Switchable Regiodivergent Reductive Alkyl–Alkyl Coupling by Nickel Catalysis: Sorting Different Alkyl–Nickel Intermediates
Abstract
Abstract Site‐selective and divergent functionalizations on saturated alkyl chain at specific unfunctionalized positions is a key challenge in organic chemistry and other related areas and offers unprecedented synthetic opportunities. Herein, a ligand‐controlled Ni‐catalyzed site‐selective and divergent alkyl–alkyl reductive coupling between two different alkyl halides has been developed. Notably, the reaction finely tunes and recognizes thermodynamic favored α‐aminoalkyl radicals over β‐aminoalkyl radicals, and distal ipso ‐alkyl radicals to deliver chemo‐ and position‐selective alkylation of unactivated α‐H and β‐H of amines under reductive conditions. Moreover, the reaction selectively functionalizes one alkyl chain over two migratable alkyl chains. By just switching the catalytic parameters, α‐ and β‐alkylation of saturated C─H bonds, and ipso ‐alkyl‐alkyl coupling allow for rapid access to three types of branched aliphatic amine architectures from identical starting materials.
Article Details
Authors (6)
Quan‐Xing Zi
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis Guangming Advanced Research Institute Shenzhen Grubbs Institute Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis Southern University of Science and Technology Shenzhen Guangdong 518055 P.R. China
Lin Min
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis Guangming Advanced Research Institute Shenzhen Grubbs Institute Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis Southern University of Science and Technology Shenzhen Guangdong 518055 P.R. China
Hai‐Wu Du
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis Guangming Advanced Research Institute Shenzhen Grubbs Institute Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis Southern University of Science and Technology Shenzhen Guangdong 518055 P.R. China
Qiong Yu
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Shenzhen Grubbs Institute, Guangming Advanced Research Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis
Yu‐Long Li
College of Chemistry and Environmental Engineering Key Laboratory of Green Catalysis of Higher Education Institutes of Sichuan Sichuan University of Science and Engineering Zigong Sichuan 643000 P.R. China
Wei Shu
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Shenzhen Grubbs Institute, Guangming Advanced Research Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis