No abstract

The 1,3-dipolar cycloaddition reactions of diazomethane with ethylene and formaldehyde as well as the nitrogen elimination reactions from the cycloadducts have been studied using density functional and conventional ab initio methods. The exothermicity of the reactions is underestimated by DFT methods with respect to CCSD(T) due to an overestimation of the C−N dissociation energy of diazomethane. For the cycloaddition reactions all methods lead to similar transition state geometries, and the potential energy barriers computed using DFT methods are similar to the CCSD(T) ones. On the other hand, for the nitrogen elimination reactions transition state geometries and energy barriers are more dependent on the level of calculation. The results obtained show that for the reaction between diazomethane and ethylene the pyrazoline intermediate is more stable than the reactants and that the Gibbs energy barrier for nitrogen elimination is larger than the barrier corresponding to its formation. On the contrary, for formaldehyde the kinetically most favorable cycloadduct, 1,2,3-oxadiazoline, is less stable than the reactants and has a lower barrier for nitrogen elimination.

The reactions between N-benzyl- and N-methylhydroxylamine and chiral enoate esters, derived from D-glyceraldehyde and (-)-verbenone, respectively, have been investigated. Theoretical calculations show that the most favorable mechanism involves the concerted cycloaddition of the hydroxylamine to the substrate. This result is in good agreement with the stereospecificity observed when the trisubstituted olefins are used. The open-chain adducts have been isolated when the processes are carried out at low temperatures and for short reaction times. These compounds evolve to the corresponding isoxazolidinones on standing at room temperature or under acid catalysis. The high pi-facial diastereoselection has been rationalized on the basis of steric effects induced by the dioxolane ring for D-glyceraldehyde derivatives or by the cyclobutane gem-dimethyl substitution for esters prepared from (-)-verbenone. As an application of these reactions, new beta-amino acids have been synthesized in a highly efficient and stereocontrolled manner.

The stereochemical outcome of diazomethane cycloadditions to several chiral electron-deficient olefins has been investigated in order to establish the origin of the pi-facial diastereoselection. Nitro olefins, vinyl sulfones, enoates, and 2-amino enoates have been used for such a purpose. These substrates have been prepared from D-glyceraldehyde acetonide through Wittig-type condensations and present an alkoxy substituent, provided by the bulky dioxolane ring, attached to the stereogenic allylic carbon. Syn-adducts have been obtained in all cases as the major isomers, independently of the Z/E stereochemistry of the double bond and the number and the nature of the substituents, the chirality of the asymmetric allylic carbon being the only thing responsible for the diastereoselection. Theoretical calculations show that steric hindrance due to the bulky dioxolane group is the main factor governing the preference for the syn-attack of diazomethane to the olefinic double bond.