Lithiated Oppolzer Enolates: Solution Structures, Mechanism of Alkylation, and Origin of Stereoselectivity

Camphorsultam-based lithium enolates referred to colloquially as Oppolzer enolates are examined spectroscopically, crystallographically, kinetically, and computationally to ascertain the mechanism of alkylation and the origin of the stereoselectivity. Solvent-and substrate-dependent structures include tetramers for alkyl-substituted enolates in toluene, unsymmetric dimers for aryl -substituted enolates in toluene, substrate-independent symmetric dimers in THF and THF/toluene mixtures, HMPA-bridged trisolvated dimers at low HMPA concentrations, and disolvated monomers for the aryl-substituted enolates at elevated HMPA concentrations. Extensive analyses of the stereochemistry of aggregation are included. Rate studies for reaction with allyl bromide implicate an HMPA-solvated ion pair with a +Li(HMPA)4 counterion. Dependencies on toluene and THF are attributed to exclusively secondary-shell (medium) effects. Aided by density functional theory (DFT) computations, a stereochemical model is presented in which neither chelates nor the lithium gegenion serves roles. The stereoselectivity stems from the chirality within the sultam ring and not the camphor skeletal core.

Automated summary

This paper examines the mechanism of alkylation and the origin of stereoselectivity using Camphorsultam-based lithium enolates. The structures of the enolates are found to be dependent on the solvent and substrate, and the stereochemistry of aggregation is extensively analyzed. The stereochemistry is determined by the chirality within the sultam ring.