- Radical Decarboxylative Carbometalation of Benzoic Acids: A Solution to Aromatic Decarboxylative Fluorination
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Abundant aromatic carboxylic acids exist in great structural diversity from nature and synthesis. To date, the synthetically valuable decarboxylative functionalization of benzoic acids is realized mainly by transition-metal-catalyzed decarboxylative cross couplings. However, the high activation barrier for thermal decarboxylative carbometalation that often requires 140 °C reaction temperature limits both the substrate scope as well as the scope of suitable reactions that can sustain such conditions. Numerous reactions, for example, decarboxylative fluorination that is well developed for aliphatic carboxylic acids, are out of reach for the aromatic counterparts with current reaction chemistry. Here, we report a conceptually different approach through a low-barrier photoinduced ligand to metal charge transfer (LMCT)-enabled radical decarboxylative carbometalation strategy, which generates a putative high-valent arylcopper(III) complex, from which versatile facile reductive eliminations can occur. We demonstrate the suitability of our new approach to address previously unrealized general decarboxylative fluorination of benzoic acids.
- Xu, Peng,López-Rojas, Priscila,Ritter, Tobias
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supporting information
p. 5349 - 5354
(2021/05/05)
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- Regioselective Electrochemical Cyclobutanol Ring Expansion to 1-Tetralones
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A mild electrochemical method for the regioselective preparation of 1-tetralones under environmentally friendly conditions from readily available cyclobutanols was developed. A series of aromatic- and heteroaromatic-fused 1-tetralones was accessed through ring expansion of the functionalized cyclobutanols via electrochemical generation of alkoxy radicals and intramolecular cyclization.
- Petti, Alessia,Natho, Philipp,Lam, Kevin,Parsons, Philip J.
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p. 854 - 858
(2021/01/12)
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- Radical-Polar Crossover Annulation: A Platform for Accessing Polycyclic Cyclopropanes
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Photoredox-mediated radical/polar crossover (RPC) processes provide unique solutions to challenging annulations. Herein, we describe an approach to the cyclopropanation of olefins that are embedded within bicyclic scaffolds. Whereas these systems are noto
- Milligan, John A.,Burns, Kevin L.,Le, Anthony V.,Polites, Viktor C.,Wang, Zheng-Jun,Molander, Gary A.,Kelly, Christopher B.
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p. 242 - 247
(2019/12/11)
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- Synthesis of Novel Pterocarpen Analogues via [3?+?2] Coupling-Elimination Cascade of α,α-Dicyanoolefins with Quinone Monoimines
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By employing triethylamine as a catalyst, [3?+?2] coupling-elimination cascade of α,α-dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.
- Chen, Hui,Zhao, Sihan,Cheng, Shaobing,Dai, Xingjie,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
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p. 1672 - 1683
(2019/04/08)
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- Decarboxylative Intramolecular Arene Alkylation Using N-(Acyloxy)phthalimides, an Organic Photocatalyst, and Visible Light
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An intramolecular arene alkylation reaction has been developed using the organic photocatalyst 4CzIPN, visible light, and N-(acyloxy)phthalimides as radical precursors. Reaction conditions were optimized via high-throughput experimentation, and electron-rich and electron-deficient arenes and heteroarenes are viable reaction substrates. This reaction enables access to a diverse set of fused, partially saturated cores which are of high interest in synthetic and medicinal chemistry.
- Sherwood, Trevor C.,Xiao, Hai-Yun,Bhaskar, Roshan G.,Simmons, Eric M.,Zaretsky, Serge,Rauch, Martin P.,Knowles, Robert R.,Dhar, T. G. Murali
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p. 8360 - 8379
(2019/09/03)
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- Design, synthesis and evaluation of novel N-phenylbutanamide derivatives as KCNQ openers for the treatment of epilepsy
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KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro and in vivo. Several compounds were found to be potent KCNQ openers. Compound 1 with favorable in vitro activity was submitted to evaluation in vivo. Results showed that compound 1 owned significant anti-convulsant activity with no adverse effects. It was also found to posses favorable pharmacokinetic profiles in rat. This research may provide novel potent compounds for the discovery of KCNQ openers in treating epilepsy.
