- Frustrated Lewis Pair Catalyzed Hydrogenation of Amides: Halides as Active Lewis Base in the Metal-Free Hydrogen Activation
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A method for the metal-free reduction of carboxylic amides using oxalyl chloride as an activating agent and hydrogen as the final reductant is introduced. The reaction proceeds via the hydrogen splitting by B(2,6-F2-C6H3)3 in combination with chloride as the Lewis base. Density functional theory calculations support the unprecedented role of halides as active Lewis base components in the frustrated Lewis pair mediated hydrogen activation. The reaction displays broad substrate scope for tertiary benzoic acid amides and α-branched carboxamides.
- Sitte, Nikolai A.,Bursch, Markus,Grimme, Stefan,Paradies, Jan
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p. 159 - 162
(2019/01/04)
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- HETEROARYL COMPOUNDS AND THEIR USE
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The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.
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Page/Page column 71
(2018/07/29)
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- Tandem Palladium and Isothiourea Relay Catalysis: Enantioselective Synthesis of α-Amino Acid Derivatives via Allylic Amination and [2,3]-Sigmatropic Rearrangement
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A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity. This methodology is most effective using 4-nitrophenylglycine esters and tolerates a variety of substituted cinnamic and styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N-methylglycine esters is also tolerated under the catalytic relay conditions without compromising stereoselectivity.
- Spoehrle, Stéphanie S. M.,West, Thomas H.,Taylor, James E.,Slawin, Alexandra M. Z.,Smith, Andrew D.
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supporting information
p. 11895 - 11902
(2017/09/07)
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- Synthesis of functionalized fullerenes by photoaddition of N-α-trimethylsilyl-ncarboxymethyl-N-benzylamines to C60
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Photoaddition reactions of fullerene C60 with N-α-trimethylsilyl-N-carboxymethyl-N-benzylamines, which contain various para-substituents, were explored in order to evaluate factors governing efficiencies of this potentially useful method for preparing functionalized fullerene derivatives. Observations made in this study show that two reaction pathways are followed in these photoreactions. The first involves initial formation of α-trimethylsilyl-aminium radicals and the C60 anion radical by SET from the amines to the triplet excited state of C60. This step is followed by desilylation to produce α-amino radicals. Coupling of these radicals with the anion radical of C60 followed by protonation or with the hydrofullerene radical generated by protonation of the anion radical of C60 then produces aminomethyl-1,2-dihydrofullerenes. When limited amounts of 3O2 are present in the reaction medium, fulleropyrrolidines are generated in low yields by a competitive pathway involving formation of singlet oxygen, which undergoes sequential H-atom abstractions from the N-α-trimethylsilyl-N-carboxymethyl-N-benzylamines to produce azomethine ylide intermediates. Dipolar cyloaddition of the ylides to C60 then produces fulleropyrrolidines. Photoreactions of the C60 and the amines in the presence of high 3O2 concentrations exclusively produce fulleropyrrolidine. In addition, the results show that photoreactions of non-silicon substituted, N-methyl-N-carboxymethyl-N-benzylamines with C60 form fulleropyrrolidines independent of the concentration of 3O2 present in the media.
- Lim, Suk Hyun,Cho, Dae Won,Mariano, Patrick S.
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p. 202 - 217
(2017/03/14)
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- Method for the synthesis of amine-functionalized fullerenes involving set-promoted photoaddition reactions of -silylamines
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A novel method for the preparation of structurally diverse fullerene derivatives, which relies on the use of single electron transfer (SET)-promoted photochemical reactions between fullerene C60 and α-trimethylsilylamines, has been developed. Photoirradiation of 10% EtOH-toluene solutions containing C60 and α-silylamines leads to high-yielding, regioselective formation of 1,2-adducts that arise through a pathway in which sequential SET-desilylation occurs to generate α-amino and C60 anion radical pair intermediates, which undergo C-C bond formation. Protonation of generated α-aminofullerene anions gives rise to formation of monoaddition products that possess functionalized α-aminomethyl-substituted 1,2-dihydrofullerene structures. Observations made in this effort show that the use of EtOH in the solvent mixture is critical for efficient photoproduct formation. In contrast to typical thermal and photochemical strategies devised previously for the preparation of fullerene derivatives, the new photochemical approach takes place under mild conditions and does not require the use of excess amounts of substrates. Thus, the method developed in this study could broaden the scope of fullerene chemistry by providing a simple photochemical strategy for large-scale preparation of highly substituted fullerene derivatives. Finally, the α-aminomethyl-substituted 1,2-dihydrofullerene photoadducts are observed to undergo photoinduced fragmentation reactions to produce C60 and the corresponding N-methylamines.
- Lim, Suk Hyun,Yi, Jinju,Moon, Gyeong Min,Ra, Choon Sup,Nahm, Keepyung,Cho, Dae Won,Kim, Kyungmok,Hyung, Tae Gyung,Yoon, Ung Chan,Lee, Ga Ye,Kim, Soojin,Kim, Jinheung,Mariano, Patrick S.
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supporting information
p. 6946 - 6958
(2014/08/18)
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- General catalytic methylation of amines with formic acid under mild reaction conditions
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A general catalytic protocol for the methylation of amines has been developed applying, for the first time, formic acid as the C1 building block and silanes as reducing agents. A broad range of aromatic and aliphatic, both primary and secondary, amines has been converted to the corresponding tertiary amines including [N-13C]-labelled drugs in good to excellent yields under mild conditions. Methylation made easy: A general catalytic protocol for the methylation of amines has been developed applying, for the first time, formic acid as the C1 building block and silanes as reducing agents. A broad range of aromatic and aliphatic, both primary and secondary, amines has been converted to the corresponding tertiary amines, including [N-13C]-labelled drugs, in good to excellent yields at mild conditions (see scheme; dppp=(1,3-bis(diphenylphosphino)propane)).
