THE N-BOC GROUP AS AN ACTIVATOR FOR THE ALPHA-LITHIATION OF CARBAMATES - SYNTHESIS OF 11-SUBSTITUTED DIBENZOXAZEPINES

A series of 11-substituted dibenzoxazepines was prepared via alpha-lit hiation utilizing the N-Boc group as an activator. The N-Boc group dir ects metalation of 5 by n-BuLi to the benzylic C-11 carbon. For 6 whic h contains 1,3 interrelated directed metalation groups, metalation wit h n-BuLi occurs at both the 11- and 9- positions. The regioselectivity for the lithiation of 6 can be increased to a ratio of 97:3, by emplo ying LDA as the base, thus providing a convenient and general route to 11-substituted 8-chloro-dibenzoxazepines. By the proper choice of the base, the regioselectivity of lithiation-substitution reactions in th e pharmaceutically important heteroaromatic ring systems (5) and (6) c an be controlled. The N-Boc group can be readily removed with mild aci d treatment.