Convergent Synthesis of Fully Functionalized Ring C Allocolchicinoids. Benzannulation Approach

摘要

A novel convergent approach to fully functionalized ring C allocolchicinoids is developed which is based on the benzannulation reaction of Fischer carbene complexes with alkynes. The efficacy of this strategy was established with the conversion of bromide 1a (R~1 = Me, R~2 = H) to the biaryl phenol 3a (R = Me, R_L = Pr, R_S = H) via the carbene complex 2a. Bromide 1b (R~1 = t-Bu, R~2 = OMe) was then used for the analogous preparation of the diastereomeric allocolchicinoids 3b (R = Me, R_L = Pr, R_S = H).