Cyanide-Free Cyanation of sp2 and sp-Carbon Atoms by an Oxazole-Based Masked CN Source Using Flow Microreactors |
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Authors: | Dr. Brijesh M. Sharma Dr. Arun V. Nikam Dr. Santosh Lahore Gwang-Noh Ahn Prof. Dr. Dong-Pyo Kim |
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Affiliation: | Center for Intelligent Microprocess of Pharmaceutical Synthesis Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673 South Korea |
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Abstract: | This work reports a cyanide-free continuous-flow process for cyanation of sp2 and sp carbons to synthesize aryl, vinyl and acetylenic nitriles from (5-methyl-2-phenyloxazol-4-yl) boronic acid [OxBA] reagent as a sole source of carbon-bound masked −CN source. Non-toxic and stable OxBA reagent is generated by lithiation-borylation of bromo-oxazole, and the consecutive Suzuki-Miyaura cross-coupling with aryl, vinyl, or acetylenic halides and demasking [4+2]/retro-[4+2] sequence were successfully accomplished to give the desired cyano compounds with reasonably good yields in a four-step flow manner. A unique feature of this cyanation protocol in flow enables to cyanate a variety of sp2 and sp carbons to produce a broad spectrum of aryl acetonitrile. It is envisaged that the OxBA based cyanation would replace existing unstable and toxic approaches as well as non-toxic cyanation using two different sources of “C” and “N” to incorporate the −CN group. |
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Keywords: | cross-coupling flow chemistry masked cyanation organolithium Retro-Diels-Alder reaction |
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