- Yang, Shaoning,Lu, Dingqiang,Ouyang, Pingkai
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supporting information
p. 3004 - 3008
(2018/07/31)
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- Highly enantioselective [3+2] coupling of cyclic enamides with quinone monoimines promoted by a chiral phosphoric acid
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Enantioselective [3+2] coupling of cyclic enamides with quinone monoimines was realised using a chiral phosphoric acid as a catalyst. This transformation allowed for the synthesis of highly enantioenriched polycyclic 2,3-dihydrobenzofurans (up to 99.9% ee). The absolute configuration of one product was determined by an X-ray crystal structural analysis. We also found a possible mechanism for this reaction.
- Zhang, Minmin,Yu, Shuowen,Hu, Fangzhi,Liao, Yijun,Liao, Lihua,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
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p. 8757 - 8760
(2016/07/15)
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- A facile and regioselective synthesis of 1-tetralones via silver-catalyzed ring expansion
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A regioselective synthesis of 1-tetralones via silver-catalyzed ring expansion is described. A variety of 1-tetralones are furnished under mild reaction conditions from tertiary cyclobutanols regardless of the electronic properties and steric hindrance of substituents, providing a new and practical method to access diverse 1-tetralone building blocks. Preliminary experimental and DFT studies revealed that a radical-mediated sequence of C-C bond cleavage/C-C bond formation is involved.
- Yu, Jiajia,Zhao, Huijun,Liang, Shuguang,Bao, Xiaoguang,Zhu, Chen
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supporting information
p. 7924 - 7927
(2015/07/27)
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- Enantioselective halogenative semi-pinacol rearrangement: Extension of substrate scope and mechanistic investigations
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The present Full Paper article discloses a survey of our recent results obtained in the context of the enantioselective halogenation-initiated semi-pinacol rearrangement. Commencing with the fluorination/semi-pinacol reaction first and moving to the heavier halogens (bromine and iodine) second, the scope and limitations of the halogenative phase-transfer methodology will be discussed and compared. An extension of the fluorination/semi-pinacol reaction to the ring-expansion of five-membered allylic cyclopentanols will be also described, as well as some preliminary results on substrates prone to desymmetrization will be given. Finally, the present manuscript will culminate with a detailed mechanistic investigation of the canonical fluorination/semi-pinacol reaction. Our mechanistic discussion will be based on in situ reaction progress monitoring, complemented with substituent effect, kinetic isotopic effect and non-linear behaviour studies.
- Romanov-Michailidis, Fedor,Romanova-Michaelides, Maria,Pupier, Marion,Alexakis, Alexandre
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supporting information
p. 5561 - 5583
(2015/03/30)
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- Design, synthesis, structure, and dehydrogenation reactivity of a water soluble o-iodoxybenzoic acid derivative bearing a trimethylammonium group
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5-Trimethylammonio-1, 3-dioxo-1, 3-dihydro-1λ5-benzo[d][1, 2]iodoxol-1-ol anion (AIBX 1a), an o-iodoxybenzoic acid (IBX) derivative having the trimethylammonium moiety on its phenyl ring, possesses very good solubility in water and distinct oxidative properties from IBX, which is demonstrated in the oxidation of various β-keto esters to the corresponding dehydrogenated products using water as cosolvent. The regeneration of AIBX 1a can be easily realized from the reaction mixture due to its good water solubility.2011 American Chemical Society.
- Cui, Li-Qian,Dong, Zhi-Lei,Liu, Kai,Zhang, Chi
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p. 6488 - 6491
(2012/02/02)
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- PROCESS FOR SYNTHESIS OF AMINO-METHYL TETRALIN DERIVATIVES
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Methods for producing a compound of formula k1 or k2 by reducing a dihydronapthalene amide compound of formula i with hydrogen gas in the presence of a ruthenium catalyst of formula j1 or j2 [in-line-formulae]Ru(Z)2(L)??j1;[/in-line-formulae] [
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Page/Page column 22; 23
(2010/07/04)
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- SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
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The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).
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Page/Page column 131; 133
(2010/11/18)
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- TETRALIN AND INDANE DERIVATIVES AND USES THEREOF
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Compounds of the formula I, II or III; or pharmaceutically acceptable salts thereof, wherein m, n, q, Ar, R1, R2, R3, R4 and R5 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formulas I-III.
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- Arylsulfonyl naphthalene derivatives and uses thereof
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Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, q, Ar, R1, R2 and R7 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formula I.
