Photosensitized Dioxygen Enables Intermolecular Cyclopropanation of Alkenes Directly with Active Methylene Compounds


Cyclopropane, a versatile synthetic intermediate, is forged as a key structural feature in many preclinical, clinical and commercial drugs, and occur as a skeletal motif in numerous natural products. The most prolific technique for its synthesis is the metal-catalyzed reaction of an alkene with a diazoalkane, a highly energetic, reactive and explosive reagent requiring stringent safety precautions. The expedient construction of cyclopropyl ring on alkenes with convenient and innocuous reagents under nonhazardous conditions remains an ongoing challenge. Herein, we report a simple photoredox-catalyzed intermolecular cyclopropanation of unactivated alkenes with a diverse set of active methylene compounds that demonstrates striking conceptual and practical synthetic advances over the known methods. The reaction proceeds with a photoredox catalyst (PC*) excited under a blue LED light in air/O2 and neutral reaction conditions in the presence of catalytic amounts of iodine, either in the form of added molecular I2 or generated in situ from alkyl iodides. . The reaction demonstrates a remarkably broad scope on the applicability of 19 different active methylene compounds in 5 different clusters from the standpoint of synthetic tolerability, and tolerates a wide range of functional groups. Moreover, the reaction is also amenable for the cyclopropanation of alkenes in complex molecular architectures, pharmaceuticals and natural products. Mechanistic investigation through the isolation of a series of intermediate products, probes, control experiments, UV-Vis and fluorescence studies indicate that photosensitized dioxygen plays a vital role in the generation of carbon-centered radicals for both the addition of active methylene compounds to alkenes and ring closure, and catalytically generated iodine recycles the PC.