Copper-Catalyzed Enantioconvergent Radical C(sp3)N Cross-Coupling: Access to α,α-Disubstituted Amino Acids

Transition-metal catalyzed enantioconvergent cross-coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural alpha,alpha-disubstituted amino acids. However, the construction of chiral C-N bonds between tertiary-carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper-catalyzed enantioconvergent radical C-N cross-coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N-ligand with a long spreading side arm. An array of alpha,alpha-disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral alpha-fully substituted amine building blocks.

Automated summary

A copper-catalyzed enantioconvergent radical C-N cross-coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions has been developed using a chiral anionic N,N,N-ligand with a long spreading side arm. This method efficiently and selectively synthesizes a range of α,α-disubstituted amino acid derivatives. The synthetic utility of the strategy has been demonstrated through the elaboration of the coupling products into different chiral α-fully substituted amine building blocks.