Copper-Catalyzed Cyclization of 2-Alkynylanilines to Give 2-Haloalkoxy-3-alkyl(aryl)quinolines

Abstract

Herein we describe a method to produce 2-haloalkoxy-3-substituted quinolines via the cyclization of 2-alkynylanilines with TMSCF3 and THF. This synthetic method uses inexpensive and easy-to-handle TMSCF3 and employs a commercially available CuI catalyst to transform a broad range of 2-alkynylanilines into versatile 2-difluoromethoxy-3-substituted quinolines and 2-iodoalkoxy-3-substituted quinolines with excellent chemoselectivity.

C–F bond functionalizations via fluorinated carbenes

“…Meanwhile, Qiu's group found that TMSCF 3 could be employed as a C1 source to undergo cyclization with 2-alkynylanilines and THF to produce 2-haloalkoxy-3-substituted quinolines with high chemoselectivity in the presence of a Cu (I) catalyst (Scheme 25b). 79 In 2023, Song and co-workers found that bromodifluoroacetate, as a useful precursor of difluorocarbene, underwent twofold C-F bond cleavage and insertion into the N-N bond of 2H-indazoles to assemble multifunctional quinazolin-4(3H)ones through a difluoro-ylide intermediate (Scheme 26). 80 The newly developed methods are further extended to modify bioactive molecules and natural products containing 2H-indazoles, which can deliver ring expansion products in moderate to good yields (76a-76e, 63%-88%).…”

“…Meanwhile, Qiu's group found that TMSCF 3 could be employed as a C 1 source to undergo cyclization with 2-alkynylanilines and THF to produce 2-haloalkoxy-3-substituted quinolines with high chemoselectivity in the presence of a Cu( i ) catalyst (Scheme 25b). 79…”