Stereospecific synthesis of (E)- and (Z)-1-chloro-1,2-difluorostyrenes

Stereospecific synthesis of unsymmetrical (E)- and (Z)-1,2-difluorostilbenes

“…Our objective for the synthesis of unsymmetrical (E)-and (Z)-1,2difluorostilbenes was to start from an easily obtained and stereospecific stating material: such as (E)-or (Z)-2-chloro-1,2-difluoro-1-iodoethene [5], (E)-or (Z)-1chloro-1,2-difluorostyrenes [6]. Initially, we carried out these reactions on a small scale to establish the stereospecificity of the final product and to assist in purification.…”

“…The aryl boronic acids were obtained commercially and used without further purification. The 1-chloro-1,2-difluorostyrenes [6] and 2chloro-1,2-difluoro-1-iodoethene [5] were synthesized according to literature. Pd(PPh3)4 was prepared by Coulson's procedure [11].…”

“…4 and 5). Two synthetic procedures were attempted: first, the zinc reagent from (Z)-2-chloro-1,2-difluoro-1-iodoethene was generated in situ followed by a Negishi coupling [6] and then a boronic acid and…”

“…(E)-and (Z)-1,2-difluorostilbenes can be readily prepared by the protocols 2, 3, or 4, since the 1,4-dioxane solvent system showed an enhanced rate as compared to the benzene/ethanol/water solvent mixture described in protocol 1. However, protocols 2 and 3 are recommended for scale up as the 1-chloro-1,2difluorostyrenes are readily prepared in good yields [6] and further derivatization from a common styrene could lead to a library of unsymmetrical (E)-and (Z)-1,2difluorostilbenes. We feel this methodology provided the best stereospecific route to unsymmetrical (E)-or (Z)-1,2-difluorostilbenes.…”