Copper-catalyzed 1,3-dipolar cycloaddition of methyleneindolinones and N,N'-cyclic azomethine imines

A copper-catalyzed stereoselective 1,3-dipolar cycloaddition of methyleneindolinones and N,N''-cyclic azomethine imines has been developed under mild reaction conditions. The spiro[pyrazolidin-3,3''-oxindoles] were obtained in moderate to high isolated yields (up to 82%) with good stereoselevtivities (up to 15:1) in the presence of 5 mol% of Cu(OAc)2 at room temperature.     

PyBidine–Cu(OTf)2‐Catalyzed Asymmetric [3+2] Cycloaddition with Imino Esters: Harmony of Cu–Lewis Acid and Imidazolidine‐NH Hydrogen Bonding in Concerto Catalysis

A bis(imidazolidine)pyridine (PyBidine)–Cu(OTf)₂ complex catalyzing the endo‐selective [3+2] cycloaddition of nitroalkenes with imino esters was applied to the reaction of methyleneindolinones with imino esters to afford spiro[pyrrolidin‐3,3′‐oxindole]s in up to 98 % ee. X‐ray crystallographic analysis of the PyBidine–Cu(OTf)₂ complex and DFT calculations suggested that an intermediate Cu enolate of the imino ester reacts with nitroalkenes or methyleneindolinones, which are activated by NH‐hydrogen bonding with the PyBidine–Cu(OTf)₂ catalyst.     

Highly Stereoselective [3+2] Cycloadditions of Chiral Palladium‐Containing N1‐1,3‐Dipoles: A Divergent Approach to Enantioenriched Spirooxindoles

A catalytic asymmetric [3+2] cycloaddition reaction of chiral palladium‐containing N¹‐1,3‐dipoles with methyleneindolinones has been successfully developed. The reaction allows an efficient construction of 3,3′‐pyrrolinyl spirooxindoles with high yields and excellent stereoselectivities (up to 93 % yield, 19:1 d.r. and >99 % ee). A synthetic application of this methodology is demonstrated and a stereocontrol mechanism is proposed.     

Insight into the origins of the reactivity and selectivity for the aminocatalytic [2+2] cycloaddition reaction

A density functional study of the [2 + 2] cycloaddition between methyleneindolinones and enals catalyzed by prolinol derivatives is presented here. The calculations show that dienamines could be generated under acid-free conditions, and the hydroxyl of the catalysts plays a key role in the formation of dienamines. The following cycloaddition process between methyleneindolinones and the new formed dienamines includes two-step intramolecular electron transfers. The stereoselectivity is mainly attributed to the charge distributions on the reaction centers and the H-bonding interaction between the catalysts and methyleneindolinones. The excellent 3,4-regioselectivity is largely ascribed to the fact that the pre-product of 1,2-reactivity is tough to hydrolyze, but could return to the precursor. Besides, the large steric hindrance of catalysts is not conducive to the 3,4-reactivity, while the H-bonding between the catalysts and methyleneindolinones has less effect on the regioselectivity.     

Catalytic Asymmetric Diels–Alder Reaction/[3,3] Sigmatropic Rearrangement Cascade of 1‐Thiocyanatobutadienes

A highly efficient asymmetric Diels–Alder/[3,3] sigmatropic rearrangement reaction of methyleneindolinones with 1‐thiocyanatobutadienes has been realized by using a chiral N,N′‐dioxide/nickel(II) complex as the catalyst. A range of cyclohexenyl isothiocyanates were synthesized in high yields with excellent diastereo‐ and enantioselectivities. Based on mechanistic studies, a catalytic cycle with possible transition‐state models were proposed to explain the process.     

Catalyst‐free Synthesis of Spiro[indoline‐3,1′‐pyrazolo[5,1‐a]isoquinolines] via Diastereoselective 1,3‐dipolar Cycloaddition under Mild Conditions

A highly efficient catalyst‐free1,3‐dipolar cycloaddition reaction of methyleneindolinones and C ,N‐cyclic azomethine imines was realized. The reactions afforded a large variety of spirooxindoles in high yields (up to 99%) and excellent diastereoselectivities (dr > 20:1). Furthermore, the configuration of one of the products was determined on the basis of X‐ray structural analysis. Accordingly, a possible transition‐state model was proposed.     

Organocatalytic stereocontrolled synthesis of 3,3'-pyrrolidinyl spirooxindoles by [3+2] annulation of isocyanoesters with methyleneindolinones

A stereoselective [3+2] cycloaddition of isocyanoesters to methyleneindolinones catalyzed by a quinine-based thiourea-tertiary amine has been successfully developed. Just by tuning the protecting groups on substrates, a variety of optically enriched 3,3'-pyrrolidinyl spirooxindole diastereomers could be obtained in excellent enantioselectivities (up to 99% ee).     

