- Access to 5,6-Spirocycles Bearing Three Contiguous Stereocenters via Pd-Catalyzed Stereoselective [4 + 2] Cycloaddition of Azadienes
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We present herein a highly diastereo- and enantioselective Pd-catalyzed [4 + 2] cycloaddition of benzofuran-derived azadienes with vinyl benzoxazinanones, which represents a rare highly stereoselective cycloaddition of this class of fused azadienes as a two-atom synthon. The use of a phosphoramidite ligand bearing a chiral secondary amine with a simple biphenyl backbone proved to be the key to construct the novel spirocyclic tetrahydroquinoline scaffold containing three contiguous stereocenters as a single diastereomer in high enantioselectivity.
- Fairuz Binte Sheikh Ismail, Siti Nur,Yang, Binmiao,Zhao, Yu
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supporting information
p. 2884 - 2889
(2021/05/05)
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- A [4+3] Cycloaddition Reaction of Aza-ortho-quinone Methides with C,N-Cyclic Azomethine Imines for Synthesis of 1,2,4-Triazepines
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The base-induced formal [4+3] cycloaddition reaction of C,N-cyclic azomethine imines with aza-ortho-quinone methides, generated in situ, is reported. This protocol provided an efficient method for the synthesis of biologically important 1,2,4-triazepine derivatives, with a wide substrate scope and excellent functional-group tolerance, and it gives moderate to excellent yields under mild conditions. Several of the derivatives exhibited in vitro antitumor activities against the A2780 cell line in a screening of the cancer cell lines HCT-116, H2228, and A2780 by an MTT assay.
- Wang, Xinyue,Li, Zefei,Feng, Chang,Zhen, Qi,Guo, Mingzhang,Yao, Yaning,Zou, Xinyu,Wang, Pengfei,Hou, Yunlei,Gong, Ping
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supporting information
p. 2090 - 2096
(2021/09/06)
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- Ynamide Smiles Rearrangement Triggered by Visible-Light-Mediated Regioselective Ketyl-Ynamide Coupling: Rapid Access to Functionalized Indoles and Isoquinolines
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In the past decades, significant advances have been made on radical Smiles rearrangement. However, the eventually formed radical intermediates in these reactions are limited to the amidyl radical, except for the few examples initiated by a N-centered radical. Here, a novel and practical radical Smiles rearrangement triggered by photoredox-catalyzed regioselective ketyl-ynamide coupling is reported, which represents the first radical Smiles rearrangement of ynamides. This method enables facile access to a variety of valuable 2-benzhydrylindoles with broad substrate scope in generally good yields under mild reaction conditions. In addition, this chemistry can also be extended to the divergent synthesis of versatile 3-benzhydrylisoquinolines through a similar ketyl-ynamide coupling and radical Smiles rearrangement, followed by dehydrogenative oxidation. Moreover, such an ynamide Smiles rearrangement initiated by intermolecular photoredox catalysis via addition of external radical sources is also achieved. By control experiments, the reaction was shown to proceed via key ketyl radical and α-imino carbon radical intermediates.
- Chen, Yang-Bo,Sun, Zhou,Wang, Ze-Shu,Ye, Long-Wu,Zhang, Hao-Wen,Zhu, Chunyin
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supporting information
p. 3636 - 3644
(2020/03/06)
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- One-pot synthesis of 2-hydroxymethylindoles: via photoredox-catalyzed ketyl-ynamide coupling/1,3-allylic alcohol transposition
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An efficient visible-light-mediated ketyl-ynamide coupling by employing ynamides bearing alkyl sulfonyl substituents to deliver eneindolin-3-ols has been developed. Subsequent 1,3-transposition of allylic alcohols in one pot is capable of synthesizing 2-hydroxymethylindoles in generally moderate to good yields. The synthetic utility of this protocol has also been demonstrated by the facile and practical synthesis of two bioactive molecules. The use of readily available substrates, a simple procedure and benign reaction conditions render this method a viable alternative for the synthesis of 2-hydroxymethylindoles. This journal is
- Chen, Yang-Bo,Wang, Kun,Wang, Ze-Shu,Xu, Zhou,Ye, Long-Wu
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supporting information
p. 4483 - 4488
(2020/08/10)
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- Visible-light-induced radical isocyanide insertion protocol for the synthesis of difluoromethylated spiro[indole-3,3′-quinoline] derivatives
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Herein, we report the first protocol for visible-light-induced radical isocyanide insertion reactions between 3-(2-isocyanobenzyl)-indoles and bromodifluoroacetates or bromodifluoroacetamides. The protocol, which has good functional group tolerance and a broad substrate scope, constitutes an efficient and general route to difluoromethylated spiro[indole-3,3′-quinoline] derivatives. This journal is
- Zhang, Jingjing,Xu, Wentao,Qu, Yi,Liu, Yuxiu,Li, Yongqiang,Song, Hongjian,Wang, Qingmin
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supporting information
p. 15212 - 15215
(2020/12/21)
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- Benzoazepine-Fused Isoindolines via Intramolecular (3 + 2)-Cycloadditions of Azomethine Ylides with Dinitroarenes
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Aminobenzaldehydes bearing a pendant 3,5-dinitrophenyl group react thermally with N-substituted α-amino acids to form unprecedented benzoazepine-fused isoindolines. The reaction proceeds via a dearomatization/rearomatization sequence involving an intramolecular (3 + 2)-cycloaddition between the in situ formed azomethine ylide and the dinitroarene. Various glycine derivatives are tolerated as well as branched substrates based on cyclic, α-mono-, and α,α-disubstituted amino acids, giving single diastereomers in many cases. The method is scalable and gives products with a nitro group ready for further manipulation.
