Stereoselective metal-free catalytic synthesis of chiral trifluoromethyl aryl and alkyl amines

Abstract

The enantioselective organocatalytic reduction of trifluoromethyl aryl and alkyl ketoimines afforded the corresponding fluorinated amines with high chemical and stereochemical efficiency. The Lewis base catalyzed reaction with trichlorosilane led to chiral products with a trifluoromethyl group directly linked to the newly generated stereocenter typically in >90% yield and up to 98% e.e.Organofluorine compounds find applications in several fields of scientific research, like pharmaceuticals, agrochemicals and veterinary, but also in materials science.

Dynamic Kinetic Resolution in Enantioselective Reductive Amination ofα-Branched Aldehydes by Lewis Base Organocatalyzed Hydrosilylation

“…al. have used a chiral 4‐chloro‐picolinamide in hydrosilylation of various ketimines and found it excellent not only in stereoselectivity but also in chemical activity –. Herein the same effect was observed in our research.…”

Cinchona‐Derived Picolinamides: Effective Organocatalysts for Stereoselective Imine Hydrosilylation

“…and the catalyst (10 mol-%) in dry CH 2 Cl 2 (Scheme 1; R 1 = H, R 2 = Ph, R 3 = Me). [11] In all cases, excellent yields and high enantioselectivities ranging from 77 to 90 % ee were obtained (Table 1). Whereas epi-quinine derivatives 2 and 3 catalyzed the reaction generally with 80 % ee, epi-quinidine derivatives 6 and 7 were more efficient in terms of both chemical and stereochemical efficiency; they afforded the chiral amine (with the opposite absolute configuration) in up to 90 % ee.…”

Enantioselective Organocatalytic Reduction of β‐Trifluoromethyl Nitroalkenes: An Efficient Strategy for the Synthesis of Chiral β‐Trifluoromethyl Amines

“…After focusing on the preparation of chiral α‐trifluoromethylamine, by trichlorosilane‐mediated enantioselective catalytic reduction of trifluoromethyl ketoimines,4 we turned our attention to chiral β‐trifluoromethylamines. Recent works on innovative, nonstereoselective, methods of trifluoromethylation to generate β‐trifluoromethyl‐substituted aza‐derivatives clearly testify for the great interest in the preparation of this class of compounds 5.…”