Reappraisal of the diastereoselectivity of intramolecular Diels–Alder reactions of some o-quinodimethanes generated by benzocyclobutene thermolysis: some complementary results and an improvement

In a synthetic approach to 19-nor steroids and in order to compare the diastereoselectivities observed for the intramolecular Diels–Alder reactions of o-quinodimethanes generated either from 1 or 2, the thermolysis of benzocyclobutenes such as 2 was reexamined. The IMDA diastereoselectivity was highly dependent on the nature of the protective group of the hydroxyl substituent at the unique chiral stereocentre of the o-quinodimethane intermediate, in a position α to the double bond of the dienophile. Consistently with previous results reported for benzocyclobutenes 2, the trans-fused cycloadducts were the major products, the trans syn or trans anti predominant isomer being determined by the hydroxyl protective group. In contrast with these previous reports, the cis-fused cycloadducts were always formed competitively, although as minor products. In the present work, the diastereoselectivity was improved by achieving the thermolysis of a benzocyclobutene 2 having a lithium alkoxide which afforded the trans syn adduct in high yield.