Bartholomew G Logan, Kim Sojung F, Oyamada Yusuke, Sbordone Federica, Carroll Joshua A, Jurczyk Justin E, Yeung Charles S, Barner-Kowollik Christopher, Sarpong Richmond
Department of Chemistry, University of California, Berkeley, Berkeley, California, 94720, USA.
School of Chemistry and Physics, Centre for Materials Science, Queensland University of Technology (QUT), Brisbane, Queensland, 4000, Australia.
Angew Chem Int Ed Engl. 2025 Jul 28;64(31):e202423803. doi: 10.1002/anie.202423803. Epub 2025 Jun 23.
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.
在此，我们报告了一项关于通过氮-碳转位将吲唑光介导转化为苯并咪唑的详细研究。已知当1H-吲唑受到高能UVC照射时，这种光转位反应的产率较低。吲唑的2H-互变异构体在较长波长下比1H-互变异构体对光的吸收更强。我们利用这种改善的吸收特性，开发了一种通用体系，可在UVB或UVA照射下将N2-衍生的吲唑（由相应的1H-吲唑制备）高产率地转化为相应的苯并咪唑，产率高达98%。对底物范围的研究表明，反应产率与吲唑底物N2处的电子密度之间存在很强的相关性，这表明该位置孤对电子的可用性对反应效率很重要。此外，通过生成光化学作用曲线对波长依赖性反应性进行评估，结果表明最高转化率不仅出现在底物的最大吸收波长处，还出现在其红移侧，这使得使用更长波长的照射也能实现高产率。基于这些见解，建立了一种连续流动方案，能够实现制备规模的光转位反应。
