- Mechanistic Insights into Copper-Catalyzed Carboxylations
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The copper-NHC-catalyzed carboxylation of organoboranes with CO2 was investigated using computational and experimental methods. The DFT and DLPNO-CCSD(T) results indicate that nonbenzylic substrates are converted via an inner-sphere carboxylation of an organocopper intermediate, whereas benzylic substrates may simultaneously proceed along both inner-and outer-sphere CO2 insertion pathways. Interestingly, the computations predict that two conceptually different carboxylation mechanisms are possible for benzylic organoboranes, one being copper-catalyzed and one being mediated by the reaction additive CsF. Our experimental evaluation of the computed reactions confirms that carboxylation of nonbenzylic substrates requires copper catalysis, whereas benzylic substrates can be carboxylated with and without copper.
- Obst, Marc F.,Gevorgyan, Ashot,Bayer, Annette,Hopmann, Kathrin H.
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Read Online
- Metal-Free Hydrosilylation of Ketenes with Silicon Electrophiles: Access to Fully Substituted Aldehyde-Derived Silyl Enol Ethers
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Little-explored hydrosilylation of ketenes promoted by main-group catalysts is reported. The boron Lewis acid tris(pentafluorophenyl)borane accelerates the slow uncatalyzed reaction of ketenes and hydrosilanes, thereby providing a convenient access to the new class of β,β-di- and β-monoaryl-substituted aldehyde-derived silyl enol ethers. Yields are moderate to high, and Z configuration is preferred. The corresponding silyl bis-enol ethers are also available when using dihydrosilanes. The related trityl-cation-initiated hydrosilylation involving self-regeneration of silylium ions is far less effective.
- Roy, Avijit,Oestreich, Martin
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supporting information
p. 8273 - 8276
(2021/05/11)
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- Isothiourea-Catalyzed Acylative Kinetic Resolution of Tertiary α-Hydroxy Esters
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A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous-flow process using a polymer-supported variant of the catalyst.
- Greenhalgh, Mark D.,Laina-Martín, Víctor,Neyyappadath, Rifahath M.,Qu, Shen,Smith, Andrew D.,Smith, Samuel M.
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supporting information
p. 16572 - 16578
(2020/09/09)
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- Mechanistic Investigation of the Nickel-Catalyzed Carbonylation of Alcohols
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The carbonylation of alcohols represents a straightforward and atom-efficient methodology for the preparation of carboxylic acids. It is desirable to perform these reactions under precious metal-free and low-pressure conditions, with regioselectivity control. In this work, we present a detailed mechanistic study of a catalytic system based on NiI2, which can carbonylate benzylic alcohols in a highly regioselective manner to the corresponding branched carboxylic acids, core motifs for nonsteroidal drugs. The combination of catalytic amounts of nickel and iodide is crucial for efficient catalytic and regioselective conversion. Quantum-chemical computations were used to evaluate the underlying mechanistic processes. They revealed that a combination of two mechanisms is responsible for the observed reactivity and that the oxidative addition of alkyl halides to the Ni(0) species follows a radical oxidation pathway via two one-electron steps.
- Comba, Peter,Ghosh, Tamal,Hashmi, A. Stephen K.,Krieg, Saskia,Menche, Maximilian,Paciello, Rocco,Rück, Katharina S. L.,Sabater, Sara,Sch?fer, Ansgar,Schaub, Thomas
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supporting information
(2020/03/19)
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- Harnessing Applied Potential: Selective β-Hydrocarboxylation of Substituted Olefins
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The construction of carboxylic acid compounds in a selective fashion from low value materials such as alkenes remains a long-standing challenge to synthetic chemists. In particular, β-addition to styrenes is underdeveloped. Herein we report a new electrosynthetic approach to the selective hydrocarboxylation of alkenes that overcomes the limitations of current transition metal and photochemical approaches. The reported method allows unprecedented direct access to carboxylic acids derived from β,β-trisubstituted alkenes, in a highly regioselective manner.
- Alkayal, Anas,Buckley, Benjamin R.,Malkov, Andrei V.,Montanaro, Stephanie,Tabas, Volodymyr,Wright, Iain A.
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supporting information
(2020/02/13)
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- Exploration of New Biomass-Derived Solvents: Application to Carboxylation Reactions
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A range of hitherto unexplored biomass-derived chemicals have been evaluated as new sustainable solvents for a large variety of CO2-based carboxylation reactions. Known biomass-derived solvents (biosolvents) are also included in the study and the results are compared with commonly used solvents for the reactions. Biosolvents can be efficiently applied in a variety of carboxylation reactions, such as Cu-catalyzed carboxylation of organoboranes and organoboronates, metal-catalyzed hydrocarboxylation, borocarboxylation, and other related reactions. For many of these reactions, the use of biosolvents provides comparable or better yields than the commonly used solvents. The best biosolvents identified are the so far unexplored candidates isosorbide dimethyl ether, acetaldehyde diethyl acetal, rose oxide, and eucalyptol, alongside the known biosolvent 2-methyltetrahydrofuran. This strategy was used for the synthesis of the commercial drugs Fenoprofen and Flurbiprofen.
- Gevorgyan, Ashot,Hopmann, Kathrin H.,Bayer, Annette
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p. 2080 - 2088
(2020/02/20)
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- Photocarboxylation of Benzylic C-H Bonds
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The carboxylation of sp3-hybridized C-H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C-H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy.
