Regitz diazo transfer

What is Regitz diazo transfer?

In 1967, Regitz reported a reaction that involves the transfer of a diazo group from an azide to an active methyl or methylene moiety of a substrate that has one or more electron-withdrawing groups. This reaction is known as the Regitz diazo transfer.

Regitz diazo transfer - general reaction scheme
Regitz diazo transfer

The commonly used azides for this reaction are tosyl azide, p-acetamidobenzenesulfonyl azide, trisyl azide, PNBSA, mesyl azide, p-carboxybenzenesulfonyl azide, trifluoromethanesulfonyl azide, 2-azido-3-ethylbenzenethiazolium tetrafluoroborate, 1-ethyl-2-azidopyridinium tetrafluoroborate, (azidochloromethylene)-dimethylammonium chloride, naphthalene-2-sulfonyl azide, p-(n-dodecyl)benzenesulfonyl azide, diphenyl phosphorazindaze, p-nitrophenyl azide, and polystyrene benzenesulfonyl azide.

The active methyl or methylene group adjacent to a single electron-withdrawing group is often acylated before diazotization, followed by deacylation. However, this reaction has some intrinsic drawbacks, such as the azo coupling of the diazo compound with the starting material, the unpredictable transfer of the azido group, and the difficulty in separating the excess reagent and p-toluenesulfonamide. Trisyl azide is a better option than TsN3 during the diazotization of cyclic ketone but mainly transfers an azido group to the acyclic imide and ester enolate.

Regitz diazo transfer has general applications in organic synthesis, especially for the 1,3-dipolar cycloaddition of diazo compounds.

References

Regitz, M. (1967), New Methods of Preparative Organic Chemistry. Transfer of Diazo Groups. Angew. Chem. Int. Ed. Engl., 6: 733-749. https://doi.org/10.1002/anie.196707331

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