Synthesis of β‐Lactams by 4‐exo‐tet Cyclization Process Induced by Electrogenerated Cyanomethyl Anion,Part 2:[1] Stereochemical Implications

An efficient electrochemically induced synthesis of chiral cis β‐lactams has been described, via deprotonation of chiral amides containing an acidic methylene group and a bromine atom as leaving group and bearing a chiral auxiliary or amine function. The electrogenerated base – cyanomethyl anion – is easily obtained by galvanostatic reduction of acetonitrile‐tetraethylammonium hexafluorophosphate solutions under very mild conditions. The yields are high and the cis‐diastereoselection complete. The use of starting chiral amides has allowed in many cases the preparation of the most abundant isomer in a pure form.     

Synthesis of 2‐Aryl‐Substituted Indole‐3‐acetic Acid Derivatives via Intramolecular Imino‐Stetter Reaction of Aldimines with Cyanide

A general method to generate umpolung of aldimines with cyanide was developed via the addition of cyanide to aldimines followed by a proton transfer from the carbon atom to the nitrogen atom in the resulting cyanide adducts. This novel method was successfully applied to the first imino‐Stetter reaction of aldimines obtained from 2‐aminocinnamic acid derivatives and aromatic aldehydes with cyanide, affording 2‐aryl‐substituted indole‐3‐acetic acid derivatives. Furthermore, the usefulness of this method was successfully demonstrated by the synthesis of an FPTase inhibitor, one of the biologically important 2‐arylindole‐3‐acetic acid derivatives.

     

First Gewald reaction ignited by sodium polysulfide: greener ultrasound-promoted synthesis of substituted 2-aminothiophenes in the absence of catalyst

In this paper, a modified and facile Gewald reaction triggered by sodium polysulfide in the absence of catalytic base was developed. This approach involves a one-pot ultrasound-irritated aqueous reaction between ketones or aldehydes, malononitrile, and sodium polysulfide, which are converted into the corresponding 2-aminothiophene derivatives in moderate to high yields. In comparison with conventional methods, the prominent features of this sonocatalyzed procedure are experimental simplicity, good functional group tolerance, atom efficiency, and the use of water as a green solvent.     

Expeditious and Convenient Synthesis of Polycyclic Difluoroboron Complexes of 2‐Oxoindoline‐3‐carboxamides by Tandem Reaction

N‐Aryl‐2‐cyanodiazoacetamides produce polycyclic difluoroboron 2‐oxoindoline‐3‐carboxamide complexes (up to pentacyclic conjugative and fused systems) directly and expeditiously in the presence of boron trifluoride etherate. The boron trifluoride serves as both a catalyst and reactant in the tandem reaction. The tandem reaction includes the carbene aromatic C H insertion, hydrolysis of the cyano group into an amide group, and boronation of the two amide carbonyl groups. The synthetic method features the advantages of wide substrate scope and excellent chemoselectivity.

     

Silver(I)‐Catalyzed Conia‐Ene Reaction: Synthesis of 3‐Pyrrolines via a 5‐endo‐dig Cyclization

A novel method has been developed for the synthesis of 3‐pyrrolines from β‐ketopropargylamines via a 5‐endo‐dig carbocyclization. This transformation involves a silver‐catalyzed Conia‐ene type reaction tolerating broad substrate scope with good to excellent yields. Furthermore, this methodology has been extended for the construction of 2‐substituted pyrroles under base‐mediated conditions.

     

Iodine‐Promoted Domino Reactions of 1‐Cyanocyclopropane 1‐Esters: A Straightforward Approach to Fully Substituted 2‐Aminofurans

A straightforward and efficient iodine‐promoted ring‐opening/cyclization domino reaction of 1‐cyanocyclopropane 1‐esters for the synthesis of fully substituted 2‐aminofurans is reported. This reaction involves the sequential ring‐opening/intramolecular cyclization reaction of 1‐cyanocyclopropane 1‐esters to give the corresponding 2‐amino‐4,5‐dihydrofurans, which were oxidized with I₂ and Et₃N in refluxing toluene to give the corresponding 2‐amino‐3‐furancarboxylates.

     

Asymmetric Aldol Reaction of 3‐Acetyl‐2H‐chromen‐2‐ones and Isatins Catalyzed by a Bifunctional Quinidine Urea Catalyst

The asymmetric aldol reaction of 3‐acetyl‐2H‐chromen‐2‐ones and isatins has been realized by using a bifunctional quinidine‐derived urea as the catalyst. The corresponding 3‐hydroxyoxindole derivatives containing a 2H‐chromen‐2‐one moiety were obtained in good yields and high enantioselectivities. When (Z)‐ethyl 2‐benzylideneacetoacetate was used as the substrate, a mixture of two diastereomers (both Z and E) was obtained due to isomerization of the double bond under the reaction conditions.

