Search

A silver-catalyzed, K2S2O8-mediated protocol to access regioselective acylarylation of unactivated alkenes was developed. The reaction between N-allyl-indoles and α-oxocarboxylic acids proceeded smoothly and involved an acyl radical addition/C–H cyclization cascade. The protocol showed a broad substrate scope and good tolerance of functional groups. The reaction proceeded with both internal and terminal alkenes to furnish many functional pyrrolo[1,2-a]indoles bearing the ketone carbonyl group, and this feature also provides the potential to construct structurally complex N-containing heterocycles.

Treatment of alkynes with diethyl phosphite and t-butyl hydroperoxide in the presence of [Cu(MeCN)4]BF4 under microwave irradiation produced the oxyphosphorylation of the triple bond, giving rise to the corresponding s-ketophosphonates in moderate-to-good yields. When the triple bond was conjugated to a carbonyl group bearing an aromatic ring, it led to the cyclization of the resulting ketone intermediate, producing eventually different phosphonylated indenones.

Crystallization-Induced Diastereomer Transformation (CIDT) of α-bromo-α'-(R)-sulfinylketones is reported. This process provides not readily accessible enantiopure stereolabile α-bromoketones, which after diastereoselective carbonyl group reduction lead to the corresponding highly value-added anti and syn-bromohydrins with excellent diastereoselectivities. As an application, a diastereodivergent synthesis of enantiopure hemlock alkaloid (+)-α-conhydrine and its diastereomer (-)-β-conhydrine is also described.

Herein we report an efficient and practical method to access chiral chromenones bearing one α-amino stereogenic center in the β position of the carbonyl group. The quinine-derived squaramide could efficiently promote Mannich/cycloketalization/dehydration tandem reactions between 1-(2-hydroxyaryl)-1,3-diketones and functionalized imines generated in situ, providing a wide range of chiral chromenones with propargylamine or α-amino ester moieties with good results (54 examples, up to 98% ee).

An effective and condition-controlled way to synthesize with high selectivity a variety of functionalized indoles with potent biological properties has been developed. Notably, 2,4-dialkynyl indole products were obtained by direct double C-H bond alkynylation, whereas alkynyl at the C4 position could convert to carbonyl to generate 2-alkynyl-3,4-diacetyl indoles fast and effectively. Additionally, a one-pot relay catalytic reaction led to 2,5-di-alkynyl-3,4-diacetyl indoles when using a carbonyl group as the directing group and by controlling the type and quantity of additives. A possible mechanism was proposed based on many studies including deuterium-exchange experiments, the necessary conditions of product conversion, and the effect of water on the reaction.

Enantioenriched α-aryl carbonyl compounds are ubiquitous in natural products and biologically active compounds. Their synthesis has been explored over the last few decades and several methods now exist that allow for the enantioselective formation of a C(sp3)-C(sp2) bond in the α-position to a carbonyl group. However, although the formation of quaternary stereocenters has been fairly well established, the enantioselective formation of tertiary stereocenters proved more challenging due to facile product post-reaction racemization. In this short review, we summarize the methods reported to date for the asymmetric α-arylation of enolates and analogues that rely on transition-metal catalysis.1 Introduction2 Nucleophile Pre-activation3 Activation via Aminocatalysis4 Formation of Constrained Stereocenters5 Concluding Remarks

A bioactivity-guided study on the leaves of Picrasma javanica led to the isolation of 19 quassinoids, including 13 new compounds. The structures of the new compounds were elucidated by a combination of spectroscopic data analysis, X-ray crystallography studies, and electronic circular dichroism (ECD) data interpretation. Compounds 1-7 are rare examples of quassinoids with a keto carbonyl group at C-12. The biological activities of 11 of the more abundant isolates were evaluated against five phytopathogenic fungi in vitro, and several of them including 6 and 15 showed moderate inhibitory effects that were comparative to those of the positive control, carbendazim. In addition, the preliminary structure-activity relationships (SARs) of these quassinoids were also investigated.

Disproportionation of aldehydes through Cannizzaro, Tishchenko, and Meerwein–Ponndorf–Verley reactions often requires the application of high temperatures, equimolar or excess quantities of strong bases, and is mostly limited to the aldehydes with no CH2 or CH3 adjacent to the carbonyl group. Herein, we developed an efficient, mild, and multifunctional catalytic system consisting AlCl3/Et3N in CH2Cl2, that can selectively convert a wide range of not only aliphatic, but also aromatic aldehydes to the corresponding alcohols, acids, and dimerized esters at room temperature, and in high yields, without formation of the side products that are generally observed. We have also shown that higher AlCl3 content favors the reaction towards Cannizzaro reaction, yet lower content favors Tishchenko reaction. Moreover, the presence of hydride donor alcohols in the reaction mixture completely directs the reaction towards the Meerwein–Ponndorf–Verley reaction.

