The Use of Tosylhydrazone Salts as a Safe Alternative for Handling Diazo Compounds and Their Applications in Organic Synthesis

• Published in: European Journal of Organic Chemistry 2005-04, Vol.2005 (8), p.1479-1492
• Main Authors: Fulton, J. Robin, Aggarwal, Varinder K., de Vicente, Javier
• Format: Article
• Language: English
• Subjects: Aziridination; Bamford-Stevens reaction; Cyclopropanation; Diazo compounds; Epoxidation; Ether synthesis; Homologation; Hydrazones; Olefination; Pyrazoles
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200400700

Diazo compounds are useful synthetic intermediates in organic synthesis but, due to their toxicity and unpredictable explosive behaviour, their unique reactivity has not been fully exploited and their use on large scale has been avoided. We have developed a reliable method that generates diazo compounds in situ. Our approach is based on the Bamford–Stevens reaction, which utilizes tosylhydrazone salts as diazo precursors. In the presence of phase‐transfer‐catalysts (PTC), we found that tosylhydrazone salts can be cleanly converted to diazo compounds under mild reaction conditions and in a wide range of solvents. These diazo compounds can then be induced to react directly with alkenes or alkynes to synthesize pyrazoles or with aldehydes to generate ketones. Alternatively, diazo compounds can react with transition metals capable of carbene transfer reactions. We have shown the usefulness of this chemistry in a number of different transformations, such as Wittig olefination reactions and the sulfur ylide mediated epoxidation, as well as aziridination and cyclopropanation chemistry as applied toward the synthesis of more complicated molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)