Copper-Catalyzed Aliphatic C–H Amination with an Amidine Moiety

Abstract

A method for amination of aliphatic C-H bonds of N-alkylamidines is described that utilizes Cu(OAc)(2) as the catalyst in the presence of PhI(OAc)(2) and K(3)PO(4). The resulting products, dihydroimidazoles and tetrahydropyrimidines, could be converted into the corresponding diamines by hydride reduction.

Copper‐Catalyzed Intramolecular Oxidative Amination of Unactivated Internal Alkenes

“…For similar reasons, a copper‐catalyzed oxidative amination of unactivated internal alkenes has yet to be reported. Drawing inspiration from both the copper‐catalyzed radical C−H amination reactions that Chemler and Chiba developed and our amidyl radical cyclization reactions, we decided to explore a copper‐catalyzed oxidative amination reaction that is mechanistically different from the palladium‐catalyzed variant and uses an amidyl radical cyclization to form the key C−N bond. Herein, we report the successful development of such an intramolecular oxidative amination reaction using a cheap copper salt, copper(II) 2‐ethylhexanoate [Cu(eh) 2 ], as the catalyst and Dess–Martin periodinane (DMP) as the oxidant (Scheme c).…”

“…A plausible mechanism of the oxidative amination reaction is proposed in Scheme . The process begins with the oxidation of 1 with the copper catalyst and DMP to give the radical cation A , or alternatively the N−Cu III species B . Both intermediates ( A or B ) can convert to the key amidyl radical C , either through deprotonation (as in A ) or homolytic cleavage of the N−Cu III bond (as in B ) .…”

Copper‐Catalyzed Site‐Selective Intramolecular Amidation of Unactivated C(sp3)H Bonds

“…[7] Inspired by recent reports on the palladium-catalyzed aminoquinoline-directed intramolecular amidation of unactivated C(sp 3 ) À H bonds, we report herein the coppercatalyzed bidentate-ligand-directed intramolecular amidation of sp 3 -carbon atoms. [11] Our investigation began with the oxidative cyclization of N-(quinolin-8-yl)pivalamide (1 a) using catalytic Cu(OAc) 2 in the presence of 1.5 equivalents of KHCO 3 as the base and 1.2 equivalents of benzoquinone (BQ) as the oxidant at 160 8C (Table 1). [9] It should also be mentioned that although copper-catalyzed coupling reactions through an sp 2 or sp 3 CÀH activation process have been extensively studied, [10] there are only few examples involving direct functionalization of unactivated sp 3 -carbon atoms.…”

Cu‐Catalyzed Heterocycle Synthesis

“…They also realized the Cu(OAC) 2 -catalyzed aminoacetoxylation of Nalkenylamidines using PhI(OAc) 2 as an oxygen source for synthesis of 4-acetoxymethyl-4,5-dihydroimidazoles [84] (Scheme 8.46). The aliphatic C-H bonds of N-alkylamidines also could be activated to various dihydroimidazoles and tetrahydropyrimidines with Cu(OAc) 2 /PhI(OAc) 2 /K 3 PO 4 catalytic system [85] (Scheme 8.46). However, the drawback of this reaction is the need of a stoichiometric PhI(OAc) 2 to maintain the catalytic turnover and it needs two-electron oxidation to realize the aliphatic C-H amination.…”