MECHANISTIC STUDIES ON THE BASE-PROMOTED ADDITION OF LITHIOPINACOLONATE TO SEVERAL AROMATIC CARBONYL-COMPOUNDS IN NONHYDROXYLIC SOLVENTS

An investigation of the reaction of lithium enolates with carbonyl compounds is continued by determining kinetic data for the aldol reaction of lithiopinacolonate with o- and p-methylbenzaldehyde in methylcyclohexane-d14 at -80-degrees-C using rapid injection proton NMR spectroscopy. The data were fit to a second-order reaction model with half-lives of 43.2 and 12.7 s, respectively. The NMR spectra showed no evidence of free radicals participating in the CIDNP phenomenon. The question of electron transfer as a feasible mechanism was tested using Eberson's criterion of estimating the barrier to single electron transfer (SET) from the free energy of single electron transfer using the redox potentials of the reactants and Marcus theory. These values were obtained using cyclic voltammetry and second-harmonic ac voltammetry in tetrahydrofuran and acetonitrile at room temperature. In comparison to the observed free energy of activation, calculated from the observed rate at -80-degrees-C, the electrochemical free energy of single electron transfer is sufficiently endergonic to eliminate the single electron transfer pathway according to this criterion. The same type of analysis was utilized for both the aldol reaction of lithiopinacolonate with benzophenone and its Claisen condensation with ethyl 4-nitrobenzoate in THF at room temperature. By this criterion, single electron transfer is also not a feasible process for either of these reactions. Three cyclizable probes were utilized to test further for a SET pathway in the aldol reactions and the Claisen condensation, namely, 7-iodo- and 7-bromo-2-methoxy-2-heptenenitrile and 8-iodo-3-methyl-3-octene. No cyclized products were found in any of the reactions tested. However, as expected, cyclized products were produced from reaction of the probes with tributyltin hydride and AIBN. Bulk electrolysis of the cyclizable probes leads to a complex mixture of products including the expected cyclized ones. None of the (admittedly questionable) criteria applied here to these reactions of lithiopinacolonate with these carbonyl electrophiles gave diagnostic evidence for an electron-transfer mechanism instead of the familiar nucleophilic addition. These results say nothing about the actual (free or aggregated) state of the lithium enolate in the transition structure.