Three-component enantioselective alkenylation of organophosphonates via nickel metallaphotoredox catalysis

The development of efficient catalytic multicomponent reactions (MCRs) is highly sought-after in chemical synthesis. However, cata-lytic asymmetric MCRs, particularly involving radical species, remain largely underdeveloped due to the exceptionally high reactivity of open-shell radical species. Herein, we report a metallaphotore-dox-cataly zed asymmetric three-component method to access a diverse array of enantio-enriched a-alkenyl phosphonates from readily available vinyl phosphonates, alkenyl halides, and alkyl tri-fluoroborates under mild conditions. This operationally simple and redox-neutral protocol exhibits broad substrate scope and excel-lent chemo-, regio-, stereo-, and enantioselectivity. Furthermore, by simple modification of the triplet energy of the photocatalyst em-ployed, both enantio-enriched trans and cis a-alkenyl phosphonates can be divergently accessed. Detailed computational and experi-mental studies were undertaken to elucidate the mechanism and origin of the observed reactivity and selectivity, which support a radical cascade sequence with a-phosphonate controlling the trajec-tory of radical capture by a chiral tetrahedral alkenyl nickel(II) spe-cies in the enantioselectivity-determining step.

Automated summary

In this study, a catalytic asymmetric three-component method was developed to access enantio-enriched α-alkenyl phosphonates. The method exhibited excellent selectivity and broad substrate scope. By modifying the triplet energy of the photocatalyst, both trans and cis α-alkenyl phosphonates with high enantioselectivity could be obtained. Detailed computational and experimental studies revealed the radical cascade mechanism and the role of α-phosphonate in determining the selectivity.