Regio- and stereoselectivity of captodative olefins in 1,3-dipolar cycloadditions. A DFT/HSAB theory rationale for the observed regiochemistry of nitrones
R. Herrera et al., Regio- and stereoselectivity of captodative olefins in 1,3-dipolar cycloadditions. A DFT/HSAB theory rationale for the observed regiochemistry of nitrones, J ORG CHEM, 66(4), 2001, pp. 1252-1263
Captodative olefins 1-acetylvinyl carboxylates proved to be highly regiosel
ective dipolarophiles in 1,3-dipolar cycloadditon to propionitrile oxide, a
rylphenylnitrile imines, diazoalkanes, and nitrones to yield the correspond
ing 5-substituted heterocycles. The addition of the latter was also stereos
elective, being slightly susceptible to steric demand of the carboxylate su
bstituent in the olefin. All atempts to cleave the isoxazolidine N-O bond u
nder reductive conditions failed, providing diverse products with side-grou
p reduction. FMO theory was unsuccessful to explain the regioselectivity ob
served with nitrones, since the opposite orientation was predicted. The rec
ently formulated DFT/HSAB theoretical model was able to rationalize this re
gioselectivity, identifying the nucleophilic and electrophilic atoms involv
ed in the process via calculation of interaction energies, suggesting the s
pecific direction of the electronic process at each of the reaction sites.