Highly regioselective Friedel-Crafts alkylation of indoles with α,β-unsaturated N-acylbenzotriazoles

The Friedel-Crafts alkylation rather than acylation of indoles was realized with α,β-unsaturated acylbenzotriazoles catalyzed by samarium(III) iodide under reflux in anhydrous THF. The reaction was highly regioselective, and a series of new 3-substituted indole derivatives were obtained in moderate to good yields with the potential to be further transformed into various indole derivatives due to the presence of active acylbenzotriazole moiety.     

Lithium Bromide/Water as Additives in Dearomatizing Samarium‐Ketyl (Hetero)Arene Cyclizations

New conditions for dearomatizing samarium‐ketyl (hetero)arene cyclizations are reported. In many examples of these samarium diiodide‐mediated reactions, lithium bromide and water can be used as additives instead of the carcinogenic and mutagenic hexamethylphosphoramide (HMPA). The best results were obtained for the cyclizations of N‐acylated indole derivatives delivering the expected indolines in good yields and excellent diastereoselectivities. A new type of cyclization delivering indolyl‐substituted allene derivatives is also described. The scope and limitations of the lithium bromide/water system are discussed.     

Samarium diiodide induced cyclizations of γ-, δ- and ε-indolyl ketones: reductive coupling, intermolecular trapping, and subsequent transformations of indolines

This comprehensive study describes our results of samarium diiodide induced 5-exo-trig to 8-exo-trig cyclization/alkylation sequences of 3'-acceptor-substituted indolyl ketones. All cyclization precursors were easily prepared by simple N-alkylation or N-acylation of indole derivatives with the corresponding iodo alkanones, acid chlorides, or lactones. After treatment of indolyl ketones with two equivalents of SmI(2), the generated stabilized carbanionic intermediates were trapped with different electrophiles leading to a variety of highly substituted indoline derivatives in good to very good yields. In general, the cyclization products were obtained as single diastereomers bearing a newly generated quaternary center, a common structural motif in various indole alkaloids. The relative configurations of the products were established by NOE experiments and by single-crystal analysis and follow the rules already established. Furthermore, the obtained products were subjected to a series of chemical transformations, such as oxidation, reduction, and metathesis reactions resulting in a range of interesting synthetic building blocks valuable for further applications.     

Evolution of a Short Route to Strychnine by Using the Samarium‐Diiodide‐Induced Cascade Cyclization as a Key Step

This comprehensive report accounts the development of a highly diastereoselective samarium diiodide‐induced cascade reaction of substituted indolyl ketones. The complexity‐generating transformation with SmI₂ allows the diastereoselective generation of three stereogenic centers including one quaternary center in one step. The obtained tetra‐ or pentacyclic dihydroindole derivatives are structural motifs of many monoterpene indole alkaloids, and their subsequent transformations gave way to one of the shortest approaches towards strychnine (14 % overall yield in ten steps, or 10 % overall yield in eight steps). During the course of this report we discuss the influence of substituents on the cyclization step, plausible mechanistic scenarios for the SmI₂‐induced cascade reaction, diastereoselective reductive amination, and regioselective dehydratization protocols towards the pentacyclic core structure of strychnos alkaloids.     

Application of samarium diiodide (SmI2)-induced reduction of gamma-acetoxy-alpha,beta-enoates with alpha-specific kinetic electrophilic trapping for the synthesis of amino acid derivatives

Gamma-acetoxy-alpha,beta-enoates were easily reduced by samarium diiodide (SmI2) in THF to generate samarium dienolates which were kinetically trapped with ease at their alpha-positions by electrophiles (proton, aldehydes or ketones) to yield (E)-alkene dipeptide isosteres or gamma-amino acid derivatives in high chemical yields.     

Metallic samarium and iodine promoted facile and efficient syntheses of trisubstituted alkenes from the acetates of Baylis-Hillman adducts

Promoted by samarium metal in the presence of a catalytic amount of iodine, the Baylis-Hillman adducts underwent reductive elimination to form (E)-methylcinnamic ester derivatives. When the iodine was used in 1:1 ratio with metallic samarium, stereospecific syntheses of allylic iodide derivatives, (2Z)-2-(iodomethyl)alk-2-enoates, were achieved. Thus, this gives a new approach to the selective construction of stereo-defined trisubstituted alkenes with the simple Sm/I₂ system.     

