- Direct Access to Primary Amines from Alkenes by Selective Metal-Free Hydroamination
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Direct and selective synthesis of primary amines from easily available precursors is attractive yet challenging. Herein, we report the rapid synthesis of primary amines from alkenes via metal-free regioselective hydroamination at room temperature. Ammonium carbonate was used as ammonia surrogate for the first time, allowing for efficient conversion of terminal and internal alkenes into linear, α-branched, and α-tertiary primary amines under mild conditions. This method provides a straightforward and powerful approach to a wide spectrum of advanced, highly functionalized primary amines which are of particular interest in pharmaceutical chemistry and other areas.
- Du, Yi-Dan,Chen, Bi-Hong,Shu, Wei
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supporting information
p. 9875 - 9880
(2021/03/29)
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- Nucleophilic RhI Catalyzed Selective Isomerization of Terminal Aziridines to Enamides
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The selective isomerization of various terminal N-Boc protected aziridines to enamides was realized using the highly reactive nucleophilic rhodium catalyst C with the Lewis acid LiNTf2 as co-catalyst under moderate conditions. The reaction proceeds smoothly with only 1 molpercent catalyst loading and excellent yields were achieved. An intermediate containing an enamide with a non-conjugated terminal C=C double bond was detected during the course of the reaction, which isomerizes to form the thermodynamically favored 2-amido styrene. Mechanistic insight is gained based on these observations.
- Tian, Yingying,Kunz, Doris
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p. 4272 - 4275
(2020/07/04)
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- Regioselective Fluorination of α-Hydroxy-β-aminophosphonates by Using PyFluor
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We report a simple protocol for the synthesis of α-fluoro-β-aminophosphonates by the regioselective fluorination of α-hydroxy-β-aminophosphonates under mild conditions. The fluorination reactions were mediated by the PyFluor reagent and occurred with the retention of configuration. The main products of this reaction were a series of α-fluoro-β-aminophosphonates, which can be used as precursors in the preparation of medicinally important compounds (e.g., dipeptide analogues).
- Ka?mierczak, Marcin,Kubicki, Maciej,Koroniak, Henryk
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p. 3844 - 3852
(2018/07/31)
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- Ligand, metal complex containing ligand, and reaction using metal complex containing ligand
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A hydrogen transfer reaction may be more efficiently promoted by using a metal complex represented by Formula (2): (wherein, R1 to R8 are the same or different, and each represents a hydrogen atom, a substituted or unsubstituted alkyl group or the like; or wherein; R1 and R2, R2 and R3, R3 and R4, R4 and R5, and R5 and R6 are respectively bonded to each other to form a bivalent hydrocarbon group; R9 are the same or different, and each represents an alkyl group or cycloalkyl group; M is ruthenium (Ru) or the like; X is a ligand; and n is 0, 1 or 2). More specifically, the metal complex enables a hydrogenation reaction of various substrates having a stable carbonyl group or the like to be advanced with a high yield under mild conditions.
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Page/Page column 46-50
(2016/10/31)
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- Probing o-diphenylphosphanyl benzoate (o-DPPB)-directed C - C bond formation: Total synthesis of dictyostatin
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Herein, we report a robust total synthesis of dictyostatin. This polyketide natural product has attracted much attention because of its impressive antiproliferative activity against several human cancer-cell lines. We accomplished its synthesis in a highly convergent manner from three fragments of equal complexity, which were prepared on multigram scale. The southern and northwestern subunits were constructed through application of our o-DPPB-directed hydroformylation and allylic substitution methodology, respectively. These methods generated the C6 and C14 stereocenters of dictyostatin with good diastereoselectivities and simultaneously allowed further elaboration of the fragments by Wittig olefination and Sharpless asymmetric epoxidation, respectively. The compelling performance of the hydroformylation and allylic substitution with regard to practicability, selectivity, and scale underline their value for the construction of propionate motifs.
