Tandem Cross‐Coupling/Spirocyclization/Mannich‐Type Reactions of 3‐(2‐Isocyanoethyl)indoles with Diazo Compounds toward Polycyclic Spiroindolines

Tandem reactions of Pd‐catalyzed cross‐coupling of 3‐(2‐isocyanoethyl)indoles with diazoacetates and subsequent spirocyclization/Mannich‐type reaction have been developed to assemble polycyclic spiroindoline skeletons. Formation of spiroindolenines has been proven as the crucial step for the following Mannich‐type cyclization reaction. Accordingly, a novel approach on chiral phosphoric acid catalyzed Mannich‐type cyclization toward the formation of diastereomerically and enantiomerically enriched pentacyclic spiroindolines has been established. Moreover, the products of the reaction are versatile building blocks in synthetic chemistry, as demonstrated by the synthesis of the key framework of aspidosperma and kopsia alkaloids.     

Ion-pair chromatography of polythionates and thiosulfate with detection based on their catalytic effects on the postcolumn azide–iodine reaction

The reduction of iodine with azide, catalyzed by polythionates (tri-, tetra-, penta- and hexathionate) and thiosulfate, has been utilized as a postcolumn reaction for chromatographic determination of these sulfur oxyanions. The method is based on the separation of polythionates and thiosulfate on an octadecylsilica column with an acetonitrile–water (20:80, v/v) mobile phase (pH 5.0) containing 3 mM tetrapropylammonium hydroxide and 6 mM acetic acid, followed by photometric measurement of the residual iodine (as triiodide) from the catalytic postcolumn azide–iodine reaction after mixing a reaction solution containing azide and iodine with the column effluent. Chromatograms obtained for the sulfur oxyanions showed negative peaks as a result of the decrease in absorbance of background. The conditions for the catalytic postcolumn reaction of the sulfur oxyanions in the column effluents were established by varying the concentrations of azide, iodine, iodide and acetic acid in the reaction solution, and varying the flow-rate, reaction temperature and length of the reaction tube. The detection limits (defined as S/N=3) were 4.3 μM for trithionate, 0.10 μM for tetrathionate, 2.7 nM for pentathionate, 5.0 nM for hexathionate and 1.1 nM for thiosulfate. When compared with earlier methods, the proposed method gave a much higher sensitivity for the determination of two polythionates (penta- and hexathionate) and thiosulfate. This method was applied successfully to the analysis of polythionates and thiosulfate added to hot-spring water samples.     

Manganese(III)-mediated oxidative annulation of vinylidenecyclopropanes with 1,3-dicarbonyl compounds

Manganese(III)-mediated oxidative annulation of vinylidenecyclopropanes with 1,3-dicarbonyl compounds in acetonitrile/acetic acid produces the corresponding functionalized dihydrofuran derivatives in moderate to good yields under mild conditions. The substrate scope has been examined and a plausible reaction mechanism has been also proposed on the basis of experimental results and previous literature.     

Synthesis,Characterization and Unusual Reactivity of Vinylbenziodoxolones—Novel Hypervalent Iodine Reagents

A novel type of hypervalent iodine(III) reagents, vinylbenziodoxolones (VBX), has been synthesized in a one-pot reaction from 2-iodobenzoic acid. VBX is bench stable, has been thoroughly characterized and the cyclic structure is supported by X-ray analysis. The reactivity of VBX was investigated in vinylation of nitrocyclohexane, and delivered vinylated products with opposite regioselectivity compared to acyclic vinyl(aryl)iodonium salts. The reagents could become a powerful tool in vinylation reactions under both metal-free and metal-catalyzed conditions.     

