Dual ligand approach increases functional group tolerance in the Pd-catalysed C–H arylation of N-heterocyclic pharmaceuticals

Abstract

Ligand combination of a 2-pyridone with traditional phosphines enables superior functional group tolerance in the C–H (hetero)arylation of pharmaceutically relevant N-heterocyclic scaffolds.

Palladium Catalysis: Dependence of the Efficiency of C−C Bond Formation on Carboxylate Ligand and Alkali Metal Carboxylate or Carboxylic Acid Additive. Part A: the C(sp2)−C(sp2), C(sp2)−C(sp3) and C(sp3)−C(sp3) Bonds

“…In contrast to the above examples, the Pd‐catalyzed C‐phenylation of imidazo[1,2‐ a ]pyridine with bromobenzene arose with less than 5% yield in the presence of catalytic amounts of AcOH, PhCO 2 H or t ‐BuCO 2 H [38] …”

“…In contrast to the above examples, the Pdcatalyzed C-phenylation of imidazo[1,2-a]pyridine with bromobenzene arose with less than 5% yield in the presence of catalytic amounts of AcOH, PhCO 2 H or t-BuCO 2 H. [38] Both regioselectivity and yield of the Heck reaction of bromobenzene with 1,3-dimethyluracil in DMF were improved by addition of t-BuCO 2 H (Scheme 4a). [39] While the reaction arises via PhPdBr under acid-free conditions, the cationic palladium intermediate PhPd � t-BuCO 2 � would be involved in the presence of t-BuCO 2 H, its formation being favored by the polarity of the solvent.…”

Microwave-Assisted One-Pot Telescoped Synthesis of 2-Amino-1,3-thiazoles, Selenazoles, Imidazo[1,2-a]pyridines, and Other Heterocycles from Alcohols

“…26 Traditional methods for synthesizing substituted imidazo-[1,2-a]pyridines involve palladium-catalyzed couplings, requiring prefunctionalization of the ring as an iodide or bromide, which can be cumbersome. 27 The one-pot, two-stage reaction method introduced in this work is straightforward, efficient, and particularly suitable for synthesizing imidazo[1,2-a]pyridines with long alkyl chains (Scheme 6). Imidazo[1,2a]pyridine 53 was obtained with an 89% yield through the reaction of 1-phenylethanol and 2-aminopyridine.…”

“…1 H NMR (500 MHz, CDCl 3 ) δ 7.40 (br t, J = 7.7 Hz, 1H), 7.37−7.31 (m, 3H), 7.29−7.26 (m, 3H), 7.18−7.14 (m, 1H), 3.34 (hept, J = 6.8 Hz, 2H), 1.22 (d, J = 6.9 Hz, 12H). 13 (27). It was obtained as a white crystal (106.4 mg, 40%), mp 147.8−149.6 °C.…”

Reductive Cross-Electrophile C(sp2)–C(sp3) Coupling Catalyzed by PtI2: In Situ Structural Determination of the Intermediates by X-ray Absorption Spectroscopy and Multinuclear NMR

“…More recently, it has been shown that XAS techniques are very productive for addressing various mechanistic issues also in homogeneous catalysis (e.g., refs – ). The success of applying XAS to homogeneous catalysts based on 4d metals − inspired us to try this technique for in situ monitoring of our reactions as well.…”