     

Regioselective Addition of Organometallic Reagents to 2‐(1‐Alkynyl)‐2‐alken‐1‐ones for an Efficient Synthesis of Substituted 1,2‐Allenyl Ketones

Highly substituted 1,2‐allenyl ketones can be easily and efficiently prepared from organometallic reagents and readily available 2‐(1‐alkynyl)‐2‐alken‐1‐ones. The synthetic application of 1,2‐allenyl ketone products was also showcased by palladium‐catalyzed further transformation.     

Rauhut–Currier‐Initiated Organocascade Reaction: Synthesis of Substituted Dispirocyclohexanes through a [2+2+2] Strategy Between 2‐Arylideneindan‐1,3‐diones and Activated Alkenes

For the synthesis of multisubstituted dispirocyclohexane derivatives, a Rauhut–Currier‐initiated organocascade reaction between 2‐arylideneindan‐1,3‐diones and activated alkenes in the presence of diazabicyclo[2.2.2]octane (DABCO) was demonstrated. The functionalized dispirocyclohexanes with a wide range of substituents were obtained in satisfactory to excellent chemical yields (58–99%) with high chemo‐ and diastereoselectivities (>95:5 dr). This organocatalytic reaction proceeded smoothly through Michael/Michael cyclization, which involves the formation of three new carbon‐carbon bonds with simultaneous construction of two all‐carbon spiro quaternary centers.

     

Palladium‐Catalyzed Two‐Component Domino Coupling Reaction of (Z)‐β‐Bromostyrenes with Norbornenes: Synthesis of 1,5‐Enynes

Polyfunctional molecules, 1,5‐enynes, have been achieved via a palladium(0)‐catalyzed domino coupling reaction of (Z)‐β‐bromostyrenes with norbornenes in the presence of cesium carbonate and N,N‐dimethylformamide. The process involves a double Heck‐type procedure, two‐fold C(sp²) H activation and formation of two carbon‐carbon bonds. There are possibilities of diversified transformation for the domino coupling of (Z)‐β‐bromostyrenes with norbornenes, the procedure is successfully driven to 1,5‐enynes via accurate adjustment of the reaction conditions.

     

CuO/Al2O3吸附SO2后的氢再生及一体化回收硫磺：表征与机理

吸附SO2饱和的CuO/Al2O3可在400℃下的尾气循环过程中用还原剂H2对其再生. 在热重仪上进行程序升温还原再生实验,以考察尾气循环过程中吸附剂上Cu和S的相态变化. DTG曲线上分别于280和330℃处出现失重峰,表明吸附剂上的CuSO4在H2气氛中依次被还原为CuO和Cu. XPS表征结果则显示吸附剂上CuS由SO2和Cu反应生成. 在400℃、进口气H2/SO2摩尔比为1.5时的硫磺制备过程中,以H2再生后的CuO/Al2O3作催化剂,可获得50%以上的硫磺产率,表明在吸附剂的H2再生过程中生成的CuS是硫磺制备过程的催化剂.     

Facile Synthesis of Enantiopure 4‐Substituted 2‐Hydroxy‐4‐ butyrolactones using a Robust Fusarium Lactonase

A facile chemo‐enzymatic process has been developed for producing stereoisomers of 4‐substituted 2‐hydroxy‐4‐butyrolactones with good to excellent enantioselectivity. This process involves an easy separation of the diastereoisomers by column chromatography and efficient enzymatic resolution by whole cells of Escherichia coli JM109 expressing Fusarium proliferatum lactonase gene. This biocatalyst shows strong tolerance towards different substrate structures and at least three out four possible isomers could be obtained in excellent enantiomeric purity. Different substrate concentrations (10 mM–200 mM) were examined, giving a substrate to catalyst ratio of up to 26:1. This general and efficient enzymatic process provides access to stereoisomers of 4‐substituted 2‐hydroxy‐4‐butyrolactones readily and cost‐effectively. The stereochemical assignments were conducted systematically based on NMR, X‐ray diffraction and circular dichroism, leading to further understanding of the enzyme’s stereoselectivity.     

