A theoretical study of addition of organomagnesium reagents to chiral alpha-alkoxy carbonyl compounds

A theoretical study on the addition of organomagnesium reagents (CH3Mg+, CH3MgCl, 2CH(3)MgCl) to the carbonyl group of chiral alpha-alkoxy carbonyl compounds (2-hydroxypropanal, 3-hydroxybutanone, and 3,4-di-O-methyl-1-O-(trimethylsilyl)-L-erythrulose) has been carried out. Analytical gradients SCF MO and second derivatives at the PM3 semiempirical procedure and the ab initio method at the HF/3-21G basis set level have been applied to identify the stationary points on potential energy surfaces. The geometry, harmonic vibrational frequencies, transition vector, and electronic structure of the transition structures have been obtained. The dependence of the results obtained upon the computing method and the model system is analyzed, discussed, and compared with available experimental data. The first step corresponds to the exothermic formation of a chelate complex without energy barrier. This stationary point corresponds to a puckered five-membered ring, determining the stereochemistry of the global process, which is retained throughout the reaction pathway. The second and rate-limiting step is associated to the C-C bond formation via 1,3-migration of the nucleophilic methyl group from the organomagnesium compound to the carbonyl carbon. For an intramolecular mechanism (addition of CH3Mg+ and CH3MgCl to different carbonyl. compounds) the transition structure can be described as a four-membered ring. The inclusion of a second equivalent of CH3MgCl, corresponding to an intermolecular mechanism, decreases the barrier height, and the process can be considered as an assisted intermolecular mechanism: the first equivalent forms the chelate structure and the second CH3MgCl carries out the nucleophilic addition to the carbonyl group. The most favorable pathway corresponds to an intermolecular mechanism via an anti attack. The analysis of the results reveals that the nature of transition structures for the intramolecular and intermolecular;mechanisms is a rather robust entity. There is a minimal molecular model with a transition structure which describes the essentials of the chemical addition process, and the corresponding transition vector is an invariant feature.