A general method for oxazole synthesis by photoinduced [3+2] cycloaddition of carbene and nitriles Argha Saha, Debabrata Maiti Indian Institute of Technology Bombay (Iit Bombay), India The design of sustainable protocols is essential to fulfill the growing demands of greener synthetic methodologies. In this context, the use of visible light as an alternative source of energy has been reshaping the organic synthesis. The photocatalysis functions via unorthodox open-shell mechanisms when merged with transition metal catalysis or with the assistance of a photosensitizer. This aspect is an ever-expanding domain in organic synthesis that has revisited and recreated the traditional modes of a plethora of organic transformations. The other mode of reactivity is via photolysis, which depends on the ability of the concerned substrate to harness of the light energy directly. 1 Diazo compounds are attractive precursors in organic synthesis, which have exhibited unique reactivity in the genre of transition metal catalysis via the generation of metal carbenes. However, the use of metals always limits the practical applicability of the protocol particularly from the sustainable perspective. 2 Noteworthy, in presence of visible light diazo compounds can undergo photolysis to singlet carbenes, which can be tapped to realize a sustainable synthesis. Utilizing these carbene species we have established a general protocol for the synthesis of substituted oxazoles by [3+2] cycloaddition reaction engaging a wide spectrum of nitriles. A library of isotope-labeled oxazole derivatives are synthesized, which includes nonsteroidal anti-inflammatory drug felbinac as well as a series of bioactive alkaloids like pimprinine, balsoxin and ugnenenazole respectively. 3 Furthermore, streamlining the synthesis of natural products and drug-diversification through late-stage functionalizations underscore the importance of this sustainable protocol. To demonstrate the application and the scalability of this methodology, the photolysis was merged with continuous-flow chemistry for the synthesis of diverse oxazoles. 4 The generation of a structurally diverse oxazole molecules taming the photo-energy demonstrates the robustness of the protocol. References 1. Yang, Z.; Stivanin, M. L.; Jurberg, I. D.; Koenigs, R. M. Visible light-promoted reactions with diazo compounds: a mild and practical strategy towards free carbene intermediates. Chem . Soc. Rev ., 2020 , 49 , 6833-6847. 2. Doyle, K. J.; Moody, C. J. The rhodium carbenoid route to oxazoles. Synthesis of 4-functionalised oxazoles; three step preparation of a bis-oxazole. Tetrahedron , 1994 , 50 , 3761-3772. 3. Loh, Y. Y.; Nagao, K.; Hoover, A. J.; Hesk, D.; Rivera, N. R., Colletti, S. L.; Davies, I. W.; MacMillan, D. W. C. Photoredox- catalyzed deuteration and tritiation of pharmaceutical compounds. Science 2017 , 358 , 1182-1187. 4. Laudadio, G.; Noël, T.Photochemical transformations in continuos-flow reactors. In Volume 2 Flow Chemistry – Applications ; Darvas, F.; Dormán, G.; Hessel, V.; Ley, S.V. (Eds.), De Gruyter, 2021, 1-30. DOI : 1515/9783110693690-001
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