Ni-Electrocatalytic Enantioselective Doubly Decarboxylative C(sp3)-C(sp3) Cross Coupling

The first examples of enantioselective doubly decarboxylativecrosscoupling are disclosed. Malonate half amides are smoothly coupledto a variety of primary carboxylic acids after formation of the correspondingredox-active esters under Ni-electrocatalytic conditions using a newchiral ligand based on PyBox, resulting in amides with alpha-alkylatedstereocenters. The scope of the reaction is broad, tolerating numerousfunctional groups, and uniformly proceeds with high ee. Finally, thepotential utility of this enantioselective radical-radicalreductive cross coupling to simplify synthesis is demonstrated withnumerous case studies.

Automated summary

The first examples of enantioselective doubly decarboxylative cross coupling are reported. Malonate half amides are successfully coupled to primary carboxylic acids via formation of redox-active esters under Ni-electrocatalytic conditions using a new chiral ligand based on PyBox. The reaction demonstrates a broad scope, tolerates various functional groups, and shows high enantioselectivity. The potential utility of this enantioselective radical-radical reductive cross coupling for synthesis simplification is demonstrated through several case studies.