1,3-Dipolar Cycloaddition - Diastereoselectivity

Diastereoselectivity

When two or more chiral centers are generated during the cycloaddition reaction, diastereomeric transition states and products can be obtained. There are two forces that influence the diastereoselectivity of 1,3-dipolar cycloadditions: the attractive π-interaction (resembling secondary orbital interactions in the Diels-Alder cycloaddition) and the repulsive steric interaction. Often these two forces can offset each other and give poor diastereoselection. An example of a diastereoselective 1,3-dipolar cycloaddition is illustrated by the reaction between benzonitrile N-benzylide and methyl acrylate. In the transition state, the phenyl and the methyl ester groups interact favorably, giving the cis-substitution as the exclusive final pyroline product. This favorable π-interaction offsets the steric repulsion between the phenyl and the methyl ester groups.