Copper(I)-Catalyzed Substitution Reactions of Propargylic Amines: Importance of C(sp)−C(sp3) Bond Cleavage in Generation of Iminium Intermediates

摘要

Amines are not suitable leaving groups for organic synthesis. Inngeneral, C-N bond activation is carried out by converting aminesninto ammonium and iminium ions.1 A few examples using aminesnas leaving groups include nucleophilic substitution reactions ofnhighly electron-deficient aromatic compounds,2 palladium-catalyzedncarbonylation,3,4 deprotection of N-allylamines,5 and palladium- andnruthenium-catalyzed amine exchange reactions.6,7 In particular,ndirect C-H activation to generate iminium intermediates in aminenexchange reactions was first reported by Murahashi and co-workers6nand has become one of the most important strategies for relatedntransformations.8 Li and co-workers developed the copper-catalyzedncross-dehydrogenative coupling (CDC)9 of tertiary amines withnterminal alkynes,10 active methylenes, and nitromethane (eq 1).11nWe have developed a palladium-catalyzed hydride transfer reactionnfor the synthesis of allenes 3 via iminium complex 2 (eq 2, pathna).12,13 In this paper, we report the copper-catalyzed substitutionnreaction of propargylic amines. In this transformation, thenC(sp)-C(sp3) bond cleavage step is essential for generating coppernacetylides and iminium intermediates 4, which undergo fragmentnexchange with additional aldehydes, amines, and alkynes to give 5n(eq 2, path b).