フッ素による反応の活性化と制御

Abstract

Fluorine has remarkable electronic effects and leaving-group ability as fluoride ion. Paying particular attention to the use of these properties in organic synthesis, we discuss the preparation of gemdifluoroolefins and their synthetic applications. gem-Difluoroolefins with a wide range of substituents are synthesized from commercially available 2, 2, 2-trifluoroethyl p-toluenesulfonate (1), wherein the two processes are included : (i) a boron-mediated alkylation leading to gem-difluorovinylboranes 4, and (ii) a variety of their direct functionalizations via gem-difluorovinylcoppers 5. This methodology provides a useful synthetic route to unsymmetrically disubstituted difluoroolefins via the introduction of difluorovinylidene unit (CF2=C). The obtained difluoroolefins readily undergo addition-elimination, cycloaddition-elimination, and cationic cyclization-elimination processes leading to new synthetic reactions. Regiocontrolled syntheses of fluorinated heterocycles, hetero Diels-Alder reactions, fluorine directed Nazarov cyclizations, Friedel-Crafts cyclizations, and tandem cyclizations in their combination are achieved to construct highly functionalized and/or fused ring systems. Throughout these reactions, fluorine substituent functions as an activator of the substrates and a controller over the reaction pathways.