Joe T. Collins

The N-Boc Group as an Activator for the a-Lithiation of Carbamates: Synthesis of 11-Substituted Dibenzoxazepines

A series of 11-substituted dibenzoxazepines was prepared via α-lithiation utilizing the N-Boc group as an activator. The N-Boc group directs metalation of 5 by n-BuLi to the benzylic C-11 carbon. For 6 which contains 1,3 interrelated directed metalation groups, metalation with 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 employing 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 the pharmaceutically important heteroaromatic ring systems (5) and (6) can be controlled. The N-Boc group can be readily removed with mild acid treatment