Manganese-Ketenimine Intermediates as Active Catalysts in the Michael Addition of Unactivated Nitriles to α,β-Unsaturated Ketones.

Abstract

The Michael addition of unactivated nitriles to α,β-unsaturated ketones is a challenging yet desirable strategy for installing alkyl cyano-groups (R-CN) in organic molecules. However, despite formidable efforts, using acetonitrile as a Michael donor in these reactions has remained a significant challenge. Herein, we report a highly active manganese(I) complex [(PCNHCP)Mn(CO)2H] (1), which chemoselectively catalyzes the 1,4-addition of unactivated nitriles (incl. acetonitrile) to α,β-unsaturated ketones. The developed methodology operates under mild conditions, does not require any additives or bases, features low catalyst loadings (1 mol %), fast reaction times (2-8 hours), and is compatible with a wide variety of functional groups, including halides, trifluoromethyl, alkenyl, alkynyl, and (hetero)aryl groups. Extensive mechanistic studies revealed that after base-free activation of the nitrile, either the N-bound manganese-ketenimine (propionitrile or benzyl cyanide) or the C-bound manganese-cyanoalkyl (acetonitrile) complex is formed. The difference in stability of these two species explains why more sterically hindered and presumably less activated nitriles (i.e., propionitrile, and butyronitrile) show higher reactivity than their corresponding more activated congeners (i.e., acetonitrile). Finally, the practicality of our approach was demonstrated through a gram-scale reaction and subsequent derivatizations of the obtained product into important organic motifs such as ene-lactams and tetrahydropyridines.