Carbenoid Reactions Promoted by Solids: From Lewis to Brønsted Catalysts.

ConspectusDiazocarbonyl compounds have become essential tools in organic synthesis, due to their ability to in situ generate reactive carbenes and be inserted in a variety of otherwise stable bonds, such as C-H, C-C, H-O, and so on. However, a soluble metal salt or complex catalyst is generally required to selectively activate and couple the carbene, and the metals employed so far are expensive (Rh, Au, Ag, Cu) and often unrecoverable. It is noteworthy that the price of ligands can make a cheaper metal catalyst (i.e., Cu) as expensive as other ligand-free noble metal catalysts. In the realm of modern sustainable chemistry, most of these methodologies are now unacceptable and must be adapted, and simple strategies for that include carbene photoactivation and the use of recoverable solid catalysts. Unfortunately, despite research in the field of carbene insertion reactions that has extended now for more than 50 years, examples with solid catalysts are still minor, and efficient solid catalysts have only been reported in the last two decades.This Account shows the journey faced by our group in the last eight years to find solid catalysts for challenging carbene insertion reactions, employing diazocarbonyl compounds as carbene precursors. We will contextualize our results with those of previous solid catalysts. The discovery in 2017 that a quasi-linear Pd₄ cluster stabilized within a metal-organic framework (MOF) was able to catalyze the Büchner and other carbene insertion reactions, spurred the design of supported metal clusters as catalysts for a variety of carbene insertion reactions. The Pd₄-MOF could be reused 20 times in batch and implemented in a flow process. Following this, other catalytic solids, including Au and Ag as metals, not only in the same MOF but also on solid oxides and zeolites as supports, showed good activity for carbene insertion reactions and were also recoverable and reusable.Our journey temporarily finishes in 2024 when "blank" experiments with a dealuminated zeolite surprisingly revealed that this simple solid acid, without any metal, easily activates the diazocarbonyl compound and catalyzes a variety of carbene insertion reactions, thus providing a cheap, commercially available, and reusable solid catalyst for these challenging reactions. Overall, rapid progress in solid-catalyzed diazocarbonyl compound activation, carbene formation, and insertion reactions has been achieved during these years, moving from expensive and difficult to prepare solid catalysts based on supported metal clusters to simple acid zeolites, pointing to confined Brønsted acids as the catalysts to study in the near future.