- Sorribes, Ivan,Junge, Kathrin,Beller, Matthias
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supporting information
p. 7879 - 7883
(2014/07/07)
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- A general catalytic methylation of amines using carbon dioxide
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Putting CO2 to work: Carbon dioxide is shown to be a general and selective methylating reagent for secondary and primary, aromatic and aliphatic amines under reductive conditions. A variety of tertiary amines are obtained from CO2 and commercially available silanes in high yields with good tolerance to nitrile, olefin, ether, ester, and hydroxy groups. Copyright
- Li, Yuehui,Fang, Xianjie,Junge, Kathrin,Beller, Matthias
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supporting information
p. 9568 - 9571
(2013/09/23)
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- ION CHANNEL MODULATORS
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The present teachings provide compounds of Formula (I) and pharmaceutically acceptable salts, hydrates, and esters thereof, wherein Ar, R1, R1', R2, R3, R4 R4', and p are defined herein. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
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Page/Page column 94
(2008/12/06)
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- Photoaddition Reactions of Acenaphthylenedione with α-Silyl n-Electron Donors via Triplet Single Electron Transfer-Desilylation and Triplet Hydrogen Atom Abstraction Pathways
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Studies have been conducted to explore single electron transfer (SET) induced photoaddition reactions of acenaphthylenedione (ACND) with the n-electron donors Et2NCH2SiMe3, n-PrSCH2SiMe3, EtOCH2SiMe3, EtCO2CH2N(CH2Ph)CH2SiMe3, and EtCO2CH2N(CH2Ph)CH3.Photoaddition of α-silyl amine Et2NCH2SiMe3 to ACND occurs in CH3OH and CH3CN to produce 2-hydroxy-2-acenaphthylen-1-one.In contrast, photoaddition of n-PrSCH2SiMe3 to ACND generates two photoadducts, 2-hydroxy-2-acenaphthylen-1-one and 2-hydroxy-2-acenaphthylen-1-one, along with a ACND photoreduction dimer.Photoaddition of EtOCH2SiMe3 to ACND produces two diastereomers of 2-hydroxy-2-acenaphthylen-1-one along with the reduction dimer.The formation of all photoproducts in these photoreactions is quenched by oxygen, indicating that the triplet of ACND is the reactive excited state.Based on a consideration of the oxidation potentials of the α-silyl n-electron donors, and the nature of photoproducts, mechanisms for these photoadditions involving triplet SET-desilylation and triplet H atom abstraction pathways are proposed.Photoaddition of EtCO2CH2N(CH2Ph)CH2SiMe3 to ACND provides two major products, 2-hydroxy-2-methyl>acenaphthylen-1-one and 2-hydroxy-2-amino>carbethoxymethyl>acenaphthylen-1-one along with several minor products.The formation of the major products via sequential SET-deprotonation pathways shows that the electron-withdrawing carbethoxy substituent serves to control the regioselectivity for deprotonation of the amine radical cation intermediate.Results obtained from the study of the photoaddition of the non-silicon-containing amino ester, EtCO2CH2N(CH2Ph)CH3, also demonstrate the effect of electron-withdrawing carbethoxy substitutent on amine radical cation deprotonation regiochemistry.
- Yoon, Ung Chan,Kim, Yong Chul,Choi, Jeong Ja,Kim, Dong Uk,Mariano, Patrick S.,et al.
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p. 1422 - 1428
(2007/10/02)
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- The Use of 2-Oxazolidinones as Latent Aziridine Equivalents. 2. Aminoethylation of Aromatic Amines, Phenols, and Thiophenols
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The utility of 2-oxazolidinones 1 as latent, carboxylated aziridine functionalities was examined.Reaction of 2-oxazolidinone (1a), 3-methyl2-oxazolidinone (1b), 3-(phenylmethyl)-2-oxazolidinone (1c), 3-phenyl-2-oxazolidinone (1d) 4,4-dimethyl-2-oxazolidinone (1e), and 5-ethyl-2-oxazolidinone (1f) with aromatic amine salts, phenol, or thiophenols at elevated temperatures (> 130 deg C) afforded aminoethylated adducts.The aminoethylation occurred with concomitant loss of carbon dioxide to furnish variously substituted N-aryl-1,2-ethanediamines 4, 1-(2-phenoxyethyl)-2-imidazolidinone (8), or 2-(arylthio)ethanamines 9 on reactions of 1 with aromatic amine salts, phenol, and thiophenols, respectively.Imidazolidinone 8 is believed to be a secondary reaction product resulting from the condensation of the initially formed 2-phenoxyethanamine with starting oxazolidinone 1a.The aminoethylation reaction did not proceed with aliphatic amine hydrochlorides or alkyl mercaptans.Preliminary mechanistic pathways for these ring openings were also investigated employing a specific, C-5 deuterium-labeled oxazolidinone 1b-d2.Ring-opening experiments of 1b-d2 with N-methylaniline hydrochloride suggest reaction can occur through either a dioxazolinium 5 and/or 5 intermediate.In contrast, reaction of 1b-d2 with thiophenol suggests ring-opening to proceed only via the dioxazolinium pathway.
- Poindexter, Graham S.,Owens, Donald A.,Dolan, Peter L.,Woo, Edmund
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p. 6257 - 6265
(2007/10/02)
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