LAUSR

The substitution of an alkyl electrophile by a nucleophile is a foundational reaction in organic chemistry that enables the efficient and convergent synthesis of organic molecules. Whereas substantial progress has been reported in recent years in exploiting transition-metal catalysis to dramatically expand the scope of nucleophilic substitution reactions using carbon nucleophiles1-4, there has been limited progress in corresponding reactions with nitrogen nucleophiles5-8. Furthermore, for many substitution reactions, the bond construction itself is not the only challenge, as there is a need to control stereochemistry at the same time. Here we describe a method for the enantioconvergent substitution of unactivated racemic alkyl electrophiles by a ubiquitous nitrogen-containing functional group, an amide, through the use of a photoinduced catalyst system based on copper, an earth-abundant metal. This process for asymmetric N-alkylation relies upon three distinct ligands: a bisphosphine, a phenoxide and a chiral diamine, that assemble, in situ, a copper/bisphosphine/phenoxide complex that serves as a photocatalyst and a chiral copper/diamine complex that catalyzes enantioselective C-N bond formation. This study thus expands enantioselective N-substitution by alkyl electrophiles beyond activated electrophiles (those bearing at least one sp- or sp2-hybridized substituent on the carbon undergoing substitution)8-13 to include unactivated electrophiles.