LAUSR

ConspectusMetal-catalyzed cross-couplings have emerged as essential tools for the construction of C-C bonds. The identification of efficient catalytic systems as well as large substrate scope made these cross-couplings key reactions to access valuable molecules ranging from materials, agrochemicals to active pharmaceutical ingredients. They have been increasingly integrated in retrosynthetic plans, allowing shorter and original route development. Palladium-catalyzed cross-couplings still largely rule the field, with the most popular reactions in industrial processes being the Suzuki and Sonogashira couplings. However, the extensive use of palladium complexes raises several problems such as limited resources, high cost, environmental impact, and frequent need for sophisticated ligands. As a consequence, the use of nonprecious and cheap metal catalysts has appeared as a new horizon in cross-coupling development. Over the last three decades, a growing interest has thus been devoted to Fe-, Co-, Cu-, or Ni-catalyzed cross-couplings. Their natural abundance makes them cost-effective, allowing the conception of more sustainable and less expensive chemical processes, especially for large-scale production of active molecules. In addition to these economical and environmental considerations, the 3d metal catalysts also exhibit complementary reactivity with palladium complexes, facilitating the use of alkyl halide partners due to the decrease of β-elimination side reactions. In particular, by using cobalt catalysts, numerous cross-couplings between alkyl halides and organometallics have been described. However, cobalt catalysis still stays far behind palladium catalysis in terms of popularity and applications, and the expansion of the substrate scope as well as the development of simple and robust catalytic systems remains an important challenge.In 2012, our group entered the cobalt catalysis field by developing a cobalt-catalyzed cross-coupling between C-bromo glycosides and Grignard reagents. The generality of the coupling allowed the preparation of a range of valuable C-aryl and C-vinyl glycoside building blocks. We then focused on the functionalization of saturated N-heterocycles, and a variety of halo-azetidines, -pyrrolidines, and -piperidines were successfully reacted with aryl and alkenyl Grignard reagents under cobalt catalysis. With the objective of preparing valuable α-aryl amides, a cobalt-catalyzed cross-coupling applied to α-bromo amides was studied and then extended to α-bromo lactams. Recently, we also reported an efficient and general cross-coupling involving cyclopropyl- and cyclobutyl-magnesium bromides. This method allows the alkylation of functionalized small strained rings by a range of primary and secondary alkyl halides.