope and high diastereoselectivities in the synthesis of versatile intermediates. The route involves a strain-release diboration of bicyclo[1.1.0]butane and intramolecular deborylative alkylation. The versatility of the bridgehead boronic ester was demonstrated in several functionalizations. Lastly, the mechanism of the reaction was investigated, and an unusual stereospecific and diastereoselective ring expansion was uncovered.