Palladium-/copper-catalyzed regioselective amination and chloroamination of indoles

A palladium-/copper-catalyzed intermolecular C-H amination reaction of indoles has been developed. This reaction proceeds in good to excellent yields to produce a variety of 2-amino-substituted indoles and exhibits excellent regioselectivity at room temperature. Furthermore, chloroamination of indoles provides a simple method for the construction of C-N and C-Cl bonds in one step.     

Parallel synthesis of an indole-based library via an iterative Mannich reaction sequence

A library of 1,3-disubstituted indoles has been prepared via an iterative Mannich reaction sequence. The first Mannich reaction with secondary amines and formaldehyde preferentially yields 3-aminomethyl indoles, while the second Mannich reaction introduces an additional aminomethyl group at the N1-position of the indole ring. A library of 25 substituted indoles has thus been prepared in moderate to good yields with purity.     

Novel Tetraindoles and Unexpected Cycloalkane Indoles from the Reaction of Indoles and Aliphatic Dialdehydes

The reaction of indoles with dialdehydes was studied for the first time. Mild reaction conditions using glacial acetic acid led to two novel kinds of reaction products: one designated as alkyl chain‐connected tetraindoles and the other one as bis(indolyl)‐substituted cycloalkane indoles. The suggested reaction pathways are discussed. The indole substituents of the cycloalkane indoles were either trans or cis orientated depending from the alkyl chain length.     

FeCl3-promoted alkylation of indoles by enamides

An efficient iron-promoted alkylation of indoles with enamides has been accomplished under mild reaction conditions. The reaction proceeded with remarkable regioselectivity leading exclusively to substitution by indoles at α-position of enamides.     

Palladium-catalyzed functionalization of indoles with 2-acetoxymethyl-substituted electron-deficient alkenes

New functionalizations of indoles via palladium-catalyzed reaction of indoles and 2-acetoxymethyl-substituted electron-deficient alkenes are reported. It was found that for N-protected indoles the reaction proceeded smoothly in the presence of 5 mol % of Pd(acac)2 and 10 mol % of PPh3 at 80 degrees C in HOAc, while for N-unprotected indoles, the reaction was carried out by using 5 mol % of Pd(dba)2 or 2.5 mol % of Pd2(dba)3.CHCl3 with 10 mol % of 2,2'-bipyridine as the catalyst in toluene. This strategy allows the selective installation of electron-deficient olefin functionality at the 3-position of indoles, which might be difficult to obtain by other methods and can be further elaborated.     

Synthesis of 3-(2-nitroalkyl) indoles by reaction of 3-(1-arylsulfonylalkyl) indoles with nitroalkanes

Sulfonyl indoles act as effective precursors of vinylogous imino derivatives in the reaction with nitroalkanes under basic conditions leading to the corresponding nitro indoles in good yield. This procedure represents an effective option to the classical conjugate addition of indoles to nitroalkenes.     

A convenient one-pot three component synthesis of 3-aminoalkylated indoles catalyzed by 3-chlorophenylboronic acid

An efficient protocol was developed for the synthesis of 3-aminoalkylated indoles using 3-chlorophenylboronic acid as a catalyst under ambient temperature conditions. The three-component reaction of indoles, aromatic aldehydes and N-methyl aniline offered corresponding 3-aminoalkylated indoles in excellent yields. This protocol presents some remarkable features such as mild reaction conditions, simple workup procedure and excellent yields.     

Intermolecular Formal Cycloaddition of Indoles with Bicyclo[1.1.0]butanes by Lewis Acid Catalysis

Herein, we develop a new approach to directly access architecturally complex polycyclic indolines from readily available indoles and bicyclo[1.1.0]butanes (BCBs) through formal cycloaddition promoted by commercially available Lewis acids. The reaction proceeded through a stepwise pathway involving a nucleophilic addition of indoles to BCBs followed by an intramolecular Mannich reaction to form rigid indoline-fused polycyclic structures, which resemble polycyclic indole alkaloids. This new reaction tolerated a wide range of indoles and BCBs, thereby allowing the one-step construction of various rigid indoline polycycles containing up to four contiguous quaternary carbon centers.     

Solventless clay-promoted Friedel-Crafts reaction of indoles with alpha-amido sulfones: unexpected synthesis of 3-(1-arylsulfonylalkyl) indoles

Friedel-Crafts reaction of indoles with alpha-amido sulfones in the presence of montmorillonite K-10 leads unexpectedly to 3-(1-arylsulfonylalkyl) indoles in good yield. The obtained products can be further desulfonylated under reductive or alkylative conditions giving linear and branched 3-substituted indoles.     

Asymmetric Friedel-crafts reaction of indoles with imines by an organic catalyst

In this communication, we report an asymmetric Friedel-Crafts reaction of indoles with imines catalyzed by a bifunctional cinchona alkaloid catalyst. This is the first efficient organocatalytic asymmetric Friedel-Crafts reaction of indoles with imines. This reaction is operationally simple and, unprecedentedly, affords high enantioselectivity for a wide range of indoles and both aryl and alkyl imines. This establishes a direct, convergent, and versatile approach to optically active 3-indolyl methanamines, a structural motif embedded in numerous indole alkaloids and synthetic indole derivatives.     

