Remarkable Differences in Reactivity between Benzothiazoline and Hantzsch Ester as a Hydrogen Donor in Chiral Phosphoric Acid Catalyzed Asymmetric Reductive Amination of Ketones

Described herein are differences in behavior between a Hantzsch ester and a benzothiazoline as hydrogen donors in the chiral phosphoric acid catalyzed asymmetric reductive amination of ketones with p-anisidine. The asymmetric reductive amination of ketones with a Hantzsch ester as a hydrogen donor provided the corresponding chiral amines exclusively, regardless of the structures of the ketones, whereas a similar transformation with a benzothiazoline provided chiral amines and p-methoxyphenyl-protected primary amines in variable yields, depending on the structures of both the ketones and benzothiazolines. Because a benzothiazoline has an N,S-acetal moiety that is vulnerable to p-anisidine, the primary amine can be formed through transimination of the benzothiazoline with p-anisidine followed by reduction of the resulting aldimine with remaining benzothiazoline.