- A Four-Component Cascade C-H Functionalization/Cyclization/Nucleophilic Substitution Reaction to Construct α-Functionalized Tetrahydroquinolines by the Strategy of in Situ Directing Group Formation
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A four-component cascade C-H functionalization/cyclization/nucleophilic substitution reactions of anilines, carboxylic anhydrides, propenol, and alkohols have been developed by a strategy of in situ directing group formation, affording an efficient and convenient synthesis of α-alkoxyl tetrahydroquinolines from basic starting materials. A plausible mechanism involving rhodium(III) catalytic C-H functionalization and double nucleophilic attacks is proposed. The nucleophilicity order of some alcohols is also obtained for the cascade reaction.
- Bai, Peng,Li, Ya-Qiong,Huang, Zhi-Zhen
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- Dehydrogenative and Redox-Neutral N-Heterocyclization of Aminoalcohols Catalyzed by Manganese Pincer Complexes
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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.
- Brzozowska, Aleksandra,Rueping, Magnus,Sklyaruk, Jan,Zubar, Viktoriia
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supporting information
(2022/03/17)
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- Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists
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The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.
- Xia, Yuehan,Yu, Mingcheng,Zhao, Yunpeng,Xia, Li,Huang, Yafei,Sun, Nannan,Song, Meiqi,Guo, Huimin,Zhang, Yunyi,Zhu, Di,Xie, Qiong,Wang, Yonghui
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supporting information
(2020/12/04)
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- Visible-Light Induced C(sp2)?H Amidation with an Aryl–Alkyl σ-Bond Relocation via Redox-Neutral Radical–Polar Crossover
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We report an approach for the intramolecular C(sp2)?H amidation of N-acyloxyamides under photoredox conditions to produce δ-benzolactams with an aryl-alkyl σ-bond relocation. Computational studies on the designed reductive single electron transfer strategy led us to identify N-[3,5-bis(trifluoromethyl)benzoyl] group as the most effective amidyl radical precursor. Upon the formation of an azaspirocyclic radical intermediate by the selective ipso-addition with outcompeting an ortho-attack, radical–polar crossover was then rationalized to lead to the rearomative ring-expansion with preferential C?C bond migration.
- Chang, Sukbok,Jeong, Jiwoo,Jung, Hoimin,Keum, Hyeyun,Kim, Dongwook
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supporting information
p. 25235 - 25240
(2021/10/25)
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- Ruthenium-catalyzed intramolecular arene C(sp2)-H amidation for synthesis of 3,4-dihydroquinolin-2(1 H)-ones
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We report the [Ru(p-cymene)(l-proline)Cl] ([Ru1])-catalyzed cyclization of 1,4,2-dioxazol-5-ones to form dihydroquinoline-2-ones in excellent yields with excellent regioselectivity via a formal intramolecular arene C(sp2)-H amidation. The reactions of the 2- and 4-substituted aryl dioxazolones proceeds initially through spirolactamization via electrophilic amidation at the arene site, which is para or ortho to the substituent. A Hammett correlation study showed that the spirolactamization is likely to occur by electrophilic nitrenoid attack at the arene, which is characterized by a negative ρ value of -0.73.
- Au, Chi-Ming,Ling, Cho-Hon,Sun, Wenlong,Yu, Wing-Yiu
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p. 3310 - 3314
(2021/05/29)
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- Room Temperature Benzofused Lactam Synthesis Enabled by Cobalt(III)-Catalyzed C(sp2)?H Amidation
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Benzofused lactams, especially indolin-2-one and dihydroquinolin-2-one are popular structural motives in durgs and natural products. Herein, we developed a room temperature and robust synthesis of benzofused lactams through cobalt(III)-catalyzed C(sp
- Tian, Xun,Li, Xin,Duan, Shengzu,Du, Ya,Liu, Tongqi,Fang, Yongsheng,Chen, Wen,Zhang, Hongbin,Li, Minyan,Yang, Xiaodong
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p. 1050 - 1058
(2020/12/18)
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- METHOD FOR PRODUCING LACTAM COMPOUND, AND LACTAM COMPOUND PRODUCED THEREBY
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The present invention relates to a method for producing a lactam compound from dioxazolone in the presence of a catalyst having a particular ligand, and to a lactam compound produced thereby, and can produce a lactam compound with excellent selectivity and an excellent yield by using the combination of a starting material having a particular functional group and a particular catalyst having a particular ligand.
