Ana Carmen Albeniz

The functionalization of aryl alkyl ketones in the alkyl group via enolate chemistry is well-known. Pd-catalyzed cross-coupling reactions of these substrates usually lead to C(sp3)–C bonds via coupling of an enolate and an organic halide (α-arylation). In contrast to this expected reactivity, we report here the selective Pd-catalyzed direct arylation of aryl alkyl ketones on the aromatic ring via C(sp2)–H activation. A variety of acetophenones and alkyl aryl ketones can be functionalized in this way, leaving the methyl(alkyl) group untouched. The key to this selectivity is the use of a cooperating bipyridone ligand that lowers the barrier for C–H activation and the use of a set of reaction conditions that keeps a low concentration of the ionic enolate species in the catalytic cycle. This is supported by a combination of experimental and computational studies, including microkinetic simulations, and analysis of primary and equilibrium kinetic isotope effects (KIEs).

The conversion of carbon dioxide into high‐value chemical scaffolds is a central challenge in modern green chemistry. In this study, we report the first heterogeneous, metal‐free organocatalytic protocol for the three‐component synthesis of propargylic esters from terminal alkynes, CO ₂ , and alkyl halides, employing a vinyl addition polynorbornene (VA‐PNB)‐supported N ‐Heterocyclic Carbene (NHC) precatalyst. Optimization studies revealed that the immobilized tert ‐butyl‐substituted NHC outperforms other structural variants, promoting the carboxylative coupling under metal‐free conditions. The catalyst can be recovered by filtration and regenerated through mild acid treatment. A gradual decrease in activity is observed upon reuse due to retained potassium carbonate used as a base in the reaction, but the catalyst activity can be recovered with further washing. The method demonstrates excellent chemoselectivity with cinnamyl‐type electrophiles, offering a sustainable and operationally simple approach to valuable functionalized esters, without the need for transition metals.

The reaction of diphosphino aryl complexes [Pd(C₆F₅)(L-L)(NCMe)](BF₄) (L-L = dppe, dppp, dppb) with diazoalkanes N₂CHR (R = -CH=CHPh, Ph) leads to η³-allyl or η³-benzyl palladium derivatives that are the organometallic products resulting from carbene-aryl coupling. The experimental trend shows that the reaction is favored for dppe > dppp > dppb. It involves several consecutive steps, i.e., diazoalkane coordination, nitrogen extrusion to give a Pd-carbene, and migratory insertion, which are experimentally inseparable, but they can be studied with the help of DFT calculations. The bulkiness and bite angle of the ligand exert a large influence in the relative rate of the steps involved in the reaction, and we have found that carbene formation by N₂ extrusion is the step with the largest barrier for dppe. In contrast, the coordination of the diazoalkane is the most energy-demanding step for the larger dppp and dppb diphosphines. Thus, ligand substitution controls the rate, an important elemental step rarely considered in mechanistic studies of carbene cross coupling reactions. Since diazoalkanes are the most common carbene precursors, either directly or generated from hydrazones, the choice of ligand can be very important to facilitate the entrance of the carbene precursor in the catalytic cycle.

The mixture of Pd(OAc)₂ and two ligands segregate into distinct active species working synergistically for the C–H arylation of simple arenes.

The behavior of 6‐hydroxypicolinic acid (pic‐6‐OH) and pyridyl‐amides as cooperating ligands in the C−H activation of arenes has been studied experimentally. When deprotonated, both compounds are chelating ligands and bear either a pyridone moiety or an N‐acyl substituent that can assist the C−H cleavage in the same way as the successful bipyridone ligands and MPAAs do. In addition, they are easily available, commercially or via straightforward syntheses. Palladium complexes of formula (NBu₄)[Pd(κ²‐O, N‐pic‐6‐O)(C₆F₅)py] (2) and [Pd(κ²‐N, N‐ py‐CH₂N(COCF₃)(C₆F₅)py] (6) have been synthesized and their decomposition in the presence of an arene gives the C₆F₅‐arene coupling product, showing that the ligands enable the C−H activation of the arene (arene=pyridine, toluene, ethyl benzoate). The amount of C₆F₅‐arene products observed leads to the following trend in cooperating ability: pic‐6‐OH > pyridyl‐amide. DFT calculations on the pyridine activation are consistent with the experimental findings. The C−H activation does not occur for the isomeric complex (NBu₄)[Pd(κ²‐O, N‐pic‐4‐O)(C₆F₅)py] (4) with the pyridone oxygen far from the metal, showing the involvement of this moiety in the C−H cleavage. The performance of these ligands in the direct arylation of arenes has been evaluated.

La funcionalización directa de hidrocarburos catalizada por complejos de paladio permite la formación de nuevos enlaces C–C desde las materias primas disponibles, sin necesidad de preparar los reactivos necesarios en reacciones de acoplamiento cruzado convencionales, y por ello es una alternativa sostenible. Estas reacciones requieren la activación de enlaces C–H, un proceso difícil y sujeto a problemas de selectividad. Este artículo recoge una perspectiva general de las reacciones de funcionalización C–H catalizadas por paladio, así como las líneas de trabajo principales en el área para conseguir sistemas catalíticos más activos y reacciones más selectivas.

Palladium complexes with mono- N -protected amino acid ligands (MPAA) have been prepared as models to experimentally study the C–H activation of arenes. Their reactivity shows the validity of the chelating model with the assistance of the acyl group.

What do you get when in situ preparing your cationic nickel catalyst? Silver salts are halide scavengers but they also trap phosphine ligands to form reactive nickel complexes, which can either bind water or induce the aldol condensation of acetone.