The ability to form multiple carbon–carbon bonds in a controlled sequence and thus rapidly build molecular complexity in an iterative fashion is an important goal in modern chemical synthesis. In recent times, transition-metal-catalysed coupling reactions have dominated in the development of C–C bond forming processes. A desire to reduce the reliance on precious metals and a need to obtain products with very low levels of metal impurities has brought a renewed focus on metal-free coupling processes. Here, we report the in situ preparation of reactive allylic and benzylic boronic acids, obtained by reacting flow-generated diazo compounds with boronic acids, and their application in controlled iterative C–C bond forming reactions is described. Thus far we have shown the formation of up to three C–C bonds in a sequence including the final trapping of a reactive boronic acid species with an aldehyde to generate a range of new chemical structures.
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The authors acknowledge Pfizer (C.B., D.M.A. and D.C.B.), the Studienstiftung des deutschen Volkes (German National Academic Foundation, F.F.), the Alexander-von-Humboldt foundation (A.H.), Erasmus+ (M.S.), the Swiss National Science Foundation (D.N.T.) and the EPSRC (S.V.L., grants nos. EP/K009494/1 and EP/M004120/1) for financial support. The authors thank J.M. Hawkins for discussions and R.M. Turner for providing assistance throughout the development of the research programme.
The authors declare no competing financial interests.
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Battilocchio, C., Feist, F., Hafner, A. et al. Iterative reactions of transient boronic acids enable sequential C–C bond formation. Nature Chem 8, 360–367 (2016). https://doi.org/10.1038/nchem.2439
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