- Wales, Steven M.,Rivinoja, Daniel J.,Gardiner, Michael G.,Bird, Melissa J.,Meyer, Adam G.,Ryan, John H.,Hyland, Christopher J. T.
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supporting information
p. 4703 - 4708
(2019/06/27)
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- Enantioselective synthesis of tunable chiral pyridine-aminophosphine ligands and their applications in asymmetric hydrogenation
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A small library of tunable chiral pyridine-aminophosphine ligands were enantioselectively synthesized based on chiral 2-(pyridin-2-yl)-substituted 1,2,3,4-tetrahydroquinoline scaffolds, which were obtained in high yields and with excellent enantioselectivities via ruthenium-catalyzed asymmetric hydrogenation of 2-(pyridin-2-yl)quinolines. The protocol features a wide substrate scope and mild reaction conditions, enabling scalable synthesis. These chiral P,N ligands were successfully applied in the Ir-catalyzed asymmetric hydrogenation of benchmark olefins and challenging seven-membered cyclic imines including benzazepines and benzodiazepines. Excellent enantio- and diastereoselectivity (up to 99% ee and >20:1 dr), and/or unprecedented chemoselectivity were obtained in the asymmetric hydrogenation of 2,4-diaryl-3H-benzo[b]azepines and 2,4-diaryl-3H-benzo[b][1,4]diazepines.
- Liu, Youran,Chen, Fei,He, Yan-Mei,Li, Chenghao,Fan, Qing-Hua
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supporting information
p. 5099 - 5105
(2019/05/29)
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- Asymmetric [4+2] cycloaddition of azlactones with dipolar copper–allenylidene intermediates for chiral 3,4-dhydroquinolin-2-one derivatives
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In this paper, a pybox-copper catalyzed enantioselective decarboxylative [4+2] cycloaddition reaction of ethynyl benzoxazinanones with azlactones has been developed, which provides optically active 3,4-dihydroquinolin-2-ones in high yields with good enantioselectivities and diastereoselectivities. In this transformation, the chiral dipolar copper–allenylidene intermediates are kinetically generated via decarboxylative ethynyl benzoxazinanones, followed by the attack of the enolate azlactones to form enantiomerically enriched 3,4-dihydroquinolin-2-one structures.
- Sun, Bing-Bing,Hu, Qing-Xian,Hu, Jia-Ming,Yu, Jie-Qiang,Jia, Jun,Wang, Xing-Wang
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supporting information
p. 1967 - 1970
(2019/06/27)
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- Catalytic Asymmetric [4 + 3] Annulation of C, N-Cyclic Azomethine Imines with Copper Allenylidenes
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The first asymmetric decarboxylative [4 + 3] annulation of propargylic carbamates with C,N-cyclic azomethine imines has been developed successfully by a copper-N-heterocyclic carbine system. This strategy led to a series of optically active isoquinoline-f
- Wang, Yanfang,Zhu, Liping,Wang, Mengran,Xiong, Jiale,Chen, Nannan,Feng, Xing,Xu, Zhaoqing,Jiang, Xianxing
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supporting information
p. 6506 - 6510
(2018/10/20)
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- Highly Diastereoselective Synthesis of Trifluoromethyl Indolines by Interceptive Benzylic Decarboxylative Cycloaddition of Nonvinyl, Trifluoromethyl Benzoxazinanones with Sulfur Ylides under Palladium Catalysis
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A highly diastereoselective synthesis of trifluoromethyl-substituted indolines under palladium catalysis is disclosed. The reaction proceeds by interceptive decarboxylative benzylic cycloaddition (IDBC) of nonvinyl, trifluoromethyl benzoxazinanones with sulfur ylides. The palladium-π-benzyl zwitterionic intermediates are suggested for this transformation, and this would be the first example of an IDBC reaction.