A regiocontrolled synthesis of substituted indoles by palladium-catalyzed coupling of 2-bromonitrobenzenes and 2-bromoacetanilides

The palladium-catalyzed cross-coupling reaction of 2-bromonitrobenzenes or 2-bromoacetanilides with ethylene has been used to produce a variety of substituted indoles. The mild reaction conditions and selectivity inherent in the coupling reaction have been utilized to produce regiochemically pure 4-, 5-, 6-, and 7-substituted indoles.     

Direct synthesis of fused indoles by gold-catalyzed cascade cyclization of diynes

A direct, concise, and atom-economical synthetic method for the generation of fused indoles, using a gold-catalyzed cascade cyclization of diynes, has been developed. The reaction gave various fused indoles, such as aryl-annulated[a]carbazoles, dihydrobenzo[g]indoles, and azepino- or oxepinoindole derivatives in good to excellent yields, through an intramolecular cascade 5-endo-dig hydroamination followed by a 6- or 7-endo-dig cycloisomerization, without producing theoretical byproduct. Three of the resulting indoles exhibited potent antifungal activities against T. mentagrophytes and T. rubrum, demonstrating the practical application of the described cascade reaction for drug discovery.     

Base-promoted three-component cascade approach to unsymmetrical bis(indolyl)methanes

Here we report a base-catalyzed reaction of two different indoles with aldehydes under heating to produce unsymmetrical bis(indolyl)methanes (BIMs), in which one of the indole ring must be N-substituted. Mixture of EtOH-H₂O is used as solvent. The reaction did not give symmetrical BIMs of N-substituted indoles or N–H indoles. However, traces of latter were formed in few cases, especially when electron-rich aldehydes were used. Diversely substituted indoles and aldehydes were used for the reaction. The reaction proceeds via 3-indolylalcohol, which we confirmed through isolation. The method also gives good yield on multigram scale reaction.     

DDQ-mediated oxidative cross-coupling between propargylic sp and indoles sp carbons

DDQ-catalyzed oxidative cross-coupling reaction between indoles and propargyl compounds is reported for the first time. The reaction involves direct carbon-carbon bond formation between sp² carbons of indoles and sp³ carbons of propargylates to yield the corresponding propargyl indoles in good yields with high selectivity.     

Iodine-promoted selective 3-selanylation and 3-sulfenylation of indoles with dichalcogenides under mild conditions

A simple method was developed for the synthesis of 3-chalcogen indoles via iodine-promoted direct 3-selanyl- and 3-sulfenylation of indoles with dichalcogenides. The reaction was carried out smoothly in EtOH under air at room temperature, selectively giving a series of 3-chalcogen indoles bearing different functional groups in good to excellent yields. The procedure has the merits of environmental friendliness, easy operation, wide substrate scope and mild reaction conditions.     

Metal Free Mono‐ and 2,3‐Bis‐sulfenylation of Indoles in Water with Sodium Sulfinates as a Sulfur Source

An iodine‐PPh₃ mediated sulfenylation of indoles in water with stable and odorless sodium sulfinates as the sulfur source is described. The reaction could afford monosulfenylated indoles in moderate to excellent yields under metal free conditions. Moreover, double C—H sulfenylation of indoles at 2‐ and 3‐positions has also been achieved by using excess sodium sulfinates under the optimized reaction conditions.     

Palladium-catalyzed functionalization of indoles with 2-acetoxymethyl substituted electron-deficient alkenes

A new functionalization of indoles via palladium-catalyzed reaction of indoles and 2-acetoxymethyl substituted electron-deficient alkenes is reported. The reaction was carried out under neutral condition and no isomerization of the carbon-carbon double bond was observed.     

Hetero-cope-umlagerungen -II. Einfache und flexible synthesen für 2-substituierte indole

The reaction of N-phenylhydroxylamine derivatives with electron withdrawing allenes gives o-alkylated anilines, which can further react to form 1,2-disubstituted indoles. 2-Substituted indoles are directly obtainable from reaction with N-phenyl-nitrones.     

Gold(I)-catalyzed rearrangement of alkynylaziridine indoles for the synthesis of spiro-tetrahydro-β-carbolines

Functionalized spiro-tetrahydro-β-carbolines were formed by an efficient gold(I)-catalyzed rearrangement reaction of alkynylaziridine indoles. The reaction involved a Friedel–Crafts type intramolecular reaction of alkynylaziridine indoles, following by hydroamination of aminoallene intermediate.     

Myoglobin‐Catalyzed C−H Functionalization of Unprotected Indoles

Functionalized indoles are recurrent motifs in bioactive natural products and pharmaceuticals. While transition metal‐catalyzed carbene transfer has provided an attractive route to afford C3‐functionalized indoles, these protocols are viable only in the presence of N‐protected indoles, owing to competition from the more facile N−H insertion reaction. Herein, a biocatalytic strategy for enabling the direct C−H functionalization of unprotected indoles is reported. Engineered variants of myoglobin provide efficient biocatalysts for this reaction, which has no precedents in the biological world, enabling the transformation of a broad range of indoles in the presence of ethyl α‐diazoacetate to give the corresponding C3‐functionalized derivatives in high conversion yields and excellent chemoselectivity. This strategy could be exploited to develop a concise chemoenzymatic route to afford the nonsteroidal anti‐inflammatory drug indomethacin.