- Wünsch, Sebastian,Breit, Bernhard
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supporting information
p. 2358 - 2363
(2015/02/05)
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- N-substituted benzenepropanamide or benzenepropenamide derivatives for use in the treatment of pain and inflammation
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Compounds for use in the treatment or prophylaxis of pain, including acute and chronic pain (e.g., nociceptive pain, neuropathic pain, headaches, migraine), represented by general formula (I) in which: the dotted line represents a single or a double bond; and R5 and R5′ are independently —H, —OH or —OR6, where R6 is a linear or branched C1-C4 alkyl; X is -0-, —CH2O—, —CH2CH2O—, —CH(CH3)CH2O— or —CH2CH(CH3)O—; Z is —CH2CH2O—, —CH(CH3)CH2O— or —CH2CH(CH3)O—; m is an integer of O or 1; and n is an integer of 0-50. The compounds of the invention are also effective for reducing inflammation and may be used alone or in combination with other analgesics.
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Page/Page column 8; 9
(2015/12/17)
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- N-Substituted Benzenepropanamide and Benzenepropenamide For Use in the Prevention or the Treatment of Affective Disorders
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Compounds for use in the treatment or prophylaxis of an affective disorder, which compound is represented by formula I in which the dotted line represents a single or a double bond; and R5 and R5′ are independently —H, —OH or —OR6, where R6 is a linear or branched C1-C4 alkyl; X is —CH2O—; Z is —CH2OH2O—, —CH(CH3)CH2O— or —CH2CH(CH3)O—; m is 1; and n is an integer of 1-5; or a pharmaceutically acceptable salt, prodrug, metabolite, or hydrate thereof.
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Paragraph 0081-0084
(2014/09/30)
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- Bis(amidate)bis(amido) titanium complex: A regioselective intermolecular alkyne hydroamination catalyst
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An efficient and selective bis(amidate)bis(amido) titanium precatalyst for the anti-Markovnikov hydroamination of alkynes is reported. Hydroamination of terminal and internal alkynes with primary alkylamines, arylamines, and hydrazines is promoted by 5-10 mol % of Ti catalyst. Various functional groups are tolerated including esters, protected alcohols, and imines. The in situ generated complex shows comparable catalytic activity, demonstrating its synthetic versatility for benchtop application. Applications of this catalyst for the synthesis of amino alcohols and a one-pot procedure for indole synthesis are described. A mechanistic proposal that invokes turnover-limiting protonolysis is presented to rationalize the observed regioselectivities.
- Yim, Jacky C.-H.,Bexrud, Jason A.,Ayinla, Rashidat O.,Leitch, David C.,Schafer, Laurel L.
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p. 2015 - 2028
(2014/04/03)
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- N- SUBSTITUTED BENZENEPROPANAMIDE AND BENZENEPROPENAMIDE FOR USE IN THE PREVENTION OR THE TREATMENT OF AFFECTIVE DISORDERS
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Compounds for use in the treatment or prophylaxis of an affective disorder, which compound is represented by formula I in which the dotted line represents a single or a double bond; and R5 and R5' are independently -H, -OH or -OR6, where R6 is a linear or branched C1-C4 alkyl; X is -CH2O-; Z is -CH2ΟΗ2O-,-CH(CH3)CH2O- or -CH2CH(CH3)O-; m is 1; and n is an integer of 1-5; or a pharmaceutically acceptable salt, prodrug, metabolite, or hydrate thereof.
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Page/Page column 23
(2013/04/10)
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- METHOD FOR PRODUCING ALCOHOL BY HYDROGENATING LACTONE AND CARBOXYLIC ACID ESTER IN LIQUID PHASE
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Disclosed is a method for producing an alcohol from a lactone or a carboxylic acid ester, which enables to produce an alcohol from a lactone or a carboxylic acid ester under relatively mild conditions with high yield and high catalytic efficiency. This method also enables to produce an optically active alcohol from an optically active lactone or an optically active carboxylic acid ester. Specifically disclosed is a method for producing an alcohol by hydrogen reducing a lactone or a carboxylic acid ester in the presence of a catalyst containing ruthenium and a phosphine compound represented by the following general formula (1): wherein R1 represents a spacer; R2, R3, R4, R5, R6 and R7 independently represent a hydrogen atom, an alkyl group having 1-12 carbon atoms, an aryl group or a heterocyclic group; and R8, R9, R10, R11, R12 and R13 independently represent an alkyl group having 1-12 carbon atoms, an aryl group or a heterocyclic group.
