Copper-Catalyzed Chemo- and Enantioselective Radical 1,2-Carbophosphonylation of Styrenes

The copper-catalyzed enantioselective radical difunctionalization of alkenes from readily available alkyl halides and organophosphorus reagents possessing a P-H bond provides an appealing approach for the synthesis of alpha-chiral alkyl phosphorus compounds. The major challenge arises from the easy generation of a P-centered radical from the P-H-type reagent and its facile addition to the terminal side of alkenes, leading to reverse chemoselectivity. We herein disclose a radical 1,2-carbophosphonylation of styrenes in a highly chemo- and enantioselective manner. The key to the success lies in not only the implementation of dialkyl phosphites with a strong bond dissociation energy to promote the desired chemoselectivity but also the utilization of an anionic chiral N,N,N-ligand to forge the chiral C(sp(3))-P bond. The developed Cu/N,N,N-ligand catalyst has enriched our library of single-electron transfer catalysts in the enantioselective radical transformations.

Automated summary

The copper-catalyzed enantioselective radical difunctionalization of alkenes provides a convenient method for synthesizing alpha-chiral alkyl phosphorus compounds. The main challenge lies in controlling the chemoselectivity due to the generation of P-centered radicals from the P-H-type reagent. This study introduces a highly chemo- and enantioselective radical 1,2-carbophosphonylation of styrenes by using dialkyl phosphites and an anionic chiral N,N,N-ligand as key components.