Functionalization of Alkyl Groups Adjacent to Azoles: Application to the Synthesis of α-Functionalized Carboxylic Acids

Abstract

AbstractA plethora of bioactive compounds and natural products bears an azole subunit within their complex structural frameworks. A footstep to realize those complex structures in atom economic fashion rely on the direct functionalization of C–H bonds adjacent to an azole group. In addition, the resulting functionalized azole compounds can be simply modified into practically significant genre of α-functionalized carboxylic acids that are otherwise inaccessible through a formal α-functionalization strategy. In this Account, we describe an up-to-date progress on the functionalization of a methyl and/or methylene group(s) adjacent to an azole ring enabled by late and earth-abundant transition metals. Contributions made by our group and that by others in the field are elaborated in this Account article.1 Introduction2 Mode of Reactivity of C–H Bonds Next to Azoles under Transition-Metal Catalysis3 Pd-Catalyzed Functionalization of Alkyl Groups Adjacent to an Azole Ring3.1 Functionalization through C–C Bond Formation3.2 Functionalization through C–Heteroatom Bond Formation4 3d-Metal-Catalyzed Functionalization of Alkyl Groups Adjacent to an Azole Ring5 Other Metal-Catalyzed Functionalization of Alkyl Groups Adjacent to an Azole Ring6 Conclusion and Future Prospects