Enantioselective Copper‐Catalyzed Radical Ring‐Opening Cyanation of Cyclopropanols and Cyclopropanone Acetals

• Published in: Advanced synthesis & catalysis Vol. 362; no. 11; pp. 2189 - 2194
• Main Authors: Wu, Lianqian, Wang, Lei, Chen, Pinghong, Guo, Yin‐Long, Liu, Guosheng
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 26.05.2020; Wiley Subscription Services, Inc
• Subjects: Acetals; Amino acids; asymmetric radical reaction; Carbonyls; Chemistry; Chemistry, Applied; Chemistry, Organic; Copper; copper-catalyzed radical relay; cyclopropanol; Derivatives; Enantiomers; Nitriles; Physical Sciences; radical ring-opening; Radicals; Science & Technology; β-carbonyl nitriles; C BOND-CLEAVAGE; ACTIVATION; DIRECT ARYLATION; REGIOSPECIFIC SYNTHESIS; MECHANISM; VINYL AZIDES; STRATEGY; copper-catalyzed radical relay; beta-carbonyl nitriles; radical ring-opening; GAMMA-LACTAMS; cyclopropanol; H BONDS; asymmetric radical reaction; CONJUGATE ADDITION
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.202000202

A novel approach for enantioselective cyanation of cyclopropanols and their derivatives through copper‐catalyzed radical relay processes has been developed. Various cyclopropanols and cyclopropanone acetals are compatible to the catalytic conditions, providing β‐carbonyl nitriles with excellent enantioselectivity. These products can be readily converted to chiral γ‐amino acids derivatives and drugs such as (R)‐baclofen. Preliminary mechanistic studies have supported a ring‐opening process for cyclopropanoxy radicals followed by copper‐catalyzed enantioselective cyanation of benzylic radicals to form the C−CN bonds in an enantioselective manner.