MODEL-CALCULATIONS OF CHEMICAL INTERACTIONS .7. ROLE OF VICINAL DELOCALIZATION IN THE REGIOCHEMICAL CONTROL OF THE CYCLOADDITION OF DIAZOMETHANE AND FORMONITRILE OXIDE TO METHYL VINYL ETHER

In strict accordance with the preceding theoretical and experimental s tudies on diastereofacial selectivity, we undertook a study of regiose lectivity in 1,3-dipolar cycloadditions; the examples chosen included the reactions of alkyl vinyl ethers with diazomethane, the most famous and difficult regiochemical experiment in the literature of 1,3-dipol ar cycloadditions and one that has yet to find a well grounded explana tion, and with formonitrile oxide, a small 1,3-dipole with a fairly hi gh dipole moment that is capable of enhancing any eventual role of ele ctrostatic effects. The cycloaddition of methyl vinyl ether (MVE) with diazomethane was checked experimentally and found to afford 3-methoxy -1-pyrazoline as the only characterized and highly abundant adduct, al though the formation of minor amounts of the other regioisomer could n ot be ruled out definitely. Concerted transitions structures (TS) were calculated at different levels of theory: 3-methoxy-1-pyrazoline and 5-methoxy-2-isoxazoline were found, in agreement with experiment, to b e the favoured regioadducts of the reactions with diazomethane and for monitrile oxide, respectively. In both cases the favoured transition s tructures were 'earlier' than the unfavoured one, and had anti-conform ations of the O-Me substituent, In spite of the lower stability of the anti conformation in free MVE. According to our analysis, the regiose lectivity of MVE 1,3-dipolar cycloadditions and the main features of t he transition structures can be explained as follows: the largest vici nal stabilization is traceable to the four-electron three-centre pi co njugation between the pi lone pair and the pi bond of the allylic frag ment O-C-C, which is also largely responsible for the rotameric potent ial-energy profile of MVE. In the TSs these vicinal interactions are d ifferently perturbed, in the different regioisomeric approaches, the m ore favourable perturbation dictating the regiochemistry; in our examp les, the favourable approach occurs when the C ... X bond (X = N, O) i s formed on the substituted carbon atom. This very same perturbation i s also the origin of the earliness of the favoured TS and of the conse quent weakness of its incipinet bond stabilization. The conformational features of the TSs are significantly affected by electrostatic effec ts.