Access semi-stabilized and unstabilized diazo compounds using iodosylbenzene

Abstract

Continuous flow chemistry has become the method of choice for the synthesis of toxic and explosive intermediates such as diazo reagents because they can be generated on demand and readily used, eliminating the need to handle hazardous materials. This inherent increase in safety makes it more feasible to use these reagents in day-to-day synthesis. Herein, we describe a continuous flow, metal-free, easy-to-use method for the preparation of semi-stabilized and unstabilized diazo reagents. The scope of the described continuous flow oxidation of hydrazones using a packed bed column with iodosylbenzene includes 13 semi-stabilized and 13 unstabilized diazo reagents in solution in dichloromethane while producing only 1 equivalent of water and iodobenzene as by-products. These otherwise difficult to access compounds are further reacted either in situ or at the reactor outlet to yield esters and ethers in good to excellent yields (47–96%).

Graphical Abstract