Palladium-catalysed C(sp 2 )-N cross-coupling (that is, Buchwald-Hartwig amination) is employed widely in synthetic chemistry, including in the pharmaceutical industry, for the synthesis of (hetero)aniline derivatives. However, the cost and relative scarcity of palladium provides motivation for the development of alternative, more Earth-abundant catalysts for such transformations. Here we disclose an operationally simple and air-stable ligand/nickel(II) pre-catalyst that accommodates the broadest combination of C(sp 2 )-N coupling partners reported to date for any single nickel catalyst, without the need for a precious-metal co-catalyst. Key to the unprecedented performance of this pre-catalyst is the application of the new, sterically demanding yet electron-poor bisphosphine PAd-DalPhos. Featured are the first reports of nickel-catalysed room temperature reactions involving challenging primary alkylamine and ammonia reaction partners employing an unprecedented scope of electrophiles, including transformations involving sought-after (hetero)aryl mesylates for which no capable catalyst system is known.

Objective To evaluate microRNA expression in synovial fluid (SF), plasma and leukocytes from patients with juvenile idiopathic arthritis (JIA). Methods MicroRNA expression in pooled JIA plasma and SF was assessed by absolute quantitative droplet digital (dd)PCR array. The results were validated in individual patient samples. MicroRNA content in leukocytes and extracellular vesicles was evaluated by real-time PCR in JIA blood and SF. Blood microRNA expression was compared with healthy controls. Principal component analysis was used to profile JIA plasma and SF microRNAs, and the potential biological consequences of microRNA dysregulation were investigated by pathway analysis. Results MiR-15a-5p and miR-409-3p levels were higher in JIA plasma than in healthy control plasma. JIA SF contained elevated levels of miR-21-5p, miR-27a-3p, miR-146b-5p, miR-155-5p and miR-423-5p, and decreased miR-192-5p and miR-451a, compared to JIA plasma. Extracellular vesicle analysis demonstrated variable encapsulation among selected microRNAs, with only miR-155-5p being represented substantially in extracellular vesicles. SF leukocytes also had higher expression of miR-21-5p, miR-27a-3p, miR-146b-5p and miR-155-5p, and lower expression of miR-409-3p and miR-451a, relative to blood. No differences were observed between JIA and healthy control blood leukocytes. Clusters of microRNAs were commonly altered in JIA joint fluid and leukocytes compared to JIA blood samples. In silico analysis predicted that differentially expressed microRNAs in JIA target the TGF-β pathway. Conclusion The expression of multiple microRNAs is dysregulated in JIA both locally and systemically, which may inhibit the TGF-β pathway. These findings advance our knowledge of JIA immunopathogenesis and may lead to the development of targeted therapies.

The utility of RockPhos, Ad‐BippyPhos, JosiPhos (CyPF‐tBu), and Mor‐DalPhos in palladium‐catalyzed C–O cross‐coupling reactions involving aliphatic alcohols and (hetero)aryl halides under analogous conditions was examined, both at room temperature and at elevated temperature (90 °C). In general, the RockPhos‐based catalyst system proved superior, especially at room temperature, but catalysts based on the other ligands examined also proved effective across a range of C–O cross‐couplings, in some cases providing better catalytic performance than RockPhos. New reactivity was established in terms of the scope of room temperature reactions. Proof‐of‐principle examples of such cross‐couplings involving aryl mesylates were also demonstrated.