FACIAL SELECTIVITY IN 1,3-DIPOLAR CYCLOADDITIONS TO CIS-3,4-DIMETHYLCYCLOBUTENE - AN EXPERIMENTAL AND COMPUTATIONAL STUDY

Facial selectivity in 1,3-dipolar cycloaddition of diazomethane (2a), 3,4-dihydroisoquinoline N-oxide (2b), pyrroline N-oxide (2c), 5,5-dime thylpyrroline N-oxide (24) and several nitrile oxides (2e-2j) with cis -3,4-dimethylcyclobutene (1) has been investigated. The stereochemistr y of the cycloaddition of 2a, 2b-2d and encumbered nitrile oxides (2i and 2j) is controlled by steric interactions with dominant formation o f the anti diastereoisomer. Syn and anti attack compete with each othe r in the cases of phenylglyoxylonitrile oxide and pyruvonitrile oxide (2g and 2h, respectively) thus disclosing the presence of contrasteric electronic syn orienting effects. Transition state structures of the cycloaddition of formonitrile oxide, diazomethane and methyleneamine N -oxide (nitrone) were located with both HF/6-31G and B3LYP/6-31G* met hods. The calculated relative free enthalpies of these transition stat es satisfactorily reproduce, at both levels, the observed facial selec tivity while geometry data suggest a higher steric demand for the nitr one with respect to the other two dipoles. To the best of our knowledg e this is the first study of diastereofacial selectivity in 1,3-dipola r cycloaddition with DFT theory.