Reaction of Ketones with Lithium Hexamethyldisilazide: Competitive Enolizations and 1,2-Additions
- 20 February 2004
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 126 (10), 3113-3118
- https://doi.org/10.1021/ja030582v
Abstract
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 α-amino alkoxide-LiHMDS mixed dimer shown to be a pair of conformers by using 6Li, 15N, and 13C 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.Keywords
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