Phototransposition of Indazoles to Benzimidazoles: Tautomer-Dependent Reactivity, Wavelength Dependence, and Continuous Flow Studies

Herein, we report a detailed investigation of the photomediated transformation of indazoles to benzimidazoles through a nitrogen-carbon transposition. This phototransposition is known to occur in low yield when 1H-indazoles are subjected to high-energy UVC irradiation. The 2H-tautomer of indazole absorbs light more strongly than the 1H-tautomer at longer wavelengths. We leveraged this improved absorbance profile to develop a general system for the high-yielding conversion of N2-derivatized indazoles (prepared from the corresponding 1H-indazoles) to the corresponding benzimidazoles under UVB or UVA irradiation in up to 98% yield. Investigation of the substrate scope revealed a strong correlation between reaction yield and electron density at N2 of the indazole substrate, suggesting the importance of the availability of the lone pair at this position for reaction efficiency. In addition, evaluation of wavelength-dependent reactivity through the generation of a photochemical action plot revealed that the highest conversion does not only occur at the substrate's maximum absorbance wavelength but also on its red-side, enabling the use of longer wavelength irradiation to achieve high yields. Building on these insights, a continuous flow protocol was established that enables the phototransposition on preparative scale.