Palladium-Catalyzed Dual Ligand-Enabled Alkylation of Silyl Enol Ether and Enamide under Irradiation: Scope, Mechanism, and Theoretical Elucidation of Hybrid Alkyl Pd(I)-Radical Species

• Published in: ACS catalysis Vol. 10; no. 2; pp. 1334 - 1343
• Main Authors: Zhao, Bin, Shang, Rui, Wang, Guang-Zu, Wang, Shaohong, Chen, Hui, Fu, Yao
• Format: Journal Article
• Language: English
• Published: American Chemical Society 17.01.2020
• Subjects: enamide; palladium; alkylation; silyl enol ether; hybrid alkyl Pd(I)-radical species
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.9b04699

We report herein that a palladium catalyst in combination with a dual phosphine ligand system catalyzes alkylation of silyl enol ether and enamide with a broad scope of tertiary, secondary, and primary alkyl bromides under mild irradiation conditions by blue light-emitting diodes. The reactions effectively deliver α-alkylated ketones and α-alkylated N-acyl ketimines, and it is difficult to prepare the latter by other methods in a stereoselective manner. The α-alkylated N-acyl ketimine products can be further subjected to chiral phosphoric acid-catalyzed asymmetric reduction with Hantzsch ester to deliver chiral N-acyl-protected α-arylated aliphatic amines in high enantioselectivity up to 99% ee, thus providing a method for facile synthesis of chiral α-arylated aliphatic amines, which are of importance in medicinal chemistry research. The N-acetyl ketimine product also reacted smoothly with various types of Grignard reagents to afford sterically bulky N-acetyl α-tertiary amines in high yields. Theoretical studies in combination with experimental investigation provide understanding of the reaction mechanism with respect to the dual ligand effect and the irradiation effect in the catalytic cycle. The reaction is suggested to proceed via a hybrid alkyl Pd­(I)-radical species generated by inner-sphere electron transfer of phosphine-coordinated Pd(0) species with alkyl bromide. This intriguing hybrid alkyl Pd­(I)-radical species is elucidated by theoretical calculation to be a triplet species coordinated by three phosphine atoms with a distorted tetrahedral geometry, and spin prohibition rather than metal-to-ligand charge transfer contributes to the kinetic stability of the hybrid alkyl Pd­(I)-radical species to impede alkyl recombination to generate Pd­(II) alkyl intermediate.