409 research outputs found
Predominance of the second cycle in the homogeneous Os-catalyzed dihydroxylation: nature of Os(VI)→Os(VIII) reoxidation and unprecedented roles for the amine-N-oxides
No full textThe homogeneous Os-catalyzed dihydroxylation of alkenes has been widely applied in organic synthesis. Mechanistic studies on the diol formation have been performed but concentrated on the osmylation step to form Os(VI) glycolate; however, the details and the origin of the reactivity of the catalytic cycle that comprises several mechanistically poorly defined steps have yet to be fully understood. Here, we report density functional theory (DFT) investigations of the Os-catalyzed non-enantioselective dihydroxylation of trans-butene under homogeneous conditions (OsO4/NMO) to demonstrate the predominant pathway to be through a second cycle, with the reoxidation of Os(VI) glycolate outpacing its hydrolysis. The putative Os(VIII) trioxoglycolate is found as a highly reactive intermediate that undergoes a highly rapid osmylation of another alkene, initiating the second cycle. The present study shows that tertiary amines like NMM, the oxidation coproduct, do not promote either reoxidation or hydrolysis of Os(VI) glycolate but inhibit the reaction by competing coordination. Utilizing the energetic span model on our proposed computed catalytic cycle, reoxidation of Os(VI) → Os(VIII) glycolate is found to be the turnover-limiting state. The hydrolysis of Os(VI) bisglycolate, formed by the second osmylation reaction, is catalyzed by NMM through a stepwise ion-pairing mechanism. In addition to the reoxidation role played by NMO, it plays another role by catalyzing the hydrolysis of the stable Os(VI) bisglycolate either through the coproduct base NMM or by NMO-assisted stabilization of the stepwise ion-pairing hydrolysis of Os(VI) bisglycolate. Besides, the reoxidation step Os(VI) → Os(VIII), with and without NMM, is studied in detail by combining localized and principal interacting orbital and distortion/interaction analysis. The findings presented in this work will encourage experimentalists to implement further studies on Os catalysis to design a more efficient catalytic version that tackles enantioselective deficiencies in the 1,2-diol formation and even in oxidative cyclization of 1,5-dienes to give tetrahydrofuran diols
Lipase-catalyzed dynamic kinetic resolution of C 1 - and C 2 -symmetric racemic axially chiral 2,2′-dihydroxy-1,1′-biaryls
No full textWe have discovered that the racemization of configurationally stable, axially chiral 2,2′‐dihydroxy‐1,1′‐biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase‐catalyzed kinetic resolution led to the first lipase/metal‐integrated dynamic kinetic resolution of racemic axially chiral biaryl compounds. The method was applied to the synthesis of various enantio‐enriched C1‐ and C2‐symmetric biaryl diols in yields of up to 98 % and enantiomeric excesses of up to 98 %, which paves the way for new developments in the field of asymmetric synthesis
Design, synthesis and hypolipidemic activity of novel 2-(m-tolyloxy) isobutyric acid derivatives
No full textNovel 2-substituted isobutyric acid derivatives were synthesized and their hypolipidemic activity was evaluated in high cholesterol diet fed rat model. The amide 5a was found to decrease the levels of serum total cholesterol, LDL cholesterol and triglycerides in hyperlipidemic rats to a greater degree than the reference gemfibrozil
N hyperpolarisation of the antiprotozoal drug ornidazole by Signal Amplification By Reversible Exchange in aqueous medium
