Metal‐Free [2+3] Dipolar Cycloaddition/Denitration Cascade between Nitroalkenes and α‐Diazoesters: Regioselective Access to Functionalized NH−Pyrazoles

• Published in: Asian journal of organic chemistry 2024-06, Vol.13 (6), p.n/a
• Main Authors: Kumar, Ganesh, Ray, Subhasish, Saha, Satyen, Shankar Singh, Maya
• Format: Article
• Language: English
• Subjects: 1,3-Dipolar cycloaddition; Cycloaddition; Denitration; DFT Studies; Nitroalkenes; Pyrazole; Pyrazoles; Regioselective; α-Diazoesters
• ISSN: 2193-5807; 2193-5815
• DOI: 10.1002/ajoc.202400077

An efficient one‐pot synthesis of 1H‐pyrazoles has been realized via cascade cyclocondensation of β‐nitroalkenes as C2 synthon with α‐diazoesters as C1N2 unit. The reaction proceeds via concomitant formation of two new (C−N & C−C) bonds in one stretch leading to ethyl‐5‐nitro‐4‐phenyl‐4,5‐dihydro‐3H‐pyrazole‐3‐carboxylate intermediate, which undergoes base mediated denitration enabling the formation of NH−pyrazoles. This protocol not only features easy operation, catalyst−free conditions, good to high yields, wide scope and late‐stage functionalization, but also opens up a new avenue for synthetically demanding and structurally non‐traditional pyrazoles. A combination of experimental and DFT studies provide evidence for the proposed mechanism. An efficient one‐pot synthesis of 1H‐pyrazoles has been realized via cascade cyclocondensation of β‐nitroalkenes as C2 synthon with α‐diazoesters as C1N2 unit. The reaction proceeds via concomitant formation of two new (C−N & C−C) bonds in one stretch leading to ethyl‐5‐nitro‐4‐phenyl‐4,5‐dihydro‐3H‐pyrazole‐3‐carboxylate intermediate, which undergoes base mediated denitration enabling the formation of NH−pyrazoles.