- Meng, Qing-Yuan,Schirmer, Tobias E.,Berger, Anna Lucia,Donabauer, Karsten,K?nig, Burkhard
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supporting information
p. 11393 - 11397
(2019/08/20)
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- Caesium fluoride-mediated hydrocarboxylation of alkenes and allenes: Scope and mechanistic insights
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A caesium fluoride-mediated hydrocarboxylation of olefins is disclosed that does not rely on precious transition metal catalysts and ligands. The reaction occurs at atmospheric pressures of CO2 in the presence of 9-BBN as a stoichiometric reductant. Stilbenes, β-substituted styrenes and allenes could be carboxylated in good yields. The developed methodology can be used for preparation of commercial drugs as well as for gram scale hydrocarboxylation. Computational studies indicate that the reaction occurs via formation of an organocaesium intermediate.
- Gevorgyan, Ashot,Obst, Marc F.,Guttormsen, Yngve,Maseras, Feliu,Hopmann, Kathrin H.,Bayer, Annette
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p. 10072 - 10078
(2019/11/14)
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- Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals
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In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.
- Wu, Fu-Peng,Li, Da,Peng, Jin-Bao,Wu, Xiao-Feng
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supporting information
p. 5699 - 5703
(2019/08/01)
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- Ruthenium-catalyzed umpolung carboxylation of hydrazones with CO2
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The first ruthenium-catalyzed umpolung carboxylation of hydrazones with CO2 to generate important aryl acetic acids is reported. Besides aldehyde hydrazones, a variety of ketone hydrazones, which have not been successfully applied in previous umpolung reactions with other reactive electrophiles, also show high reactivity and selectivity under mild conditions. Moreover, this operationally simple protocol features good functional group tolerance, is readily scalable, and offers easy derivation of important structures, including bioactive felbinac and adiphenine. Computational studies reveal that this umpolung reaction proceeds through the generation of a Ru-nitrenoid followed by concerted [4 + 2] cycloaddition with CO2.
- Yan, Si-Shun,Zhu, Lei,Ye, Jian-Heng,Zhang, Zhen,Huang, He,Zeng, Huiying,Li, Chao-Jun,Lan, Yu,Yu, Da-Gang
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p. 4873 - 4878
(2018/06/07)
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- Copper-catalyzed carboxylation of hydroborated disubstituted alkenes and terminal alkynes with cesium fluoride
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A protocol for the hydrocarboxylation of disubstituted alkenes and terminal alkynes providing access to different secondary carboxylic acids and malonic acid derivatives has been developed. This methodology relies on an initial hydroboration using 9-BBN followed by carboxylation with carbon dioxide in the presence of a copper catalyst and the additive, cesium fluoride. Different cyclohexene, styrene, and stilbene derivatives could be utilized, and alkynes could be transformed into their corresponding dicarboxylic acids in good yields. Finally, six different terpenoids were carboxylated using the developed procedure. (Chemical Equation Presented).
- Juhl, Martin,Laursen, Simon L. R.,Huang, Yuxing,Nielsen, Dennis U.,Daasbjerg, Kim,Skrydstrup, Troels
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p. 1392 - 1396
(2017/05/24)
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- Facile microwave-assisted synthesis of monodispersed ball-like Ag@AgBr photocatalyst with high activity and durability
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We reported a rapid one-step microwave-assisted approach to synthesize a plasmonic photocatalyst of ball-like AgBr nanoparticles (ca. 290 nm in average diameter) with a small amount of metal Ag anchored on the surface. The obtained Ag@AgBr nanocomposites were characterized by means of X-ray diffraction, scanning electron microscopy, Transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy and UV-visible diffuse reflectance spectroscopy. The shape, size, and compositions of the Ag@AgBr photocatalysts could be controlled by tuning the microwave irradiation time and the concentrations of polyvinylpyrrolidone (PVP) in the reaction solution. The as-prepared Ag@AgBr plasmonic photocatalysts show excellent visible-light photocatalytic performance and good reusability for decomposing organic pollutant of Rhodamine B (RhB) due to the surface plasmon resonance (SPR) effect of Ag nanoparticles. Meanwhile, the possible degradation pathways of RhB and a mechanism of the plasmonic photocatalytic process were also proposed.
- Xu, Xiang,Shen, Xiaoping,Zhou, Hu,Qiu, Dezhou,Zhu, Guoxing,Chen, Kangmin
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p. 183 - 192
(2013/05/21)
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- Laboratory evolution of enantiocomplementary Candida antarctica lipase B mutants with broad substrate scope
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Candida antarctica lipase B (CALB) is a robust and easily expressed enzyme used widely in academic and industrial laboratories with many different kinds of applications. In fine chemicals production, examples include acylating kinetic resolution of racemic secondary alcohols and amines as well as desymmetrization of prochiral diols (or the reverse hydrolytic reactions). However, in the case of hydrolytic kinetic resolution of esters or esterifying kinetic resolution of acids in which chirality resides in the carboxylic acid part of the substrate, rate and stereoselectivity are generally poor. In the present study, directed evolution based on iterative saturation mutagenesis was applied to solve the latter problem. Mutants with highly improved activity and enantioselectivity relative to wild-type CALB were evolved for the hydrolytic kinetic resolution of p-nitrophenyl 2-phenylpropanoate, with the selectivity factor increasing from E = 1.2 (S) to E = 72 (S) or reverting to E = 42 (R) on an optional basis. Surprisingly, point mutations both in the acyl and alcohol pockets of CALB proved to be necessary. Some of the evolved CALB mutants are also efficient biocatalysts in the kinetic resolution of other chiral esters without performing new mutagenesis experiments. Another noteworthy result concerns the finding that enantiocomplementary CALB mutants for α-substituted carboxylic acid esters also show stereocomplementarity in the hydrolytic kinetic resolution of esters derived from chiral secondary alcohols. Insight into the source of stereoselectivity was gained by molecular dynamics simulations and docking experiments.
