Allyl‐Palladium‐Catalyzed α,β‐Dehydrogenation of Carboxylic Acids via Enediolates

A highly practical and step‐economic α,β‐dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl‐palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)₂⋅2 LiCl as a base in the presence of excess ZnCl₂, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2‐enoic acids allows derivatization by numerous approaches.     

Synthesis of Carboxylic Acids by Palladium‐Catalyzed Hydroxycarbonylation

The synthesis of carboxylic acids is of fundamental importance in the chemical industry and the corresponding products find numerous applications for polymers, cosmetics, pharmaceuticals, agrochemicals, and other manufactured chemicals. Although hydroxycarbonylations of olefins have been known for more than 60 years, currently known catalyst systems for this transformation do not fulfill industrial requirements, for example, stability. Presented herein for the first time is an aqueous‐phase protocol that allows conversion of various olefins, including sterically hindered and demanding tetra‐, tri‐, and 1,1‐disubstituted systems, as well as terminal alkenes, into the corresponding carboxylic acids in excellent yields. The outstanding stability of the catalyst system (26 recycling runs in 32 days without measurable loss of activity), is showcased in the preparation of an industrially relevant fatty acid. Key‐to‐success is the use of a built‐in‐base ligand under acidic aqueous conditions. This catalytic system is expected to provide a basis for new cost‐competitive processes for the industrial production of carboxylic acids.     

Palladium‐Catalyzed Difluoroalkylation of Aryl Boronic Acids: A New Method for the Synthesis of Aryldifluoromethylated Phosphonates and Carboxylic Acid Derivatives

The palladium‐catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed. This method provides a facile and useful access to a series of functionalized difluoromethylated arenes (ArCF₂PO(OEt)₂, ArCF₂CO₂Et, and ArCF₂CONR¹R²) that have important applications in drug discovery and development. Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle.     

Ligand‐Controlled Palladium(II)‐Catalyzed Regiodivergent Carbonylation of Alkynes: Syntheses of Indolo[3,2‐c]coumarins and Benzofuro[3,2‐c]quinolinones

Regiodivergent syntheses of indolo[3,2‐c]coumarins and benzofuro[3,2‐c]quinolinones through a controllable palladium(II)‐catalyzed carbonylative cyclization are established. The chemo‐ and regioselectivity are exclusively tuned by the ligand on the palladium catalyst. The rigid framework of the electron‐deficient ligand promotes the O‐attack/N‐carbonylation cyclization leading to benzofuro[3,2‐c]quinolinones, while a sterically bulky and electron‐rich ligand facilitates N‐attack/O‐carbonylation cyclization to generate indolo[3,2‐c]coumarins. Furthermore, various other nucleophiles are applicable for delivering a variety of indoloquinolinones, pyranoquinolones, and chromeno[3,4‐c]quinolinones in one step, and serves as a method for creating compound libraries for drug discovery.     

Palladium‐Catalyzed Intermolecular [4+1] Spiroannulation by C(sp3)−H Activation and Naphthol Dearomatization

A novel palladium‐catalyzed [4+1] spiroannulation was developed by using a C(sp³)?H activation/naphthol dearomatization approach. This bimolecular domino reaction of two aryl halides was realized through a sequence of cyclometallation‐facilitated C(sp³)?H activation, biaryl cross‐coupling, and naphthol dearomatization, thus rendering the rapid assembly of a new class of spirocyclic molecules in good yields with broad functional‐group tolerance. Preliminary mechanistic studies indicate that C?H cleavage is likely involved in the rate‐determining step, and a five‐membered palladacycle was identified as the key intermediate for the intermolecular coupling.