Synthesis of alpha,gamma-Chiral Trifluoromethylated Amines through the Stereospecific Isomerization of alpha-Chiral Allylic Amines

Chiral gamma-branched aliphatic amines are present in a large number of pharmaceuticals and natural products. However, enanti-oselective methods to access these compounds are scarce, and rely on the use of designed chiral transition-metal complexes. Herein, we have combined an organocatalytic method for the stereospecific isomerization of chiral allylic amines with a dia-stereoselective reduction of the chiral imine/enamine intermediates, leading to gamma-trifluoromethylated aliphatic amines with two noncontiguous stereogenic centers, in excellent yields and with high diastereo- and enantioselectivities. This approach has been used with primary amine substrates. Additionally, a gram-scale reaction demonstrates the applicability of this syn-thetic procedure.