Synthesis of tryptamines by the Fischer method using synthetic precursors and latent forms of amino-butanal (review)

Information on the synthesis of tryptamines using the Fischer reaction is reviewed. A comparative analysis is made of the methods of production and the reactivity of the various synthetic precursors and latent forms of aminobutanal — the carbonyl component in the synthesis of tryptamines by the Fischer method. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 493–538, April, 2008.     

The Grandberg reaction in the synthesis of biologically active compounds

The review is focused on the Grandberg synthesis, namely, the synthesis of tryptamines from arylhydrazines and γ-halocarbonyl compounds, as an exceptionally useful and efficient methodology to access biologically active indole heterocycles.     

Indolylalkylamines from arylhydrazines and γ- or δ-halocarbonyl compounds (review)

A series of papers devoted to the synthesis of tryptamines and related structures (tryptophols, homotryptamines, eserines, azatryptamines, etc.) from halocarbonyl compounds and arylhydrazines are correlated. The data on the mechanism of the reaction can be successfully applied to the Fischer indole synthesis.     

Palladium-catalyzed synthesis of tryptamines and tryptamine homologues: synthesis of psilocin

A new Pd-catalyzed method for the synthesis of tryptamines is developed, and its applications to the synthesis of Corey's aspidophytine tryptamine 15 and psilocin 20 are also described.     

Enantioselective Synthesis of 3a‐Amino‐Pyrroloindolines by Copper‐Catalyzed Direct Asymmetric Dearomative Amination of Tryptamines

A direct asymmetric dearomative amination of tryptamines with O‐(2,4‐dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr‐bisoxazoline complex as a catalyst, affording 3a‐amino‐pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (?)‐psychotriasine in a highly concise manner.     

Investigations into the mechanism of lactamization of lactones yielding in a novel route to biologically active tryptamine derivatives

The mechanism of lactamization of corresponding lactones was investigated by means of gas chromatography and synthesis of possible intermediates as references. Lactones react with amines via the amino acid with subsequent elimination of water to the corresponding lactams. In the first step, also hydroxyamides are in equilibrium with the lactones and amines, respectively, which are not able to form the amide though. This mechanism opens a new approach for the synthesis of N^β-disubstituted tryptamines.     

Synthesis of 5-(Sulfamoylmethyl)indoles by Mild Negishi Coupling and Their Application in Almotriptan

A new synthetic route of almotriptan was described. The application of Negishi coupling reaction simplified the process and significantly improved the yield. The synthetic route was also expected to be general for the synthesis of other tryptamines like sumatriptan and avitriptan.     

Stereoselective oxidative rearrangement of 2-aryl tryptamine derivatives

The oxidation of 2-aryl tryptamines followed by a stereoselective rearrangement provides a versatile strategy for the synthesis of C3-quaternary oxindoles bearing a C3-aryl group. Treatment of optically active 2-aryl hydroxyindolenines with scandium trifluoromethanesulfonate in toluene at 110 degrees C leads to complete and stereoselective isomerization to the corresponding C3-aryl oxindoles which represent versatile intermediates for the synthesis of C3a-aryl hexahydropyrroloindoles.     

Synthesis of substituted tryptamines and their homologs: A new aspect in the Fischer reaction

A number of cyclic imines and amino ketones were studied as the starting material for indole synthesis. Amino ketone arylhydrazones are key intermediates undergoing the Fischer rearrangement; the possibility of the reaction is determined by the structure of an amino carbonyl compound. A convenient one-step method for the synthesis of indolylalkylamines allowed tryptamines and their homologs to be obtained in high yields. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1186–1194, May, 2005.     

Synthesis of some new fluorine containing 3-dialkylaminomethyl indoles, 3-indolylglyoxamides and tryptamines

Several new 2-(fluoroaryl)-3-dialkylaminomethylindoles, 3-acetyl-2-(fluoroaryl)-indoles, 2-(fluoroaryl)-3-indolylglyoxamides and corresponding tryptamines have been prepared as possible psychopharmacological agents. 2-(Fluoroaryl)-indoles have been synthesized by theFischer indole synthesis. 2-(Fluoroaryl)-indoles on treatment with oxalyl chloride and subsequent reaction with amines, gave 2-(fluoroaryl)-3-indolylglyoxamides. Some of these indolylglyoxamides were reducted with lithium aluminium hydride, to the corresponding tryptamines. 2-(Fluoroaryl)-indoles when subjected toMannich reaction afforded 3-dialkylaminomethyl-2-(fluoroaryl)-indoles. All these new compounds have been characterized by IR spectral studies.Possible Psychopharmacological Agents, Part XII, Part XI, J. Indian. Chem. Soc.57, 423 (1980).     

