Modular Synthesis of Furans with up to Four Different Substituents by a trans-Carboboration Strategy

Abstract

Propargyl alcohols, on treatment with MHMDS (M=Na, K), B2(pin)2, an acid chloride and a palladium/copper co-catalyst system, undergo a reaction cascade comprised of trans-diboration, regioselective acylation, cyclization and dehydration to give trisubstituted furylboronic acid pinacol ester derivatives in good yields; subsequent Suzuki coupling allows a fourth substituent of choice to be introduced and hence tetrasubstituted (arylated) furans to be formed. In terms of modularity, the method seems unrivaled, not least because each product can be attained by two orthogonal but convergent ways (“diagonal split”). This asset is illustrated by the “serial” formation of a “library” of all twelve possible furan isomers that result from systematic permutation of four different substituents about the heterocyclic core.