112197-15-6Relevant articles and documents
Synthesis of N-pyridyl azoles using a deprotometalation-iodolysis-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells
Hedidi, Madani,Erb, William,Bentabed-Ababsa, Ghenia,Chevallier, Floris,Picot, Laurent,Thiéry, Valérie,Bach, Stéphane,Ruchaud, Sandrine,Roisnel, Thierry,Dorcet, Vincent,Mongin, Florence
, p. 6467 - 6476 (2016)
N-Arylation of pyrrole with 3-iodo-4-methoxypyridine was investigated by copper catalysis under different conditions. The best conditions, that proved to be protocol A (CuI, DMEDA or TMEDA, K3PO4, DMF at 110?°C) and above all protocol B (Cu2O, Cs2CO3, DMSO at 110?°C), were applied to the synthesis of various N-(methoxypyridyl) pyrroles, indoles and benzimidazoles. The behavior of the different iodinated methoxypyridines was rationalized by evaluating the partial positive charge on the carbon bearing iodine from the1H NMR chemical shift of the corresponding deiodinated substrates. The reaction was next connected with the deprotometalation-iodolysis step generating iodinated methoxypyridines: straight involvement of the crude iodo intermediates in pyrrole N-arylation afforded the expected N-(methoxypyridyl) pyrroles in good yields. Several synthesized N-(methoxypyridyl) azoles exerted low to moderate antiproliferative activity in A2058 melanoma cells.
Copper-catalyzed trifluoromethylation of alkoxypyridine derivatives
Farkas, Emese,Gyorfi, Nandor,Kotschy, Andras,Nemet, Norbert,Novak, Zoltan,Weber, Csaba
, (2020/10/27)
The trifluoromethylation of aromatic and heteroaromatic cores has attracted considerable interest in recent years due to its pharmacological relevance. We studied the extension of a simple copper-catalyzed trifluoromethylation protocol to alkoxy-substituted iodopyridines and their benzologs. The trifluoromethylation proceeded smoothly in all cases, and the desired compounds were isolated and characterized. In the trifluoromethylation of 3-iodo-4-methoxyquinoline, we observed a concomitant O-N methyl migration, resulting in the trifluoromethylated quinolone as a product. Overall, the described procedure should facilitate the broader use of copper-catalyzed trifluoromethylation in medicinal chemistry.
Decarboxylative Suzuki-Miyaura coupling of (hetero)aromatic carboxylic acids using iodine as the terminal oxidant
Quibell, Jacob M.,Duan, Guojian,Perry, Gregory J.P.,Larrosa, Igor
supporting information, p. 6445 - 6448 (2019/06/07)
A novel methodology for the decarboxylative Suzuki-Miyaura-type coupling has been established. This process uses iodine or a bromine source as both the decarboxylation mediator and the terminal oxidant, thus avoiding the need for stoichiometric amounts of transition metal salts previously required. Our new protocol allows for the construction of valuable biaryl architectures through the coupling of (hetero)aromatic carboxylic acids with arylboronic acids. The scope of this decarboxylative Suzuki reaction has been greatly diversified, allowing for previously inaccessible non-ortho-substituted aromatic acids to undergo this transformation. The procedure also benefits from low catalyst loadings and the absence of stoichiometric transition metal additives.
Transition-Metal-Free Decarboxylative Iodination: New Routes for Decarboxylative Oxidative Cross-Couplings
Perry, Gregory J. P.,Quibell, Jacob M.,Panigrahi, Adyasha,Larrosa, Igor
supporting information, p. 11527 - 11536 (2017/08/30)
Constructing products of high synthetic value from inexpensive and abundant starting materials is of great importance. Aryl iodides are essential building blocks for the synthesis of functional molecules, and efficient methods for their synthesis from chemical feedstocks are highly sought after. Here we report a low-cost decarboxylative iodination that occurs simply from readily available benzoic acids and I2. The reaction is scalable and the scope and robustness of the reaction is thoroughly examined. Mechanistic studies suggest that this reaction does not proceed via a radical mechanism, which is in contrast to classical Hunsdiecker-type decarboxylative halogenations. In addition, DFT studies allow comparisons to be made between our procedure and current transition-metal-catalyzed decarboxylations. The utility of this procedure is demonstrated in its application to oxidative cross-couplings of aromatics via decarboxylative/C-H or double decarboxylative activations that use I2 as the terminal oxidant. This strategy allows the preparation of biaryls previously inaccessible via decarboxylative methods and holds other advantages over existing decarboxylative oxidative couplings, as stoichiometric transition metals are avoided.