Steric effects on the regioselectivity in two-step Diels-Alder reactions of 1,2,4,5-tetrazines with 2-cyclopropylidene-4,5-dihydro-1,3-dimethyl-imidazolidine

The regioselectivity of the two-step Diels-Alder reaction of unsymmetrically substituted tetrazines 4 with 2-cyclopropylidene-imidazolidine 6 is investigated. The first reversible step of the cycloaddition affording zwitterions 7 and 8 is controlled by steric effects, which are explained using a simple model. The overall regioselectivity, however, is determined in the second step of the cycloaddition or at an even later stage. (C) 2000 Elsevier Science Ltd. All rights reserved.