A wide range of aziridines--three-membered rings containing one nitrogen and two carbon atoms--are now accessible through an electrochemical process that requires no metal catalysts or oxidation reagents. Its organic chemist inventors at the University of Toronto believe the strategy will be adaptable to a wide range of chemical transformations.

Developing synthetic methods that generate minimal amounts of waste has become an important challenge for chemists. So Toronto assistant professor of chemistry Andrei K. Yudin and his graduate student Tung Siu were hoping to improve a method of preparing aziridines by reducing the amount of lead oxidant it required.

	Yudin PHOTOS BY SHAHLA YEKTA
	Siu

"Our initial goal was to learn how to run the reaction with only catalytic amounts of toxic metals such as lead," Yudin tells C&EN. "The thought was that we might find a redox shuttle between lead's oxidation states using electrodes in electron transfer. Fortuitously, we discovered that, in the lead-based olefin aziridination, nitrogen transfer can be run using just electricity in the redox 'window' where lead(IV) normally operates, with no added lead catalysts or reagents."

Aziridines are valuable synthetic intermediates because the strained three-membered ring can be opened by a variety of nucleophiles, leading to a pattern of heteroatom substitution that appears regularly in natural products and drugs. Yudin and Siu's approach springs from a common method of making aziridines by metal-mediated transfer of a nitrene to an olefin. The electrochemical strategy, which uses two platinum electrodes and a reference silver electrode in a divided cell, employs N-aminophthalimide as the nitrene precursor. It succeeds with a wide range of olefins, both electron-rich and electron-poor [J. Am. Chem. Soc., 124, 530 (2002)].

Although electrochemical processes are widely used on a massive scale in industry, many organic chemists shy away from them. Yudin thinks that is because electrochemistry tends to be taught in an analytical, rather than organic synthesis, context. He himself learned the subject by reading the book "Synthetic Organic Electrochemistry" by Albert J. Fry, professor of organic chemistry at Wesleyan University, Middletown, Conn.

Fry comments that the Toronto work is interesting as a new and efficient route to N-phthalimidoaziridines. "But it remains to be seen whether it's a general process for synthesis of aziridines bearing other groups on nitrogen, and in its present form, it does not appear adaptable to synthesis of enantiomerically pure aziridines," he notes. "The need for controlled potential electrolysis and a divided cell will make it difficult to scale up to large quantities in a flow cell."

Yudin says his group is already working on enantioselective versions of the reaction and on using other amines and hydrazines as nitrene precursors. The researchers are also delving into combinatorial electrosynthesis. [Curr. Opin. Chem. Biol., 5, 269 (2001)].

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