Synthetic approaches to amino analogues of N-acetylcolchinol

A straightforward synthesis of aminodibenzoxepines, new analogues of N-acetylcolchinol, is reported by using two different strategies. The first strategy involves a Grignard addition, a biaryl Suzuki-Miyaura coupling, and a HF-mediated cyclodehydration as key steps. A second strategy, better adapted to the synthesis of analogues bearing a benzylic substituent, was designed by inverting the order of the Grignard addition and the biaryl coupling. This allowed the rapid and reliable production of a series of substituted aminodibenzoxepines. A chelate model was proposed to account for the diastereoselectivity observed in the Grignard addition step.