- Wu, Qi,Soni, Pankaj,Reetz, Manfred T.
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supporting information
p. 1872 - 1881
(2013/08/24)
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- Thiophilic nucleophilic trifluoromethylation of α-substituted dithioesters. Access to S-trifluoromethyl ketene dithioacetals and their reactivity with electrophilic species
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The nucleophilic trifluoromethylation of dithioesters bearing a nucleofugal group in α-position, using CF3TMS under fluoride activation, afforded unprecedented S-CF3 ketene dithioacetals via a domino process thiophilic trifluoromethylation-β-elimination. The best results were obtained with non-enolisable α-carbamoyloxydithioesters. The higher homologues S-C2F5 ketene dithioacetals were prepared by a similar way. These new dithioacetals react with methylating reagents quantitatively and chemoselectively at sulfur to give stable dimethylsulfonium type salts. They react more classically with triflic acid, protonation taking place at the β-carbon to give a dithiolium salt, characterized in solution but non-isolable.
- Gouault-Bironneau, Sonia,Timoshenko, Vadim M.,Grellepois, Fabienne,Portella, Charles
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experimental part
p. 164 - 171
(2012/02/15)
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- Highly enantioselective direct alkylation of arylacetic acids with chiral lithium amides as traceless auxiliaries
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A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable.
- Stivala, Craig E.,Zakarian, Armen
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supporting information; experimental part
p. 11936 - 11939
(2011/09/19)
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- The synthesis of optically active calix[4]arenes with one or three substituents on the methylene bridges
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A facile synthesis of optically active mono and trisubstituted calix[4]arenes is described wherein the chirality at the methylene bridges arises from centers of chirality present in the diyne and the bis-carbene complex from which they are constructed.
- Gopalsamuthiram, Vijay,Huang, Rui,Wulff, William D.
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supporting information; experimental part
p. 8213 - 8215
(2010/12/20)
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- Synthesis of 3,3-and 4,4-alkyl-phenyl-substituted pyrrolidin-2-one derivatives
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Syntheses of 3,3-and 4,4-alkyl-phenyl-substituted pyrrolidin-2-one derivatives are described. The final compounds were obtained by the reductive cyclization of relevant cyanoalkanoate esters using NaBH4 and CoCl2.6H2O. The obtained pyrroIidin-2-one derivatives are pharmacophoric fragments for the synthesis of various biologically active compounds.
- Kulig,Ignasik,Malawska
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experimental part
p. 1629 - 1636
(2010/07/06)
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- Resolution of secondary arylalkyl alcohols using pentafluorophenyl 2-phenylbutanoate and zinc chloride
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The resolution of racemic secondary arylalkyl alcohols using pentafluorophenyl 2-phenylbutanoate and zinc chloride is discussed. The levels of enantiomeric recognition were high leading to enantiomerically enriched alcohols in good yield.
- Coulbeck, Elliot,Eames, Jason
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scheme or table
p. 4449 - 4451
(2009/12/01)
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- Expanding the substrate scope of enzymes: Combining mutations obtained by CASTing
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In a previous paper, the combinatorial active-site saturation test (CAST) was introduced as an effective strategy for the directed evolution of enzymes toward broader substrate acceptance. CASTing comprises the systematic design and screening of focused libraries around the complete binding pocket, but it is only the first step of an evolutionary process because only the initial libraries of mutants are considered. In the present study, a simple method is presented for further optimization of initial hits by combining the mutational changes obtained from two different libraries. Combined lipase mutants were screened for hydrolytic activity against six notoriously difficult substrates (bulky carboxylic acid esters) and improved mutants showing significantly higher activity were identified. The enantioselectivity of the mutants in the hydrolytic kinetic resolution of two substrates was also studied, with the best mutant-substrate combination resulting in a selectivity factor of E=49. Finally, the catalytic profile of the evolved mutants in the hydrolysis of simple nonbranched carboxylic acid esters, ranging from acetate to palmitate, was studied for theoretical reasons.