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Page/Page column 16
(2010/01/29)
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- Stable aziridinium salts as versatile intermediates: Isolation and regio- and stereoselective ring-opening and rearrangement
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Rock trapping and exploration: Aziridinium bromide salts were discovered serendipitously during bromination of N,N-dicarboxymethylated β-amino alcohols. Regiospecific ring-opening and rearrangement of the isolated, surprisingly stable aziridinium salts produces useful molecules including C-functionalized oxomorpholines and α,β-unsaturated amines. 2009 Wiley-VCH Verleg GmbH & Co. KGaA, Weinheim.
- Song, Hyun A.,Dadwal, Mamta,Lee, Yeseul,Mick, Emily,Chong, Hyun-Soon
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supporting information; experimental part
p. 1328 - 1330
(2009/06/30)
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- Use of Syk Tyrosine Kinase Inhibitors for the Treatment of Cell Proliferative Disorders
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The invention relates to polyalkylene glycol compounds and their use in treating cell proliferative disorders, more specifically Syk tyrosine kinase-mediated disorders.
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Page/Page column 6
(2009/12/24)
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- A catalyst-free, convenient construction of eight-membered [1,4]oxazocane-5,8-dione heterocycles from aminoethanols with divinyl succinate
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A convenient protocol for the synthesis of [1,4]oxazocane-5,8-dione heterocycles by direct cyclization using 2-substituted aminoethanols and divinyl succinate without any catalysts and additives was established. This strategy is quite simple and effective to obtain eight-membered rings incorporating lactone and lactam functional groups. Georg Thieme Verlag Stuttgart.
- Chen, Wan-Qin,Zhang, Qing-Yi,Liu, Bo-Kai,Wu, Qi,Lin, Xian-Fu
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scheme or table
p. 1829 - 1832
(2009/04/07)
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- New one-carbon degradative transformation of β-alkyl-β-azido alcohols
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A new transformation of 2-azido-1-hydroxy-containing compounds to nitriles with one carbon less than the starting materials by oxidation was reported. The reaction can be performed under mild conditions.
- Fan, Qiu-Hua,Ni, Nan-Ting,Li, Qin,Zhang, Li-He,Ye, Xin-Shan
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p. 1007 - 1009
(2007/10/03)
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- Method of treating addiction or dependence using a ligand for a monoamine receptor or transporter
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One aspect of the present invention relates to a method of treating of drug addiction or drug dependence in a mammal, comprising the step of administering to a mammal in need thereof a therapuetically effective amount of a heterocyclic compound, e.g., a 3-substituted piperidine. In a preferred embodiment, the method of the present invention treats cocaine addiction or methamphetamine addiction.
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- IMPROVEMENTS IN OR RELATING TO COMPOUNDS FOR USE IN THE TREATMENT OF AIDS AND OTHER VIRAL DISEASES AND HIV-RELATED INFECTIONS AND COMPOSITIONS CONTAINING SUCH COMPOUNDS, METHODS OF TREATING SUCH DISEASES AND INFECTIONS AND METHODS OF MAKING SUCH COMPOUNDS AND COMPOSITIONS
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The present invention provides methods for treating Acquired Immunodeficiency Syndrome (AIDS) and other viral diseases and Human Immunodeficiency Virus (HIV) related infections by administering one or more compounds of formula I: wherein: the dotted line represents a single or a double bond; and R1 and R2 are the same or different and independently of each other represent - CH2OH, -CH2OR4, -CH(OH)CH3, -CH(OR4)CH3 or a group represented by the formula: or salts or hydrates thereof in a carrier which minimizes micellar formation or van der Waals attraction of molecules of said compound. The invention also provides S enantiomeric forms of such compounds which possess the ability to inhibit cell growth whilst being of low toxicity to such cells and methods of making such compounds.
