A One-Pot Synthesis-Functionalization Strategy for Streamlined Access to 2,5-Disubstituted 1,3,4-Oxadiazoles from
Daniel Matheau-Raven1, Darren J Dixon1
1Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, U.K.
Abstract:
A one-pot 1,3,4-oxadiazole synthesis-arylation strategy for accessing 2,5-disubstituted 1,3,4-oxadiazoles, from carboxylic acids, N-isocyaniminotriphenylphosphorane (NIITP), and aryl iodides, is reported. The reaction sequence, featuring a second stage copper-catalyzed 1,3,4-oxadiazole arylation, was found to tolerate (hetero)aryl, alkyl, and alkenyl carboxylic acids, and (hetero)aryl iodide coupling partners. The effectiveness of the two-stage strategy was exemplified by the late-stage functionalization of five carboxylic acid-containing APIs, and an extension to the synthesis of aminated 1,3,4-oxadiazoles using N-benzoyloxy amine coupling partners was also demonstrated.
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