Palladium-catalyzed the Sonogashira coupling reaction of 3-halogen-2-aminopyridines 1 with terminal alkynes 2 afforded the corresponding 21 target products 3a-3u in the presence of palladium catalyst. The structure of...Palladium-catalyzed the Sonogashira coupling reaction of 3-halogen-2-aminopyridines 1 with terminal alkynes 2 afforded the corresponding 21 target products 3a-3u in the presence of palladium catalyst. The structure of target products 3a-3u was confirmed and characterized by 1H NMR, 13C NMR, and HRMS. The influences of different kinds of catalyst loading, bases, substrates and temperature were also investigated. Under the optimized conditions, including 2.5 mol% Pd?(CF3COO)2, 5 mol% PPh3 and 5 mol% CuI as additive, 1 mL Et3N, substrate 1 with terminal alkynes 2 for the cross-coupling reactions at 100°C for 3 h in DMF afforded the corresponding products of 2-amino-3-alkynylpyridines 3 in moderate to excellent yields (72%?-?96%). The present methodology has provided an effective synthetic method including operational convenience, high efficiency and wide-application.展开更多
The mechanism of palladium-catalyzed Sonogashira cross-coupling reaction has been studied theoretically by DFT （density functional theory） calculations. The model system studied consists of Pd（PH3）2 as the startin...The mechanism of palladium-catalyzed Sonogashira cross-coupling reaction has been studied theoretically by DFT （density functional theory） calculations. The model system studied consists of Pd（PH3）2 as the starting catalyst complex, phenyl bromide as the substrate and acetylene as the terminal alkyne, without regarding to the co-catalyst and base. Mechanistically and energetically plausible catalytic cycles for the cross-coupling have been identified. The DFT analysis shows that the catalytic cycle occurs in three stages： oxidative addition of phenyl bromide to the palladium center, alkynylation of palladium（Ⅱ） intermediate, and reductive elimination to phenylacetylene. In the oxidative addition, the neutral and anionic pathways have been investigated, which could both give rise to cis-configured palladium（Ⅱ） diphosphine intermediate. Starting from the palladium（Ⅱ） diphosphine intermediate, the only identifiable pathway in alkynylation involves the dissociation of Br group and the formation of square-planar palladium（Ⅱ） intermediate, in which the phenyl and alkynyl groups are oriented cis to each other. Due to the close proximity of phenyl and alkynyl groups, the reductive elimination of phenylacetylene proceeds smoothly.展开更多
An efficient palladium-catalyzed copper- and amine-free Sonogashira coupling reaction of aryl bromides and chlorides was studied using a sterically hindered monooxychlorophosphine as new ligand.The use of 2 mol%Pd（OA...An efficient palladium-catalyzed copper- and amine-free Sonogashira coupling reaction of aryl bromides and chlorides was studied using a sterically hindered monooxychlorophosphine as new ligand.The use of 2 mol%Pd（OAc）_2 in the presence of K_2CO_3 allows the coupling reaction to proceed at mild condition with good to excellent yields.展开更多
Excellent results have been achieved in the Cu（OAc）2-catalyzed Sonogashira cross-couplings of aryl iodides and activated aryl bromides utilizing TBAF （tetrabutylammonium fluoride） as the base and 4,6-dimethoxypyri...Excellent results have been achieved in the Cu（OAc）2-catalyzed Sonogashira cross-couplings of aryl iodides and activated aryl bromides utilizing TBAF （tetrabutylammonium fluoride） as the base and 4,6-dimethoxypyrimidin-2-amine as the ligand. It is noteworthy that the reaction is conducted under aerobic, solvent-free and palladium-free conditions.展开更多
文摘Palladium-catalyzed the Sonogashira coupling reaction of 3-halogen-2-aminopyridines 1 with terminal alkynes 2 afforded the corresponding 21 target products 3a-3u in the presence of palladium catalyst. The structure of target products 3a-3u was confirmed and characterized by 1H NMR, 13C NMR, and HRMS. The influences of different kinds of catalyst loading, bases, substrates and temperature were also investigated. Under the optimized conditions, including 2.5 mol% Pd?(CF3COO)2, 5 mol% PPh3 and 5 mol% CuI as additive, 1 mL Et3N, substrate 1 with terminal alkynes 2 for the cross-coupling reactions at 100°C for 3 h in DMF afforded the corresponding products of 2-amino-3-alkynylpyridines 3 in moderate to excellent yields (72%?-?96%). The present methodology has provided an effective synthetic method including operational convenience, high efficiency and wide-application.
基金Supported by the NNSFC (No. 20464001 and 20674034)
文摘The mechanism of palladium-catalyzed Sonogashira cross-coupling reaction has been studied theoretically by DFT （density functional theory） calculations. The model system studied consists of Pd（PH3）2 as the starting catalyst complex, phenyl bromide as the substrate and acetylene as the terminal alkyne, without regarding to the co-catalyst and base. Mechanistically and energetically plausible catalytic cycles for the cross-coupling have been identified. The DFT analysis shows that the catalytic cycle occurs in three stages： oxidative addition of phenyl bromide to the palladium center, alkynylation of palladium（Ⅱ） intermediate, and reductive elimination to phenylacetylene. In the oxidative addition, the neutral and anionic pathways have been investigated, which could both give rise to cis-configured palladium（Ⅱ） diphosphine intermediate. Starting from the palladium（Ⅱ） diphosphine intermediate, the only identifiable pathway in alkynylation involves the dissociation of Br group and the formation of square-planar palladium（Ⅱ） intermediate, in which the phenyl and alkynyl groups are oriented cis to each other. Due to the close proximity of phenyl and alkynyl groups, the reductive elimination of phenylacetylene proceeds smoothly.
基金Henan University of Technology for financial support(The Introduction of Talent Fund)
文摘An efficient palladium-catalyzed copper- and amine-free Sonogashira coupling reaction of aryl bromides and chlorides was studied using a sterically hindered monooxychlorophosphine as new ligand.The use of 2 mol%Pd（OAc）_2 in the presence of K_2CO_3 allows the coupling reaction to proceed at mild condition with good to excellent yields.
基金Project supported by the Key Project of Chinese Ministry of Education （No. 206102）, Fok Ying Dong Education Foundation （No. 101012）, Scientific Research Fund of Hunan Provincial Education Department （No. 05B038）, Hunan Provincial Natural Science Foundation of China （No. 05JJ1002） and the National Natural Science Foundation of China （Nos. 20572020 and 20202002）
文摘Excellent results have been achieved in the Cu（OAc）2-catalyzed Sonogashira cross-couplings of aryl iodides and activated aryl bromides utilizing TBAF （tetrabutylammonium fluoride） as the base and 4,6-dimethoxypyrimidin-2-amine as the ligand. It is noteworthy that the reaction is conducted under aerobic, solvent-free and palladium-free conditions.