- Reetz, Manfred T.,Carballeira, Jose Daniel,Peyralans, Jerome,Hoebenreich, Horst,Maichele, Andrea,Vogel, Andreas
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p. 6031 - 6038
(2007/10/03)
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- Observable enols of anhydrides: Claimed literature systems, calculations, and predictions
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The literature describing the observation of enols of carboxylic anhydrides and mixed carboxylic-sulfuric anhydrides was examined. In the phenylbutyric anhydride system, the alleged enol was shown to be ethylphenylketene, and the monoenol EtC(Ph)=C(OH)OC(=O)CH(Ph)Et (5) and the dienol (6) should not be observed according to calculations. Calculations also show that the claimed enols H2C=C(OH)OSO2Y, Y= SO3-, Ac (15) and the enol of 2H-pyran-2,6(3H)-dione (7) are too unstable to be observed. The bulky enols of β,β-ditipylacetic formic (35a) or trifluoroacetic (35b) anhydride were calculated to be unstable with pKEnol=7.7 (6.2). The suggestion that compounds with the 3-acyl or 3-aroyl-2H-pyran-2,6(3H)-dione skeleton are enolic was examined. In the solid state, all the known structures show that enolization takes place on C(5)=O. However, B3LYP/6-31G** calculations show that, for 3-acetyl-4-methyl-2H-pyran-2,6(3H)-dione (10, R1=Me, R2=H), which is completely enolic, the enol on the acetyl group (cf. 12) is only 0.9 kcal/mol more stable than the enol on the anhydride (cf. 11). Calculations also revealed that 3-(trifluoroacetyl)-2H-pyran-2,6(3H)-dione (28) should exist in nearly equal amounts of the enol of anhydride (cf. 30) and the enol of the acyl group (cf. 29), whereas the enol of anhydride (cf. 32) is the only stable species for 3-(methoxycarbonyl)-2H-pyran-2,6(3H)-dione (31). Furan-2,5-diol (27) and 5-hydroxyfuran-2-one (26) are calculated not to give observable isomers of succinic anhydride (25) (pKEnol=30 and 18, resp.) in spite of the expected aromatic stabilization of 27. Surprisingly, the calculations reveal that the enol (NC)2C=C(OH)OCHO (38) is less stable than its tautomeric anhydride (37) (pKEnol=1.6). Comparison of calculated pKEnol values for (NC)2CHC(=O)X (41) and MeC(=O)X indicates that the assumption that substitution by two β-CN groups affects similarly all the systems regardless of X is incorrect. A pKEnol((NC)2CHC(=O)X) vs. pKEnol(MeC(=O)X) plot is linear for most substituents with severe and mild negative deviations, respectively, for X=NH2 and MeO. Appropriate isodesmic reactions have shown that the β,β-(CN)2 substitution increases the stabilization of the enol of amide (X=NH2) by 14.6 kcal/mol over that for the anhydride (X=OCHO), whereas the amide form is 7.1 kcal/mol less destabilized than for the anhydride. The pKEnol value for (MeOCO)2CHCOOCHO (43) is 3.6, i.e., stabilization by these βelectron-withdrawing groups is insufficient to make the enols observable.
- Rappoport, Zvi,Lei, Yi Xiong,Yamataka, Hiroshi
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p. 1405 - 1431
(2007/10/03)
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- Carbonylation of vinyl aromatics: Convenient regioselective synthesis of 2-arylpropanoic acids
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(equation presented) Various substituted and nonsubstituted 2-arylpropanoic acids have been synthesized in high turnovers with high regioselectivity by palladium-catalyzed carbonylation of vinyl aromatics. Both terminal and internal olefins are carbonylated, though hindered olefins are less reactive. In all the cases high yields and high selectivity are observed. Olefins with electron-withdrawing para substituents gave the highest regioselectivity in the formation of the corresponding 2-arylpropanoic acids.
- Seayad,Jayasree,Chaudhari
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p. 459 - 461
(2008/02/11)
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- Unexpected formation of 3,3a,4,7a-tetrahydrobenzofuran-2,5-dione as well as arene carboxylic acids upon formal double exo nucleophilic addition of R1R2C-COO- to anisolechromium tricarbonyl complexes
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Bis(trimethylsily)ketene acetals of the general structure 2 (R1 = H,Me,R2 = Me,Et,Pr(i),CMe = CH2) react at -78°C in the presence of Bu(t)OK with a series of arenechromium tricarbonyl complexes 3 to give as expected, after oxidation with I2 followed by silica gel chromatography, arylcarboxylic acids 7. In the case of anisolechromium tricarbonyl 8, besides the m-methoxyarylcarboxylic acids, tetrahydrobenzofuran-2,5-diones 11, are formed as the result of a double nucleophilic addition.
- Bellassoued, Moncef,Chelain, Evelyne,Collot, Jerome,Rudler, Henri,Vaissermann, Jacqueline
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p. 187 - 188
(2007/10/03)
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- Solvent isotope effect on the hydroxide-ioncatalyzed hydration of ketenes in aqueous solution
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Five ketenes, phenyl(ethyl)ketene, phenyl(methylthio)ketene, diphenylketene, pentafluorophenylketene, and 1-naphthylketene, were generated flash photolytically and solvent isotope effects (H2O vs. D2O) on their hydroxide-ioncatalyzed hydration in aqueous solution were determined. The values obtained are all weakly reverse and closely similar (k(HO)/k(DO) = 0.76-0.97), as expected for these fast, hydroxide-ion-consuming reactions, known to proceed by nucleophilic attack of hydroxide on the ketene carbonyl group. The characteristic magnitude of these isotope effects should prove useful in identifying new examples of this reaction.