Determination of phenolic compounds using high-performance liquid chromatography with Ce-Tween 20 chemiluminescence detection

A novel method for the simultaneous determination of phenolic compounds such as salicylic acid, resorcinol, phloroglucinol, p-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, and m-nitrophenol by high-performance liquid chromatography (HPLC) coupled with chemiluminescence (CL) detection was developed. The procedure was based on the chemiluminescent enhancement by phenolic compounds of the cerium(IV)-Tween 20 system in a sulfuric acid medium. The separation was carried out with an isocratic elution or with a gradient elution using a mixture of methanol and 1.5% acetic acid. For six phenolic compounds, the detection limits (3σ) were in the range 1.40-5.02 ng/ml and the relative standard deviations (n=11) for the determination of 0.1 μg/ml compounds were in the range 1.9-2.9%. The CL reaction was well compatible with the mobile phase of HPLC, no baseline drift often occurred in HPLC-CL detection was observed with a gradient elution. The method has been successfully applied to the determination of salicylic acid and resorcinol in Dermatitis Clear Tincture and p-hydroxybenzoic acid in apple juices.     

Cu(I)/Chiral Bisoxazoline-Catalyzed Enantioselective Doyle-Kirmse Reaction of Allenyl Sulfides with α-Diazoesters

Herein, a Cu(I)-catalyzed enantioselective Doyle-Kirmse reaction of allenyl sulfides and α-diazoesters is reported, which provides an efficient synthetic route to enantio-enriched chiral tertiary homopropargylic sulfides. This reaction features high enantioselectivities (up to 96 % ee) and good functional group tolerance. The alkyl substituted α-diazoester has also been demonstrated as the efficient substrates in the asymmetric Doyle-Kirmse reaction. Mechanistic studies, including kinetic experiments, were conducted to gain insights into the details of the reaction pathway. The potential synthetic utility of this protocol has also been demonstrated.     

Metal‐Free,Room‐Temperature,Radical Alkoxycarbonylation of Aryldiazonium Salts through Visible‐Light Photoredox Catalysis

The first radical alkoxycarboxylation of aryldiazonium salts using CO gas through visible‐light‐induced photoredox catalysis (16 W blue LEDs) has been developed. This reaction is entirely metal‐free, is carried out at room temperature with a low loading of an organic dye as a photocatalyst (0.5 mol %), and provides a wide range of arylcarboxylic acid esters in high yields. Importantly, this photocatalytic system can be successfully extended to other carboxylation reactions.     

Acid cyclization of amino-substituted heterocycles. Synthesis of 1,3-dioxo- pyrrolo[3,4-<Emphasis Type="Italic">c</Emphasis>]- and thieno[3,4-<Emphasis Type="Italic">c</Emphasis>]isoquino- lines and cinnolines

The reaction of 3-amino-4-(3,4-dimethoxyphenyl)maleimide and the methyl esters of 3-amino-4-(3,4-dimethoxyphenyl)-5-R-thiophene-2-carboxylic acids with carbonyl compounds and nitrous acid has been investigated. Dioxopyrrolo[3,4-c]- and thieno[3,4-c]isoquinolines and cinnolines were obtained. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 449-454, March, 2009.     

Screening and analysis of potentially active components in Shenxiong glucose injection using UHPLC coupled with photodiode array detection and MS/MS

Shenxiong glucose injection, a pharmaceutical preparation containing a water extract of the roots of Salvia miltiorrhizae and ligustrazine hydrochloride, is widely used in clinical to treat cardiovascular diseases in China. The chemical components of the water extract have been reported and the cardioprotective effects of the injection have been evaluated. However, the chemical constituents of the injection and their correlations with its pharmacological effects have not been established. In this study, 13 chemical constituents of the injection have been identified or characterized by ultra‐high performance liquid chromatography with diode array detection and electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry. Besides, the potentially active compounds of this preparation that directly act on cardiac cells have been screened by cell extraction and ultra high performance liquid chromatography targeted multiple reaction monitoring. As a result, eight potentially active compounds, danshensu ( 1 ), ligustrazine hydrochloride ( 4 ), salvianolic acid I/H ( 7 ), lithospermic acid ( 8 ), salvianolic acid D ( 9 ), rosmarinic acid ( 10 ), salvianolic acid B ( 12 ), and salvianolic acid C ( 13 ), were obtained and structurally characterized from the 11 target compounds used for screening. The liquid chromatography with quadrupole time‐of‐flight mass spectrometry and liquid chromatography with multiple reaction monitoring tandem mass spectrometry combination method has demonstrated its potency for the screening, detection, and structural identification of bioactive compounds in a complex matrix.     

