Reversible Enolization of β-Amino Carboxamides by Lithium Hexamethyldisilazide

The enolization of β-amino carboxamides by lithium hexamethyldisilazide (LiHMDS) in THF/toluene and subsequent diastereoselective alkylation with CH3I are reported. In situ IR spectroscopic studies reveal that β-amino carboxamides coordinate to LiHMDS at −78 °C before enolization. Comparison with structurally similar carboxamides suggests that the β-amino group promotes the enolization. IR spectroscopic studies also show that the enolization is reversible. Efficient trapping of the enolate by CH3I affords full conversion to products. 6Li and 15N NMR spectroscopic studies reveal that lithium enolate−LiHMDS mixed dimers and trimers as well as a homoaggregated enolate are formed during the reaction. At ambient temperature, racemization of the β-position through a putative reversible Michael addition was observed.