Asymmetric Double Michael Reaction Catalyzed by Simple Primary Amine Catalysts: A Straightforward Approach to Construct Spirocyclic Oxindoles

The enantioselective double Michael reaction of N‐Boc‐3‐nonsubstitued oxindoles with dienones catalyzed by chiral monoimide protected cyclohexane‐1,2‐diamines was developed. A wide range of optically active spirocyclic oxindoles were obtained up to 98% yield and up to 89% ee.     

Highly efficient and diastereoselective construction of bispirooxindoles through a cascade Michael-cyclization reaction

A series of bispirooxindole derivatives have been synthesized via a cascade Michael-Cyclization reaction between isothiocyanato oxindoles and methyleneindolinones with high yields (up to 98%) and excellent diastereoselectivities (up to >95:5 dr) under mild conditions. The structure and effect on the reaction of less studied 4-substituted methyleneindolinones have also been investigated.     

2-氨基噻唑5位的羟甲基化和胺甲基化

采用微波法、封管加热以及酯基还原三种方法,在2-氨基噻唑衍生物的5位引入羟甲基,得到一系列新的5位羟甲基取代的新衍生物.并将三种方法进行对比,结果表明,封管加热对底物热稳定性要求苛刻,反应时间长,反应液杂,反应收率低.酯基还原的方法需在合成噻唑前引入酯基后还原,路线长,且收率低.采用微波法,反应时间短,转化率高,反应液副产物少,收率明显高于其他两种合成方法.同时报道了用NaH作碱制得氰基酯钠盐,再经关怀关环、还原得到一系列5位为氨甲基的噻唑新衍生物.     

Transition‐Metal‐Free Synthesis of N‐Hydroxy Oxindoles by an Aza‐Nazarov‐Type Reaction Involving Azaoxyallyl Cations

A novel transition‐metal‐free method to construct N‐hydroxy oxindoles by an aza‐Nazarov‐type reaction involving azaoxyallyl cation intermediates is described. A variety of functional groups were tolerated under the weak basic reaction conditions and at room temperature. A one‐pot process was also developed to make the reaction even more practical. This method provides alternative access to oxindoles and their biologically active derivatives.     

Palladium-catalyzed cascade synthesis of spirocyclic oxindoles via regioselective C2-H arylation and C8-H alkylation of naphthalene ring

A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an efficient method for synthesizing various aryl-substituted spirocyclic oxindoles.The protocol enables three C-C bonds formation via an intramolecular Heck reaction and sequentially regioselective C-H bond activation.     

Quinine-catalyzed asymmetric domino Michael-cyclization reaction for the synthesis of spirocyclic oxindoles bearing two spiro quaternary centers and three consecutive stereocenters

An efficient organocatalytic diastereo- and enantioselective method for the construction of spirocyclic oxindole derivatives bearing two spiro quaternary centers and three consecutive stereocenters via a domino Michael/cyclization process has been developed. Using commercially available quinine as catalyst, the reactions of 3-isothiocyanato oxindoles with unsaturated pyrazolones and unsaturated isoxazolones proceeded smoothly under mild reaction conditions for giving two classes of spirocyclic oxindole compounds in high to excellent yields with moderate to good diastereoselectivities and enantioselectivities. A plausible dual activation working model was tentatively proposed to account for the stereochemistry of the domino Michael/cyclization process.     

Synthesis of substituted oxindoles from alpha-chloroacetanilides via palladium-catalyzed C[bond]H functionalization

A novel method for the synthesis of oxindoles is described. In the presence of catalytic palladium acetate and 2-(di-tert-butylphosphino)biphenyl, alpha-chloroacetanilides are converted to oxindoles in good to excellent yields with high functional group compatibility using triethylamine as a stoichiometric base. The cyclization is highly regioselective, obviating the need for prefunctionalized arenes. Plausible mechanistic pathways for the reaction are discussed.     

A novel method for the synthesis of functionalized spirocyclic oxindoles by one-pot tandem reaction of vinyl malononitriles with isatylidene malononitriles

One-pot synthesis of novel spirocyclic oxindoles was achieved via vinylogous Michael addition of vinyl malononitriles on isatin-malononitrile adducts as the key step followed by a sequential tandem reaction.     

Covert Mannich Reaction via Carbon Transfer

1,3‐Dimethylbenzimidazolidine reacts with ketones, which can provide activating α hydrogens and primary or secondary amines under acidic conditions, to yield aminomethylation derivatives by a covert Mannich reaction.     

Diastereo- and enantioselective conjugate addition of 3-substituted oxindoles to enones via bifunctional catalysts

This paper presents a synthetically challenging vicinal quaternary-tertiary C–C forming reaction of 3-substituted oxindoles and chalcones by a simple aryl substituted bifunctional thiourea catalyst. The reactions work with a broad range of chalcones, giving chiral 3,3′-substituted oxindoles type compounds with adjacent quaternary-tertiary stereocenters in high yields (up to 99%), very good dr (up to >98:2) and very good ee (up to 96%).     

