Transannular Cyclizations of 5-(Hydroxyamino)dibenzocyclooctatrienes. Regioselective Synthesis of Dibenzohomotropane Analogues

Article abstract of DOI:10.1021/jo00294a023

Solvolyses of 5-<(tosyloxy)methyl>dibenzocycloheptenes 18 provided substituted dibenzocyclooctatriene-5-ols 19 and 20, the product distribution implicating the intermediacy of cyclopropyl phenonium ions 22 and 23.Treatment of 5-methyl-5-hydroxydibenzocyclooctatrienes (e.g. 9) with hydroxylamine under acidic conditions led to the exclusive formation of N-hydroxy dibenzohomotropanes (e.g. 30).Cyclization of substituted derivatives, followed by reductive cleavage of the N-hydroxy groups, gave derivatives 2, 35-42, and 46, which are ring homologues of theuncompetitive NMDA antagonist MK-801 (1).The more rapid rate of ring closure of 5-(hydroxyamino)dibenzocyclooctatrienes (e.g. 28) relative to the corresponding cycloheptenes is rationalized by differences in strain energy in the transition states required for cyclization.