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Paragraph 0174-0175; 0177
(2020/11/30)
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- Synthesis of Lactams via Ir-Catalyzed C-H Amidation Involving Ir-Nitrene Intermediates
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x-membered lactams were synthesized via either an amidation of sp3 C-H bonds or an electrophilic substitution of arenes via Ir-nitrene intermediates. With the employment of a readily available iridium catalyst in dichloromethane or hexafluoro-2-propanol, a wide range of lactams were synthesized in good to excellent yields with high selectivity.
- Li, Xiaoxun,Liu, Jitian,Tang, Weiping,Wang, Shuojin,Ye, Wenjing,Zheng, Junrong
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- Revisiting Arene C(sp2)?H Amidation by Intramolecular Transfer of Iridium Nitrenoids: Evidence for a Spirocyclization Pathway
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Two mechanistic pathways, that is, electrocyclization and electrophilic aromatic substitution, are operative in most intramolecular C?H amination reactions proceeding by metal nitrenoid catalysis. Reported here is an alternative mechanistic scaffold leading to benzofused δ-lactams selectively. Integrated experimental and computational analysis revealed that the reaction proceeds by a key spirocyclization step followed by a skeletal rearrangement. Based on this mechanistic insight, a new synthetic route to spirolactams has been developed.
- Hwang, Yeongyu,Park, Yoonsu,Kim, Yeong Bum,Kim, Dongwook,Chang, Sukbok
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p. 13565 - 13569
(2018/09/25)
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- Multibond Forming Tandem Reactions of Anilines via Stable Aryl Diazonium Salts: One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones
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A fast and effective one-pot tandem process that generates Heck coupled products from readily available anilines via stable aryl diazonium tosylate salts was developed. The mild and simple procedure involves rapid formation of aryl diazonium salts using a polymer-supported nitrite reagent and p-tosic acid, followed by a base-free Heck-Matsuda coupling with acrylates and styrenes. Using 2-nitroanilines as substrates, the one-pot tandem process was extended for the direct synthesis of 3,4-dihydroquinolin-2-ones. In this case, following diazotization and Heck-Matsuda coupling to give methyl cinnamates, addition of hydrogen and reutilization of the palladium catalyst for reduction of the nitro group and hydrogenation of the alkene resulted in efficient formation of 3,4-dihydroquinolin-2-ones. The synthetic utility of this one-pot, four-stage process was demonstrated with the five-pot synthesis of a quinolinone-based sodium ion channel modulator.
- Faggyas, Réka J.,Grace, Megan,Williams, Lewis,Sutherland, Andrew
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p. 12595 - 12608
(2018/10/15)
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- Traceless Directing-Group Strategy in the Ru-Catalyzed, Formal [3 + 3] Annulation of Anilines with Allyl Alcohols: A One-Pot, Domino Approach for the Synthesis of Quinolines
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A unique, ruthenium-catalyzed, [3 + 3] annulation of anilines with allyl alcohols in the synthesis of substituted quinolines is reported. The method employs a traceless directing group strategy in the proximal C-H bond activation and represents a one-pot Domino synthesis of quinolines from anilines.
- Kumar, Gangam Srikanth,Kumar, Pravin,Kapur, Manmohan
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supporting information
p. 2494 - 2497
(2017/05/24)
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- Regiodivergent access to five- and six-membered benzo-fused lactams: Ru-catalyzed olefin hydrocarbamoylation
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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
- Li, Bin,Park, Yoonsu,Chang, Sukbok
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p. 1125 - 1131
(2014/02/14)
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- Novel approach to 3,4-dihydro-2(1H)-quinolinone derivatives via cyclopropane ring expansion
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N-(1'-Alkoxy)cyclopropyl-2-haloanilines are transformed to 3,4-dihydro-2(1H)-quinolinones via palladium-catalyzed cyclopropane ring expansion. The reaction tolerates a variety of functional groups such as ester, nitrile, ether, and ketone group
- Tsuritani, Takayuki,Yamamoto, Yuhei,Kawasaki, Masashi,Mase, Toshiaki
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supporting information; experimental part
p. 1043 - 1045
(2009/09/05)
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- The tandem reaction combining radical and ionic processes: an efficient approach to substituted 3,4-dihydroquinolin-2-ones
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3,4-Dihydroquinolin-2-ones are of great importance in the areas of pharmaceuticals. However, the direct intramolecular radical cyclizations of the corresponding amide compounds favor 5-exo products 2. Reports on the radical cyclization reactions producing
- Zhou, Wang,Zhang, Liangren,Jiao, Ning
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experimental part
p. 1982 - 1987
(2009/08/07)
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- Synthesis of five-, six-, and seven-membered ring lactams by Cp*Rh complex-catalyzed oxidative N-heterocyclization of amino alcohols
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A new effective catalytic system consisting of [Cp*RhCl 2]2/K2CO3 (Cp* = pentamethylcyclopentadienyl) for the lactamization of amino alcohols has been developed. As an example, the reaction of 3-(2-aminophenyl)-1-propanol in the presence of [Cp*RhCl2]2 (5.0% Rh) and K 2CO3 (10%) in acetone gives 3,4-dihydro-2(1H)-quinolinone in an isolated yield of 80%. A variety of five-, six-, and seven-membered benzo-fused lactams are synthesized by this catalytic system.
