Catalytic asymmetric C–H insertion reactions of vinyl carbocations

From the preparation of pharmaceuticals to enzymatic construction of natural products, carbocations are central to molecular synthesis. Although these reactive intermediates are engaged in stereoselective processes in nature, exerting enantiocontrol over carbocations with synthetic catalysts remains challenging. Many resonance-stabilized tricoordinated carbocations, such as iminium and oxocarbenium ions, have been applied in catalytic enantioselective reactions. However, their dicoordinated counterparts (aryl and vinyl carbocations) have not, despite their emerging utility in chemical synthesis. We report the discovery of a highly enantioselective vinyl carbocation carbon–hydrogen (C–H) insertion reaction enabled by imidodiphosphorimidate organocatalysts. Active site confinement featured in this catalyst class not only enables effective enantiocontrol but also expands the scope of vinyl cation C–H insertion chemistry, which broadens the utility of this transition metal–free C(sp3)–H functionalization platform. Description Biasing vinyl cation insertions Forming a vinyl cation leaves a doubly bonded carbon center stranded with just six electrons instead of eight. Because of this deficiency, these intermediates tend to react extremely quickly and indiscriminately with any other bond in the vicinity. Nistanaki et al. report that a negatively charged, phosphorus-based catalyst can engage a vinyl cation just tightly enough to steer an ensuing intramolecular carbon–hydrogen insertion reaction toward just one of two mirror-image products. Isotopic labeling and computational analysis elucidate the likely mode of induction. —JSY Organocatalysts impart enantiocontrol over dicoordinated vinyl carbocations in C(sp3) –H functionalization reactions.