No full textSignal amplification by reversible exchange (SABRE) offers a cost‐effective route to boost nuclear magnetic resonance (NMR) signal by several orders of magnitude by employing readily available para‐hydrogen as a source of hyperpolarisation. Although 1H spins have been the natural choice of SABRE hyperpolarisation since its inception due to its simplicity and accessibility, limited spin lifetimes of 1H makes it harder to employ them in a range of time‐dependent NMR experiments. Heteronuclear spins, for example, 13C and 15N, in general have much longer T1 lifetimes and thereby are found to be more suitable for hyperpolarised biological applications as demonstrated previously by para‐hydrogen induced polarisation (PHIP) and dynamic nuclear polarisation (DNP). In this study we demonstrate a simple procedure to enhance 15N signal of an antibiotic drug ornidazole by up to 71,000‐folds with net 15N polarisation reaching ~23%. Further, the effect of co‐ligand strategy is studied in conjunction with the optimum field transfer protocols and consequently achieving 15N hyperpolarised spin lifetime of >3 min at low field. Finally, we present a convenient route to harness the hyperpolarised solution in aqueous medium free from catalyst contamination leading to a strong 15N signal detection for an extended duration of time
A new route to platencin via decarboxylative radical cyclization
No full textA new approach to platencin, a potent antibiotic isolated from Streptomyces platensis, has been established. The highly congested tricyclic core of the natural product was successfully constructed by decarboxylative radical cyclization of an alkynyl silyl ester with Pb(OAc)4 in the presence of pyridine in refluxing 1,4-dioxane. The key decarboxylation, which likely takes place via lead(IV) esterification followed by carbon-centered radical generation and subsequent capture of the radical with a triple bond, allows the rapid construction of the twisted polycyclic system
Base-promoted lipase-catalyzed kinetic resolution of atropisomeric 1,1′-biaryl-2,2′-diols
No full textHerein we report a dramatic acceleration of the lipase-catalyzed kinetic resolution of atropisomeric 1,1′-biaryl-2,2′-diols by the addition of sodium carbonate. This result likely originates from the increased nucleophilicity of the phenolic hydroxyl group toward the acyl-enzyme intermediate. Under these conditions, various substituted C2-symmetric and non-C2-symmetric binaphthols and biphenols were efficiently resolved with ∼50% conversion in only 13–30 h with excellent enantioselectivity
Hyperpolarised [2-13C]-pyruvate by 13C SABRE in an acetone/water mixture
No full textSignal Amplification By Reversible Exchange (SABRE) can provide strong signal enhancement (SE) to an array of molecules through reversible exchange of parahydrogen (pH2) derived hydrides and a suitable substrate coordinated to a transition metal. Among the substrates that can be used as a probe for hyperpolarised NMR and MRI, pyruvate has gained much attention. SABRE can hyperpolarise pyruvate in a low cost, fast, and reversible fashion that does not involve technologically demanding equipment. Most SABRE polarization studies have been done using methanol-d4 as a solvent, which is not suitable for in vivo application. The main goal of this work was to obtain hyperpolarized pyruvate in a solvent other than methanol which may open the door to further purification steps and enable a method to polarize pyruvate in water in future. This work demonstrates hyperpolarization of the [2-13C]pyruvate as well as [1-13C]pyruvate by SABRE in an acetone/water solvent system at room temperature as an alternative to methanol, which is commonly used. NMR signals are detected using a 1.1 T benchtop NMR spectrometer. In this work we have primarily focused on the study of [2-13C]pyruvate and investigated the effect of catalyst concentration, DMSO presence and water vs. acetone solvent concentration on the signal enhancement. The relaxation times for [2-13C]-pyruvate solutions are reported in the hope of informing the development of future purification methods
Facile one-pot three-component synthesis of 4,6-diaryl-3,4-dihydropyrimidine-2(1H)-thiones under ultrasonic irradiation
No full textWe developed a facile one-pot procedure for the synthesis of 4,6-diaryl-3,4-dihydropyrimidine-2(1H)-thione under ultrasonic irradiation. The method is based on a three components reaction of aldehydes, ketones, and thiourea under basic conditions affording isolated yields of up to 95% within a reaction time of 30–90 min
Stereoselective α-quaternization of 3-methoxycycloalk-2-enones via 1,4-diastereoinduction of alkoxy dienolates
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