Ligand-Enabled Palladium(II)-Catalyzed γ-C(sp³)–H Arylation of Primary Aliphatic Amines

Abstract

The Pd(II)/sulfoxide-2-hydroxypyridine catalytic system shows promising activity in C−H activation chemistry. In this study, we showcase how this catalytic system solves the problem of native primary amine-directed γ-C(sp 3 )−H arylation. Primary amines with different complexities are compatible with the established methodology, and the range of applicable substrates can be expanded to include pyridine, oxime ether, and pyridine N-oxide.

Site-selective C(sp3)–H functionalization of primary aliphatic amines

“…More recently, Jiao and co-workers developed a catalytic system by combining a palladium( ii ) catalyst with sulfoxide-2-hydroxypyridine as a ligand for the γ-C(sp 3 )–H arylation of primary aliphatic amines 53 (Scheme 22). 56 The reaction exhibited a broad substrate scope with respect to both free amines and aryl iodides. A variety of γ-arylamines 54 could be obtained in good yields.…”

Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)‐Catalyzed Enantioselective C(sp3)−H Functionalization

“…Recently, we developed sulfoxide-2-hydroxypyr-idine (SOHP) ligands, [10] showcasing remarkable efficiency in the enantioselective C(sp 3 )À H arylation of aliphatic tertiary amides [11] and primary amines. [12] In these reactions, elucidating the reaction mechanism is crucial for the development of efficient and selective catalytic systems through rational design. [3a] In principle, the whole transformation can be divided into two stages: the CÀ H activation stage, where the activation of CÀ H bonds occurs to form a palladacycle intermediate, and the functionalization stage, where the palladacycle reacts with a reagent to introduce the desired functional group.…”

“…Previously, we accomplished the enantioselective CÀ H functionalization of aliphatic tertiary amides [11] and primary amines [12] using the Pd(II)/SOHP catalytic system, which implied that the chiral SOHP ligand has a good potential for inducing chirality in palladacycle formation. Due to the observation that SOHP ligands exhibited good coordination ability to Pd(II), we hoped to attempt the isolation of…”

Directed C(sp3)-H Arylation of Free α-Aminophosphonates: Dual Models Exploration via Palladium Catalysis

“…Furthermore, the free amino group itself works in synergy with palladium to accomplish C­(sp 3 )-H functionalization of aliphatic amine and amino acid side chains . In this strategy, Gaunt, Yu, Li, and Jiao achieved a series of breakthroughs in the C–H bond activation of aliphatic amines through ligand modulation . In addition, the C–H arylation, acetoxylation of amines, amino acid esters, and peptides could also be achieved by modulating the coordination ability of free amino groups through protonation strategies, reported by Shi, Bannister, and Yao .…”