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

Abstract

The intramolecular dehydrogenative amidation of aliphatic amides, directed by a bidentate ligand, was developed using a copper‐catalyzed sp3 CH bond functionalization process. The reaction favors predominantly the CH bonds of β‐methyl groups over the unactivated methylene CH bonds. Moreover, a preference for activating sp3 CH bonds of β‐methyl groups, via a five‐membered ring intermediate, over the aromatic sp2 CH bonds was also observed in the cyclometalation step. Additionally, sp3 CH bonds of unactivated secondary sp3 CH bonds could be functionalized by favoring the ring carbon atoms over the linear carbon atoms.

Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons

“…Synthesis of lactams via transition metal-catalysed C–H functionalization is of current research interest because of the biological importance of these molecules 43 44 . In the past two years, Pd-, Cu- or Ni-catalysed process for the formation of β- or γ-lactams has been achieved 45 46 47 48 49 50 51 . However, all of these approaches suffer from their own limitations on the substrate scope.…”

“…Noticeably, the replacement of the quinolyl group with 5-methoxyquinolyl group had no apparent effect on the reaction ( 2c ). Moreover, the removability of 5-methoxyquinolyl moiety of β- or γ-lactams has been well documented 45 48 49 50 51 .…”

Copper‐Catalyzed Oxidative C(sp3)−H/N−H Cross‐Coupling of Hydrocarbons with P(O)−NH Compounds: the Accelerating Effect Induced by Carboxylic Acid Coproduct

“…Reactions of copper‐chelation system can be performed even at room temperature ,,. The intramolecular dehydrogenative amidation protocol have been well established by researchers such as Shi, Kanai, Ge,, Shi, and Bedford (Scheme c). In contrast, intermolecular processes are rarely reported.…”

Rhodium(III)‐Catalyzed Activation of CH Bonds and Subsequent Intermolecular Amidation at Room Temperature

“…[6][7][8] Despite significant advantages,s uch as high selectivity and atom efficiency, most of the precedented examples have been restricted to C sp 3 ÀHa ctivation/intramolecular amination, [9] and intermolecular amination was developed initially. [6][7][8] Despite significant advantages,s uch as high selectivity and atom efficiency, most of the precedented examples have been restricted to C sp 3 ÀHa ctivation/intramolecular amination, [9] and intermolecular amination was developed initially.…”

“…Recently,t he approach toward direct C sp 3 À Ha mination involving aC À Ha ctivation process has attracted much attention. [6][7][8] Despite significant advantages,s uch as high selectivity and atom efficiency, most of the precedented examples have been restricted to C sp 3 ÀHa ctivation/intramolecular amination, [9] and intermolecular amination was developed initially. [10] Palladium has been established to enable unreactive C sp 3 À Hb ond activation/intermolecular amination.…”