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Page/Page column 29-30
(2008/06/13)
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- Properties and Reactions of Substituted 1,2-Thiazetidine 1,1-Dioxides: Chiral Mono- and Bicyclic 1,2-Thiazetidine 1,1-Dioxides from α-Amino Acids
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New chiral mono- and bicyclic β-sultams, valuable building blocks for drug synthesis, have been prepared from L-Ala, L-Val, L-Leu, L-Ile, L-Phe, L-Cys, L-Ser, L-Thr, and D-penicillamine by transformation of the COOH group into a methylsulfonyl chloride function, followed by cyclization under basic conditions. Selected properties, derivatives, and reactions of the β-sultams are described.
- Meinzer, Alexandra,Breckel, Andrea,Thaher, Bassam Abu,Manicone, Nico,Otto, Hans-Hartwig
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- NOVEL COMPOUNDS FOR USE IN THE TREATMENT OF AUTOIMMUNE DISEASES, IMMUNO-ALLERGICAL DISEASES AND ORGAN OR TISSUE TRANSPLANTATION REJECTION
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The present invention provides compounds, pharmaceutical compositions and methods for treating, immuno-allergical diseases, autoimmune diseases, and organ or tissue rejection following transplantation.
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- Ligands for monoamine receptors and transporters, and methods of use thereof
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One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.
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- New, convenient methods of synthesis and resolution of 1,2-amino alcohols
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Oximes of α-keto esters are reduced to obtain the corresponding amino alcohols using NaBH4 in combination with I2, CH 3COOH, TiCl4, ZrCl4, COCl2, H 2SO4, and TMS-Cl in 60-85% yields. The racemic phenylglycinol, phenylalaninol, and 2-aminobutanol are resolved using dibenzoyl-L-tartaric acid to obtain enantiomeric samples of >98% ee.
- Periasamy, Mariappan,Sivakumar, Sangarappan,Reddy, Meda Narsi
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p. 1965 - 1967
(2007/10/03)
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- Reduction of nonpolar amino acids to amino alcohols to enhance volatility for high-precision isotopic analysis
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Amino adds are routinely derivatized using carbon-containing groups prior to gas chromatography continuous-flow isotope ratio mass spectrometry (GCC-IRMS). Derivative C contaminates analyte C because the entire derivatized compound is eombusted to CO2. Correction procedures are required to extract the analyte isotope ratio. We present a method for reduction of six nonpolar amino adds to their corresponding amino alcohols, demonstrate a GC strategy to produce acceptable peak shapes from the resulting strongly H-bonding analytes, and present isotopic analysis for amino acids and their corresponding amino alcohols to evaluate any possible isotopic fractionation. Alanine, valine, leucine, isoleucine, methionine, or phenylalanine was reduced using NaBH4 in THF with Ia as an electrophile. Reactions were performed with 2 g of analyte to permit isotopic analysis by conventional elemental analysis-IRMS. All reactions were quantitative as assessed by IR spectra, melting points, and GC. Recovery from the reaction mixture was 60-84%. GC separation of a mixture of the six amino alcohols was achieved using a thick stationary-phase (5 μm) capillary column to avoid tailing due to hydrogen bonding to the walls of the fused-silica capillary. The reproducibility of GCC-IRMS determinations of amino alcohols averaged SD(δ13C) = 0.25 ± 0.19‰. The absolute differences between δ13C of amino acids measured by an elemental analyzer coupled to IRMS and amino alcohols measured by GCC-IRMS was Δδ13C = 0.14‰ and showed no general trend. Reactions performed with 2 mg of analyte yielded equivalent chromatograms. These data indicate that the reduction method does not induce isotopic fractionation and can be used for continuous-flow isotopic analysis to avoid addition of contaminating carbon.