- Andraos,Chiang,Eustace,Kresge,Paine,Popik,Sung
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p. 459 - 462
(2007/10/03)
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- Regioselective Metallation of Propylbenzene with Superbase: A Convenient Route to Stilbene Derivatives
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The benzylic metallation of propylbenzene has been elaborated with LIC-KOR superbase; the method has been applied in a new synthesis of stilbene derivatives.
- Thurner, Angelika,Agai, Bela,Faigl, Ferenc
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p. 158 - 159
(2007/10/03)
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- Efficient transformations of aldehydes and ketones into one-carbon homologated carboxylic acids
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Peterson olefination of aldehydes and ketones with trimethylsilyl(methoxy)(benzotriazol-1-yl)methyl anion 6 afforded 1-(benzotriazol-1-yl)-1-methoxyalk-1-enes 7 which were treated without isolation with zinc bromide and hydrochloric acid, to yield the corresponding one-carbon homologated carboxylic acids 4 in good overall yields.
- Katritzky, Alan R.,Toader, Dorin,Xie, Linghong
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p. 1425 - 1427
(2007/10/03)
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- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
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A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
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p. 1125 - 1128
(2007/10/02)
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- Studies on Fungal Products. Part 19. Isolation and Structure of a Novel Indoloditerpene, Emindole SA, from Emericella striata
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A novel compound designated emindole SA (1), C28H39NO, isolated from the mycelium of Emericella striata, was identified by spectroscopic and chemical investigation.Emindole SA is a novel type of indoloditerpene and is a diastereoisomer of emindole DA (2), isolated from Emericella desertorum.
- Nozawa, Koohei,Yuyama, Mari,Nakajima, Shoichi,Kawai, Ken-ichi
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p. 2155 - 2160
(2007/10/02)
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- Studies on the Oxidative Cleavage of the CC Triple Bond during the Autoxidation of Acetylenic Hydrocarbons. II. Studies Concerning the Reaction of Ketocarbenes with Molecular Oxygen
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α-Diazoacetophenone, α-diazopropiophenone, α-diazobutyrophenone and α-diazodesoxybenzoin were thermally and photochemically decomposed in the presence and in the absence of oxygen using benzene, cyclohexane and chlorobenzene as solvents.The products expected from the reaction of the short-lived intermediate ketocarbenes with oxygen (α-diketones and lower carboxylic acids, especially benzoic acid) could not be detected.No substantial difference was found between the composition of the reaction mixtures formed in the presence and absence of oxygen.The results show that the oxidative cleavage of the CC triple bond during the autoxidation of acetylenic hydrocarbons does not proceed via the corresponding oxirenes or the valence-isomeric ketocarbenes.
- Rao, T. S. S.,Pritzkow, W.
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p. 617 - 625
(2007/10/02)
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- Oxidative Rearrangement of Alkynes to Carboxylic Acid Esters by benzene in Methanol
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A direct synthesis of methyl aryl alkanoate via oxidative rearrangement of alkynes using benzene in methanol is described.
- Moriarty, Robert M.,Vaid, Radhe K.,Duncan, Michael P.,Vaid, Beena K.
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p. 2845 - 2848
(2007/10/02)
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- Asymmetric Synthesis Using Chiral Acetals: Studies on the Nucleophilic Addition of Organometallics to Chiral α-Keto Acetals in Cyclic Systems
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Four chiral cyclic α-keto acetals (3a-d) were prepared through transacetalization of the α-hydroxydimethyl acetals with (-)-(2S,3S)-1,4-dimethoxy-2,3-butanediol or (-)-(2R,3R)-2,3-butanediol and reacted with organometallic reagents (Grignard reagents and organolithium reagents).The reactions of the α-keto acetals (3a, 3b) derived from 1 and (-)-(2S,3S)-1,4-dimethoxy-2,3-butanediol with Grignard reagents proceeded in a highly diastereoselective manner.Keywords-Asymmetric synthesis; diastereoselective nucleophilic addition; chiral cyclic α-keto-acetal; (-)-(2S,3S)-1,4-dimethoxy-2,3-butanediol; (-)-(2R,3R)-2,3-butanediol; Grignard reagent; organolithium reagent
- Tamura, Yasumitsu,Annoura, Hirokazu,Kondo, Hiroshi,Fuji, Masahiro,Yoshida, Takayuki,Fujioka, Hiromichi
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p. 2305 - 2313
(2007/10/02)
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- Secondary Mould Metabolites. Part 16. Stemphyltoxins, New Reduced Perylenequinone Metabolites from Stemphylium botryosum var. Lactucum
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The structure and stereochemistry of stemphyltoxins I-IV (1)-(4), four epoxy derivatives of reduced perylenequinones isolated from the fungus Stemphylium botryosum var.Lactucum, have been elucidated, mainly on the basis of n.m.r. evidence.A further metabolite, stemphyperylenol (5), is a hexahydro-1,4,7,10-tetrahydroxyperylene-3,9-quinone, a structure which suggests an unusual head-to-tail biosynthetic coupling of two pentaketide units.
- Arnone, Alberto,Nasini, Gianiuca,Merlini, Lucio,Assante, Gemma
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p. 525 - 530
(2007/10/02)
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- NEO-CLERODANE DITERPENOIDS FROM BACCHARIS MACRAEI
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Key Word Index - Baccharis macraei; Compositae; diterpenes; neo-clerodanes. From the aerial parts of Baccharis macraei two new clerodane diterpenes, bacchasmacranone and 2β-hydroxybacchasmacranone, were isolated besides the known hardwickiic and hautriwaic acids.The structures of the new compounds were elucidated by spectroscopic methods.
