A convenient synthesis of chiral 1,2,4-oxadiazoles from N-protected (α-aminoacyl)benzotriazoles

Abstract

Abstract1,2,4-Oxadiazoles (4a-k, 6a-c, 7a-d, and 11a-f) derived from chiral α-amino acids were synthesized in 70-94% yields via a fast and easy procedure under mild conditions. They were shown to be at least 97% enantiomerically pure by HPLC and NMR.

The new era of 1,2,4-oxadiazoles

“…Chirality in 1,2,4-oxadiazole based molecules is important to confer new properties to light interacting materials 15 and increase selectivity as bioactive molecules. 5, 16 In this context, while the introduction of elicity into 1,2,4-oxadiazole systems remains relatively unexplored, the direct linkage of a chiral center into 1,2,4-oxadiazoles can be easily achieved using a N-protected activated amino acid as a source for the C(5) 16 such as in the case of compound 34 bearing two chiral orthogonally protected amino moieties (Fig. 2).…”

1,2,3-Triazoles

“…The methodology can be readily extended to tripeptides <2006S411> . Reactions of derivatives 938 with amidoximes lead to 5-(α-aminoalkyl)-1,2,4-oxadiazoles 939 in high yields and with preservation of chirality <2005ARK(vii)36> ( Scheme 155 ). Reactions of aminoacylbenzotriazoles 938 with pyrrole and N -methylpyrrole in the presence of AlCl 3 give chiral 2-(aminoacyl)pyrroles 940 .…”

Acylbenzotriazoles as Advantageous N-, C-, S-, and O-Acylating Agents

“…Thus, we have demonstrated a convenient procedure for chiral 1,2,4-oxadiazoles from amino acids using the N-acylation and subsequent O-acylation as illustrated in Scheme 11. 14 The N-acylation of ptolyl amidoxime with N-protected (aminoacyl)benzotriazoles occurred at 23°C within 1 minute in ethanol in the presence of Et 3 N (cat. ), and subsequently the intermediates were quantitatively converted into the chiral 1,2,4oxadiazoles under reflux within 5 minutes with preservation of the original chirality supported by HMR and HPLC analysis.…”