- Zaideh,Saad,Lewis,Brenna
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p. 799 - 802
(2007/10/03)
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- Zirconium borohydride - A versatile reducing agent for the reduction of electrophilic and nucleophilic substrates
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Zirconium borohydride, a potential reducing agent, reduces acids, esters, imines to the corresponding alcohols and secondary amines in good yield at room temperature within two hours. This facile reducing property was taken advantage off in the synthesis of pheromones and some novel chiral precursors for asymmetric synthesis.
- Narasimhan,Balakumar
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p. 4387 - 4395
(2007/10/03)
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- Synthesis of dolastatin 10
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A complicated but extremely important scheme of synthesis has been developed for synthesizing, dolaisoleuine, dolaproine, dolaphenine and dolavaline from readily available starting materials such as Z-(S,S)isoleucine, S-phenylalaline, S-phenylalaninol, S-prolinol, S-mandelate, and S-valine. The requisite amino acids have been combined using several peptide coupling procedures to create pharmaceutically pure dolastatin 10.
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- Reduction of Carboxylic Acid Derivatives by BH4(1-) in Acidic Dimethyl Sulfoxide
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Carboxylic acid amides of all degrees of substitution, both aliphatic and aromatic, can be reduced to the corresponding primary, secondary or tertiary amines in good yield by a combination of NaBH4 and CH3SO2OH in dimethyl sulfoxide.The procedure also reduces aliphatic carboxylic acids and their esters to primary alcohols, but not conjugated aromatic acids.Crotonic acid is readily reduced to butanol.Isolated double bonds and nitriles also react, but the major products are not those of simple reduction.Michler's ketone is reduced to4,4'-bis(dimethylamino)diphenylmethane.The acid probably facilitates the amide reduction by protonating the carbonyl oxygen.The mechanism of the other reductions is less clear.The method does not require an anhydrous solvent, does not involve a hazardous reagent, has somewhat different selectivity than techniques in general use, and may sometimes be the method of choice.
- Wann, Steven R.,Thorsen, Peter T.,Kreevoy, Maurice M.
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p. 2579 - 2581
(2007/10/02)
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- Reaction Pathway for the Formation of 3,3-Diphenyl-1-benzenesulfonamidopropane in the Aluminum Chloride Catalyst Reaction of 1-Benzenesulfonyl-2-(bromomethyl)ethylenimine and Benzene
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The Friedel-Crafts reaction of 1-benzenesulfonyl-2-(bromomethyl)ethylenimine-2-(14)C and benzene yields 3,3-diphenyl-1-benzenesulfonamidopropane-2-(14)C.This finding, coupled with the results of an earlier tracer study, shows that the order of atoms in the three-carbon chain of the starting etylenimine persists unchanged in the product.If so, a previously suggested pathway becomes unacceptable.Of the several test compounds exposed to the action of aluminum chloride and benzene as described in the present work, only 1-benzenesulfonyl-2-benzylethylenimine and 1-benzenesulfonyl-2-phenylazetidine gave 3,3-diphenyl-1-benzenesulfonamidopropane.Since the azetidine compound could be eliminated as an intermediate in the ethylenimine process, this left only the benzyl derivative as an eligible intermediate.These data led to a revised pathway, which accommodates all the facts.An early stage in the mechanism is taken as conversion of the ethylenimine starting material to 1-benzenesulfonyl-2-benzylethylenimine.Under the reaction conditions, the latter compound generates a carbocationoid center on the middle carbon atom of its three-carbon chain.By a 1,2 hydride shift, this carbocation rearranges to the more stable benzylic carbocation, which combines with benzene to form the final product.
- Gensler, Walter J.,Dheer, Surendra K.
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p. 4051 - 4057
(2007/10/02)
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- Reduction of amino acids in the presence of boron trifluoride
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Organic compounds containing both an amino group and a carboxylic acid group are reduced when treated with boron trifluoride followed by diborane, a borane-ether or borane-organic sulfide complex. The presence of the boron trifluoride is responsible for an increase in the rate of reduction of the carboxylic acid group and eliminates the need for the large excess of the borane complex normally required due to the competing formation of boron-nitrogen compounds. Hydrolysis of the reaction mixture provides a useful and convenient method for separating the corresponding amino alcohol.
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