Tandem Heck-Suzuki-Miyaura reaction: Application to the synthesis of constrained analogues of combretastatin A-4

A series of compounds related to combretastatin A-4 has been synthesized by a tandem Heck-carbocyclization/Suzuki coupling process. From various alkynamides and 3,4,5-trimethoxyphenyl boronic acid or the corresponding styryl derivative, (E)-3-arylmethyleneoxindoles (type I) and (EE)-3-alkylideneoxindoles (type II) were efficiently obtained in a stereoselective manner. Factors influencing yield and stereoselectivity are detailed.

An efficient synthesis of (E)-3-arylmethyleneoxindoles (type I) and (EE)-3-alkylideneoxindoles (type II) have been developed from various anilides.