Synthesis of (S)-(−)-N-acetylcolchinol using intramolecular biaryl oxidative coupling

Abstract

An asymmetric synthesis of the tubulin polymerisation inhibitor (S)-(−)-N-acetylcolchinol is reported based on an intramolecular biaryl oxidative coupling of a 1,3-diarylpropyl acetamide intermediate using phenyliodonium bis(trifluoroacetate) as the final step. Three syntheses of the penultimate 1,3-diarylpropyl acetamide intermediate (S)-(−)-N-[1-[3-(tert-butyldimethylsilyloxy)phenyl)]-3-(3,4,5-trimethoxyphenyl)propyl] acetamide are described which differ in the means by which the stereogenic centre was introduced.