- Fujita, Ken-Ichi,Takahashi, Yoshinori,Owaki, Maki,Yamamoto, Kazunari,Yamaguchi, Ryohei
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p. 2785 - 2788
(2007/10/03)
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- Benzo[c]quinolizin-3-ones: A novel class of potent and selective nonsteroidal inhibitors of human steroid 5α-reductase 1
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The synthesis and biological evaluation of a series of novel, selective inhibitors of isoenzyme 1 of human 5α-reductase (5αR) (EC 1.3.99.5) are reported. The inhibitors are 4aH- (19-29) or 1H-tetrahydrobenzo[c]quinolizin-3-ones (35-47) bearing at position
- Guarna,Machetti,Occhiato,Scarpi,Comerci, Alessandra,Danza, Giovanna,Mancina, Rosa,Serio, Mario,Hardy, Kimber
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p. 3718 - 3735
(2007/10/03)
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- Aluminium chloride-catalyzed intermolecular vs intramolecular friedel-crafts reaction of acrylanilides and 3-chloropropanamides
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3-Phenylpropionanilide (4a) is obtained in a yield of 89% from acrylanilide by the treatment with AlCl3/ benzene, compared with a yield of 39% by the 1,4-conjugate addition of phenyllithium. The formation of 4a indicated that an intermolecular Friedel-Crafts reaction occurred, rather than the relatively more facile intramolecular ring cyclization, and provided a more efficient route than a conjugate addition of phenyllithium for the preparation of 3-phenylpropionanilide and its derivatives. Although the methoxy group is an activator of the nucleophilic substitution, introduction of a methoxy substituent at N-phenyl did not increase the competitive capability of the intramolecular cyclization because of AlCl3-catalyzed demethylation to form the ArOAlCl2 complex which decreased the availability of the π-electron in the N-phenyl aromatic system.
- Chen, I.-Li,Wang, Tai-Chi,Chen, Yeh-Long,Tzeng, Cherng-Chyi
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p. 155 - 162
(2007/10/03)
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- Titanium(III)-induced transformation of hydroxylamines to imines or secondary amines
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N,N-Disubstituted and cyclic hydroxylamines can be converted into the corresponding imines efficiently upon treatment with anhydrons titanium trichloride in THF at room temperature. Similar treatment of N-allylhydroxylamines with anhydrous titanium trichloride gives 1-azadienes, which are versatile synthetie intermediates for aza-Diels-Alder reactions. On the other hand, the same hydroxylamines can be converted into the corresponding secondary amines upon treatment with aqueous titanium trichloride in methanol. It is noteworthy that optically active hydroxylamines, which have chirality at the α-position to nitrogen, can be converted into optically active secondary amines without loss of chirality. Dihydro-2(1H)-quinolinones can be prepared upon treatment of 1-hydroxy-3,4-dihydro-2(1H)-quinolinones with aqueous titanium trichloride. The substrates of N,N-disubstituted and cyclic hydroxylamines can be prepared readily upon treatment of nitrones with nucleophiles. Since nitrones can be prepared by metal-catalyzed oxidations of secondary amines with hydrogen peroxide, the present titanium(III)-promoted reaction of hydroxylamines will provide a convenient method for the synthesis of either α-substituted imines or amines from secondary amines.
- Kodera,Watanabe,Imada,Murahashi
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p. 2542 - 1549
(2007/10/02)
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- Reinvestigation by Carbon-13 NMR Spectroscopy of the Aluminium Chloride catalysed Cyclisation of Methyl-substituted β-Chloropropionanilides to 3,4-Dihydroquinolin-2(1H)-ones
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Aluminium chloride-catalysed cyclisation of methyl-substituted β-chloropropionanilides occurs via kinetically controlled intramolecular Friedel-Crafts cyclisation to give 3,4-dihydroquinolin-2(1H)-ones.In the case of the ortho-methylanilide, ipso attack i
- Fuller, Michael W.,Quacchia, Rodney H.,Weigold, Josephine A.
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p. 771 - 773
(2007/10/02)
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