Iridium-Catalyzed Hydrogenation of Enamines to Access Chiral Tertiary Amines

Abstract

Significance: Prior to this work several asymmetric transition-metal-catalyzed hydrogenation reactions using Ti, Rh, and Ir as metal sources have been investigated, providing chiral tertiary amines. In the present study, the authors utilized an iridium complex derived form N,P ligand L1. This system provides modest to good enantioselectivities for the hydrogenation of various acetophenone derived enamines.Comment: While one of the earliest examples of asymmetric enamine hydrogenation utilizing a titanocene catalyst was reported in 1994 by Buchwald and co-workers (J. Am. Chem. Soc. 1994, 116, 5985), synthesis of chiral tertiary amines still remains a challenging endeavor. The authors' iridium system gives relatively good selectivities for various non-cyclic amines; however, use of cyclic amines lead to a significant diminution of the ee value. A clearer understanding and resolution of this problem could lead to a more tolerant catalyst system. N PPh 2 O N L 1 R 1 N R 3 R 2 + H 2 R 1 N R 3 R 2 [L1Ir(cod)] + [BAr F ] -(0.5 mol%) CH 2 Cl 2 , r.t., 6 h (50 bar) R 1 = Ar R 2 ,R 3 = aliphatic, cyclic, Ar * 66-99% yield 20-87% ee 9 examples S e l e c t e d e x a m p l e s : NEt 2 N N N 99% yield 84% ee 99% yield 79% ee 66% yield 33% ee (R) 99% yield 20% ee SYNFACTS Contributors: