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2,2,2-Trifluoroethanol was found to be a suitable co-solvent for the electrochemical oxidation of organic compounds such as cyclic ethers, gamma-butyrolactone derivatives, primary alcohols, and toluenes substituted with electron-withdrawing groups, all of which were resistant toward oxidation in methanol. The oxidation products could be utilized as worthwhile synthetic intermediates.

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Rationale When dopants are introduced into the buffer gas of an ion mobility spectrometer, spectra are simplified due to charge competition. Methods We used electrospray ionization to inject tetrahydrofuran-2-carbonitrile (F, 2-furonitrile or 2-furancarbonitrile) as a buffer gas dopant into an ion mobility spectrometer coupled to a quadrupole mass spectrometer. Density functional theory was used for theoretical calculations of dopant-ion interaction energies and proton affinities, using the hybrid functional X3LYP/6-311++(d,p) with the Gaussian 09 program that accounts for the basis set superposition error; analytes structures and theoretical calculations with Gaussian were used to explain the behavior of the analytes upon interaction with F. Results When F was used as a dopant at concentrations below 1.5 mmol m-3 in the buffer gas, ions were not observed for alpha-amino acids due to charge competition with the dopant; this deprotonation capability arises from the production of a dimer with a high formation energy that stabilized the positive charge and created steric hindrance that deterred the equilibrium with analyte ions. F could not completely strip other compounds of their charge because they either showed steric hindrance at the charge site that deterred the approach of the dopant (2,4-lutidine, and DTBP), formed intramolecular bonds that stabilized the positive charge (atenolol), had high proton affinity (2,4-lutidine, DTBP, valinol and atenolol), or were inherently ionic (tetraalkylammonium ions). Conclusions This selective deprotonation suggests the use of F to simplify spectra of complex mixtures in ion mobility and mass spectrometry in metabolomics, proteomics and other studies that generate complex spectra with thousands of peaks.

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One-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from carboxylic acids and nitriles was optimized to parallel chemistry. The method was validated on a 141 member library; the desired products were recovered with a high success rate and in moderate yields. Practical application of the approach was demonstrated in the synthesis of bioactive compound pifexole and agonists of free fatty acid receptor 1. A library of 4 948 100 synthesizable drug-like 3,5-disubstituted 1,2,4-oxadiazoles was enumerated based on the method and available validated reagents.

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The intramolecular oxymercuration of the 1-(2-tetrahydrofuryl)-4-penten-1-ols (5) by mercuric salts followed by reductive demercuration affords the 2-methyl-5-tetrahydrofuryltetrahydrofuran (9) as a mixture of cis and trans isomers in good yields.By using mercuric acetate, each isomer threo 5a and erythro 5b gives the trans isomer, 9d and 9b, respectively, as the major products.On the other hand, cyclization carried out with mercuric chloride are not stereoselective.

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Tertiary chlorides are readily cyanated in a one-pot procedure using trimethylsilyl cyanide in the presence of SnCl4.The mechanism of this novel and synthetically useful reaction involves initial isonitrile formation followed by rearrangement to the tertiary nitrile.Other SN1 active compounds also undergo smooth cyanation.

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The one-step conversion of aliphatic carboxylic acids to the corresponding nitriles has been accomplished via the merger of visible light mediated photoredox and cyanobenziodoxolones (CBX) reagents. The reaction proceeded in high yields with natural and non-natural alpha-amino and alpha-oxy acids, affording a broad scope of nitriles with excellent tolerance of the substituents in the alpha position. The direct cyanation of dipeptides and drug precursors was also achieved. The mechanism of the decarboxylative cyanation was investigated both computationally and experimentally and compared with the previously developed alkynylation reaction. Alkynylation was found to favor direct radical addition, whereas further oxidation by CBX to a carbocation and cyanide addition appeared more favorable for cyanation. A concerted mechanism is proposed for the reaction of radicals with EBX reagents, in contrast to the usually assumed addition elimination process.

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A general and practical synthetic protocol for the direct transformation of unreactive C(sp3)-H bonds to C(sp3)-CN bonds has been developed. The homolytic cleavage of the C-H bond is initiated by photo-excited benzophenone, and the resulting carbon radical subsequently reacts with tosyl cyanide to afford the corresponding nitrile in a highly efficient manner. The present methodology is widely applicable to various starting materials including ethers, alcohols, amine derivatives, alkanes, and alkylbenzenes. This newly developed C-H cyanation protocol provides a powerful tool for selective one-carbon elongation for the construction of architecturally complex molecules. Georg Thieme Verlag Stuttgart – New York.

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Cyanotrimethylsilane adds to some alpha,beta-unsaturated ketones in conjugate manner under the catalytic action of Lewis acids such as triethylaluminium, aluminium chloride, and SnCl2.Hydrolysis of the products gives beta-cyano ketones which are identical to the hydrocyanated products of the starting enones.The title silicon reagent reacts with acetals and orthoesters under the catalytic action of SnCl2 or BF3*OEt2 affording 2-alkoxy- and 2,2-dialkoxyalkanenitriles.Application of the reaction to O-protected beta-D-ribofuranoses gives selectively beta-D-ribofuranosyl cyanide in excellent yield.

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Highly enantioenriched (R)-4-bromo-1-cyanobutyl acetate and (R)-5-bromo-1-cyanopentyl acetate were prepared by acetylcyanation of 4-bromobutanal and 5-bromopentanal, respectively, catalyzed by (S,S)-[(4,6-bis(t-butyl)salen)Ti(mu-O)]2 and triethylamine followed by enzymatic hydrolysis of the minor enantiomer. A cyclic procedure employing the same two chiral catalysts provided inferior results due to a slowly reached steady state and, in reactions with the former substrate, to ring-closure of the free cyanohydrin formed as an intermediate in the reaction. Hydrolysis of the acylated cyanohydrins followed by AgClO4-promoted cyclization provided (R)-2-cyanotetrahydrofuran and (R)-2-cyanotetrahydropyran in essentially enantiopure form.

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Self-promoted nucleophilic addition of hexafluoro-2-propanol to vinyl ethers

In spite of its low nucleophilicity, hexafluoro-2-propanol easily adds to vinyl ethers, without catalyst, to afford a range of hexafluoroisopropyloxy acetals. This addition reaction also occurred in the presence of a competitive, more nucleophilic alcohol. Kinetic studies showed the importance of hydrogen bond parameters in the rate and course of the reaction.

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