Sulfamic Acid as a Cost‐Effective and Recyclable Catalyst for β‐Amino Carbonyl Compounds Synthesis

Sulfamic acid was used as a catalyst in the synthesis of β‐amino carbonyl compounds from amines, acetophenone and aldehyde. The reaction was carried out at room temperature. High selectivity, mild reaction temperature, cost‐effective catalyst, simple product separation and catalyst recycle were notable achievements in the reaction. Another feature was that the reaction could be performed on a relatively larger scale to the model reaction (50 times), which also gave good yields. In particular, the first preparation of β, β'‐diamino diketone derivatives via the direct coupling of amines, acetophenone and isophthalic aldehyde promoted by sulfamic acid has been developed.     

Iron‐Catalyzed Allylic Amination Directly from Allylic Alcohols

Allylic amination, directly from alcohols, has been demonstrated without any Lewis acid activators using an efficient and regiospecific molecular iron catalyst. Various amines and alcohols were employed and the reaction proceeded through the oxidation/reduction (redox) pathway. A direct one‐step synthesis of common drugs, such as cinnarizine and nafetifine, was exhibited from cinnamyl alcohol that produced water as side product.     

Catalytic Asymmetric Construction of 3,3′‐Spirooxindoles Fused with Seven‐Membered Rings by Enantioselective Tandem Reactions

The first catalytic asymmetric construction of a spirooxindole scaffold incorporated with a seven‐membered benzodiazepine moiety has been established by a three‐component (isatin, 1,2‐phenylenediamine, cyclohexane‐1,3‐dione) tandem reaction catalyzed by a chiral phosphoric acid. Structurally complex spirobenzodiazepine oxindoles with one quaternary stereogenic center are obtained in high yield with excellent enantioselectivity (up to 99 % yield, enantiomeric ratio>99.5:0.5). This approach takes advantage of organocatalytic asymmetric tandem reactions to efficiently construct the structurally rigid spirobenzodiazepine oxindole architecture with high enantiopurity in a single transformation, which involves a cascade enamine–imine formation/intramolecular Mannich reaction sequence.     

Selective Benzylic and Allylic Alkylation of Protic Nucleophiles with Sulfonamides through Double Lewis Acid Catalyzed Cleavage of sp3 Carbon–Nitrogen Bonds

The acid‐catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon? carbon and carbon? heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp³ carbon–nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl₂‐TMSCl (TMSCl: chlorotrimethylsilane), 1,3‐diketones, β‐keto esters, β‐keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl‐activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross‐coupling reaction of 1,3‐dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one‐step synthesis of polysubstituted furans and benzofurans.     

某些含三唑取代的苯甲酸苯甲酰甲酯衍生物的合成

以三乙胺为缚酸剂，通过苯甲酸同ω－（１Ｈ－１，２，４－三唑－１－基）－ω－溴化苯乙酮反应，合成了六种含三唑取代的苯甲酸甲酰甲酯类化合物，具有较高收率。     

钯配合物催化烯烃氧化合成酮类物质的研究进展

本文系统地评述了钯配合物催化烯烃氧化合成酮类物质的研究进展。综述了改进Wacker 类催化剂催化活性的几种方法。总结了烯烃氧化合成酮类物质反应的几种典型催化体系及其作用机理。着重介绍了Pd (Ⅱ) HPA (杂多酸)、Pd (Ⅱ) FePc (酞菁铁)、Pd (Ⅱ) HQ (氢醌) FePc、Pd (Ⅱ) HQHPA、Pd (Ⅱ) CuSO₄ HPA 等Wacker 类催化体系在烯烃氧化合成酮类物质中的应用; 对Pd (Ⅱ) LCoNO₂、PdCl₂(MeCN)₂ CuCl、Pd (OAc)₂ 吡啶、氟两相等非Wacker 类催化体系在烯烃氧化合成酮类物质中的应用也作了讨论。     

