Reaction of ketones with lithium hexamethyldisilazide: competitive enolizations and 1,2-additions.

Reaction of 2-methylcyclohexanone with lithium hexamethyldisilazide (LiHMDS, TMS(2)NLi) displays highly solvent-dependent chemoselectivity. LiHMDS in THF/toluene effect enolization. Rate studies using in situ IR spectroscopy are consistent with a THF concentration-dependent monomer-based pathway. LiHMDS in pyrrolidine/toluene affords exclusively 1,2-addition of the pyrrolidine fragment to form an alpha-amino alkoxide-LiHMDS mixed dimer shown to be a pair of conformers by using (6)Li, (15)N, and (13)C NMR spectroscopies. Rate studies are consistent with a monomer-based transition structure [(TMS(2)NLi)(ketone)(pyrrolidine)(3)](). The partitioning between enolization and 1,2-addition is kinetically controlled.