553-03-7Relevant articles and documents
Dehydrogenative and Redox-Neutral N-Heterocyclization of Aminoalcohols Catalyzed by Manganese Pincer Complexes
Brzozowska, Aleksandra,Rueping, Magnus,Sklyaruk, Jan,Zubar, Viktoriia
, (2022/03/17)
A new manganese catalyzed heterocyclization of aminoalcohols has been accomplished. A wide range of heterocycles were synthesized, including 1,2,3,4-tetrahydroquinolines, dihydroquinolinones, and 2,3,4,5-tetrahydro-1H-benzo[b]azepines. The reaction is performed under mild reaction conditions using air and moisture stable manganese catalysts. The desired heterocycles were obtained in good to excellent yields.
DMSO/t-BuONa/O2-Mediated Aerobic Dehydrogenation of Saturated N-Heterocycles
Cai, Hu,Tan, Wei,Xie, Yongfa,Yang, Ruchun,Yue, Shusheng
, p. 7501 - 7509 (2020/07/07)
Aromatic N-heterocycles such as quinolines, isoquinolines, and indolines are synthesized via sodium tert-butoxide-promoted oxidative dehydrogenation of the saturated heterocycles in DMSO solution. This reaction proceeds under mild reaction conditions and has a good functional group tolerance. Mechanistic studies suggest a radical pathway involving hydrogen abstraction of dimsyl radicals from the N-H bond or α-C-H of the substrates and subsequent oxidation of the nitrogen or α-aminoalkyl radicals.
Formal Deoxygenative Hydrogenation of Lactams Using PNHP-Pincer Ruthenium Complexes under Nonacidic Conditions
Ogata, Osamu,Nara, Hideki,Matsumura, Kazuhiko,Kayaki, Yoshihito
supporting information, p. 9954 - 9959 (2019/12/24)
A formal deoxygenative hydrogenation of amides to amines with RuCl2(NHC)(PNHP) (NHC = 1,3-dimethylimizadol-2-ylidene, PNHP = bis(2-diphenylphosphinoethyl)amine) is described. Various secondary amides, especially NH-lactams, are reduced with H2 (3.0-5.0 MPa) to amines at a temperature range of 120-150 °C with 1.0-2.0 mol % of PNHP-Ru catalysts in the presence of Cs2CO3. This process consists of (1) deaminative hydrogenation of secondary amides to generate primary amines and alcohols, (2) dehydrogenative coupling of the transient amines with alcohols to generate imines, and (3) hydrogenation of imines to give the formally deoxygenated secondary amine products.
Multi-Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
Li, Yushu,Wong, Luet L.
supporting information, p. 9551 - 9555 (2019/08/06)
Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L?1 day?1). Other oxidase activities, such as C?C bond desaturation, aromatization, and C?C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.
Enabling CO Insertion into o-Nitrostyrenes beyond Reduction for Selective Access to Indolin-2-one and Dihydroquinolin-2-one Derivatives
Yang, Li,Shi, Lijun,Xing, Qi,Huang, Kuo-Wei,Xia, Chungu,Li, Fuwei
, p. 10340 - 10348 (2018/10/20)
The transition metal-catalyzed reductive cyclization of o-nitrostyrene in the presence of carbon monoxide (CO) has been developed to be a general synthetic route to an indole skeleton, wherein CO was used as a reductant to deoxidize nitroarene into nitrosoarene and/or nitrene with CO2 release, but the selective insertion of CO into the heterocyclic product with higher atom economy has not yet been realized. Herein, the Pd-catalyzed reduction of o-nitrostyrene by CO and its regioselective insertion were efficiently achieved to produce synthetically useful five- and six-membered benzo-fused lactams. Detailed investigations revealed that the chemoselectivity to indole or lactam was sensitive to the nature of the counteranions of Pd2+ precursors, whereas ligands significantly decided the carbonylative regioselectivity by different reaction pathways. Using PdCl2/PPh3/B(OH)3 (condition A), an olefin hydrocarboxylation was primarily initiated followed by partial reduction of the NO2 moiety and cyclization reaction to give N-hydroxyl indolin-2-one, which was further catalytically reduced by CO to afford the indolin-2-one as the final product with up to 95% yield. When the reaction was conducted under the Pd(TFA)2/BINAP/TsOH·H2O system (condition B), complete deoxygenation and carbonylation of the NO2 group occurred initially to yield the corresponding isocyanate followed by internal hydrocyclization to generate 3,4-dihydroquinolin-2-one with up to 98% yield. Importantly, the methodology could be efficiently applied in the synthesis of marketed drug Aripiprazole.