DFT study was employed to gain insight into methylene oxidation catalyzed by Mn(CF3-PDP)(NCMe)2 (SbF6)2/H2O2/HOAcCl(OACCl ═OC(O)CH2Cl). The active catalyst was characterized to be [Mn](O)OAcCl ([Mn]═Mn(CF3-PDP)2+) which is generated via a sequence from [Mn] to [Mn]OH to [Mn]OAcCl to [Mn]OOH. With the active catalyst, the methylene group is sequentially oxidized to an alcohol and then to a carbonyl group via rebound mechanism. The mechanism explains the observed site selectivity.

Although stannosilicate zeolites are active and selective in Baeyer–Villiger (B-V) oxidation because of their unique Lewis acidity, which is useful to activate the carbonyl group of ketone rather than peroxide, the role of their pore-opening structure and hydrophobicity in selective oxidation still needs to be explored. In the present work, stannosilicate zeolites with different topologies were synthesized and characterized in detail, especially in terms of the coordination states of the Sn species in the isomorphically substituted Sn zeolite Sn-MSE (Sn-MCM-68). The catalytic properties of the synthesized zeolites were evaluated in B-V oxidation. The results show that Sn-MCM-68 possesses some superior catalytic properties in B-V oxidation in comparison with other zeolites, because of its three-dimensional 12 × 10 × 10-membered ring (MR) pore-opening channels and relatively higher hydrophobicity.

Intramolecular hydroarylation via C-H activation is one of the most powerful methods to synthesize carbo- and heterocyclic compounds, whereas we still have room for developing a highly enantioselective variant of the reaction. Here we describe Ir-catalyzed enantioselective intramolecular hydroarylation of m-allyloxyphenyl ketones. The enantioselective cyclization was efficiently catalyzed by a cationic iridium complex coordinated with a conventional chiral bisphosphine ligand to give benzofurans in high yields with high enantioselectivity. A carbonyl group of ketones functioned as an effective directing group for the C-H activation. In terms of synthetic utility, we also achieved one-pot synthesis of chiral 3-substituted dihydrobenzofurans from readily available allylic carbonates and m-hydroxyacetophenones via sequential Pd-catalyzed allylic substitution and Ir-catalyzed intramolecular hydroarylation.

Inspired by a geranyl-originated undecanoate acid ethyl ester (biosynthetic fragment, 9), elodeoidins A–H (1–8), representing four unprecedented rearranged acylphloroglucinol meroterpenoids, were discovered from the herb of Hypericum elodeoides. Their structures were elucidated by HRESIMS, NMR, Mosher, ECD, quantum chemical calculations, and biosynthetic pathways. Structurally, the six-membered acylphloroglucinol core rearranged to a five-membered β-diketone unit possessing an exocyclic carbonyl group (C-1 or C-3) through an α-ketol rearrangement. Subsequently, key cyclizations with C-1 or C-3 established a 2-cyclopentyltetrahydrofuran moiety in 1 and 2, a [5,5]-spiroketal-fused 5–5–5–5 skeleton in 3 and 4, a 1,2-dioxonane-bridged 5–9–5 framework in 5 and 6, and a 2,5-dioxabicyclo[2.2.2]octane caged structure in 7 and 8. (±)-5 and 6 showed significant anti-inflammatory activity (IC50: 6.06 ± 0.41–10.46 ± 0.14 μM). These diversiform skeletons indicated that the biosynthetic fragment inspired discovery and elucidation strategy is valuable for the discovery of novel and unprecedented natural products.

Driven by the continuous demand for optically active fluoro-containing molecules from the chemical society, the field of fluorochemistry has emerged as a hot topic recently. While protocols focusing on catalytic asymmetric fluorination, (di)fluoroalkylation, and trifluoromethylation have been well developed, elegant strategies for the synthesis of enantioenriched monofluoro- and gem-difluoroalkenes remain highly sought after. As two vital subunits of organofluorides, both monofluoro- and gem-difluoroalkenes are pervasive within many biologically active molecules. They serve as the mimics of alkenyl, enol, and peptide bonds and the carbonyl group, respectively, which may enhance the bioactivities of the parent molecules. In addition, they are active handles for the construction of other fluorinated molecules. In this review, insightful discussions on the latest achievements of the catalytic asymmetric strategies associated with the facile synthesis of both monofluoro- and gem-difluoroalkenes are provided. The related mechanism considerations, applications in streamlining syntheses, limitations, and the opportunities of the state-of-the-art methodologies will be highlighted. We hope that this will trigger novel ideas, helping in pushing current frontiers further.

