Organocatalytic Remote‐Controlled Enantioselective 1,10‐Additions of In Situ Generated Alkynyl 2,4′‐Biphenyl Quinone Methides

Abstract

The strategic incorporation of auxiliary groups has recently established α‐functionalized alcohols as versatile electrophilic alkylation reagents, enabling remotely controlled conjugate additions. Strikingly, while quinone methide chemistry has been extensively developed, their extended analogues—featuring spatially separated carbonyl and methide units across biphenyl systems—remain unexplored. Building on the prior work with alkynyl 4,4′‐biphenyl quinone methides, an organocatalytic remotely controlled enantioselective 1,10‐additions of in situ‐generated alkynyl 2,4′‐biphenyl quinone methides from α‐[4‐(2‐ hydroxyphenyl)phenyl]propargyl alcohols with 3‐arylindoles and indole‐2‐carboxylates is reported, affording a broad scope of enantioenriched 3H‐pyrrolo[1,2‐a]indoles and axially chiral tetrasubstituted allenes, respectively. Combined with control experiments, density functional theory calculations elucidate the reaction mechanism, revealing that the dehydration of α‐functionalized alcohols to generate 2,4′‐biphenyl quinone methides constitutes the rate‐limiting step, while enantioselectivity arises from the nucleophilic addition of alkynyl biphenyl quinone methides. Notably, beyond proving 2,4′‐biphenyl quinone methides as competent intermediates, this work breaks new ground by demonstrating their participation in previously unreported stereoselective 1,10‐additions.