Supported Gold Nanoparticles for Efficient α-Oxygenation of Secondary and Tertiary Amines into Amides
Jin, Xiongjie,Kataoka, Kengo,Yatabe, Takafumi,Yamaguchi, Kazuya,Mizuno, Noritaka
supporting information, p. 7212 - 7217 (2016/07/06)
Although the α-oxygenation of amines is a highly attractive method for the synthesis of amides, efficient catalysts suited to a wide range of secondary and tertiary alkyl amines using O2as the terminal oxidant have no precedent. This report describes a novel, green α-oxygenation of a wide range of linear and cyclic secondary and tertiary amines mediated by gold nanoparticles supported on alumina (Au/Al2O3). The observed catalysis was truly heterogeneous, and the catalyst could be reused. The present α-oxygenation utilizes O2as the terminal oxidant and water as the oxygen atom source of amides. The method generates water as the only theoretical by-product, which highlights the environmentally benign nature of the present reaction. Additionally, the present α-oxygenation provides a convenient method for the synthesis of18O-labeled amides using H218O as the oxygen source.
Imidazole derivatives as accelerators for ruthenium-catalyzed hydroesterification and hydrocarbamoylation of alkenes: Extensive ligand screening and mechanistic study
Konishi, Hideyuki,Muto, Takashi,Ueda, Tsuyoshi,Yamada, Yayoi,Yamaguchi, Miyuki,Manabe, Kei
, p. 836 - 845 (2015/03/14)
Imidazole derivatives are effective ligands for promoting the [Ru3(CO)12]-catalyzed hydroesterification of alkenes using formates. Extensive ligand screening was performed to identify 2-hydroxymethylated imidazole as the optimal ligand. Neither carbon monoxide gas nor a directing group was required, and the reaction also showed a wide substrate generality. The Ru-imidazole catalyst system also promoted intramolecular hydrocarbamoylation to afford lactams. A Ru-imidazole complex was unambiguously analyzed by X-ray crystallography, and it had a trinuclear structure derived from one [Ru3(CO)12] and two ligands. This complex was also successfully used for hydroesterification. The mechanism was examined in detail by using D- and 13C-labeled formates, indicating that the hydroesterification reaction proceeds by a decarbonylation-recarbonylation pathway. Effective imidazole assistant: [Ru3(CO)12]-catalyzed hydroesterification of alkenes by using formates is drastically accelerated by imidazole derivatives and exhibits a broad substrate scope for both alkenes and formates. The Ru-imidazole complex also catalyzes the intramolecular hydrocarbamoylation of alkenes.
Regiodivergent access to five- and six-membered benzo-fused lactams: Ru-catalyzed olefin hydrocarbamoylation
Li, Bin,Park, Yoonsu,Chang, Sukbok
supporting information, p. 1125 - 1131 (2014/02/14)
We report herein a new strategy of the Ru-catalyzed intramolecular olefin hydrocarbamoylation for the regiodivergent synthesis of five- and six-membered benzo-fused lactams starting from N-(2-alkenylphenyl)formamides. Using a combined catalyst of Ru3
Multicomponent multicatalyst reactions (MC)2R: One-pot synthesis of 3,4-dihydroquinolinones
Zhang, Lei,Sonaglia, Lorenzo,Stacey, Jason,Lautens, Mark
, p. 2128 - 2131 (2013/06/05)
A Rh/Pd/Cu catalyst system led to an efficient synthesis of dihydroquinolinones in one-pot, two operations. The reaction features the first triple metal-catalyzed transformations in one reaction vessel, without any intermediate workup. The conjugate-addition/amidation/amidation reaction sequence is highly modular, divergent, and practical.
A nitrophenyl-based prodrug type for colorectal targeting of prednisolone, budesonide and celecoxib
Marquez Ruiz, Juan F.,Kedziora, Kinga,Pigott, Maria,Keogh, Brian,Windle, Henry,Gavin, Jason,Kelleher, Dermot P.,Gilmer, John F.
, p. 1693 - 1698 (2013/04/10)
Celecoxib is a COX-2 inhibitor drug that can be used to reduce the risk of colorectal adenocarcinoma. Glucocorticoids are used in the treatment of inflammatory bowel disease. A limitation to the use of both drug types is that they undergo absorption from the intestinal tract with serious side effects. The prodrug systems introduced here involve forming a nitro-substituted acylsulfonamide group in the case of celecoxib and a nitro-substituted 21-ester for the glucocorticoids. Drug release is triggered by the nitro reductase action of the colonic microflora, liberating a cyclization competent species. The release of the active parent drugs was evaluated in vitro using Clostridium perfringens and epithelial transport through Caco-2 monolayer evaluation was carried out to estimate the absorption properties of the prodrugs compared to the parental drugs.
