Carlos T. Nieto, David Díez and Narciso M. Garrido
The asymmetric Aza-Michael addition of homochiral lithium benzylamides to α,β-unsaturated esters represents an extended protocol to obtain enantioenriched β-amino esters. A QM/MM transition state protocol is presented, revising the original proposed mechanism. Theoretical results, a Si/Re 99:1 diastereoselective ratio, in good agreement with experimental results, is reported. Two TS conformers in a “V-stacked” orientation of the amide's phenyl rings, differing in the THF molecule arrangement coordinated to lithium, are the most suitable TS geometries.