Investigation of Masked N-Acyl-N-isocyanates: Support for Oxadiazolones as Blocked N-Isocyanate Precursors.

In contrast to carbon-substituted isocyanates that are common building blocks, N-substituted isocyanates remain underdeveloped and reports on their N-acyl derivatives (i. e. amido-isocyanates) are exceedingly rare. Herein, amido-isocyanates were investigated in the context of syntheses of aza-tripeptide and hydantoins subunits starting from simple bench-stable precursors. A key finding is that the amido-isocyanate formed in situ cyclized to yield an oxadiazolone, and that under suitable reaction conditions this heterocycle is a traceless blocked (masked) N-isocyanate. Using organic bases as catalysts and upon heating, oxadiazolone formation is observed, and various nucleophiles to provide the desired aza-dipeptides or hydantoins in moderate to high yields. Further support for an amido-isocyanate intermediate was obtained using carboxylic acids as nucleophiles, affording N-acylhydrazide products.