Synthesis of gem-Difluorinated Heterocycles Using aDi fluoropropargyl Molecular Scaffold

摘要

The practical syntheses of gem-difluoro homo propargyl-alcohols, -ethers, -esters, -amides and -ketones are reported.The fluorinated alcohols cyclize under AgNO3 catalysis to givesubstituted tetra-, dihydrodifluorofurans and fluorofurans; theyalso yield tri-substituted fluorofurans under basic conditionsand iodine trapping followed by a cross-coupling reaction.gem-Difluorohomopropargyl ethers furnish difluoroiso-chromans after a rhodium-catalyzed [2+2+2] cycloaddition,whereas gem-difluoroamides are converted to thecorresponding β- or y-lactams selectively via a 4-exo-digonalor 5-endo-digonal cyclization modes, respectively. Altern-atively these amides could be converted into 4,4-difluoro-3-oxoisoquinolines using enyne ring closing meta-thesisfollowed by a Diels-Alder rection. These isoquinolines, inturn, react in a Diels-Alder fashion to yield a heterotricyclicsystem. Finally, gem-difluoroamides yield difluoro-1,4-dihydro-3(2H)-isoquinolinones via a [2+2+2] rhodium-catalyzed cycloaddition.