Organocatalytic Asymmetric Synthesis of α-Trifluoromethyl Homoallylic Amine Derivatives from Trifluoromethyl-Containing Ketoimines and Isatin-Derived Morita-Baylis-Hillman Carbonates

The asymmetric gamma-regioselective-alkylation reaction which is catalyzed by a chiral tertiary amine ((DHQ)(2)PHAL) and takes advantage of isatin-derived Morita-Baylis-Hillman carbonates and CF3-contained ketoimines, delivered chiral alpha-trifluoromethylamine derivatives and incorporated an oxindole motif in yields of 65-98%, diastereoselectivities (> 20:1 in most cases) and enantioselectivities of 73-99%. The subsequent deprotection gave alpha- trifluoromethyl amines in a stereoselective manner. Furthermore, fused polycyclic frameworks can be furnished by subsequent derivatization of the product without eroding its stereoselectivity.

Automated summary

This article introduces an asymmetric gamma-regioselective-alkylation reaction catalyzed by a chiral tertiary amine ((DHQ)(2)PHAL) which utilizes isatin-derived Morita-Baylis-Hillman carbonates and CF3-containing ketoimines. The reaction delivers chiral alpha-trifluoromethylamine derivatives and incorporates an oxindole motif with high yields, diastereoselectivities, and enantioselectivities. The subsequent deprotection reaction produces alpha-trifluoromethyl amines in a stereoselective manner. Furthermore, the product can be further derivatized to furnish fused polycyclic frameworks without compromising its stereoselectivity.