- Gambaro, Vicente,Chamy, Maria C.,Garbarino, Juan A.,San-Martin, Aurelio,Castillo, Mariano
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p. 2175 - 2178
(2007/10/02)
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- XENIOLONE AND ISOXENIOLONE TWO NEW DITERPENES HAVING A PERHYDROAZULENE SKELETON FROM AN OKINAWAN SOFT CORAL OF XENIA SP.
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Two new diterpenes, named xeniolone (1) and isoxeniolone (2), were isolated from an Okinawan soft coral of Xenia sp. and their absolute configurations having a perhydroazulene skeleton were determined on the basis of chemical and physicichemical evidence.KEYWORDS - xeniolone; isoxeniolone; perhydroazulene diterpene; solf coral; Xenia sp.; Horeau's method
- Kobayashi, Motomasa,Zheng, Cui,Yang, Cai,Kyogoku, Yoshimasa,Kitagawa, Isao
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p. 1309 - 1312
(2007/10/02)
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- N-Alkyl barbiturates. A series of compounds for the study of metabolic structure-activity relationships
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Many therapeutic agents are metabolised along multiple pathways, but up to now there have been few investigations addressing the question of which chemical features of drugs govern the participation in, and quantitative significance of, different biotransformation pathways. To assess the influence of variations of the chemical structure upon metabolim, a series of novel barbiturate analogues has been synthesized. The N1-monoalkylated and N1,N2-dialkylated phenobarbitones and 2-desoxyphenobarbitones have been synthesized via condensation of ethylphenylmalonic acid derivatives with different N-alkylated ureas or thioureas, and/or by base-catalyzed N-alkylation of different barbituric acids.
- Treston,Hooper
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p. 1627 - 1629
(2007/10/02)
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- STRUCTURAL AND STEREOCHEMICAL STUDIES ON MARINE NORTERPENE CYCLIC PEROXIDES
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Isolation of a new norditerpene cyclic peroxide (12) and three new norsesterpene cyclic peroxides (1, 2, 26) has permitted a detailed study of the stereostructures of this unusual class of marine natural product.A procedure for assigning relative and absolute stereochemistry about the peroxy moiety is outlined.An absolute stereostructure for muqubilin (11) and a revision of the previously assigned absolute stereochemistry of the sigmosceptrellins (5-10) is proposed, the latter based on the Horeau procedure.
- Capon, Robert J.,Macleod, John K.
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p. 3391 - 3404
(2007/10/02)
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- 2,3-Isopropylidene ribonic acid, 1,4-lactones
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Racemic carboxylic acids are resolved into their enantiomers using optically active enantiomers of four lactones as resolving agents. The four lactones are 2,3-isopropylidene-ribonic acid-1,4-lactone, 1,2-isopropylideneglucofuranurono-3,6-lactone, 2-hydroxy-3,3-dimethyl-1,4-butyrolactone and 3,4-isopropylidene-arabino-1,5-lactone. Novel diastereoisomeric esters of the acids with the lactones are disclosed.
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- The Autoxidation of 1-Phenylalk-1-ynes. Proof of Oxirenes as Intermediates in the Oxidation of Acetylenes
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In the autoxidations of 1-phenylprop-1-yne, 1-phenylbut-1-yne, and 1-phenyl-3-methylbut-1-yne a considerable attack at the CC triple bond takes place.Both products of the oxidative cleavage of the CC bond and products formed through the corresponding oxirenes were detected.The oxirenes rearrange via the isomeric ketocarbenes to ketenes, which yield the corresponding carboxylic acids or their esters.A part of the intermediate ketenes is oxidized with decarboxylation to lower ketones.All products were identified and quantitatively determined after LiAlH4 reduction to the corresponding alcohols.
- Dao, Le Thi Anh,Blau, Karla,Pritzkow, Wilhelm,Schmidt-Renner, Wolfgang,Voerckel, Volkmar,Willecke, Lothar
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- Tremorgenic Mycotoxins from Penicillium crustosum. Structure Elucidation and Absolute Configuration of Penitrems B-F
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The assingment of structures (2)-(6) to penitrems B-F, tremorgenic mycotoxins isolated from cultures of Penicillium crustosum, is based on a detailed study of their high field 1H and 13C n.m.r. spectra.The relative configuration of penitrems B-F was deduced from the magnitude of the proton-proton coupling constants.The absolute configuration of these metabolites is based on comparisons with that of penitrem A and on the absolute configuration of penitrem D determined by the 'partial resolution' method of Horeau.
- Jesus, Amelia E. de,Steyn, Pieter S.,Heerden, Fanie R. van,Vleggaar, Robert,Wessels, Philippus L.,Hull, William E.
