Organocatalytic asymmetric double Michael reaction of Nazarov reagents with alkylidene azlactones for the construction of spiro-fused cyclohexanone/5-oxazolone system

A bifunctional thiourea-tertiary amine-catalyzed enantioselective double Michael reaction of Nazarov reagents and alkylidene azlactones was realized. Using this protocol, a series of optically active spiro-fused cyclohexanone/5-oxazolone derivatives, bearing three consecutive chiral centers including one Spiro quaternary chiral center, were obtained in good yields with good stereoselectivities (up to 93% yield, 99:1 dr, and 91% ee). The synthetic utility of the products for the formation of chiral cyclic quaternary amino-acid derivatives was also demonstrated. (C) 2014 Elsevier Ltd. All rights reserved.