Axially chiral cyclic and acyclic amides are frequently found in natural products and bioactive molecules, but catalytic asymmetric synthesis of these atropisomers with high efficiency has been a formidable challenge. We herein describe an unprecedented palladium-catalyzed asymmetric carbonylation of ArI with carbon monoxide (CO) to atroposelectively expand a class of 2-arylisoindoline-1,3-diones and N-acetyl-N-phenyl benzamides in good yields with high enantioselectivities, which represents the first example that inlays the carbonyl group in the axially chiral amides via a carbonylative reaction. Besides, a pair of enantiomorphous isomers of 2-arylisoindoline-1,3-diones can be elegantly obtained by controlling substituents at different positions.

Umpolung is a unique strategy which converts the property of an atom into the opposite one. An efficient and general method for the construction of quinoline N-oxides via umpolung of carbonyl group...

Some derivatives of 1-carbamoylhydantoins undergo cleavage at the N1–C(O) bond on heating in solution. 1-Carbamoylhydantoins in aqueous and alcoholic ammonia rearrange via opening of the imidazole ring, followed by recyclization. Prolonged treatment of 1-carbamoylhydantoins with aqueous ammonia can lead to elimination of the C2=O carbonyl group.

A series of ferrocenyl chalcones using acetylferrocene, with ferrocenyl group at the keto carbonyl group, and different aldehydes were synthesized and their bioefficacy evaluation was done against ...

A newly devised radical-based strategy enabled coupling between multiply oxygenated α-alkoxyacyl tellurides and 2-hydroxybenzaldehyde derivatives. A reagent combination of Et3 B, Et2 AlCl, and O2 promoted the formation of the α-alkoxy carbon radical from the α-alkoxyacyl telluride and the addition of the radical to the carbonyl group of 2-hydroxybenzaldehyde. The reaction chemo- and stereoselectively forged the hindered C-C bond between two oxygen-functionalized carbons at ambient temperature. The method was applied to the preparation of 12 coupling adducts with three to six contiguous stereocenters and to the concise synthesis of an antitumor compound, LLY-283.

New derivatives of piperidine bearing a 1,2,3-triazole ring designed and synthesized smoothly over six steps from N-protected piperidone-4-one. These steps included reduction of the carbonyl group/...

Reaction of 2,2′,2″-(2,4,6-trioxo-1,3,5-triazinane-1,3,5-triyl)triacetic acid derivatives with nucleophiles in aqueous medium involved opening of the triazinane ring with elimination of carbonyl group, followed by recyclization to 1-carbamoylhydantoins.

Herein we have disclosed a Zn(OTf)2 catalyzed synthesis of C2-alkyl substituted indole derivatives via unprecedented carbonyl group migration from o-amido alkynols. The key features of this protoco...

A convenient synthesis of N-phenacylbenzimidazoles in high yields (90–95%) by the N-alkylation reaction of 1H-benzimidazole with phenacyl bromides is provided. The carbonyl group reduction in the products offered the respective N-(2-aryl-2-hydroxyethyl)benzimidazoles in yields up to 97%. In the optimization of reaction conditions for preparing these N-substituted benzimidazoles (ketones and alcohols), a comparative study between eco-friendly methods (microwave and ultrasound) and conventional heating is described. These antifungal azoles analogs were tested for in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, where the alcohols chlorine substituted (4-Cl and 2,4-Cl2) showed the best activity (MIC50 = 31.2 × 10–6 g/cm3).

gem-Difluoroalkene bearing a carbonyl group is a challenging target to synthesize by conventional methods. Herein we report a mild and concise route to access the target compounds through the visible-light-mediated direct β-C-H gem-difluoroallylation of aliphatic aldehydes and cyclic ketones. Upon a synergistic combination of photoredox catalysis and organocatalysis, various α-CF3 alkenes were employed as the gem-difluoroallylation reagents via the C-F bond cleavage.

A new synthetic route has been developed for the construction of the main skeleton of ω-aryloxyprostaglandin (PG) via 1,2-addition of lithiated 3-methyl-3-(trimethylsilyloxy)pent-1-yne to the ketone carbonyl group of ethyl 7-(5-oxocyclopent-1-en-1-yl)heptanoate. The addition reaction was accompanied by the formation of cyclopentenone dimer as minor product. The 1,2-adduct containing a tertiary hydroxy group was oxidized with pyridinium chlorochromate to 13-dehydro-PGB1 ethyl ester.

