Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides

Abstract

The pervasive occurrence of saturated stereogenic carbon centers in pharmaceuticals, agrochemicals, functional organic materials, and natural products has stimulated great efforts toward the construction of such saturated carbon centers. We report a reaction mode for the enantioselective construction of alkyl-alkyl bond to access saturated stereogenic carbon centers by asymmetric reductive cross-coupling between different alkyl electrophiles in good yields with great levels of enantioselectivity. This reaction mode uses only alkyl electrophiles for enantioselective C sp3 -C sp3 bond-formation, rendering reductive alkyl-alkyl cross-coupling as an alternative to traditional alkyl-alkyl cross-coupling reactions between alkyl nucleophiles and alkyl electrophiles to access saturated stereogenic carbon centers without the use of organometallic reagents. The reaction displays a broad scope for two alkyl electrophiles with good functional group tolerance. Mechanistic studies reveal that the reaction undergoes a single electron transfer that enabled the reductive coupling pathway to form the alkyl-alkyl bond.