Enantioselective Hydrogenation of N−H Imines

Abstract

N-H ketoimines 3a-3v are readily prepared in high yield via organometallic addition to nitriles and isolated as corresponding bench-stable hydrochloride salts. Homogeneous asymmetric hydrogenation of unprotected N-H ketoimines 3a-3v using Ir-(S,S)-f-binaphane as catalyst provides chiral amines 4a-4v in 90-95% yield with enantioselectivities up to 95% ee.

Sequential Reductive Amination‐Hydrogenolysis: A One‐Pot Synthesis of Challenging Chiral Primary Amines

“…[15b] Finally, other methods for ortho-substituted phenylethylamine synthesis are known but less frequently reported on, [16] of these Zhangs two-step method entails the enantioselective reduction of unactivated imines which could be considered as forward looking.…”

Asymmetric Hydrogenation of Imines

“…The rigid binaphthyl moiety and the electron-rich ferrocene backbone are helpful in achieving high enantioselectivities, and the larger P-M-P bite angle could contribute to better accommodation of more sterically hindered imine substrates. These ferrocenebased ligands were later found to be outstandingly efficient for the asymmetric hydrogenation of N-H imines [43], HCl salts of unprotected β-enamine esters [44], and different cyclic imines [45][46][47][48]. In another approach to probe the mechanism of the high efficacy of Ir complexes of diphosphines and the need for additives such as I 2 , Dervisi et al synthesized the diphosphine ligand ddppm from D-isomannide and its Ir complex, and displayed good to high enantioselectivities in the hydrogenation of N-arylimines using cationic [Ir(COD)(ddppm)]PF 6 catalyst (up to 94% ee, Scheme 15) [49].…”

Tertiary Carbinamine Synthesis by Rhodium‐Catalyzed [3+2] Annulation of N‐Unsubstituted Aromatic Ketimines and Alkynes

“…[6] For the current study, we initially focused our attention on relatively less studied, N-unsubstituted diaryl ketimine substrates with the following considerations: First, diaryl ketimines can be prepared conveniently by Grignard reactions by using readily available aryl halides and aryl cyanides. [13] This modular synthetic approach would also allow us to explore reactivity dependence on various aromatic substituents (see below). Second, [3 + 2] annulations with N-unsubstituted diaryl ketimines would be operationally simple and without the need for additional deprotection procedures.…”