Advances in the synthesis of indazoles: regioselective C-7 functionalization by directed ortho metalation and progress towards indazole based azaborine compounds

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Cullen, Fu
indazole , directed ortho metalation , azaborine
As one of the fundamental heterocyclic building blocks, indazole and its derivatives have spurred significant research interest and patented applications. In particular, C-7 substituted indazole derivatives are of prime interest due to their significant bioactivities. Azaborine molecules incorporating the B-N structural motif are also of prime interest to chemists and material scientists stemming from their distinctive photophysical properties. The aim of this thesis is to construct new azaborine targets incorporating the indazole framework using Directed ortho Metalation (DoM) reactions as a key step, as well as devise new methods for C-7 functionalization of indazole heterocycles using DoM reactions. Successful N-1 functionalization of indazoles enabled the subsequent Suzuki-Miyaura or Sonogashira cross coupling reactions to prepare C-3 substituted indazoles. Efforts in Directed ortho Metalation (DoM) reactions at the C-3 aryl groups of substituted indazoles towards azaborine targets were unsuccessful. Internal alkyne bearing substituted indazole was subjected to hydroboration conditions but without any conversion to the desired products. C-3 protected Indazoles bearing N- Directed Metalation Groups (DMGs) enabled their C-7 functionalization using DoM chemistry, and thereby led to the development of a new general route to these derivatives.
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