Carboxylic acids are among the most used feedstock chemicals due to their great structural diversity and easy handling. The use of carboxylic acids and their derivatives in decarboxylative couplings has proven to be a valuable tool for the construction of C−C and C‐heteroatom bonds. This synthetic strategy provides a complementary bond disconnection to traditional cross‐coupling methods. In this review, we provide a comprehensive overview of decarboxylation‐initiated intermolecular C‐heteroatom bond formation, outlining several main mechanistic concepts combined with early examples and highlighting the achievements made in the past decade until January 2021. In these reactions, carboxylic acids and their derivatives undergo initial decarboxylation and then react with other heteroatom electrophiles and nucleophiles, thus replacing the carboxylate group with a valuable and prevalent heteroatom functionality.

The unique reactivity profile of the dinuclear Pd I complex [Pd I (µ-Br) t Bu 3 P] 2 as an isomerization co-catalyst has enabled orthogonal tandem processes ranging from styrene syntheses to biodiesel refining. We have now elucidated the mechanistic basis of its distinct catalytic profile by DFT calculations and experimental studies. Activation of the catalyst proceeds intramolecularly, giving rise to a dinuclear complex composed of a reactive palladium hydride and an inert palladacycle. This complex mediates double-bond migrations with an energy span of 9.5 kcal/mol, which is well below those calculated for known catalysts. Its dissociation leads to an even more active monophosphinopalladium hydride catalyst and an inert dinuclear bispalladacycle. In the main deactivation pathway, two mononuclear Pd species react with each other, liberating a hydrogenation product and regenerating the catalyst precursor [Pd I (µ-Br) t Bu 3 P] 2. The experimentally observed build-up of dinuclear palladacycles during the catalysis is, thus, the result of a conversion of binuclear into mononuclear Pd-H catalyst. Phosphines, which would deactivate metathesis cocatalysts, are not liberated at any stage. This explains the unique suitability of [Pd I (µ-Br) t Bu 3 P] 2 for isomerizing metatheses. The mechanistic insights were used for the in silico casting of a catalyst generation, targeting complexes with a reduced barrier towards the formation of dinuclear Pd-H species, a low energy span of the catalytic cycles, and increased barriers either towards deactivation or, alternatively, towards dissociation to short-lived mononuclear complexes. Complexes with bisadamantyl-n-butylphosphine ligands were identified as lead structures. Experimental studies with model catalysts confirmed the validity of the predicted structureactivity relationship. SUPPORTING INFORMATION The Supporting Information is available free of charge on the ACS Publications website at DOI: xx.xxxx/jacs.xxxxxxx. Further mechanistic routes and energy profiles Full experimental and computational details

Halogen-bridged methylnaphthyl (MeNAP) palladium dimers are presented as multipurpose Pd-precursors, ideally suited for catalytic method development and preparative organic synthesis.B ys imply mixing with phosphine or carbene ligands,t hey are in situ converted into well-defined monoligated complexes.T heir catalytic performance was benchmarked against state-of-the-art systems in challenging Buchwald-Hartwig, Heck, Suzuki and Negishi couplings,and ketone arylations.T heir use enabled record-setting activities, beyond those achievable by optimization of the ligand alone. The MeNAP catalysts permit syntheses of tetra-ortho-substituted arenes and bulky anilines in near-quantitative yields at room temperature,a llowm ono-arylations of small ketones, and enable so far elusive cross-couplings of secondary alkyl boronic acids with aryl chlorides.

A facile insertion of ruthenium into aromatic C-H and allylic C-N bonds are the key steps in a [Ru( p-cymene)Cl]-catalyzed ortho-C-H allylation of benzoic acids. This protocol allows drawing on the large pool of allylic amines for state-of-the-art ortho-functionalizations of arenes, turning neutral amines into leaving groups. Concise syntheses of biologically active compounds provide further evidence of the synthetic potential of this methodology.