Asymmetric Formal Aza-Diels–Alder Reaction of Trifluoromethyl Hemiaminals with Enones Catalyzed by Primary Amines

A primary
amine-catalyzed asymmetric formal aza-Diels–Alder
reaction of trifluoromethyl hemiaminals with enones was developed
via a chiral gem-diamine intermediate. This novel
protocol allowed facile access to structurally diverse trifluoromethyl-substituted
piperidine scaffolds with high stereoselectivity. The utility of this
method was further demonstrated through a concise approach to biologically
active 4-hydroxypiperidine. More importantly, a stepwise mechanism
involving an asymmetric induction process was proposed to rationalize
the positive correlation between the chirality of the gem-diamine intermediate and the formal aza-Diels–Alder product.