Safe and Facile Access to Nonstabilized Diazoalkanes Using Continuous Flow Technology. Issue 20 (19th April 2018)

• Record Type: Journal Article
• Authors: Rullière, Pauline; Benoit, Guillaume; Allouche, Emmanuelle M. D.; Charette, André B.
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 20(2018)
• Page Start: 5777
• Page End: 5782
• Publication Date: 2018-04-19
• Subjects: continuous flow -- cycloaddition -- diazo compounds -- esterification -- hydrazones; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201802092
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Despite the high synthetic potential of nonstabilized diazo compounds, their utilization has always been hampered by stability, toxicity, and safety issues. The present method opens up access to the most reactive nonstabilized diazoalkanes. Among diazo compounds, nonstabilized alkyl diazo compounds are the least represented because of their propensity to degrade during preparation. The continuous flow oxidation process of hydrazones on a silver oxide column afforded an output stream of base‐ and metal‐free pure diazo solution in dichloromethane. Starting from innocuous ketones and aldehydes, this methodology allows the production of a broad range of unprecedented diazoalkanes compounds in excellent yields, while highlighting their synthetic potential and the possibility of safe large‐scale diazo production. Abstract : Red carpet treatment : Toxicity and safety issues still impede the common use of diazo reagents in academia and industry. Reported here is the safe and scalable production of the most sensitive and reactive diazo reagents, nonstabilized alkyl diazoalkanes. The ease of access to these reactive diazoalkanes allowed their use in esterification, cycloaddition, and Michael‐induced ring‐closure reactions.