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p. 1857 - 1861
(2007/10/02)
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- Tremorgenic Mycotoxins from Penicillium crustosum: Isolation of Penitrems A-F and the Structure Elucidation and Absolute Configuration of Penitrem A
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The isolation and characteristics of six tremorgenic mycotoxins, penitrems A-F from cultures of Penicillium crustosum are reported.The assignment of structure (2) to penitrem A is based on a detailed study of its high-field 1H and 13C n.m.r. spectra.The conformation and relative configuration of penitrem A was deduced from the observed proton-proton nuclear Overhauser effects (n.O.e) and the magnitude of the proton-proton coupling constants.The chirality of C-25 was determined as S by the 'partial resolution' method of Horeau and penitrem A must therefore have the (12R, 14S, 15R, 18S,19R, 22S, 23S, 24R, 25S, 26R, 28S, 31R, 32S) absolute configuration.
- Jesus, Amelia E. de,Steyn, Pieter S.,Heerden, Fanie R. van,Vleggaar, Robert,Wessels, Philippus L.,Hull, William E.
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p. 1847 - 1856
(2007/10/02)
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- New Methods and Reagents in Organic Synthesis. 34. Diphenyl Phosphorazidate (DPPA) as a 1,3-Dipole. A Simple, Efficient Conversion of Alkyl Phenyl Ketones to 2-Phenylalkanoic Acids
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Propiophenone (11) was conveniently converted to its enamines 12a-c using boron trifluoride etherate as a catalyst.Reaction of diphenyl phosphorazidate (DPPA) with the enamines 12a-c efficiently afforded the N-phosphorylated amidines 14a-c by the 1,3-dipolar cycloaddition of DPPA to the enamine double bond, followed by the evolution of nitrogen from the intermediate triazoline 13, and 1,2-migration of the phenyl group. 1,3-Dipolar elimination products 15a-c were also formed, though in very low yields.Some chemical properties of the N-phosphorylated amidine 14a, as well as the 1,3-dipolar character of DPPA, were investigated.By the same reaction sequences (enamine formation followed by the 1,3-dipolar cycloaddition of DPPA), some alkyl phenyl ketones 29a-c were conveniently converted to the N-phosphorylated amidines 31a, 31b, and 27 via the enamines 30a-c.However , in the case of acetophenone and its derivatives 33a-c, these reaction sequences proceeded sluggishly.Alkaline hydrolysis of the N-phosphorylated amidines 14a, 31a, 31b and 27 with potassium hydroxide afforded 2-phenylalkanoic acids 25 and 32a-c, respectively, in excellent yields.The overall three-step process of successive treatment of alkyl phenyl ketones (alkylmethyl) with pyrrolidine, DPPA, and potassium hydroxide may provide a new general method for the efficient conversion of alkyl aryl ketones to 2-arylalkanoic acids.Keywords - enamine; diphenyl phosphorazidate; boron trifluoride etherate; 1,3-dipolar cycloaddition; 1,2-migration; N-phosphorylated amidine; alkaline hydrolysis; alkyl aryl ketone; 2-arylalkanoic acid
- Kawai, Nobutaka,Shioiri, Takayuki
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p. 2564 - 2573
(2007/10/02)
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- Steiractinolides from Aspilia and Wedelia Species
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The reinvestigation of the polar fractions of Aspilia parvifolia afforded eight further steiractinolides and one geranylgeraniol derivative.The aerial parts of a new Wedelia species gave three derivatives of 4,5-dihydrosteiractinolides.The structures were elucidated by detailed 1H NMR studies.The configurations of some eudesmanolides from Wedelia trilobata were corrected and the absolute configuration of the steiractinolides has been determined by using the Horeau method.
- Bohlmann, Ferdinand,Zdero, Christa,Jakupovic, Jasmin,Ates(Goeren), Nezhun,King, Robert M.,Robinson, Harold
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p. 1257 - 1266
(2007/10/02)
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- STRUCTURE OF EPHEDRANNIN A, A HYPOTHENSIVE PRINCIPLE OF EPHEDRA ROOTS
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Abstract - a novel flavano-flavanol ephedrannin A showing the hypotensive activity has been isolated from the crude drug "mao-kon", the roots of Ephedra plants.The stereostructure of ephedrannin A has been elucidated as that represented by formula I on the basis of chemical and phisical evidence.
