Ethyl-2-Cyano-2-(2-Nitrophenylsulfonyloximino)Acetate (ortho-NosylOXY) Mediated One-Pot Racemization Free Synthesis of Ureas, Carbamates, and Thiocarbamates via Curtius Rearrangement

Direct conversion of carboxylic acids to ureas, carbamates, and thiocarbamates in a single pot via Curtius rearrangement is accomplished. One recently established coupling reagent, Ethyl-2-cyano-2-(2-nitrophenylsulfonyloximino)acetate (ortho-NosylOXY, I), is successfully used for the racemization free synthesis of ureas, di-peptidyl ureas, and carbamates with moderate to good yield (82-69%). This single-pot hassle-free procedure works with a diverse range of N-protecting groups Fmoc, Boc, and Cbz. Various amine, including aromatic, methyl esters of amino acids, t-butylamine, alcohols, and thiols, are used as nucleophiles. A detailed NMR-based mechanism study is incorporated here. Racemization suppression, easy removal of by-products, and less waste generation make this methodology useful.

Automated summary

The direct conversion of carboxylic acids to ureas, carbamates, and thiocarbamates in a single pot via Curtius rearrangement is achieved successfully using Ethyl-2-cyano-2-(2-nitrophenylsulfonyloximino)acetate (ortho-NosylOXY, I) as a coupling reagent. This method enables the synthesis of target products with moderate to good yield and is compatible with a diverse range of N-protecting groups, while suppressing racemization generation.