- Punna, Nagender,Das, Pulakesh,Gouverneur, Véronique,Shibata, Norio
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supporting information
p. 1526 - 1529
(2018/03/23)
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- Enantioselective Construction of Tetrahydroquinazoline Motifs via Palladium-Catalyzed [4 + 2] Cycloaddition of Vinyl Benzoxazinones with Sulfamate-Derived Cyclic Imines
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A palladium-catalyzed enantioselective [4 + 2] cycloaddition reaction of vinyl benzoxazinones with sulfamate-derived cyclic imines is described, affording the tetrahydroquinazolines bearing several functional rings in high yields (up to 99% yield) with good to excellent diastereoselectivities and excellent enantioselectivities (up to 96% ee). This reaction represents the first Pd-catalyzed asymmetric decarboxylative cycloaddition of vinyl benzoxazinones with imines.
- Wang, Chang,Li, Yan,Wu, Yang,Wang, Qijun,Shi, Wangyu,Yuan, Chunhao,Zhou, Leijie,Xiao, Yumei,Guo, Hongchao
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supporting information
p. 2880 - 2883
(2018/05/29)
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- Pd-Catalyzed Three-Component Domino Reaction of Vinyl Benzoxazinanones for Regioselective and Stereoselective Synthesis of Allylic Sulfone-Containing Amino Acid Derivatives
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A Pd-catalyzed, highly regioselective and stereoselective three-component domino allylic substitution/N-H carbene insertion reaction under mild conditions is described. This reaction demonstrates a wide substrate scope and satisfactory functional group tolerance, providing a broad range of allylic sulfone-containing amino acid derivatives. Moreover, DBU mediates highly diastereoselective cross-dehydrogenative coupling annulation of allylic sulfones without using peroxides or any metal oxidants. This developed protocol affords 7-membered ring heterocyclic compounds incorporating both sulfone-containing amino acid esters and one quaternary carbon center. Mechanistic studies indicate that an unusual umpolung of glycine occurred in this annulation.
- Hao, Jiping,Xu, Yi,Xu, Zhongliang,Zhang, Zhiqiang,Yang, Weibo
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supporting information
p. 7888 - 7892
(2019/01/04)
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- Catalytic Asymmetric Construction of the Tryptanthrin Skeleton via an Enantioselective Decarboxylative [4 + 2] Cyclization
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The first catalytic asymmetric construction of the tryptanthrin skeleton has been established, taking advantage of a palladium(0)/chiral ligand-catalyzed enantioselective decarboxylative [4 + 2] cyclization of vinyl benzoxazinanones with isatins. This rea
- Mei, Guang-Jian,Bian, Chen-Yu,Li, Guo-Hao,Xu, Shao-Li,Zheng, Wen-Qin,Shi, Feng
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supporting information
p. 3219 - 3222
(2017/06/23)
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- Lewis Acid-Catalyzed C(sp3)–C(sp3) Bond Forming Cyclization Reactions for the Synthesis of Tetrahydroprotoberberine Derivatives
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An efficient Lewis acid-catalyzed C(sp3)–C(sp3) bond forming annulation reaction has been developed. This strategy serves as a new method for the facile synthesis of tetrahydro-5H-isoquinolino[2,1-g][1,6]naphthyridine derivatives. A wide range of 2-methylquinoline-3-carbaldehydes and 1,2,3,4-tetrahydroisoquinolines can be applied for this process to afford structurally diverse tetrahydroprotoberberine derivatives in excellent yields. (Figure presented.).
