A theoretical study on the mechanism and diastereoselectivity of the Kulinkovich hydroxycyclopropanation reaction.
A detailed mechanism for the Kulinkovich hydroxycyclopropanation reaction has been explored with density functional theory calculations on the reactions between R(1)COOMe and Ti(OMe)(2)(CH(2)CHR(2)) (R(1) and R(2) are hydrogen and alkyl groups). Addition of ester to titanacyclopropane is found to be fast, exothermic, and irreversible. It has a preference for the alpha-addition manifold over the beta-addition manifold in which its cycloinsertion transition states suffer from the steric repulsion between the R(2) and ester. The following intramolecular methoxy migration step is also exothermic with reasonable activation energy. The cyclopropane-forming step is the rate-determining step, which affords the experimentally observed cis-R(1)/R(2) diastereoselectivity 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 contrary, the unfavored beta-addition manifold offers the diastereoselectivity contradicting the experimental observations. The effects of R(1) and R(2) on the regio- and stereoselectivity are also discussed.
Wu
Y D
YD
Department of Chemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Yu
Z X
ZX