A theoretical study on the mechanism and diastereoselectivity of the Kulinkovich hydroxycyclopropanation reaction

A detailed mechanism for the Kulinkovich hydroxycyclopropanation reaction h as been explored with density functional theory calculations on the reactio ns between (RCOOMe)-C-1 and Ti(OMe)(2)(CH2CHR2) (R-1 and R-2 are hydrogen a nd alkyl groups). Addition of ester to titanacyclopropane is found to be fa st, exothermic, and irreversible. It has a preference for the alpha -additi on manifold over the beta -addition manifold in which its cycloinsertion tr ansition states suffer from the steric repulsion between the R-2 and ester. The following intramolecular methoxy migration step is also exothermic wit h reasonable activation energy. The cyclopropane forming step is the rate-d etermining step, which affords the experimentally observed cis-R-1/R-2 dias tereoselectivity in the alpha -addition manifold by generating cis-R-1/R-2 1,2-disubstituted cyclopropanol when R-1 is primary alkyl groups. On the co ntrary, the unfavored beta -addition manifold offers the diastereoselectivi ty contradicting the experimental observations. The effects of R-1 and R-2 on the regio- and stereoselectivity are also discussed.