Abstract
The nornicotine catalyzed Mannich reaction and its mechanism are analyzed with quantum chemical calculations by M06-2X/6-31++G(d,p) method and the polarizable continuum model (PCM) for the solvent effect of dimethyl sulfoxide. The Mannich reaction with nornicotine as a catalyst can be separated into three steps. First, the nornicotine-derived enamine is generated from nornicotine and a ketone with the aid of a water molecule. Second, the nornicotine-derived enamine forms a C-C bond with the imine to produce a chiral intermediate with the assistance of a water molecule. There are four possible stereo-control paths and the analysis suggests that nornicotine as a catalyst favors the S- over R-Mannich product. Third, water catalyzes the release of the original nornicotine catalyst from the Mannich product. The calculation indicates that water is a key element in the proposed mechanism and that nornicotine can catalyze the Mannich reaction in wet solvents or even pure water.