Catalysis

Enantioselective synthesis

Electrophile

Receptor

Alkyl

Biochemistry

Stereochemistry

Medicinal chemistry

Ligand (biochemistry)

Organic chemistry

Trifluoromethanesulfonate

Radical

Chemistry

Steric effects

Nature Chemistry

In contrast with the well-established enantioconvergent radical C(sp3)–C cross-coupling of racemic secondary alkyl electrophiles, the corresponding coupling of tertiary electrophiles to forge all-carbon quaternary stereocentres remains underexplored. The major challenge arises from the steric hindrance and the difficult enantio-differentiation of three distinct carbon substituents of prochiral tertiary radicals. Here we demonstrate a general copper-catalysed enantioconvergent C(sp3)–C(sp) cross-coupling of diverse racemic tertiary alkyl halides with terminal alkynes (87 examples). Key to the success is the rational design of chiral anionic N,N,N-ligands tailor-made for the computationally predicted outer-sphere radical group transfer pathway. This protocol provides a practical platform for the construction of chiral C(sp3)–C(sp/sp2/sp3) bonds, allowing for expedient access to an array of synthetically challenging quaternary carbon building blocks of interest in organic synthesis and related areas.                                                                  A general copper-catalysed enantioconvergent C(sp3)–C(sp) cross-coupling of diverse racemic tertiary alkyl halides with terminal alkynes has been developed, forging all-carbon quaternary stereocentres. Key to the success is the rational design of chiral anionic N,N,N-ligands tailor-made for the computationally predicted outer-sphere radical group transfer pathway.

Mechanism-based ligand design for copper-catalysed enantioconvergent C(sp3)–C(sp) cross-coupling of tertiary electrophiles with alkynes