Ni-Electrocatalytic Enantioselective Doubly Decarboxylative C(sp<sup>3</sup>)–C(sp<sup>3</sup>) Cross Coupling
Yang Gao, Benxiang Zhang, Jiayan He, Phil S. Baran
Abstract
The first examples of enantioselective doubly decarboxylative cross coupling are disclosed. Malonate half amides are smoothly coupled to a variety of primary carboxylic acids after formation of the corresponding redox-active esters under Ni-electrocatalytic conditions using a new chiral ligand based on PyBox, resulting in amides with α-alkylated stereocenters. The scope of the reaction is broad, tolerating numerous functional groups, and uniformly proceeds with high ee. Finally, the potential utility of this enantioselective radical-radical reductive cross coupling to simplify synthesis is demonstrated with numerous case studies.
Topics & Concepts
ChemistryEnantioselective synthesisStereocenterMalonateLigand (biochemistry)StereochemistryCoupling reactionAmideCombinatorial chemistryAlkylationDecarboxylationMedicinal chemistryOrganic chemistryCatalysisReceptorBiochemistryRadical Photochemical ReactionsCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling Reactions