A THEORETICAL-STUDY OF ADDITION OF ORGANOMAGNESIUM REAGENTS TO CHIRALALPHA-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 c arbonyl compounds (2-hydroxypropanal, 3-hydroxybutanone, and ,4-di-O-m ethyl-1-O-(trimethylsilyl)-L-erythrulose) has been carried out. Analyt ical gradients SCF MO and second derivatives at the PM3 semiempirical procedure and the ab initio method at the HF/3-21G basis set level hav e been applied to identify the stationary points on potential energy s urfaces. The geometry, harmonic vibrational frequencies, transition ve ctor, and electronic structure of the transition structures have been obtained. The dependence of the results obtained upon the computing me thod and the model system is analyzed, discussed, and compared with av ailable experimental data. The first step corresponds to the exothermi c formation of a chelate complex without energy barrier. This stationa ry point corresponds to a puckered five-membered ring, determining the stereochemistry of the global process, which is retained throughout t he reaction pathway. The second and rate-limiting step is associated t o 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 f our-membered ring. The inclusion of a second equivalent of CH3MgCl, co rresponding to an intermolecular mechanism, decreases the barrier heig ht, and the process can be considered as an assisted intermolecular me chanism: the first equivalent forms the chelate structure and the seco nd CH3MgCl carries out the nucleophilic addition to the carbonyl group . The most favorable pathway corresponds to an intermolecular mechanis m via an anti attack. The analysis of the results reveals that the nat ure of transition structures for the intramolecular and intermolecular ;mechanisms is a rather robust entity. There is a minimal molecular mo del with a transition structure which describes the essentials of the chemical addition process, and the corresponding transition vector is an invariant feature.