- Li, Jianjun,Qin, Cong,Yu, Yang,Fan, Huaqiang,Fu, Yiwei,Li, Hao,Wang, Wei
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supporting information
p. 2191 - 2195
(2017/07/07)
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- Asymmetric synthesis of isoquinolinonaphthyridines catalyzed by a chiral Br?nsted acid
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A catalytic asymmetric method for the synthesis of chiral isoquinolinonaphthyridines has been developed. A chiral disulfonimide catalyzes a redox cyclization reaction between 2-methyl-3-aldehydeazaarenes and 1,2,3,4-tetrahydroisoquinolines to deliver a range of isoquinolinonaphthyridines with good to high yields (up to 91%) and up to 92:8 er.
- Li, Jianjun,Fu, Yiwei,Qin, Cong,Yu, Yang,Li, Hao,Wang, Wei
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supporting information
p. 6474 - 6477
(2017/08/16)
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- Tandem [3 + 2] cycloaddition/1,4-addition reaction of azomethine ylides and aza-o-quinone methides for asymmetric synthesis of imidazolines
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An enantioselective synthesis of biologically important imidazolidines has been achieved via a tandem [3 + 2] cycloaddition/1,4-addition reaction of azomethine ylide and aza-o-quinone methides. With the use of this tool, various imidazolidine derivatives are obtained in good yields with excellent diastereoselectivities and enantioselectivities.
- Jia, Hao,Liu, Honglei,Guo, Zhenyan,Huang, Jiaxing,Guo, Hongchao
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supporting information
p. 5236 - 5239
(2017/11/06)
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- Metal free carboamination of internal alkynes - An easy access to polysubstituted quinolines
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A metal free carboamination of unactivated alkynes towards highly substituted quinolines was realized in the presence of a synergistic Br?nsted acid catalyst system. Supported by mechanistic probes, the reaction proceeds via a highly reactive vinyl cation in a C-C bond formation - Schmidt reaction sequence. The irreversible extrusion of N2, as a powerful driving force, allows for a general conversion of poorly nucleophilic aliphatic alkynes.
- Stopka,Niggemann
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supporting information
p. 5761 - 5764
(2016/05/19)
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- Cycloadditions with Bromo-Substituted Morita-Baylis-Hillman Adducts of Isatins and N-(ortho-Chloromethyl)aryl Amides
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Efficient construction of a challenging aza-spirocycloheptane oxindole scaffold is reported through an unprecedented [4 + 3] cycloaddition reaction with bromo-substituted Morita-Baylis-Hillman adducts of isatins and N-(ortho-chloromethyl)aryl amides. Both reactive intermediates, the allylic phosphonium ylides and aza-o-quinone methides, were in situ generated, chemoselectively facilitated by a Lewis base and Bronsted base, respectively.
- Zhan, Gu,Shi, Ming-Lin,He, Qing,Du, Wei,Chen, Ying-Chun
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supporting information
p. 4750 - 4753
(2015/10/12)
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- N-heterocyclic carbene-catalyzed enantioselective intramolecular N-tethered aldehyde-ketone benzoin reactions
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The N-heterocyclic carbene-catalyzed enantioselective intramolecular benzoin reaction of N-tethered substrates was realized. With 15 mol % of d-camphor-derived triazolium salt E and 10 mol % of NaOAc, the aldehyde-ketone cross benzoin reactions of various substituted N-tethered substrates proceeded smoothly to afford dihydroquinolinone derivatives with a quaternary carbon stereocenter in moderate to good yields and excellent ee.
- Jia, Min-Qiang,You, Shu-Li
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supporting information
p. 622 - 624
(2013/05/09)
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- Synthesis of quinolinomorphinan derivatives as highly selective δ opioid receptor ligands
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We have reported previously the novel δ opioid agonist KNT-127 which showed high affinity and selectivity for the δ receptor. Moreover, the analgesic effect of subcutaneously administered KNT-127 was more potent than that of a prototypical δ agonist (-)-TAN-67 in the acetic acid writhing test. This study of the structure-activity relationship of KNT-127 derivatives focused on the introduction of substituents onto the 5′-, 6′-, 7′- or 8′-position of the quinoline ring and revealed that many derivatives with 5′- or 8′-substituents showed high affinities and selectivities for the δ receptor. Especially, SYK-153 with an 8′-OH group showed the highest affinity and the most balanced and highest selectivity for the δ receptor among the synthesized compounds.
