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Herein, an efficient and expedient method was developed for α‐alkylation of aromatic ketones with secondary alcohols to produce β‐disubstituted ketones using phosphine‐free pincer ruthenium complexes as the catalyst. Single α‐alkylated ketone is produced in high yields even in reactions where a mixture of products is possible. Interestingly, challenging substrates such as unsubstituted and nonhindered acetophenone compounds are effectively alkylated under the reaction conditions. The scope of the reaction can span with a verities of aliphatic, cyclic, and acyclic secondary alcohols. Functionalization of a cholesterol molecule is also possible under the reaction conditions. Substitution on cyclohexyl ring afforded products as a mixture of diastereoisomers, wherein the major isomer is found as 1,4‐cis conformation of the cyclohexyl ring. Origin of the cis stereoselectivity in the alkylation process was explored by DFT calculation study. Mechanistic studies reveal that the dehydrogenation of alcohols follows a proton shuttle‐type of TS, involvement of cross‐aldol condensation and borrowing hydrogen catalysis. Notably, this selective, catalytic C−C bond forming reaction proceeds with low catalyst load, catalytic amount of base under air and produces H2O as the only byproduct, making the process environmentally benign and atom efficient. [ABSTRACT FROM AUTHOR]

A boronic acid catalyzed one-pot reduction of quinolines with Hantzsch ester followed by N-arylation via external base-free Chan–Evans–Lam coupling has been demonstrated. This step-economical synthesis of N -aryl tetrahydroquinolines has been accomplished from readily available quinoline, Hantzsch ester, and arylboronic acid under mild reaction conditions. The dual role of boronic acid as a catalyst (in the reduction of quinolines) and a reagent (in the N-arylation) has been realized for the first time. The use of an inexpensive N-arylation protocol, aerobic reaction conditions, and functional group diversity are important practical features. [ABSTRACT FROM AUTHOR]

A regioselective cyanation of heteroaromatic N‐oxides with trimethylsilyl cyanide has been developed to obtain 2‐substituted N‐heteroaromatic nitrile without the requirement of any external activator‐, metal‐, base‐, and solvent. The present protocol is a straightforward, one‐pot heteroaromatic C−H cyanation process, and proceeds smoothly in conventional heating but also under microwave irradiation with shorter reaction times. This approach now allows access to a broad class of quinoline N‐oxides and other heteroarene N‐oxides with high to good yields and can also be scaled up to obtain gram quantities. Further application of this process was observed and utilized in late‐stage cyanation of the anti‐malarial drug quinine as well as transformation of the 2‐cyanoazines to a series of biologically important molecules. Based on the experimental observations, a plausible mechanism has also been proposed highlighting the dual role of trimethylsilyl cyanide as a nitrile source and as an activating agent. [ABSTRACT FROM AUTHOR]

An improved method to synthesize the highly abundant and biomedically important urinary metabolite 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) is reported. The modified protocol is based on an indium-mediated sonochemical Reformatsky reaction. The synthesis is a simple two-step route as opposed to a complex four-step route previously reported in the literature that requires specialized equipment, flammable materials, and high-pressure reaction vessels. The described procedure also provides an expedient route to prepare a 13C isotopically labeled HPHPA that can be used as a standard for quantitative LC-MS analysis. This report also illustrates how the synthesized metabolite standard was used to detect and accurately quantify its presence in human urine samples using both NMR and LC-MS techniques. [ABSTRACT FROM AUTHOR]

We report the development of MagMet-W (magnetic resonance for metabolomics of wine), a software program that can automatically determine the chemical composition of wine via 1 H nuclear magnetic resonance (NMR) spectroscopy. MagMet-W is an extension of MagMet developed for the automated metabolomic analysis of human serum by 1 H NMR. We identified 70 compounds suitable for inclusion into MagMet-W. We then obtained 1D 1 H NMR reference spectra of the pure compounds at 700 MHz and incorporated these spectra into the MagMet-W compound library. The processing of the wine NMR spectra and profiling of the 70 wine compounds were then optimized based on manual 1 H NMR analysis. MagMet-W can automatically identify 70 wine compounds in most wine samples and can quantify them to 10-15% of the manually determined concentrations, and it can analyze multiple spectra simultaneously, at 10 min per spectrum. The MagMet-W Web server is available at https://www.magmet.ca., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

C-C bond forming reaction of ketone with aldehyde is well-studied for the synthesis of α, β-unsaturated ketones, however, the reaction with two different ketones to unsaturated carbonyl compound has not yet been systematically studied. Probably due to the relatively low reactivity of ketones as electrophiles (aldol acceptors), its propensity for retro-aldol reaction. The reactions often suffer from unsatisfactory chemoselectivity (self- vs. crossed aldol products) and regioselectivity (thermodynamic vs. kinetic enolate). In this quest, we report here for the first time selective cross-coupling reaction of ketones to β-branched β, γ-unsaturated ketones by using ruthenium catalysis. Interestingly, single crossed aldol condensation products are formed even in reactions where a mixture of products is possible. Reaction is highly chemoselective, regioselective and produces H 2 O as the only byproducts making the protocol environmentally benign. Method is compatible with a wide variety of sensitive functional group and applicable for even problematic aliphatic ketones as substrates. Notably, acetone was found as a three-carbon feedstock for the syntheses of simple β, γ-unsaturated ketone compounds. The process can further be extended to the gram-scale reaction and late-stage functionalization of natural products. With the help of DFT calculations, several control experiments, and deuterium-labeling experiments, the mechanistic finding demonstrated that initial aldol-condensation of ketones to a β, β-disubstituted α, β-unsaturated ketone, which further isomerizes to a β, γ- unsaturated ketone via η 3 -allyl ruthenium complex., (© 2023 Wiley-VCH GmbH.)