ConspectusTransition-metal-catalyzed cross-coupling reactions are widely used in both academia and industry for the construction of carbon-carbon and carbon-heteroatom bonds. The vast majority of cross-coupling reactions utilize aryl (pseudo)halides as the electrophilic coupling partner. Carboxylic acid derivatives (RC(O)X) represent a complementary class of electrophiles that can engage in decarbonylative couplings to produce analogous products. This decarbonylative approach offers the advantage that RC(O)X are abundant and inexpensive. In addition, decarbonylative coupling enables both intramolecular (between R and X of the carboxylic acid derivative) as well as intermolecular bond-forming reactions (in which an exogeneous nucleophile is coupled with the R group derived from RC(O)X). In these intermolecular reactions, the X-substituent on the carboxylic acid can be tuned to facilitate both oxidative addition and transmetalation, thus eliminating the need for an exogeneous base. This Account details our group's development of a diverse variety of base-free decarbonylative coupling reactions catalyzed by group 10 metals. Furthermore, it highlights how catalyst design can be guided by stoichiometric organometallic studies of these systems.Our early studies focused on intramolecular decarbonylative couplings that transform RC(O)X to the corresponding R-X with extrusion of CO. We first identified Pd and Ni monodentate phosphine catalysts that convert aryl thioesters (ArC(O)SR) to the corresponding thioethers (ArSR). We next expanded this reactivity to fluoroalkyl thioesters, using readily available fluoroalkyl carboxylic acids as the fluoroalkyl (RF) source. A Ni-phosphinoferrocene catalyst proved optimal, and the large bite angle bidentate ligand was necessary to promote the challenging RF-S bond-forming reductive elimination step.We next pursued intramolecular decarbonylative couplings of aroyl halides. Palladium-based catalysts bearing dialkylbiaryl ligands (e.g., BrettPhos) were identified as optimal for converting aroyl chlorides (ArC(O)Cl) to aryl chlorides (ArCl). These ligands were selected based on their ability to facilitate the key C-Cl bond-forming reductive elimination step of the catalytic cycle. In contrast, all attempts to convert aroyl fluorides [ArC(O)F)] to aryl fluorides (ArF) were unsuccessful with either Pd- or Ni-based catalysts. Organometallic studies of the Ni-system show that C(O)-F oxidative addition and CO deinsertion proceed smoothly, but the resulting nickel(II) aryl fluoride intermediate fails to undergo C-F bond-forming reductive elimination.In contrast to its inertness to reductive elimination, this nickel(II) aryl fluoride proved highly reactive toward transmetalation. The fluoride ligand serves as an internal base, such that no additional base is required. We leveraged this "transmetalation active" intermediate to achieve base-free Ni-catalyzed intermolecular decarbonylative coupling reactions between aroyl fluorides and boron reagents to access both biaryl and aryl-boronate ester products. By tuning the electrophile, transmetalating reagent, and catalyst, this same approach also proved applicable to base-free intermolecular decarbonylative fluoroalkylation (between difluoromethylacetyl fluoride and arylboronate esters) and aryl amination (between phenol esters and silyl amines).Moving forward, a key goal is to identify catalyst systems that enable more challenging bond constructions via this manifold. In addition, CO inhibition remains a major issue leading to the requirement for high temperatures and high catalyst loadings. Identifying catalysts that are resistant to CO binding and/or approaches to remove CO under mild conditions will be critical for making these reactions more practical and scalable.