Dedicated to Prof. Yao-Zhong Jiang on the occasion of his 70th birthday
The in situ generation of an iminium ion from a chiral aminocatalyst and a carbonyl compound is thought to lower the LUMO energy of the system and is a powerful strategy for a range of asymmetric transformations. [1] The commonly applied catalysts are ammonium salts of secondary amines derived from chiral a-amino acids or 1,2-diphenylethylenediamine. Highly efficient asymmetric reactions, including conjugate addition and pericyclic reactions, have been described for a,b-unsaturated aldehydes, even at very low temperatures. [2] However, the reactions of a,b-unsaturated ketones catalyzed by secondary amine salts usually suffer from a sluggish reaction rate at room temperature, [3] and some reactions could not be promoted at all, probably because of poor generation of the corresponding iminium cations. Therefore, an alternative catalyst with stronger activating ability, broader applicability, and improved enantioselectivity would be highly desirable.
Recently, we reported that the electron-deficient a,adicyanoalkenes could act as versatile direct vinylogous donors in asymmetric Michael addition reactions of nitroalkenes and a,b-unsaturated aldehydes with excellent chemo-and stereoselectivity. [4] These activated alkenes also behave as good hydride acceptors in conjugate reduction reactions. [4a-b, 5] It is intriguing to consider that a,a-dicyanoalkenes might be applied successively as Michael donors and Michael acceptors in some domino sequences. Inspired by the recent reports on tandem iminium-enamine activation of a,b-unsaturated aldehydes by chiral secondary aminocatalysts, [6] we envisaged that sequential Michael-Michael addition reactions would be possible between a,a-dicyanoalkenes and a,b-unsaturated ketones, as outlined in Scheme 1, to provide a straightforward protocol for the synthesis of chiral cyclic products with multiple substituents.