Abstract

Taming Diazo Transfer Chemistry in Flow

Anita Maguire, Professor of Pharmaceutical Chemistry, University College Cork

While diazo chemistry offers a myriad of diverse, synthetically powerful transformations, the challenges associated with the safe handling of potentially shock sensitive reactants and intermediates render them unattractive for large scale process chemistry. Use of flow chemistry to generate and use toluenesulfonyl azide in situ as a diazo transfer reagent enables safe synthesis of significant amounts of diazo compounds without ever having to isolate, store or handle the shock sensitive reagent. To enhance this further, a safety quench has been devised to eliminate any unreacted diazo transfer agent in the event of an inefficient reaction. In addition, the ability to control the process through continuous flow, enables enhanced yields and purity, providing diazocarbonyl compounds sufficiently pure to use in synthesis without chromatographic purification. As an illustrative example, In some instances the yield of sensitive diazosulfoxides has been enhanced 2-3 fold compared to standard batch conditions. Another aspect of our work is focused on the use of flow chemistry to conduct complex multistep cascade processes, offering enhanced process control relative to standard batch conditions.