Highly Enantioselective Direct Asymmetric Reductive Amination of 2-Acetyl-6-Substituted Pyridines

A highly direct asymmetric reductive amination of a variety of ketone substrates, including 2-acetyl-6-substituted pyridines, beta-keto esters, beta-keto amides, and 1-(6-methylpyridin-2yl)propan-2-one, has been disclosed for the first time (94.6% to >99.9% ee). With ammonium trifluoroacetate as the nitrogen source, various chiral corresponding primary amines were prepared in excellent enantioselectivity and conversion in the presence of a commercially available and inexpensive chiral catalyst, Ru(OAc)(2){(S)-binap}, under 0.8 MPa of hydrogen gas pressure.

Automated summary

This study presents a highly efficient direct asymmetric reductive amination, successfully achieving reactions on various ketone substrates for the first time, including 2-acetyl-6-substituted pyridines. Excellent enantioselectivity and conversion rates were achieved through the use of commercially available and inexpensive Ru(OAc)(2){(S)-binap} catalyst under 0.8 MPa of hydrogen gas pressure.