Facial selectivity in 1,3-dipolar cycloadditions to cis-3,4-dimethylcyclobutene. An experimental and computational study

Abstract

Facial selectivity in 1,3-dipolar cycloaddition of diazomethane (2a), 3,4-dihydroisoquinoline N-oxide (2b), pyrroline N-oxide (2c), 5,5-dimethylpyrroline N-oxide (2d) and several nitrile oxides (2e–2j) with cis-3,4-dimethylcyclobutene (1) has been investigated. The stereochemistry of the cycloaddition of 2a, 2b–2d and encumbered nitrile oxides (2i and 2j) is controlled by steric interactions with dominant formation of the anti diastereoisomer. Syn and anti attack compete with each other 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* methods. The calculated relative free enthalpies of these transition states satisfactorily reproduce, at both levels, the observed facial selectivity while geometry data suggest a higher steric demand for the nitrone with respect to the other two dipoles. To the best of our knowledge this is the first study of diastereofacial selectivity in 1,3-dipolar cycloaddition with DFT theory.