Synthesis 2017; 49(20): 4670-4675
DOI: 10.1055/s-0036-1590802
special topic
© Georg Thieme Verlag Stuttgart · New York

1,3,4-Oxadiazole and Heteroaromatic-Fused 1,2,4-Triazole Synthesis­ Using Diverted Umpolung Amide Synthesis

Kazuyuki Tokumaru*, Kalisankar Bera, Jeffrey N. Johnston*
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health (GM 063557).
Further Information

Publication History

Received: 02 May 2017

Accepted after revision: 29 May 2017

Publication Date:
07 August 2017 (eFirst)

Published as part of the Special Topic Modern Strategies for Heterocycles Synthesis

Abstract

Umpolung Amide Synthesis (UmAS) has emerged as a superior alternative to conventional amide synthesis methods based on carbonyl electrophiles in a range of situations, particularly when epimerization-prone couplings are prescribed. In an unanticipated development during our most recent studies, we discovered that diacyl hydrazide products from UmAS were not formed as intermediates when using an acyl hydrazide as the amine acceptor. This resulted in a new preparation of 1,3,4-oxadiazoles from α-bromonitroalkane donors. We hypothesized that a key tetrahedral intermediate in UmAS was diverted toward a more direct pathway to the heterocycle product rather than through formation of the diacyl hydrazide, a typical oxadiazole progenitor. In studies reported here, diversion to 1,2,4-triazole products is described, a behavior hypothesized to also result from an analogous tetrahedral intermediate, but one formed from heteroaromatic hydrazine acceptors.

Supporting Information

 
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