A Transient Directing Group Strategy Enables Enantioselective Multicomponent Organofluorine Synthesis

The
vicinal fluorofunctionalization of alkenes represents an expedient
strategy for converting feedstock olefins into valuable fluorinated
molecules and as such has garnered significant attention from the
synthetic community; however, current methods remain limited in terms
of scope and selectivity. Here we report the site-selective palladium-catalyzed
three-component coupling of alkenylbenzaldehydes, arylboronic acids,
and N-fluoro-2,4,6-trimethylpyridinium hexafluorophosphate
facilitated by a transient directing group. The synthetically enabling
methodology constructs vicinal stereocenters with excellent regio-,
diastereo-, and enantioselectivities, forging products that map onto
bioactive compounds.

烯烃的邻位氟官能化（vicinal fluorofunctionalization）是将原料烯烃转化为高价值含氟分子的便捷策略，因此受到合成化学界的广泛关注；但当前方法在反应范围与选择性方面仍存在局限。本文报道了由瞬态导向基（transient directing group）辅助的位点选择性钯催化烯基苯甲醛、芳基硼酸与六氟磷酸N-氟-2,4,6-三甲基吡啶鎓的三组分偶联反应。该具备合成应用价值的方法能够以优异的区域选择性、非对映选择性和对映选择性构建邻位手性中心，所得产物可对应于生物活性化合物的分子结构。