Copper-Catalyzed Selective 1,4-Allylboration/Silylcinnamylation of 2-Trifluoromethyl-1,3-Enynes for Synthesis of Multifunctional Tetrasubstituted Allenes

Abstract

A copper-catalyzed three-component 1,4-allylboration/silylcinnamylation (simultaneous installation of silyl and cinnamyl groups) of 2-trifluoromethyl-1,3-enynes with allyl halogen and B2pin2 or BpinSiMe2Ph is reported. This method provides a direct and regioselective route to tetrasubstituted allenes bearing a trifluoromethyl group, boryl/silyl and allyl/cinnamyl units in a single step. This transformation proceeds with exclusive chemo- and regi-oselectivity, tolerating an extensive library of aryl, heteroaryl, alkenyl and functionalized substrates, including complex natural product-derived skeletons. Practical synthetic utility is demonstrated via gram-scale preparation and diversified downstream derivatization: conjugated dienes, cyclic frameworks, diverse boron derivatives, among others. Mechanistic investigations validate the trifluoromethyl substituent acts as an indispensable di-recting group, which enables selective migratory insertion of borylcopper or silylcopper species into the alkene C=C bond rather than the alkyne C≡C triple bond; control experiments exclude any radical-mediated catalytic cy-cle. This protocol establishes a straightforward platform for assembling structurally diverse allyl-substituted allene building blocks for drug discovery and synthetic methodology.