吲哚衍生物合成与应用的研究进展

综述了以苯胺衍生物(或硝基苯衍生物)为原料合成吲哚衍生物的方法和吲哚衍生物的应用。吲哚类化合物的合成方法主要有：Fischer合成法,苯胺衍生物合成法,硝基衍生物合成法和Nenitzescu合成法等。吲哚衍生物在制药、染料和香料等领域有重要应用。参考文献105篇。     

Catalytic activity of some organolanthanoid derivatives in styrene and propene polymerization

Organolanthanoids of several classes were examined as potential styrene and propene polymerization catalysts. They are: molecular hydrides of divalent lanthanoids (samarium, europium, ytterbium); naphthalene and stilbene complexes of neodymium(III), samarium(II), europium(II), ytterbium(II), lutetium(III); amides and alkoxides (including heterobifunctional derivatives) of praseodymium(III), neodymium(III), samarium(II), europium(II), thulium(III), ytterbium(II, III); thiolate of samarium(III); phenyl and phenylethinyl derivatives of europium(II), thulium(III), ytterbium(II); methylytterbium cluster Yb₈ (μ‐CH₃)₁₄(μ‐CH₂)(THF)₆; heterobimetallic samarium(II), ytterbium(II, III) complexes; diazabutadiene ytterbium(III) derivatives; metallic praseodymium and ytterbium, activated by iodine. The highest activity in styrene polymerization revealed hydrides, naphthalene and stilbene complexes of samarium(II), europium(II) and ytterbium(II). In the propene polymerization only [(η⁵‐C₅H₄)CH₂CH­(CH₂OBu)(η¹‐O)]YbMe(THF) displayed noticeable activity.Copyright © 2001 John Wiley & Sons, Ltd.     

On the Synthesis and Reactions of Indole-2-carboxylic Acid Hydrazide

Summary.  Indole-2-carboxylic acid hydrazide was prepared and allowed to react with aromatic aldehydes in acidic medium to give the corresponding hydrazone derivatives in good yields. The hydrazones were cyclized to indolo[2,3-d]pyridazine derivatives by refluxing with acetyl chloride. The indole carbohydrazide was converted to 2-triazolylindoles which acted as starting materials for several indole derivatives. A number of new indole derivatives were also prepared and structurally confirmed. Received October 17, 2000. Accepted (revised) December 12, 2000     

单萜吲哚生物碱Uleine及其衍生物的合成进展

生物碱uleine及其衍生物从结构上看属于单萜吲哚生物碱,它们共同的结构特征是吲哚核与碱性氮原子之间只有一个碳相隔,而不像其它单萜吲哚生物碱有两个碳原子.由于其结构特异,天然含量少,因而其合成工作一直吸引着化学工作者.总结uleine生物碱及其衍生物的合成方法,根据构建环的种类不同,把合成方法分为五类.大部分方法都是以吲哚和吡啶衍生物为起始原料进行四环的合成,有几条合成路线简短易行.     

Unexpected formation of fluorine-containing tetrahydrocarbazole during the reaction of indole, paraformaldehyde, and fluorine-containing β-ketoesters

A surprise and mild method to prepare fluorine-containing indole derivatives through a one-pot three-component condensation reaction sequence is presented. To our surprise, during the reaction of preparation of fluorine-containing indole derivatives, unexpected formation of fluorine-containing tetrahydrocarbazole was found. Moreover, this method has been demonstrated in the preparation of functionalized polycyclic indole derivatives in a straightforward and atom-economical manner.     

Characterizing the electrospray ionization mass spectral fragmentation pattern of indole derivatives synthesized from 2-keto glycosides

Four indole derivatives synthesized from 2-keto glycosides were analyzed by electrospray ionization tandem mass spectrometry (ESI-MSn) with low-energy collision-induced dissociation to establish a general structural elucidation of indole derivatives. Their fragmentation pathways are proposed on the basis of the MSn studies and deuterium-labeled experiments. Indole derivatives undergo complicated gas-phase rearrangements in addition to simple bond cleavages. A rearrangement, which involves a contraction of the six-membered ring, was observed and a mechanism was proposed. The observations may have some potential applications in the interpretation of the mass spectra of indole derivatives.     

