Development of new fluorinated synthons (E)/(Z)-1-chloro-1,2-difluoro-2-iodoethenes: A single step or sequentially two steps stereospecific preparation of alpha,beta-difluoro ethenyl compounds with symmetrical or unsymmetrical substituents.

摘要

Stereospecific introduction of the alpha,beta-difluoroethenyl unit into organic molecules is very important and challenging. We expect that a fluorinated synthon approach has advantages over other fluorination methods in achieving this goal.; Two important fluorinated synthons with stereospecific alpha,beta-difluoroethenyl unit and two different functional groups, cis/trans-1-tributylstannanyl-2-trimethylsilyl-1,2-difluoroethenes, were synthesized from the commercially available starting material, bromotrifluoroethene, by a method reported by our group. The hydride addition-elimination reaction and the radical catalyzed photoisomerization enabled the stereospecific introduction of the stannanyl and silyl groups into the alpha,beta-difluoroethenyl structure.; Hypervalent iodonium chemistry allowed the stereospecific formation of ethenyl chlorides from the stannyl moieties of cis/trans-1-tributylstannanyl-2-trimethylsilyl-1,2-difluoroethenes. Further elaboration incorporated ethenyl iodides into these difluoroethenyl synthons to afford cis/trans-1-chloro-2-iodo-1,2-difluoroethene with absolute stereochemical control.; The ethenyl iodide groups in dihalogenated alpha,beta-fluorinated ethenyl synthons were excellent in generating the corresponding zinc reagents, which were utilized in Negishi type coupling reactions to afford various kinds of beta-chloro-alpha,beta-difluorostyrenes.; Suzuki type coupling reactions were used in order to functionalize the ethenyl chlorides groups, which performed best with K3PO4 base in dioxane solvent. Additionally, because of the reactivity difference between vinyl iodide and chloride, the Suzuki reactions could be successfully applied with 1-chloro-2-iodo-1,2-difluoroethene. This dual Suzuki reaction could afford either symmetrical or unsymmetrical alpha,beta-difluorinated stilbenes in a one-pot reaction or sequentially in two steps.; A fluorinated 1,3-butadienyl structure could be obtained stereospecifically by assembling 1-chloro-2-iodo-1,2-difluoroethene and another difluorinated synthon by the Negishi reaction. This method possibly affords all of the stereoisomers of 1,2,3,4-tetrafluoro-buta-1,3-dienes stereospecifically. Stereospecific synthesis of higher polyenes is conceptually possible by analogous assembly.; These new fluorinated synthons, cis/trans-1-chloro-2-iodo-1,2-difluoroethene, provided a useful synthetic pathway to alpha,beta-difluorinated stilbenes and a fluorinated 1,3-butadienyl structure with total stereochemical control. This new fluorinated synthon could be valuably utilized in the synthesis of organic molecules with stereospecific alpha,beta-difluoroethenyl units.