- Ida, Yoshihiro,Matsubara, Ayaka,Nemoto, Toru,Saito, Manabu,Hirayama, Shigeto,Fujii, Hideaki,Nagase, Hiroshi
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p. 5810 - 5831
(2012/11/06)
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- AROMATIC SULFONE COMPOUND AS ALDOSTERONE RECEPTOR MODULATOR
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The present invention provides a compound represented by the following formula (I): [wherein, A represents a group of the following formula (A-1): etc., R1 and R2 each independently represent a hydrogen atom etc., Z represents CR3 etc., W represents CR4 etc., Q represents CR5 etc., R3, R4 and R5 each independently represent a hydrogen atom etc., Y represents an oxygen atom or sulfur atom, X represents an oxygen atom etc. and B represents an optionally substituted aryl group or optionally substituted heteroaryl group], the prodrug thereof or the pharmaceutically acceptable salt thereof for preventing or treating various diseases such as hypertesion, cerebral stroke, cardiac failure, etc.
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Page/Page column 26
(2010/11/28)
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- COMPOUNDS USEFUL IN THERAPY
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Compounds of formula (I), or a pharmaceutically acceptable derivative thereof, wherein: X represents NR or O; R represents hydrogen, C1-8 alkyl or SO2[C,1-8 alkyl]; W represents N or CH; Y and Y' independently represent hy
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Page/Page column 33
(2010/02/13)
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- SUBSTITUTED TRIAZOLE DERIVATIVES AS OXYTOCIN ANTAGONISTS
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This invention relates to compounds of formula (I) with activity as oxytocin antagonists, uses thereof, processes for the preparation thereof and compositions containing said inhibitors. These inhibitors have utility in a variety of therapeutic areas including sexual dysfunction, particularly premature ejaculation (P.E.).
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- TRIAZOLE COMPOUNDS USEFUL IN THERAPY
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A compound of formula (I), or a pharmaceutically acceptable derivative thereof, wherein V represents -(CH2)d(O)e-, -CO-, or -CH(C1-6 alkyl)-; W is -0-, -S(O)a , or -N(R1')-R1 rep
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- A convenient access to benzo-substituted phthalazines as potential precursors to DNA intercalators
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2-Nitro-5-methoxybenzaldehyde is converted to amines 2 and 7 via two alternative routes. Upon diazotisation and Sandmeyer reaction, halides 4 and 9 are formed, which, through lithiation and formylation lead to the o-phthalaldehyde. Further cyclisation with hydrazine gives the 5-methoxy-substituted phthalazine.
- Tsoungas, Petros G,Searcey, Mark
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p. 6589 - 6592
(2007/10/03)
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- Inhibitors of cyclic AMP phosphodiesterase. 1. Analogues of cilostamide and anagrelide
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Evaluation of a series of lactam heterocyclic analogues of cilostamide as inhibitors of cyclic AMP phosphodiesterase derived from both human platelets and rat heart in comparison with their corresponding methoxy-substituted heterocycles has revealed that the N-cyclohexyl-N-methyl-4-oxybutyramide side chain of 2 is an important lipophilic and/or steric pharmacophore. Attachment of this side chain to the parent heterocycle of the potent cyclic AMP phosphodiesterase inhibitor anagrelide afforded the hybrid structure RS-82856, shown to be more potent than either of its progenitors as an inhibitor of cyclic AMP phosphodiesterase or of ADP-induced platelet aggregation. The available in vitro data suggest that 1 possesses potentially useful antithrombotic and cardiotonic properties.
- Jones,Venuti,Alvarez,Bruno,Berks,Prince
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p. 295 - 303
(2007/10/02)
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- Substituted benzoxazin-2-ones and pharmaceutical compositions containing them
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This invention is directed to novel benzoxazin-2-ones of the formula STR1 wherein A is a sulfur atom or an SO, SO2, R--N=S, or R--N=SO2 group where R is a hydrogen atom or an acyl group; D is an alkylene group; R1 is an al
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- 1,3-Benzoxazine trichloromethyl derivatives, compositions and use
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The invention relates to novel heterocyclic trichloromethyl derivatives, particularly 2-trichloromethyl-substituted quinazoline, benzo[d]-[1,3]-oxazine and benzo[e]-[1,3]-oxazine derivatives, for example 1,2-dihydro-2-trichloromethylquinazolin-4-one. The compounds of the invention are at least as effective as prior art trichloromethyl derivatives, which reduce the production of methane during the rumen metabolism of ruminant animals, and increase the formation of propionate at the expense of acetate, and hence improve the animals' rate of growth and their efficiency of food utilization.
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