Indoles

The formation of tryptamines instead of the usual Fischer cyclization is observed when salts of arylhydrazines are heated with -halo carbonyl compounds. Bisulfite derivatives of -halo carbonyl compounds with both arylhydrazines themselves and with their salts can also be used in the synthesis of the tryptamines.For Communication XLV see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1085–1088, August, 1974.     

A direct synthesis of β-carbolines via a three-step one-pot domino approach with a bifunctional Pd/C/K-10 catalyst

A rapid, microwave-assisted synthesis of β-carbolines via a successive condensation/cyclization/dehydrogenation approach is described. This methodology involves the coupling of various tryptamines with aromatic aldehydes/glyoxals. The product imine undergoes a Pictet-Spengler cyclization followed by a final dehydrogenation to yield β-carbolines in a three-step domino reaction. The use of the bifunctional catalyst Pd/C/K-10 combined with microwave irradiation enabled the synthesis of β-carbolines in short reaction times and in good to excellent yields.     

Direct Synthesis of Structurally Divergent Indole Alkaloids from Simple Chemicals

A direct and structurally divergent synthesis of indole alkaloids from very simple 2‐vinylanilines, alkynes and TBN via a novel substrate fragmentation/cycloaddition strategy has been developed, which provides an efficient noble‐metal‐free approach to access a library of highly valuable indole derivatives of tryptamines and tryptamine‐related oximes, lactams, and lactones, as well as β‐carbolines, spiroindolines, and hexa‐hydropyrrolo[2,3‐b]indoles.     

Application of iridium catalyzed allylic substitution reactions in the synthesis of branched tryptamines and homologues via tandem hydroformylation-Fischer indole synthesis

Combination of enantioselective allylation reactions with a tandem hydroformylation-Fischer indole synthesis sequence as a highly diversity-oriented strategy for the synthesis of tryptamines and homologues was explored. This modular approach allows the substituents at C3 of the indole core, the type of the amine moiety, and the distance of the amine moiety to the indole core in the final synthetic step to be defined. The starting materials required for the hydroformylation step were synthesized via iridium catalyzed enantioselective allylic substitution reactions in high yields and excellent enantioselectivities. The Rh catalyzed hydroformylation step in the presence of phenyl hydrazine, allows the in situ formed aldehyde to be trapped as the hydrazone. Subsequent acid catalyzed indolization furnishes the desired indole structures in moderate to good yields.     

Indole derivatives. 125. Synthesis of disubstitutep tryptamines

Disubstituted tryptamines, containing methyl, methoxy, nitro, and amino groups, chlorine, and bromine in the benzene ring, were synthesized. The influence of substituents on the course of individual stages of synthesis was noted.For communication 124, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1093–1100, August, 1984.     

Enantioselective Construction of Pyrroloindolines via Chiral Phosphoric Acid Catalyzed Cascade Michael Addition-Cyclization of Tryptamines

Enantioselective construction of pyrroloindolines via chiral phosphoric acid catalyzed cascade Michael addition-cyclization of tryptamines has been realized. With 5 mol % of chiral phosphoric acid, enantioenriched pyrroloindoline derivatives were obtained in good yields and enantioselectivity (up to 95% yield and 83% ee) from readily available tryptamines and enones.     

Synthesis of tryptamines containing a sulfo group in the benzene ring

It has been shown that sulfophenylhydrazines can be used successfully in a single stage synthesis of tryptamines from arylhydrazines and -chlorocarbonyl compounds.K. A. Timiryazev Agricultural Academy, Moscow 127550, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 623–624, May, 2000.     

One‐Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides

A general and efficient one‐pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper‐catalyzed alkyne and azide cycloaddition to N‐sulfonyl‐1,2,3‐triazole, rhodium‐catalyzed selective insertion of α‐iminocarbenes onto the C3?H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH₃ or palladium catalyst, in one‐pot. The reaction also showed excellent functional‐group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one‐pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro‐β‐carboline and tryptoline.     

A Brønsted Acid Catalyzed Cascade Reaction for the Conversion of Indoles to α-(3-Indolyl) Ketones by Using 2-Benzyloxy Aldehydes

A Brønsted acid catalyzed, operationally simple, scalable route to several functionalized α-(3-indolyl) ketones has been developed and the long-standing regioisomeric issue has been eliminated by choosing appropriate carbonyls. A readily available and cheap bottle reagent was used as the catalyst. This protocol was also applicable to the synthesis of densely functionalized α-(3-pyrrolyl) ketones. A detailed mechanistic study confirmed the involvement of enolether as a reaction intermediate. Several postsynthetic modifications along with easy access to β-carboline, tryptamines, tryptophols, and spiro-indolenine proclaim the synthetic utility of this powerful building block. On the basis of this concept, functionalized carbazoles were constructed by a cascade annulation strategy.