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Page/Page column 29
(2008/06/13)
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- TETRALIN AND INDANE DERIVATIVES AND USES THEREOF
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Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein R2 is (CR3R4)n-NR5R6 and m, p, q, Ar, R1, R3, R4, R5 and R6 are as defined in the claims, which are selective antagonists of 5-HT6 and/or 5-HT2A. Also provided are compositions comprising these compounds and their use in the preparation of medicaments for treating central nervous system disease states selected from psychoses, schizophrenia, manic depressions, neurological disorders, memory disorders, attention deficit disorder, Parkinson’s disease, amyotrophic lateral scierosis, Alzheimer’s disease, food uptake disorders and Huntington’s disease.
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Page/Page column 71-73
(2008/06/13)
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- TETRALIN AND INDANE DERIVATIVES AND USES THEREOF
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Compounds of the formula (I) or pharmaceutically acceptable salts thereof, wherein R2 is a group of formula (II) and m, n, p, q, r, Rl and X are as defined in the claims, which are selective agonists of 5-HT6 and 5-HT2A. Also provided are compositions comprising these compounds and methods for their use in the preparation of medicaments for treating central nervous system disease states and disorders of the gastrointestinal tract.
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Page/Page column 21-22
(2008/06/13)
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- TETRALIN AND INDANE DERIVATIVES AND USES THEREOF AS 5-HT ANTAGONISTS
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Compounds of the formula (I) or pharmaceutically acceptable salts thereof, wherein m, p, q, Ar, R1 and R 2 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formula (I).
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Page/Page column 23; 24
(2008/06/13)
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- 4,5-DIHYDRONAPHTHO [1,2-b] THIOPHENE DERIVATIVE
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A 4,5-dihydronaphtho[1,2-b]thiophene derivative expressed by the formula: (wherein R1 is a C1 to C10 1-hydroxyalkyl group or a C1 to C10 acyl group, and R2 and R3 separately substitute in the 6-, 7-, 8-, or 9-positions, and are each independently a hydrogen atom, a halogen atom, a C1 to C10 alkyl group, a hydroxy group, a C1 to C10 alkoxy group, a C1 to C5 alkenyloxy group, a C1 to C5 alkynyloxy group, a benzyloxy group, or the like, provided that when R1 is an acyl group and R2 is a hydrogen atom, then R3 is neither a hydrogen atom nor an acetyl group), or a pharmaceutically acceptable salt thereof. This is a novel compound that is effective in reducing triglyceride levels in the liver and reducing blood glucose levels.
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Page/Page column 15
(2010/11/08)
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- BICYCLIC SUBSTITUTED INDOLE-DERIVATIVE STEROID HORMONE NUCLEAR RECEPTOR MODULATORS
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The present invention provides a compound of the formula: Formula (I); or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising an effective amount of a compound of Formula I in combination with a suitable carrier, diluent, or excipient, and methods for treating physiological disorders, particularly congestive heart disease, hypertension, and atherosclerosis, comprising administering to a patient in thereof an effective amount of a compound of Formula I. X-16125
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Page/Page column 2
(2010/02/14)
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- Aminomethylcarboxylic acid derivatives
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The present invention relates to aminomethylcarboxylic acid derivatives general formula (I), wherein Z is (CH2)n, O, S, SO, SO2or N—R5; n is 0, 1 or 2; X represents 1-3 substituents independently selected from hydrogen, halogen, (C1-6)alkyloxy, (C3-6)cycloalkyloxy, (C6-12)aryloxy, (C6-12)aryl, thienyl, SR6, SOR6, SO2R6, NR6R6, NHR6, NH2, NHCOR6, NSO2R6, CN, COOR6and (C1-4)alkyl, optionally substituted with halogen, (C6-12)aryl, (C1-6)alkyloxy or (C6-12)aryloxy; or 2 substituents at adjacent positions together represent a fused (C5-6)aryl group, a fused (C5-6)cycloalkyl ring or O—(CH2)m—O; m is 1 or 2; Y represents 1-3 substituents independently selected from hydrogen, halogen, (C1-4)alkyloxy, SR6, NR6R6and (C1-4)alkyl, optionally substituted with halogen; R1is COOR7or CONR8R9; R2and R6are (C1-4)alkyl; R3, R4and R5are independently hydrogen or (C1-4)alkyl; R7, R8and R9are independently hydrogen, (C1-4)alkyl, (C6-12)aryl or arylalkyl; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these aminomethylcarboxylic acid derivatives in therapy, more specifically for the treatment of CNS disorders.
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- Synthesis of 6/7-halotetralones
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The title compounds were prepared from halobromobenzenes via a palladium catalysed coupling followed by cyclisation.
- Owton,Brunavs
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p. 981 - 987
(2007/10/02)
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