Enantioselective cyanation via radical-mediated C–C single bond cleavage for synthesis of chiral dinitriles

• Published in: Nature communications Vol. 10; no. 1; pp. 5373 - 9
• Main Authors: Wang, Tao, Wang, Yi-Ning, Wang, Rui, Zhang, Bo-Chao, Yang, Chi, Li, Yan-Lin, Wang, Xi-Sheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/403/935; Acids; Asymmetry; Catalysis; Catalysts; Cleavage; Covalent bonds; Diamines; Enantiomers; Esters; Humanities and Social Sciences; Ligands; Light emitting diodes; Mediation; multidisciplinary; Optical activity; Oxime esters; Science; Science (multidisciplinary); Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13369-x

Ring-opening reaction via selective cleavage of C–C bond is known as a powerful strategy for construction of complex molecules. Complementary to the ionic process focusing on mostly small ring systems, radical-mediated C–C bond cleavage offers a solution for further diverse enantioselective functionalization benefited from its mild conditions, whereas such asymmetric transformations are still limited to three-membered rings so far. Herein, we describe radical-mediated ring-opening and enantioselective cyanation of four- and five-membered cycloketone oxime esters to access chiral 1,5- and 1,6-dinitriles. Employment of dual photoredox/copper catalysis is essential for the asymmetric ring-opening cyanation of cyclopentanone oxime esters. Both reactions proceed under mild conditions giving chiral dinitriles in high yields and enantioselectivity with low catalyst loading and broad substrate scope. The products dinitriles can be converted to valuable optically active diamides and diamines. Mechanistic studies indicate that the benzylic radical generated via C–C single bond cleavage is involved in the catalytic cycle. Ring-opening reaction via selective cleavage of C–C bond is a powerful strategy to increase molecular complexity. Here the authors present the facile synthesis of chiral 1,5- and 1,6-dinitriles via the radical-mediated ring-opening and enantioselective cyanation of cycloketone oxime esters.