A novel and diastereoselective construction of H-pyrazolo[3,2-a]isoquinoline fused spirooxindoles via [3+2] cycloaddition

A one-pot, highly efficient and diastereoselective construction of 1,2-dihyro-10′bH-spiro[indole-3,1′-pyrazole[3,2-a]isoquinoline]-2′-carboxylates via silver triflate-catalyzed [3+2] cycloaddition of N′-(2–alkynylbenzylidene)hydrazide with methyleneindolinones in good to excellent yield has been described. The transformation involves initially a condensation followed by 6-endo-intramolecular cyclization forming dipole which then undergoes [3+2]-cycloaddition with methyleneindolinones and finally, β-hydrogen elimination.     

Core-structure-motivated design of a phosphine-catalyzed [3+2] cycloaddition reaction: enantioselective syntheses of spirocyclopenteneoxindoles

A novel organocatalytic asymmetric [3+2] cycloaddition reaction between methyleneindolinones and allylic compounds yielding complex spirocyclopentaneoxindoles has been developed. It provides extraordinary levels of enantioselective control involving a chiral phosphine as a nucleophilic organocatalyst. Simple precursors were used under mild conditions to construct oxindole derivatives with high enantiopurity and structural diversity. This method should be useful in medicinal chemistry and diversity-oriented syntheses of these intriguing compounds.     

Diastereospecific entry to pyrrolidinyldispirooxindole skeletons via three-component 1,3-dipolar cycloadditions

Practical and diastereospecific three-component 1,3-dipolar cycloaddition reactions of methyleneindolinones, isatins and diverse primary amino acids have been well established. A range of pyrrolidinyldispirooxindole scaffolds with wide structural diversity and complexity were obtained facilely in excellent yields under mild conditions, which hold promising applications in their further pharmacological studies.     

One-pot reaction for the concise synthesis of spiro[benzofuran-2,2′-naphthalen]-1′-one derivatives

A novel one-pot two-step protocol has been developed to synthesize various spiro[benzofuran-2,2′-naphthalen]-1′-one derivatives from the three-component reaction of tetralones, 2-hydroxyphenyl functionalized α,β-unsaturated ketones, and iodine. One C–C bond and one C–O bond have formed during this process. The notable features of this protocol are simple and mild reaction conditions, applicable to a wide range of readily available starting materials, good yields (up to 91%), and excellent stereoselectivities (up to 97:3).     

Combining prolinamides with 2-pyrrolidinone: Novel organocatalysts for the asymmetric aldol reaction

Peptides and especially prolinamides have been identified as excellent organocatalysts for the aldol reaction. The combination of prolinamides with derivatives bearing the 2-pyrrolidinone scaffold, deriving from pyroglutamic acid, led to the identification of novel organocatalysts for the intermolecular asymmetric aldol reaction. The new hybrids were tested both in organic and aqueous media. Among the compounds tested, 22 afforded the best results in petroleum ether, while 25 afforded the products in brine in high yields and selectivities. Then, various ketones and aldehydes were utilized and the products of the aldol reaction were obtained in high yields (up to 100%) with excellent diastereo- (up to 97:3 dr) and enantioselectivities (up to 99% ee).     

Synthesis of naphthoxindoles,anthraoxindoles and phenanthrofuranones from arynes

An efficient process for the synthesis of naphthoxindoles, anthraoxindoles and phenanthrofuranones by Diels−Alder reactions and dehydrogenation aromatization reactions of benzyne or naphthyne with methyleneindolinones or methylenebenzofuranones in good yields. The photophysical, redox, and thermal properties of oxadisilole fused naphthoxindoles and anthraoxindoles have been determined. This compounds show potential applications for organic light-emitting materials due to their high fluorescence quantum yields and thermal stabilities.     