合成3,3-二芳基氧化吲哚的新方法

报道了一种合成3,3-二芳基氧化吲哚的新方法。以取代靛红为起始原料,THF为溶剂,在室温下用新制芳基格氏试剂与靛红的3-位羰基发生双芳基化反应,合成了12个未见文献报道的3,3-二芳基氧化吲哚(3a~3l),产率56%~78%,其结构经¹H NMR, ¹³C NMR和HR-MS（ESI-TOF）表征。并分析了3a(CCDC: 1960434)和3b(CCDC: 1960436)的单晶结构。结果表明：3a属triclinic晶系,P-1空间群,晶胞参数a=8.736(2) , b=8.887(2) , c=13.862(3) , α=77.505(18)°, β=72.01(2)°, γ=64.68(2)°; 3b属monoclinic晶系,P2₁/c空间群,晶胞参数a=8.8877(10) , b=24.734(2) , c=8.5441(8) , α=90°, β=113.994(12)°, γ=90°。     

Palladium-catalyzed C-H functionalization of N-arylpropiolamides with aryliodonium salts: selective synthesis of 3-(1-arylmethylene)oxindoles

A selective and efficient method for the synthesis of 3-(1-arylmethylene)oxindoles by palladium-catalyzed C-H functionalization of anilides with aryliodonium salts has been developed. In the presence of Pd(OAc)2 and Et3N, a variety of anilides underwent the reaction with aryliodonium salts to afford the corresponding 3-(1-arylmethylene)oxindoles in moderate to good yields. It is noteworthy that the reaction can be conducted providing moderate yields even without bases. The mechanism of the reaction was also discussed.     

N-Chlorophthalimide as a mild and efficient chlorination reagent in the Gassman ortho alkylation of aromatic amines. Synthesis of 3-(methylthio)oxindoles

A practical modification of the Gassman 3-(methylthio)oxindole synthesis is reported. In our method, substituted anilines and 2-(methylthio)acetamide were reacted under mild reaction conditions, in the presence of N-chlorophthalimide as a chlorinating agent to give α-amidosulfides, which, in the next step of the process, were cyclized to give 3-(methylthio)oxindoles. The method was successfully applied for the synthesis of the key intermediate, 2-(2-amino-3-benzoylphenyl)-2-(methylthio)acetamide, in the process of the preparation of nepafenac, a commonly used ophthalmic drug.     

8-氨甲基取代木犀草素衍生物的合成和抗炎活性研究

以木犀草素为先导化合物,对其A环8-位碳上进行Mannich反应,合成了10个未见文献报道的8-氨甲基化衍生物,并用1HNMR,IR和MS(HRMS)进行了结构表征。利用二甲苯诱发小鼠耳廓肿胀模型对所合成的七个目标化合物进行了抗炎活性的药理筛选,初步结果表明部分化合物具有良好的抗炎活性。     

An expedient approach for the synthesis of dispiropyrrolidine bisoxindoles, spiropyrrolidine oxindoles and spiroindane-1,3-diones through 1,3-dipolar cycloaddition reactions

A series of dispiropyrrolidine bisoxindoles were synthesized via a multicomponent 1,3-dipolar cycloaddition reaction of isatin, sarcosine and isatylidene malononitrile in refluxing methanol. Also a series of spiropyrrolidine oxindoles and spiroindane-1,3-diones were synthesized using 2-(1H-Indole-3-carbonyl)-3-phenyl-acrylonitrile and 2-(1,3-dioxo-indan-2-ylidene)-malononitrile as dipolarophiles, respectively.     

A convenient cyclopropanation process of oxindoles via bromoethylsulfonium salt

A practical convenient conversion of oxindoles into the corresponding spirocyclopropyl oxindoles is achieved efficiently using bromoethylsulfonium salt, which is easily prepared on a large scale and is stable crystalline. This reaction of bromoethylsulfonium salt with different substituted unprotected oxindoles proceeded under mild condition and provided moderate yields.     

Access to Enantioenriched Spiro-ϵ-Lactam Oxindoles by an N-Heterocyclic Carbene-Catalyzed [4+3] Annulation of Flexible Oxotryptamines with Enals

Oxotryptamines were firstly used as flexible four-atom synthons in an NHC-catalyzed formal [4+3] annulation, providing a novel enantioselective method to access structurally diverse spiro-ϵ-lactam oxindoles with excellent enantioselectivities. This metal-free reaction features a broad substrate scope, excellent functional-group tolerance and proceeds under mild reaction conditions. Importantly, enantiopure privileged hexahydropyrroloindoles could be easily constructed by a one-pot process from the resulting spiro-ϵ-lactam oxindoles.     

无金属催化烯烃自由基环化合成多氟取代吲哚酮

一种无金属催化的活泼烯烃与全氟碘代丁烷自由基环化合成含氟吲哚酮的反应被发展。 在廉价易得的的偶氮二异丁腈(AIBN)介导下, 多种N-芳基丙烯酰胺类化合物与全氟碘代丁烷发生自由基串联环化反应,以53%~85%的产率合成了一系列的潜在生理活性的多氟取代吲哚酮。 此工作为潜在药用价值的多氟取代吲哚酮合成提供了一条高效、廉价、绿色的新途径。     

有机催化靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应

研究了手性磷酸催化的靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应, 以良好至优秀的收率(高达97%)、 对映选择性(高达99% e.e.)以及非对映选择性(均>20∶1 d.r.)得到一系列含噁唑酮骨架的手性3,3′-二取代氧化吲哚化合物. 该反应可以进行扩大化和衍生反应.     

Scope of aminomethylations via Suzuki-Miyaura cross-coupling of organotrifluoroborates

We previously reported the Suzuki-Miyaura reaction of N,N-dialkylaminomethyltrifluoroborates with aryl bromides. Herein, we report a further investigation of the scope and limitations of this palladium-catalyzed aminomethylation reaction. Aryl chlorides, iodides, and triflates coupled in good to excellent yields to give N,N-dialkylbenzylic amines. The aminomethylation of alkenyl bromides was also examined.