A facile synthesis of 3-substituted indoles

1-Benzoyl-3-bromomethylindole (2a) or 1-benzenesulfonyl-3-bromomethylindole (2b) reacts with C, N, O, and P-containing nucleophiles to give potential intermediates for the synthesis of a wide range of indole alkaloids and pharmacologically important substances, in good to excellent yields.     

Solid-state synthesis of novel 3-substituted indoles

Poly(N-bromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS] and N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide [TBBDA] were used as efficient catalysts for the one-pot synthesis of 3-substituted indoles in good to high yields from indole, aldehydes, and arylamines under solid-state conditions at room temperature.     

New synthesis of 3-substituted indoles using lithium trimethylsilyldiazomethane

Lithium trimethylsilyldiazomethane smoothly reacted with N-tosyl-o-acylanilines to give 3-substituted indoles in good to high yields.     

Facile synthesis of 3-substituted indoles containing highly polarized double bonds

In this paper, an effective procedure is described for the synthesis of novel indoles containing highly polarized double bonds. The strategy involves the preparation of (indolylmethyl)malononitriles via the one-pot three-component reaction of an aldehyde, malononitrile and indole in the presence of Zn(OAc)₂/NaOAc under silent and ultrasonic conditions. The reaction further proceeds through oxidative elimination under solvent-free conditions in the presence of Ca(OCl)₂ to furnish indolylacrylonitriles in high yields and short reaction times.     

An expedient synthesis of 3-substituted indoles via reductive alkylation with ketones

3-Alkylindoles were prepared in one step from indoles and ketones via a convenient reductive alkylation procedure using triethylsilane and trichloroacetic acid. Under this particular condition, unsubstituted indoles could be tolerated to afford good yields of 3-sec-alkylation products.     

Carboxylic acid catalyzed three-component aza-Friedel-Crafts reactions in water for the synthesis of 3-substituted indoles

[reaction: see text] The carboxylic acid catalyzed three-component aza-Friedel-Crafts reactions of aldehydes, primary amines, and indoles in water have been developed. The aza-Friedel-Crafts products could be easily transformed to various 3-substituted indoles including biologically active compounds. This system offers a novel efficient method for the synthesis of 3-substituted indoles.     

Benzannulation of 3-substituted pyrroles to indoles

In a new general indole synthesis, the anion derived from benzotriazolyl derivative 5b underwent regioselective 1,4-addition to various alpha,beta-unsaturated ketones; subsequent acid-catalyzed cyclization formed the corresponding indoles 1a-f.     

FeCl3-catalyzed alkylation of indoles with 1,3-dicarbonyl compounds: an expedient synthesis of 3-substituted indoles

Indoles undergo smooth alkylation at the 3-position with 1,3-dicarbonyl compounds in the presence of 20 mol % of FeCl₃ under mild reaction conditions to produce a wide range of 3-substituted indoles in excellent yields and with high E-selectivity.     

Highly enantioselective synthesis of chiral 3-substituted indolines by catalytic asymmetric hydrogenation of indoles

[reaction: see text] N-Tosyl 3-substituted indoles were hydrogenated with high enantioselectivities (95-98% ee) by use of a trans-chelating chiral bisphosphine, (S,S)-(R,R)-PhTRAP ligand. The chiral catalyst, which was generated in situ from [Rh(nbd)(2)]SbF(6), PhTRAP, and Cs(2)CO(3), is useful for enantioselectively synthesizing a range of diverse optically active indolines possessing a chiral carbon at the 3-position.     

Synthesis of 3-substituted indoles via N-acylindolium ions

3-Substituted N-(N′N′-diethylcarbamyl)indoles are prepared from indole-3-carboxaldehyde in good overall yield via N-acylindolium ion intermediates.     

Sc(OTf)3-catalyzed alkylation of indoles with propargyl alcohols: an expeditious synthesis of 3-substituted indoles

Indoles undergo smooth alkylation with propargylic alcohols in the presence of 10 mol % of scandium triflate under mild conditions to produce 3-propargylated indoles in excellent yields with high selectivity.     

