Peptide bonds using acyl azides

Peptide bonds can be formed with very little racemization by the use of the azido-phosphonium salt (96). The reagents are simply mixed in DMF at 0 C. Acyl azides can also be obtained from the intermediate salt (97) by raising the temperature. ... 

The acyl azide of Curtius [9, 10] and the acid chloride of Fisher [11] were the predominant methods of peptide bond formation until 1955 when Sheehan [12], Khorana [13], and their co-workers introduced the highly efficient A, N -dicyclohexylcarbodiimide (DCC) coupling reagent. In contrast to the older reagents, DCC did not require carboxyl group pre-activation, and could be used in situ. The convenience and efficiency of DCC were quickly recognized and incorporated into many peptide synthesis protocols. 

The photochemistry of aryl azides is quite complex, suggesting that the nitrene 14 may not be the only reactive intermediate and that insertion reactions may not be the only route to form photoconjugates.Although aryl nitrenes are much less susceptible to rearrangements than acyl nitrenes, they may still occur and lead to the formation of reactive intermediates such as azepines, which may go on to react with nucleophiles.[911 141 Addition of nitrenes to double bonds will generate azirines, while dimerization will produce azobenzenesJ11 Aryl azides are stable to most of the procedures used in the course of peptide synthesis except for reduction reactions. Non-photochemical reduction of aryl azides to the primary amines by thiols has been reported by Staros et al.[15]... 

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