We report a Cu(II)-catalyzed cyclization/coupling of alkenyl aldimines with arylzinc reagents to create indole-3-diarylmethane derivatives (Sapkota et al. ChemRxiv 2022,
We report a Cu(II)-catalyzed cyclization/coupling of alkenyl aldimines with arylzinc reagents to create complex indole-3-diarylmethane derivatives. The aldimines are readily available by simple dehydration, making the process a formal three-component reaction that strategically combines alkenyl aldehydes, anilines and arylzinc reagents to generate substituted indole-3-diarylmethane cores. Since the cyclization/coupling of alkenyl aldimines is unknown to date, the current method discloses an uncharted chemical space with regard to both the substrate and product diversity for this class of reaction.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.