Ru-Catalyzed Asymmetric Reductive Amination of Aryl-Trifluoromethyl Ketones for Synthesis of Primary α-(Trifluoromethyl)arylmethylamines

The ruthenium-catalyzed asymmetric reductive aminationof aryl-trifluoromethylketones affording high value primary & alpha;-(trifluoromethyl)aryl-methylaminesusing cheap NH4OAc as the nitrogen source and H-2 as the reductant is reported. This user-friendly and simple catalyticmethod tolerates various aromatic functions with electron-withdrawingor -donating substituents at the para- or meta-positions and as wellchallenging heteroaromatic functions, yielding primary & alpha;-(trifluoromethyl)aryl-methylamineswith excellent chemoselectivities, enantioselectivities, and usefulyields (80-97% ee, 51-92% isolated yields). Finally,scalable and concise synthesis of key drug intermediates using thismethodology is presented.

Automated summary

A user-friendly and simple catalytic method for the synthesis of high value primary &α;-(trifluoromethyl)aryl-methylamines via ruthenium-catalyzed asymmetric reductive amination of aryl-trifluoromethylketones using cheap NH4OAc as the nitrogen source and H-2 as the reductant is reported. This method tolerates various aromatic functions with electron-withdrawing or -donating substituents, as well as challenging heteroaromatic functions, leading to the formation of primary &α;-(trifluoromethyl)aryl-methylamines with excellent chemoselectivities, enantioselectivities, and useful yields (80-97% ee, 51-92% isolated yields).