Synthesis of indoles via amidoselenation

The reaction of 2-styrylacetanilides (2) with N-phenylselenosuccinimide affords 1-N-acetyl-2-phenyl-3-phenylselenoindoles (3) and 1-N-acetyl-2-phenylindoles (4) . The reaction of 2-vinylacetanilides (5) with phenylselenenyl bromide proceeds to form indoles via an intramolecular amidoselenation.     

Synthesis of indoles with a polyfluorinated benzene ring

A two-step sequence consisting of a Sonogashira coupling of polyfluorinated 2-iodoanilines with terminal alkynes, followed by a KOH promoted cyclization of the 2-alkynylanilines thus formed, has been developed as a one-pot synthesis of 2-R-indoles (R=n-Bu, Ph, CH₂OTHP→CH₂OH, C(CH₃)₂OH→H) containing a polyfluorinated benzene moiety.     

Synthesis of indoles via alkylidenation of acyl hydrazides

Indoles have been synthesised via alkylidenation of acyl phenylhydrazides using phosphoranes and the Petasis reagent, followed by in situ thermal rearrangement of the product enehydrazines. The Petasis reagent provides an essentially neutral equivalent of the [acid-catalysed] Fischer indole synthesis, but with acyl phenylhydrazides as starting substrates. Alkylidene triphenylphosphoranes convert aroyl phenylhydrazides to indoles, but acyl phenylhydrazides derived from aliphatic carboxylic acids undergo a Brunner reaction to form indolin-2-ones.     

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.     

Synthesis of azaphenanthridines via anionic ring closure

A new and convergent synthesis of azaphenanthridines via an anionic ring closure is reported. Ortho-lithiation/in situ borylation of cyanopyridines produces the corresponding cyanopyridylboronic esters, which undergo a Suzuki-Miyaura cross-coupling to give the key intermediates. Addition of lithium morpholide produces the azaphenanthridines.     

Synthesis of [6,n] cis-fused ring compounds via Cr-mediated dearomatisation-ring-closing metathesis

cis-Fused [6,8], [6,7], [6,6] and [6,5] ring systems containing a cyclohexadiene ring unit, a cycloenone ring and a quaternary carbon at the ring junction were obtained in only two steps from [Cr(CO)3(eta6-p-methoxyphenyl oxazoline)]. The sequence proceeds via diastereoselective addition of three C-substituents across an arene double bond, followed by allylation and ring closing metathesis (RCM). RAMP-hydrazone and (R)-isopropyloxazoline were used as chiral auxiliaries to provide, after removal of the auxiliaries, the enantiomerically highly enriched [6,7] cis-fused system.     

5-Endo-Trigonal ring closures of unsaturated sulfones.

The γ -functionalized unsaturated sulfones 5a-5d, 8, 11 and 15 respectively cyclize to the 5-membered heterocycles 6a-6d, 9, 14 and to the 5-membered carbocycle 16 in good yields. These ring closures are all 5-Endo-Trig processes.     

Amidomethylation of the benzene ring of indoles

The benzene ring of indoles was amidomethylated by various agents in the presence of sulfuric acid. The amidomethylation of 2-methyl- and 2,3-dimethylindoles takes place in the 5 position. When there is a methyl or methoxy group in the 5 or 7 position, the substituent enters the 6 position. Hydrazinolysis or hydrolysis of the amidomethylation products gives 5- or 6-aminomethylindoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1066–1069, August, 1978.     

Radical ring closures of 4-isocyanato carbon-centered radicals

The 2-(2-isocyanatophenyl)ethyl radical was generated from the corresponding bromide with tributyltin and tris(trimethylsilyl)silyl radicals and shown to ring close in the 6-endo-mode to afford 3,4-dihydro-1H-quinolin-2-one as the major product. Cyclization in the 5-exo-mode to produce 2,3-dihydroindole-1-carbaldehyde, after hydrogen abstraction, was a minor reaction. Rate constants for the two processes were estimated and compared with reaction enthalpies computed by the DFT method.     

Synthesis of 1-aryl indoles via coupling reaction of indoles and aryl halides catalyzed by CuI/metformin

Ullmann-type C–N coupling reaction has been developed for the synthesis of 1-aryl indole derivatives by indoles and aryl halides in the presence of CuI/metformin (CuI/Met) in DMF. This method is very easy, rapid, and high yielding reaction for the synthesis of 1-aryl indoles. In particular, the metformin, which is used as ligand, is inexpensive and nontoxic that is considered to be relatively environmentally benign.     

Synthesis of indoles via domino reaction of N-aryl amides and ethyl diazoacetate

A general and concise synthesis of functionalized indoles via domino reaction of N-aryl amides and ethyl diazoacetate has been developed. The methodology offers a great potential for the synthesis of biologically active and naturally occurring indole derivatives.     

Synthesis of tryptamine derivatives via a direct, one-pot reductive alkylation of indoles

An efficient, one-pot reductive alkylation of indoles with N-protected aminoethyl acetals in the presence of TES/TFA is reported. It represents the first general method for the direct synthesis of tryptamine derivatives from indoles and nitrogen-functionalized acetals. This convergent and versatile approach employs safe and inexpensive reagents, proceeds under mild conditions, and tolerates several functional groups. The new procedure was efficiently applied to a gram-scale synthesis of both luzindole, a reference MT2-selective melatonin receptor antagonist, and melatonin.     

Synthesis of 2-substituted indoles via a palladium-catalyzed domino Heck reaction and dealkylation

A palladium-catalyzed domino Heck reaction and dealkylation for the preparation of 2-substituted indoles is described. This novel transformation is based on an intramolecular Heck reaction followed by dealkylation.     

Synthesis of 2-vinylic indoles and derivatives via a Pd-catalyzed tandem coupling reaction

A novel one-step synthesis of valuable 2-vinylic indoles and their tricycle derivatives is described. This reaction, which utilizes a gem-dibromovinyl unit as a readily available starting material, occurs via an efficient Pd-catalyzed tandem Buchwald-Hartwig/Heck reaction.     

Synthesis of seven-membered ring glycals via endo-selective alkynol cycloisomerization

[reaction: see text] Alkynyldiols 1 undergo cycloisomerization to the corresponding seven-membered cyclic enol ethers 2 under tungsten carbonyl catalysis. This novel transformation proceeds with good yields and virtually complete regioselectivity for all diastereomers of 1, favoring the product 2 resulting from endo-mode cyclization. The unexpected regioselectivity may be dependent on the presence of the dioxolane structure tethering the terminal alkyne and diol functional groups.     

Synthesis of fused 4,5-disubstituted indole ring systems by intramolecular friedel-crafts acylation of 4-substituted indoles

4-Substituted indoles containing a variety of electrophiles and N-substituents undergo Friedel-Crafts acylation to give exclusively the products of cyclization at the 5-position of indole. These indanones and tetralones have been scarcely prepared and are subunits in natural products and analogues of potential biological significance.     

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.     

Synthesis of noval benzoylated indoles

It has been shown that Friedel-Crafts p-nitrobenzoylation of 2,2-dicarbethoxybis(5-indoyl)methane occurs at the bridging group. From the products of p-nitrobenzoylation of 2-carbethoxy-5-methylindole, 2-carbethoxy-5-hydroxy-indole and 2,7-dicarbethoxy-1H,6H-pyrrolo[2,3-e]indole there were obtained corresponding amines and an oxime.Iv. Dzhavakhishvili State University, Tbilisi 380028. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1202–1205, September, 1994. Original article submitted September 15, 1994.