Palladium‐Catalyzed Efficient and One‐Pot Synthesis of Diarylacetylenes from the Reaction of Aryl Chlorides with 2‐Methyl‐3‐butyn‐2‐ol

An efficient and practical synthetic method has been developed for the preparation of symmetrical diarylacetylenes from the direct reaction of aryl chlorides with 2‐methyl‐3‐butyn‐2‐ol catalyzed by palladium(II) chloride‐bis(tricyclohexylphosphine) [PdCl₂(PCy₃)₂] under mild reaction conditions. Unsymmetrical diarylated acetylenes could be also obtained by using two different aryl chlorides simultaneously. The catalytic procedure includes a novel one‐pot palladium‐catalyzed, double Sonogashira coupling of inactivated aryl chlorides without use of copper(I) as co‐catalyst.     

An Efficient Combined Electrochemical and Ultrasound Assisted Synthesis of Imidazole‐2‐Thiones

The electrochemical reduction of 1,3‐dialkylimidazolium ionic liquids gave the corresponding N‐heterocyclic carbenes that, after reaction with elemental sulfur and ultrasound irradiation, yielded 1,3‐dialkylimidazole‐2‐thiones in very high yields. The reaction is very clean, produces no side‐products and avoids the use of any other added reagent.     

A Thermostable Aldolase for the Synthesis of 3‐Deoxy‐2‐ulosonic Acids

A stereochemically promiscuous 2‐keto‐3‐deoxygluconate aldolase has been used as an efficient biocatalyst to catalyse the aldol reaction of pyruvate with C₃‐ and C₄‐aldoses to afford syn‐ and anti‐3‐deoxy‐2‐ulosonic acids in poor to good de. A continuous flow bioreactor containing immobilised aldolase has been developed that enables gram quantities of C₆‐ and C₇‐3‐deoxyhept‐2‐ulosonic acids to be produced in an efficient manner.     

N‐Bromosuccinimide‐Mediated Radical Cyclization of 3‐Arylallyl Azides: Synthesis of 3‐Substituted Quinolines

Visible light irradiation of N‐bromosuccinimide serves as an effective means to convert methyl 2‐(azidomethyl)‐3‐arylpropenoates and 2‐(azidomethyl)‐3‐arylacrylonitriles to the corresponding iminyl radicals via α‐hydrogen abstraction and subsequent extrusion of dinitrogen. Thus formed iminyl radicals then undergo intramolecular ortho attack on the aryl ring, affording methyl quinoline‐3‐carboxylates and quinoline‐3‐carbonitriles respectively.

     

Synthesis of Benzoindolines via a Copper‐Catalyzed Reaction of 1‐Bromoethynyl‐2‐(cyclopropylidenemethyl)arenes with N‐Allylsulfonamide

A copper‐catalyzed tandem reaction of 1‐bromoethynyl‐2‐(cyclopropylidenemethyl)arenes with N‐allylsulfonamide proceeds smoothly, affording functionalized benzoindolines in moderate to good yields. The transformation is a four‐step cascade involving Ullmann coupling, aza‐Claisen rearrangement, 6π‐electrocyclization, and intramolecular rearrangement.     

Aluminum‐Catalyzed Formation of Functional 1,3,2‐Dioxathiolane 2‐Oxides from Sulfur Dioxide: An Easy Entry towards N‐Substituted Aziridines

Aluminum(III) complexes derived from aminotriphenolate ligands are shown to be excellent catalysts for the formation of cyclic sulfites from a range of (functionalized) terminal and internal epoxides, and ex situ generated sulfur dioxide. The developed catalytic protocol is characterized by its operational simplicity, wide scope in epoxide reaction partners, good to excellent isolated yields and mild reaction conditions [50–70 °C, p(SO₂) <1 bar]. The synthetic potential of these cyclic sulfites in organic synthesis is demonstrated in the preparation of N‐substituted aziridines through a three‐step protocol.

     

An Enantioselective Three‐Component Sulfa‐Michael/Aldol Cascade Reaction and its Application to the Synthesis of Thioaryl Substituted (−)‐Bestatin Derivatives

An efficient catalytic asymmetric three‐component sulfa‐Michael/aldol cascade reaction has been developed using a chiral multi‐functional catalyst. This reaction provided facile access to γ‐sulfur‐β‐nitro‐α‐hydroxy esters bearing three consecutive linear stereocenters in high yields (up to 97%) with excellent diastereo‐ (up to >97:3 dr) and enantioselectivities (>99% ee). These compounds were readily converted into 2‐nitroallylic alcohols and potentially bioactive γ‐sulfur‐β‐amino‐α‐hydroxy esters, which could be further used for the synthesis of Bestatin derivatives.