Synthesis of 3-substituted cyclopenta[b]indoles

When reacting with I₂, 2-(cyclopent-2-enyl)anilines undergo cyclization into 3-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles in high yields. The minor reaction products were 3,5- or 3,7-diiodoindolines. Ammonolysis of 3-iodo-5-methyl-1,2,3,3a,4,8b-hexahydro-cyclopenta[b]indole or itsN-chloroacetyl derivative results in 3-amino-5-methyl-1,2,3,3a,48b-hexahydro- and 5-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles. Published inIzvestiya Akademii Nauk. Seriya Khimischeskaya, No. 10, pp. 1789–1793, October, 2000.     

Room-temperature phosphorescence of 3- and 5-substituted indoles

The room-temperature phosphorescence of indole and thirteen substituted indoles on Schleicher and Schüll 2040A filter paper is reported. Caesium and iodide ions are effective in increasing the emission intensity. In the presence of iodide, the excitation and emission wavelengths of indole are 279 and 440 nm respectively. The excitation and emission wavelengths of indoles with aliphatic groups in the 3-position are 288-289 and 443-449 nm respectively. Indoles with 3,5-substitution have excitation and emission wavelengths of 300-308 and 448-460 nm respectively. Indoxylsulphate and indoxyl-beta-d-glucoside were the only indoles surveyed for which variations in the excitation and emission wavelengths depended on the heavy-atom ion present. These compounds had excitation wavelengths ranging from 288 to 388 nm, depending on which heavy-atom perturber was used. Emission wavelengths were 460-500 nm. Log-log plots of intensity vs. concentration were linear between 0.05 and 700 microg/ml for all the compounds studied, with detection limits in the nanogram range.     

Rearrangement of 3,3-disubstituted indolenines and synthesis of 2,3-substituted indoles

Synthesis of 2,3-substituted indoles from phenylhydrazine and alpha-branched aldehydes via rearrangement of 3,3-disubstituted indolenine intermediates is reported. [reaction: see text]     

Synthesis of 2-substituted indoles

2-Substituted indoles are obtained upon the cyclocondensation of (2-R-2-oxoethyl) trimethylammonium bromides.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 509–511, February, 1991.     

Novel synthesis of fused indoles and 2-substituted indoles by the palladium-catalyzed cyclization of N-cycloalkenyl-o-haloanilines

A new palladium-catalyzed cyclization of N-alkenyl-o-haloanilines with selective isomerization of a double bond followed by formal 5-endo-trig cyclization was developed. A variety of fused and 2-substituted indoles were synthesized from enaminoesters prepared by condensation of β-ketoesters and o-iodoaniline.     

One-pot sequential multi-component reaction: Synthesis of 3-substituted indoles

Here, we have developed a 3-component one-pot sequential approach to 3-substituted indoles. The main advantages of this process are step economy, reduced waste, and operational simplicity. The method involves in situ generation of 3-indolylalcohols from the reaction of indoles and aldehydes in the presence of base. Further, nucleophilic substitution of 3-indolylalcohols with various nucleophiles affords 3-substituted indole derivatives. The reaction does not requires any hazardous and expensive metal catalyst. In addition, the reaction is carried out in (1:1) ethanol–water which is considered as environmentally benign solvent. On the other hand, nonsequential 3-component reaction results in the formation of unwanted bisindolylmethanes.     

A convenient synthesis of pyrrolopyridines and 2-substituted indoles by gold-catalyzed cycloisomerization

We have developed a gold-catalyzed intramolecular cyclization of variously substituted acetylenic amines under mild conditions, which yields pyrrolopyridines and 2-substituted indoles, quantitatively. The cycloisomerization of acetylenic amines was achieved with AuCl₃ as catalyst without the use of base, acid or N-protecting group.     

Palladium-catalyzed synthesis of 3-alkoxysubstituted indoles

Indoles having an electron-donating alkoxy-group in the 3-position were prepared from 1-(2-nitrophenyl)-1-alkoxyalkene derivatives via a palladium-catalyzed reductive N-heteroannulation using carbon monoxide as the ultimate reducing agent. The required starting materials were prepared by a Stille coupling of 2-halonitroarenes with tributyl(1-ethoxyethenyl)stannane or tributyl(3,4-dihydro-2H-pyran-6-yl)stannane.