Reaction of Ketones with Lithium Hexamethyldisilazide: Competitive Enolizations and 1,2-Additions

摘要

Reaction of 2-methylcyclohexanone with lithium hexamethyldisilazide (LiHMDS, TMS2NLi) 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 -amino alkoxide-LiHMDS mixed dimer shown to be a pair of conformers by using ~6Li, ~(15)N, and ~(13)C NMR spectroscopies. Rate studies are consistent with a monomer-based transition structure [(TMS2NLi)(ketone)(pyrrolidine)3]. The partitioning between enolization and 1,2-addition is kinetically controlled.