5-甲基-2，3-二苯基-1，5-苯并硫氮杂卓-4(5H)-酮的合成

以2-甲硫基苯胺为原料,通过酰化、碘环化以及Suzuki交叉偶联反应,合成了5-甲基-2,3-二苯基-1,5-苯并硫氮杂卓-4(5H)-酮。 分别考察了催化剂对酰化反应、溶剂对碘环化反应的影响,以及催化剂、配体、碱和温度等因素对Suzuki交叉偶联反应的影响,在最佳的反应条件下,反应总收率为68.5%,中间产物和目标产物的结构经IR、NMR和MS等测试技术得以确证。     

金鸡纳生物碱-9-O-三甲基硅衍生物催化的不对称“中断的”Feist-Bénary反应

将6种金鸡纳生物碱-9-O-三甲基硅(TMS)衍生物用于催化环己二酮与溴乙酰甲酸乙酯/β-取代的溴乙酰甲酸乙酯的不对称“中断的”Feist-Bénary反应,得到了高的化学产率(85％～97％)和最高达90％ee的立体选择性。     

Direct asymmetric aldol reaction co-catalyzed by l-proline and isothiouronium salts

An efficient, simple, and highly selective protocol for the direct asymmetric aldol reaction between cyclohexanone and aromatic aldehydes using l-proline as a chiral catalyst is reported. Catalytic amounts of achiral isothiouronium iodide salt 1d have been used for the first time as a co-catalyst for this reaction, which proved to be an excellent catalyst, producing good to excellent yields (up to 93%) with good stereoselectivities (up to 93:7 dr and 99% ee). These aldols are formed under solvent-free catalytic system, inside a standard laboratory refrigerator, and without stirring.     

Iron-catalyzed oxidation of thioethers by iodosylarenes: stereoselectivity and reaction mechanism

Catalytic properties of a series of iron(III)-salen (salen=N,N'-bis(salicylidene)ethylenediamine dianion) and related complexes in asymmetric sulfoxidation reactions, with iodosylarenes as terminal oxidants, have been explored. These catalysts have been found to efficiently catalyze oxidation of alkyl aryl sulfides to sulfoxides with high chemoselectivity (up to 100 %) and moderate-to-high enantioselectivity (up to 84 % with isopropylthiobenzene and iodosylmesitylene), the TON (TON=turnover number) approaching 500. The influence of the ligand (electronic and steric effects of the substituents), oxidant, and substrate structures on the oxidation stereoselectivity has been investigated systematically. The structure of the reactive intermediates (complexes of the type [Fe(III)(ArIO)(salen)] and the reaction mechanism have been revealed by both mechanistic studies with different iodosylarenes and direct in situ (1)H NMR observation of the formation of the reactive species and its reaction with the substrate.     

Experimental study of a diffusion-controlled reaction involving a chain molecule with terminal reactive sites

Diffusion-controlled reaction of electron transfer from diphenylsilane radical anions to the series of α- and α,ω-bromoalkanes with alkane chain length up to 18 atoms has been studied in n-dodecane solutions. At room temperature, reaction rate constants have been determined and corresponding reaction radii have been evaluated. It has been shown that a not-too-long chain molecule, which contains two terminal reaction sites and participates in the diffusion-controlled reaction, may be considered as a rapidly rotating pair of reacting sinks with a distance between their centers equal to the mean-square end-to-end distance of the molecule.     

Highly Efficient Enantioselective Construction of Bispirooxindoles Containing Three Stereocenters through an Organocatalytic Cascade Michael–Cyclization Reaction

Bispirooxindole derivatives containing three stereocenters, including two spiro quaternary centers, were synthesized in a high‐yielding, atypically rapid, and stereocontrolled cascade Michael–cyclization reaction between methyleneindolinones and isothiocyanato oxindoles catalyzed by a bi‐ or multifunctional organocatalyst. Mild conditions were used to construct bispirooxindoles with excellent enantio‐ and diastereomeric purities within less than 1 min. Catalyst reconfiguration offered access to the opposite enantiomer. This exceptionally highly efficient procedure will allow diversity‐oriented syntheses of this intriguing class of compounds with potential biological activities.     

Recyclable C2-symmetric tertiary amine-squaramide organocatalysts: Design and application to asymmetric synthesis of γ-nitrocarbonyl compounds

Simple C₂-symmetric chiral tertiary amines bearing squaramide fragments along with the 1,2-di(pyridin-2-yl)ethane spacer group have been synthesized. Among them, amine 8b with a different configuration of stereocenters in 1,2-di(pyridin-2-yl)ethane and 1,2-diaminocyclohexane units efficiently catalyzed asymmetric additions of β-dicarbonyl compounds to nitroolefins and domino reaction of ortho-(tosylamino)chalcone with β-nitrostyrene in wet (20 equiv. of H₂O) DCM, affording corresponding adducts in up to 99% yield and 94% ee. The developed procedure is scalable. Due to poor solubility in organic solvents and water, the catalyst could be readily separated from the reaction mixture and over 10 times reused in the reaction without compromising enantiomeric enrichment and yield of product.