Sodiated Oppolzer enolates: solution structures, mechanism of alkylation, and origin of stereoselectivity

Abstract

NMR spectroscopic studies reveal camphorsultam-derived sodium enolates known as Oppolzer enolates reside as monomers in neat THF and THF/HMPA solutions and as dimers in toluene when solvated by N,N,N′,N′-tetramethylethylenediamine (TMEDA) and N,N,N′,N′′,N′′-pentamethyldiethylenediamine (PMDTA). Density functional theory (DFT) computations attest to the solvation numbers. Rate studies show analogy with previously studied lithiated Oppolzer enolates in which alkylation occurs through non-chelated solvent-separated ion pairs. The origins of the selectivity trace to transition structures in which the alkylating agent is guided to the exo face of the camphor owing to stereoelectronic preferences imparted by the sultam sulfonyl moiety. Marked secondary-shell solvation effects are gleaned from the rate studies.