Mono-organotin(IV) compounds as esterification and transesterification catalysts

A series of monoorganotin(IV) compounds has been investigated as transesterification catalysts for the reaction of butyl propionate with methanol. The most active catalysts were found to be those which contain tin-halogen bonds, e.g. monobutyltin trichloride (BuSnCl₃), and the least effective were the coordinatively saturated monoorganotin derivatives. Certain of the mono(2-carboalkoxyethyl)tin compounds were found to undergo a facile autocatalysed transesterification reaction with alcohols. Coordination of the carbonyl group in the ester to the tin catalyst is an important factor influencing its activity. A study of the catalysis of the esterification of propionic acid by BuSnCl₃ is reported.     

Pentafluorophenyl carbonyl compounds in the Reformatsky-type reactions promoted with Fe(CO)5-based metal complex systems

Iron pentacarbonyl is an effective promoter for additions of halogenated acid esters and nitriles to pentafluorophenyl carbonyl compounds 1, 4, and 5 by the Reformatsky-type reaction and reductive coupling of compound 1. The electron-withdrawing character of the pentafluorophenyl group has a significant effect on the reaction pathway and the type of the reaction products. The reactions involving metal complex systems derived from Fe(CO)₅ have a number of advantages such as a simple procedure for carrying out, the lack of necessity to use anhydrous solvents and an inert atmosphere. The schemes of the reactions have been proposed and the conditions for preparative syntheses of most products have been optimized.     

Practical azidation of 1,3-dicarbonyls

An operationally simple, direct azidation of 1,3-dicarbonyl compounds has been developed. The reaction proceeds readily under ambient conditions using sodium azide and an iodine-based oxidant such as I(2) or 2-iodoxybenzoic acid (IBX)-SO(3)K/NaI. In particular, the latter method, as a new and well-balanced oxidizing agent, shows excellent functional group tolerance and substrate scope and thus allows access to a variety of tertiary 2-azido and 2,2-bisazido 1,3-dicarbonyl compounds that would be more difficult to access by using traditional methods. Because the azide-containing products easily undergo 1,3-dipolar cycloaddition with alkynes, our report represents a novel route to analogues of sensitive complex molecules.     

New stereoselective methodology for the synthesis of dihydroxerulin and xerulin, potent inhibitors of the biosynthesis of cholesterol

A new stereoselective methodology for the synthesis of both dihydroxerulin and xerulin has been devised. The key step required cross-coupling reactions between the bromo trienyne, (1E,3E,5E)-1-bromo-8-trimethylsilyl-1,3,5-octatrien-7-yne and the appropriate conjugated diynes. The palladium-catalyzed tandem cross-coupling/cyclization reaction of the resulting polyenynes with (Z)-3-iodo-2-propenoic acid led directly to dihydroxerulin or xerulin with a high degree of stereoselectivity.     

A Mild and Efficient Route to 3-Vinylchromones in Aqueous Micellar Media

A simple, mild, and ecofriendly method has been developed for the synthesis of 3-vinylchromones from 4-oxo-4H-1-benzopyran-3-carboxaldehyde (3-formylchromone) by simple Knoevenagel condensation with various active methylene compounds (AMC) in aqueous micellar media in the presence of catalytic amounts of cetyl trimethylammonium bromide (CTAB) and 1,4-diazabicyclo[2.2.2]octane (DABCO). In the case of malonic acid as AMC, the reaction resulted in formation of only Doebner decarboxylated products under the standard reaction condition. It has been also observed that 3-formylchromone derivatives primarily undergo tandem Knoevenagel and Michael reactions in the presence of > 2 equiv. of ethyl acetoacetate to produce benzophenone derivatives, by opening of pyran ring, as the sole product in good yields.