Ruthenium Catalyzed Regioselective β‐C(sp3)−H Functionalization of N‐Alkyl‐N′‐p–nitrophenyl Substituted Piperazines using Aldehydes as Alkylating Agents

• Published in: Advanced synthesis & catalysis Vol. 363; no. 2; pp. 453 - 458
• Main Authors: Murugesh, V., Sahoo, Apurba Ranjan, Achard, Mathieu, Sharma, Gangavaram V. M., Bruneau, Christian, Suresh, Surisetti
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 19.01.2021; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Aldehydes; Alkylation; C(sp3)−H functionalization; Catalysis; Chemical Sciences; Chemistry; Chemistry, Applied; Chemistry, Organic; Dehydrogenation; Hydrogen bonds; Physical Sciences; piperazine; Regioselective; Regioselectivity; Ruthenium; ruthenium catalysis; Science & Technology; Substitutes; HYDROGENATION; STRATEGY; piperazine; COMPLEXES; ARYLATION; CASCADE; ruthenium catalysis; C-H FUNCTIONALIZATION; Regioselective; CARBONYLATION; C(sp)-H functionalization; ALPHA-ALKYLATION; alkylation; BOND ACTIVATION; CYCLIC AMINES; C(sp 3 )-H functionalization
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.202001060

Herein, we disclose a ruthenium‐catalyzed regioselective β‐C(sp3)−H bond functionalization on the piperazine core using aldehydes as alkylating agents. The present transformation appears to go through the dehydrogenation of the piperazine to propagate to enamine in situ, followed by nucleophilic addition to the aldehyde and hydrogenation to result in the regioselective β‐C(sp3)−H alkylation. A variety of aromatic, heteroaromatic, aliphatic aldehydes were employed for the C‐3 alkylation of N‐alkyl‐N′‐p‐nitrophenyl substituted piperazines.