Functionalization of Alkenes through Telescoped Continuous Flow Aziridination Processes

Abstract

Alkenes can be efficiently aziridinated using highly soluble iminoiodane derivatives under continuous flow conditions. By combining the aziridine generation with nucleophilic ring opening reactions, a variety of products can be made without the need to handle or isolate these potentially hazardous intermediates. Additionally, this chemistry can be used to make and use aziridines that are difficult to isolate and purify because of their high reactivity.

Iodonium imides in organic synthesis

“…Alkenes can be efficiently aziridinated using highly soluble iminoiodanes 11 in the presence of copper catalysts under continuous flow conditions. 63 This approach can be used to synthesize and use in subsequent reactions aziridines that are difficult to isolate and purify because of their high reactivity.…”

Continuous-Flow Synthesis of (–)-Oseltamivir Phosphate (Tamiflu)

“…Due to the safety concerns of handling aziridines, [24][25][26][27] we further demonstrated in situ generation and consumption of aziridine 6 to afford 3-pentyl ether 7 in 87% yield in 20 s residence time (Figure 4).…”

Continuous Flow Technology as an Enabler for Innovative Transformations Exploiting Carbenes, Nitrenes, and Benzynes

“…In 2016, the Shipman group reported the telescoped continuous flow synthesis of aziridines and their subsequent ring opening. 58 Arylsulfonylimino phenyliodanes can be used as nitrene precursors; however, some commonly used derivatives such as those based on tosyl and nosyl systems (PhI = NTs and PhI = NNs) are insoluble in organic solvents, making them unsuitable for use in flow. Through modification of the iminoiodane structure improved solubility can be achieved.…”