Nickel‐Catalyzed Asymmetric Transfer Hydrogenation of Hydrazones and Other Ketimines

Abstract

We report the use of nickel catalysts for the catalytic transfer hydrogenation of hydrazones and other ketimines with formic acid. Strongly donating bisphosphines must be used to support the catalysts. As in enzymatic catalysis, attractive weak interactions may be important for stereochemical control by the nickel/binapine catalyst.

Nickel‐Catalyzed N‐Alkylation of Acylhydrazines and Arylamines Using Alcohols and Enantioselective Examples

“…In comparison, as imilar catalyst, CyPF-tBu, was completely inactive,although it was known to effectively catalyze transfer hydrogenation of an N-benzohydrazone of acetophenone in 99 % ee,i nt he presence of formic acid. [27] Thus,w es uspect that this catalyst of CyPF-tBu has ap roblem in the dehydrogenation of 1a.F urthermore,o ther electron-rich diphosphines,including Me-DuPhos,Ph-BPE, and QuinoxP* were also catalytically inactive. [29] Acetic acid was anecessary additive to promote condensation of hydrazones under the catalytic conditions.W ithout it, the nickel/binapine catalyst afforded 11 a in less than 10 %yield.…”

“…In our previous studies in transfer hydrogenation of hydrazones using formic acid, [27] binapine was the optimal ligand. This parallelism with the borrowing hydrogen reaction of acylhydrazines herein (Scheme 3a)s upports the putative borrowing-hydrogen mechanism through the intermediacyof hydrazones.A dditionally,t he fact that the nickel-catalyzed amination proceeded well with aliphatic alcohols (Scheme 2a)a lso argues against an alternative pathway involving h 3 -benzylnickel species.…”

“…During our previous study of nickel-catalyzed asymmetric reductive amination of arylamines, [27] N-isopropylaniline was isolated in moderate yield, and was derived from the Nalkylation of isopropanol, the reaction solvent. Herein, we report nickel-catalyzed N-alkylation of both acylhydrazines and arylamines using alcohols,and additionally,anasymmetric process of acylhydrazines to produce chiral benzylamines.…”

Nickel‐Catalyzed Enantioselective Reductive Amination of Ketones with Both Arylamines and Benzhydrazide

“…Recently, Beller et al disclosed examples of reactions between aryl methyl ketones and aromatic amines under 50 bar of H 2 gas, using dual catalysis of an achiral iron catalyst (Knçlkers complex) and a chiral phosphate counterion. Our group has also reported nickel-catalyzed transfer hydrogenation of enamides, conjugated olefins, and hydrazones, [16] using formic acid as a safe and cheap source of hydrogen. [10] Reactions of aliphatic methyl ketones, however, only provided products in around 70 % ee.…”

“…[13] The Hamada and Chirik groups have separately disclosed nickel catalysts with chiral bisphosphine ligands for the asymmetric hydrogenation of ketones [14] and a,b-unsaturated esters, [15] but high pressure (33-100 bar) H 2 gas was needed. Our group has also reported nickel-catalyzed transfer hydrogenation of enamides, conjugated olefins, and hydrazones, [16] using formic acid as a safe and cheap source of hydrogen. [17] In this work, we successfully applied nickel catalysis to reductive amination of ketones with both arylamines and benzhydrazide.…”