The synthesis of 3-fluoro-2,5-disubstituted furans from gem-difluorocyclopropyl ketones was accomplished using trifluoromethanesulfonic acid (CF3SO3H) through ring expansion owing to the activation of the carbonyl group in the starting material. The present synthesis of 3-fluorofurans tolerates substrates designed for products with aromatic substituents at the C-2 and C-5 positions.

Direct carbonylation of the C-H bond is a great tool for installing a carbonyl group in a wide variety of substrates. This review summarizes the C-H bond carbonylation methodologies using the cobalt-catalyzed C-H bond functionalization approach. Despite the fact that cobalt-catalyzed carbonylation methodologies have been known since Murahashi's report in 1955, this area is still underdeveloped, particularly carbonylation of the C(sp3)-H bond.

The first asymmetric total synthesis of isolinearol has been achieved with high stereoselectively. The synthetic method includes enatio- and diastereoselective reductive desymmetrization, stereocontrolled introduction of the methallyl group, regio- and stereocontrolled allylation and introduction of the side chain carbonyl group using olefin cross-metathesis with a pinacol vinyl boronic ester.

With the goal of obtaining fused dilactones, the carbohydrate moiety of diastereoisomeric Michael adducts of levoglucosenone and cyclohexanone was converted to δ-lactone and its derivatives fused to an octahydrochromene fragment. The subsequent oxidative cleavage of the C-C bridge in the latter by the action of pyridiniun chlorochromate (PCC) afforded nonano-9-lactone fused at the C6-C7 bond to δ-lactone or methyl-δ-lactol. The presence of a carbonyl group in the carbohydrate moiety was found to prevent C-C bond cleavage.

A detailed analysis of the absorption spectra of mono- and bidesmoside triterpene glycosides was performed. It is suggested that the maximum in the region of 198–208 nm is attributed to the absorption of the double bond in the cyclohexene ring of the aglycone. The second less seen maximum at a wavelength of 280 nm is observed in the spectrum of saponin Quillaja Saponaria and is almost completely absent in the spectrum of saponin Mukorossi Sapindus. Identification of this maximum is extremely difficult, since its presence can be due to both the aldehyde group in the aglycone and the hydroxyl and carboxyl groups in the carbohydrate molecules. Using the method of differential spectrophotometry, a method for decomposing the UV spectrum of saponins into its constituent components is proposed and justified. A spectral analysis was performed, including the assignment of the absorption bands to the functional groups of the studied compounds. The possibility of estimating changes in the spectral properties of glycoside solutions with changes in the acidity of the medium is considered. The possibility of a bathochromic shift of the maximum absorption of the aglyconic part of saponin depending on the microenvironment (the structure of the carbohydrate part) and changes in the pH of the solution is established. It is shown that the bands at 274, 280.5 nm correspond to n-π* transitions of carbonyl and carboxyl groups and are determined only in the regions of high concentrations in Quillaja Saponaria saponin solutions. Based on the results obtained, calibration models for the quantitative determination of saponins in solutions are proposed. The regression analysis of the calibration equations is carried out, the main statistical indicators are calculated., Проведен подробный анализ спектров поглощения моно- и бидесмозидных тритерпеновых гликозидов. Высказано предположение об отнесении максимума в области 198–208 нм к поглощению двойной связи в циклогексеновом кольце агликона. Второй менее выраженный максимум при длине волны 280 нм наблюдается в спектре сапонина Quillaja Saponaria и практически полностью отсутствует в спектре сапонина Mukorossi Sapindus. Идентификация данного максимума крайне затруднительна, поскольку его наличие может быть обусловлено как альдегидной группой в составе агликона, так и гидроксильными и карбоксильными группами в молекулах углеводов. С использованием метода дифференциальной спектрофотометрии предложен и обоснован способ разложения УФ-спектра сапонинов на составляющие компоненты. Проведен спектральный анализ, включающий отнесение полос поглощения к функциональным группам исследованных соединений. Рассмотрена возможность оценки изменения спектральных свойств растворов гликозидов при изменении кислотности среды. Установлена возможность батохромного смещения максимума поглощения агликоновой части сапонина в зависимости от микроокружения (структуры углеводной части) и изменения рН раствора. Показано, что полосы при 274, 280.5 нм соответствуют n-π* переходам карбонильных и карбоксильных групп и определяются только в областях больших концентраций в растворах сапонина Quillaja Saponaria. На основании полученных результатов предложены градуировочные модели количественного определения сапонинов в растворах. Проведен регрессионный анализ градуировочных уравнений, рассчитаны основные статистические показатели.