The Synthesis Of Z-alkenes Via Visible Light Promoted Photocatalytic Isomerization Of Alkenes And Its Application In The Synthesis Of Anti-tumor Agent Combretastatin A4

In this research,a green and efficient strategy for the synthesis of cis-alkenes was presented by exploring the photocatalytic isomerization of alkenes under visible light.This new strategy was also applied into the synthesis of an antitumor agent named Combretastatin A4.Two parts were involved in this paper:1)visible-light promoted photocatalytic isomerization of alkenes under metal-free condition;2)synthesis of Combretastatin A4 via visible-light promoted photocatalytic isomerization of alkenes.1?Visible-light promoted photocatalytic isomerization of alkenes under metal-free conditionAn important challenge in the synthesis of thermodynamically less favorable cis-alkenes is the precise control of the stereo-chemistry with an efficient and green method.Herein,we present a novel organocatalytic approach through the exploration of photocatalytic trans-to-cis isomerization.This protocol features metal-free reaction condition using a readily accessible 2-iodo-9-fluorenone as photosensitizer in the presence of visible light,which is operationally simple,remarkably clean,and allows for the synthesis of both electron-rich and deficient cis-alkenes with diverse functional groups.2.Synthesis of Combretastatin A4 via visible-light promoted photocatalytic isomerization of alkenes.Combretastatin A-4(CA-4)with cis-1,2-diphenylethene as core structure,displays excellent anti-tumor activity as an antitubulin agent.However,the lack of green and effecient synthetic approach strongly restricts the further drug development of CA-4 and its derivates.Herein,in combination with wittig reaction,a new synthetic method of CA-4 was presented by emploring visible-light promoted photocatalytic isomerization reaction of alkenes,which was proved a green and efficient strategy for the synthesis of cis-alkenes.This study provides an alternative method for the synthesis of CA-4 and further optimization is still ongoing in our lab.