Regioselective functionalization of aryl azoles as powerful tool for the synthesis of pharmaceutically relevant targets.

Aryl azole scaffolds are present in a wide range of pharmaceutically relevant molecules. Their ortho-selective metalation at the aryl ring is challenging, due to the competitive metalation of the more acidic heterocycle. Seeking a practical access to a key Active Pharmaceutical Ingredient (API) intermediate currently in development, we investigated the metalation of 1-aryl-1H-1,2,3-triazoles and other related heterocycles with sterically hindered metal-amide bases.

Photochemical C-H Hydroxyalkylation of Quinolines and Isoquinolines.

We report herein a visible light-mediated C-H hydroxyalkylation of quinolines and isoquinolines that proceeds via a radical path. The process exploits the excited-state reactivity of 4-acyl-1,4-dihydropyridines, which can readily generate acyl radicals upon blue light absorption. By avoiding the need for external oxidants, this radical-generating strategy enables a departure from the classical, oxidative Minisci-type pattern and unlocks a unique reactivity, leading to hydroxyalkylated heteroarenes.

Formation of XPhos-Ligated Palladium(0) Complexes and Reactivity in Oxidative Additions.

Understanding the nature of the intermediate species operating within a palladium catalytic cycle is crucial for developing efficient cross-coupling reactions. Even though the XPhos/Pd(OAc) catalytic system has found numerous applications, the nature of the active catalytic species remains elusive. A Pd complex ligated to XPhos has been detected and characterized in situ for the first time using cyclic voltammetry and NMR techniques.

A Redox-Active Nickel Complex that Acts as an Electron Mediator in Photochemical Giese Reactions.

We report a simple protocol for the photochemical Giese addition of C(sp )-centered radicals to a variety of electron-poor olefins. The chemistry does not require external photoredox catalysts. Instead, it harnesses the excited-state reactivity of 4-alkyl-1,4-dihydropyridines (4-alkyl-DHPs) to generate alkyl radicals.

Evidence for a Cooperative Mechanism Involving Two Palladium(0) Centers in the Oxidative Addition of Iodoarenes.

Oxidative addition of iodoarenes (ArI) to Pd ligated by 1-methyl-1H-imidazole (mim) in polar solvents leads to cationic arylpalladium(II) complexes [ArPd(mim) ] . Kinetic analyses evidence that this reaction is second order with respect to the concentration of Pd , and a mechanism involving the cooperative intervention of two Pd centers has been postulated to explain this finding. This unusual behavior is also observed with other nitrogen-containing ligands and it is general for iodobenzenes substituted with electron-donating or weakly electron-withdrawing groups.