Photosensitized O ₂ enables intermolecular alkene cyclopropanation by active methylene compounds

Abstract

Cyclopropanes are key features in many preclinical, clinical, and commercial drugs, as well as natural products. The most prolific technique for their synthesis is the metal-catalyzed reaction of an alkene with a diazoalkane, a highly energetic reagent requiring stringent safety precautions. Discovery of alternative innocuous reagents remains an ongoing challenge. Herein, we report a simple photoredox-catalyzed intermolecular cyclopropanation of unactivated alkenes with active methylene compounds. The reaction proceeds in neutral solvent under air or dioxygen (O 2 ) with a photoredox catalyst excited by blue light-emitting diode light and an iodine co-catalyst that is either added as molecular iodine or generated in situ from alkyl iodides. Mechanistic investigations indicate that photosensitized O 2 plays a vital role in the generation of carbon-centered radicals for both the addition of active methylene compounds to alkenes and the ring closure.

Optoelectronic materials as emerging photocatalysts: opportunities in sustainable organic synthesis

“…However, the most prolific technique for their synthesis is the metal-catalyzed reactions with highly energetic diazoalkanes, photoredox-catalyzed intermolecular cyclopropanation of unactivated alkenes constitutes a challenging, but more mild approach. 19 Consistent with the superior optical and electronic properties, PTH-POP2 showed higher activity than that of PTH-POP1. Control experiments verified the importance of a photocatalyst, visible light, and inert atmosphere.…”

Nitrogen‐doped Carbon Dots as Efficient Photocatalysts for High Selectivity of Dehalogenative Oxyalkylation of Styrene

“…Undoubtedly, the transfer of electrons from excited N-CDs to substrate 2 a is possible. Based on the above mechanism experiments and literature reports, [58] the possible reaction mechanism is proposed and depicted in Figure 4b. Firstly, N-CDs were excited to the excited state ([N-CDs]*) under 395 nm LEDs irradiation.…”

Thermal/photochemical micro-flow probe system for direct C–H bond functionalization of biologically active molecules

“…After the successful completion of the two-step diazo-transfer and light-induced N–H insertion, we realized that most diazo compounds 4 synthesized via two individual steps require refrigeration storage and must be kept in dark conditions because of their self-dimerization reaction to generate impurities. 43,44 Thus, a safe and efficient integrated 45–50 chemical approach is needed to expand the scope of the diazo-transfer and light-induced N–H insertion, including sulfonyl azide chemistry, towards new unexplored dimensions. The need of the hour is to realize a reactor platform consisting of microfluidic devices that could enable in situ generation of highly energetic diazo compounds with toxic sulfonyl azide reagents, 51,52 which would subsequently aid in the synthesis of the desired amine product, all in a safe and sequential manner.…”