- Hikino, Hiroshi,Takahashi, Michiko,Konno, Chohachi
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p. 673 - 676
(2007/10/02)
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- Heterocycles. XIII. Syntheses and Absolute Configurations of Chiral Benzophenanthridines
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Chiral benzophenanthridines have been synthesized.Aminolysis of the(-)-epoxyhydroxy lactone (3) with methylamine stereospecifically gives the (+)-trihydroxy lactam (5), from which the (+)-10b-hydroxychelidonine (7) and (+)-11-epichelidonine analogs (10) are derived.The absolute configurations of the compounds obtained are assigned on the basis of that of (-)-3 and the results obtained from the subsequent stereocontrolled reactions.The absolute configurations of (+)-7 and (+)-10 are confirmed by Horeau's method.Keywords- chiral benzophenanthridine; absolute configuration; circular dichroism; optical rotatory dispersion; proton magnetic resonance (contact shift)
- Harigaya, Yoshihiro,Takamatsu, Seiko,Yamaguchi, Hiroko,Onda, Masayuki
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p. 1244 - 1250
(2007/10/02)
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- Chemical Transformation of Terpenoids. III. Syntheses of (3R)-1-Vinyl-, (3R)-1-Hydroxypropenyl-, and (3R)-1-Epoxyethyl-5-methoxy-1,2,2-trimethylcyclopentane Derivatives from d-Camphor via 5-Oxo-d-bornyl Acetate
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As a continuation of our transformation studies on terpenoids , three optically active 5-methoxy-1,2,2-trimethylcyclopentane derivatives,i.e., (+)-(1R,3R,5S)-3-acetoxymethyl-5-methoxy-1,2,2-trimethyl-1-vinylcyclopentane (7), (+)-(1R,3R,5S)-3-acetoxymethyl-1-(3'-hydroxypropenyl)-5-methoxy-1,2,2-trimethylcyclopentane (8), and (-)-(1R,3R,5S,1'R)-3-acetoxymethyl-1-(1',2'-epoxyethyl)-5-methoxy-1,2,2-trimethylcyclopentane (9), were synthesized from d-camphor (1) via 5-oxo-d-bornyl acetate (6).All three compounds (7,8,9) retain the C-4 configuration of d-camphor at their C-3 positions.Keywords- d-camphor; 5-oxo-d-bornyl acetate; 5-methoxy-1-vinyl-1,2,2-trimethylcyclopentane; 1-hydroxypropenyl-5-methoxy-1,2,2-trimethylcyclopentane; 1-epoxyethyl-5-methoxy-1,2,2-trimethylcyclopentane; Horeau's method
- Shibuya, Hirotaka,Fujioka, Hiromichi,Kajiwara, Akiharu,Yamamoto, Yoshio,Kitagawa, Isao
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p. 1271 - 1279
(2007/10/02)
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- CHEMICAL TRANSFORMATION OF TERPENOIDS. I. SYNTHESES OF (3S)-1-VINYL-, (3S)-1-HYDROXYPROPENYL-, AND (3S)-1-EPOXYETHYL-1,2,2-TRIMETHYLCYCLOPENTANE DERIVATIVES FROM d-CAMPHOR VIA d-CAMPHORIC ACID
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As part of a series of studies on the transformation of terpenoids, four 1,2,2-trimethylcyclopentane derivatives, i.e., (+)-(1S,3S)-3-acetoxymethyl-1,2,2-trimethyl-1-vinylcyclopentane (5), (+)-(1S,3S)-3-acetoxymethyl-1-(3'-hydroxypropenyl)-1,2,2-trimethylcyclopentane (7), (+)-(1R,3S,1'S)-3-acetoxymethyl-1-(1',2'-epoxyethyl)-1,2,2-trimethylcyclopentane (8), and (+)-(1R,3S,1'R)-3-acetoxymethyl-1-(1',2'-epoxyethyl)-1,2,2-trimethylcyclopentane (9), were synthesized from d-camphor (1) via d-camphoric acid (2).All four compounds (5,7,8,9) retain the C-4 configuration of d-camphor at their C-3 positions.Keywords: - d-camphor; d-camphoric acid; 1-vinyl-1,2,2-trimethylcyclopentane; 1-hydroxypropenyl-1,2,2-trimethylcyclopentane; 1-epoxyethyl-1,2,2-trimethylcyclopentane; Horeau's method
- Kitagawa, Isao,Shibuya, Hirotaka,Fujioka, Hiromichi,Kajiwara, Akiharu,Yamamoto, Yoshio,et al.
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p. 2540 - 2547
(2007/10/02)
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- Piperidenylmethylidene phosphonylamidines
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A process for the preparation of carboxylic acids represented by a formula STR1 wherein R1 represents hydrogen atom or a lower alkyl radical, R2 represents hydrogen atom, lower alkyl or allyl radical and R3 represents phenyl, substituted phenyl, substituted naphthyl, dibenzofuranyl or substituted biphenyl. Following novel enamine and amidine compounds as intermediates for manufacturing the carboxylic acids and processes for the manufacture of said enamine and amidine compounds STR2 wherein R1, R2 and R3 represent the meanings as referred to and R4 represents dimethylamino, pyrrolidyl, piperidyl or morpholyl.
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- Soft drugs: III. A new class of anticholinergic agents
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A new class of antimuscarinic drugs was designed and synthesized. The compounds are 'soft' quaternary ammonium esters in which there is only one carbon atom separating the ester oxygen and the quaternary head. The compounds are potent anticholinergics when derived from hindered 'umbrella' acids and cholinergics when derivatives of simple aliphatic acids. The more potent anticholinergics have up to 10 times higher acetylcholine antagonist activity than atropine, but they have a much shorter duration of action. The compounds cleave hydrolytically with simultaneous destruction of the quaternary head. The compounds are promising as selective, local agents, particularly as inhibitors of eccrine sweating.
- Bodor,Woods,Raper,et al.
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p. 474 - 480
(2007/10/02)
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- Process for preparing phenyl-acetic acid esters
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A process for preparing a substituted phenyl-acetic acid ester of the formula (I), SPC1 wherein R1 is an ethyl group or an isopropyl group, R2 is a hydrogen atom, a C1 -C4 alkyl group, a methoxy group, a halogen atom or a methylenedioxy group, which comprises reacting a quaternary ammonium salt of the formula (III), SPC2 wherein X is a halogen atom, and A is an alkylamine, pyridine or an N-alkylaniline, with a carboxylic acid of the formula (II), SPC3 wherein R1 and R2 are each as defined above, its reactive derivative, or a mixture of the acid and its reactive derivative.
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