SmI(2)-promoted radical addition reactions with N-(2-Indolylacyl)oxazolidinones: synthesis of bisindole compounds

The treatment of N-acyl oxazolidinones of N-benzyl 2-indolecarboxylic acids varying in the substitution pattern of the indole ring with samarium diiodide at -78 degrees C led to the formation of two indole dimer products. The major product isolated in yields from 55 to 59% represents an unsymmetrical dimer arising from 1,4-addition to the 2-indolecarboxylic acid derivative of a possible ketyl-type radical anion intermediate originating from the reduction of the exocyclic carbonyl group of the N-acyl oxazolidinone. The minor dimer, represented by a symmetrical diketone, was produced in yields ranging from 11 to 23%. Even in the presence of an alpha,beta-unsaturated amide, dimerization was the preferred pathway rather than the formation of a gamma-keto amide. Upon treatment with acid, the unsymmetrical indole dimer cyclized to form a diindolequinone. Finally, the N-acyl oxazolidinones of pyrrole-2-carboxylic acid and 3-indolecarboxylic acid preferred in both cases to undergo C-C bond formation with an acrylamide in the presence of SmI2 rather than dimerization.     

New synthesis of condensed hydropyridazine derivatives. VI

The reactivity of some indole derivatives towards the semicarbazone of ω-bromoacetophenone has been reported. Substituents at position 1 and 2 of the indole ring greatly affect the course of the reaction. 1,4,4a,9a-Tetrahydro-9H-pyridazino[3,4-b]indole derivatives or 3-indolyl derivatives were obtained depending on the substituents. The structures were assigned on the basis of satisfactory analytical and spectroscopic data.     

Synthesis of Indole Derivatives Attached to Polyethylene Oxides)

N-Benzyl 5-, 6-, and 7-bromoindolines were converted to the respective organosodium derivatives and used as initiators for the anionic polymerization of ethylene oxide. The resulting indoline derivatives attached to polyethylene oxide were dehydrogenated to the indole derivatives, which in turn were converted through suitable reactions to the tryptamine and indole acetic acid derivatives.     

Catalytic Functionalization of Indoles in a New Dimension

140 Years ago Adolf von Baeyer proposed the structure of a heteroaromatic compound which revolutionized organic and medical chemistry: indole. After more than a century, indole itself and the complexity of naturally occurring indole derivatives continue to inspire and influence developments in synthetic chemistry. In particular, the ubiquitous presence of indole rings in pharmaceuticals, agrochemicals, and functional materials are testament to the ever increasing interest in the design of mild and efficient synthetic routes to functionalized indole derivatives. This Review emphasizes the achievements in the selective catalytic functionalization of indoles (C? C bond‐forming processes) over the last four years.     

Application of Fischer Indolization under Green Conditions using Deep Eutectic Solvents

Indole and its derivatives captured the attention of organic chemists due to their applications in medicinal chemistry. The examples covered here are intricate polycyclic indole derivatives and these include: azapolyquinanes, cyclophanes, spirocycles and other heterocycles. We found that deep eutectic mixture such as L‐(+)‐tartaric acid (TA) and dimethyl urea (DMU) is useful to prepare complex unnatural indole derivatives. These conditions from time to time produced indole derivatives which are not possible by conventional methods. Various substrates containing multiple carbonyl groups were shown to undergo Fischer indolization (FI) in deep eutectic mixtures and thus expand its scope to a higher level.     

The Glc Separation of Indole Amines and Indole Alcohols as Heptafluorobutyryl Derivatives

Abstract

Indole amines and indole alcohols were converted to heptafluoro-butyryl (HFB) derivatives by an acyl transfer reaction with heptafluoro-butyrylimidazole. The indole NH group as well as all amino and hydroxyl groups were acylated. The HFB derivatives have excellent gas chroma-tographic properties and can be used with either hydrogen flame or electron capture detection systems. Mass spectra of the HFB derivatives of biologic N, N-dialkyl indole amines are very characteristic; these compounds can be identified easily by GLC-MS methods.     

Et2Zn-catalyzed intramolecular hydroamination of alkynyl sulfonamides and the related tandem cyclization/addition reaction

Intramolecular hydroamination of alkynyl amides was effected by a catalytic amount of Et2Zn (20 mol %) to form indole derivatives, and a tandem cyclization/nucleophilic addition procedure involving reaction of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient approach to C3-substituted indole derivatives when an excess of Et2Zn (120 mol %) was used.     

A one-pot three-component reaction for the preparation of highly functionalized tryptamines

We have developed a general one-pot method to provide highly functionalized tryptamine derivatives, via a Fischer indole type pathway. In this article, we demonstrate optimal conditions for a one-pot indole synthesis, allowing for the synthesis of a broad scope of 2-methyl tryptamine derivatives and a precursor for the synthesis of the core structure of some akuammiline alkaloids. Additionally, further modification of the indole products is described.