Use of the Pictet-Spengler reaction for the synthesis of 1,4-disubstituted-1,2,3,4-tetrahydro-β-carbolines and 1,4-disubstituted-β-carbolines: formation of γ-carbolines

Microwave-assisted conjugate addition of indole on nitro-olefins furnished nitro compounds, which were reduced to tryptamines. Further, by using Pictet-Spengler condensation, new 1,4-disubstituted-1,2,3,4-tetrahydro-β-carbolines were synthesized in diastereoselective manner. Dehydrogenation of the tetrahydro-β-carbolines produced new 1,4-disubstituted-β-carbolines. As a new observation, in some of the cases, Pictet-Spengler condensation and dehydrogenation gave two products, namely 1,4-disubstituted-β-carbolines and 1,4-disubstituted-γ-carbolines. A mechanism is proposed for this observation.     

o-Benzenedisulfonimide as a reusable acid catalyst for an easy, efficient, and green synthesis of tetrahydroisoquinolines and tetrahydro-β-carbolines through Pictet-Spengler reaction

The synthesis of tetrahydroisoquinolines and tetrahydro-β-carbolines, using the Pictet-Spengler reaction, was carried out in the presence of a catalytic amount of o-benzenedisulfonimide, which worked as a Brønsted acid organocatalyst. The reaction conditions were mild and green and good target product yields were achieved. The catalyst was easily recovered and purified, ready to be used in further reactions with economic and ecological advantages.     

α-Trifluoromethyl-β-aryl enamines in the synthesis of trifluoromethylated heterocycles by the Fischer and the Pictet-Spengler reactions

α-Trifluoromethyl-β-aryl enamines were successfully used as synthetic equivalents of benzyltrifluoromethyl ketones in both the Fischer indole synthesis and the Pictet-Spengler reaction. Accordingly, 2-trifluoromethyl indoles and a variety of trifluoromethylated 4,5,6,7-terahydro-1H-pyridines including carbolines were synthesized in moderate to good yields.     

β-(Cycloalkylamino)ethanesulfonyl azides as novel water-soluble reagents for the synthesis of diazo compounds and heterocycles

Chemistry of Heterocyclic Compounds - Novel water-soluble sulfonyl azides were synthesized, which are basic by nature. The obtained compounds were used as donors of the diazo group in the diazo...     

A versatile route to the synthesis of 1-substituted β-carbolines by a single step Pictet-Spengler cyclization

A one-step conversion of l-tryptophan and activated aldehydes (1,2-dicarbonyl compounds) directly to 1-substituted β-carbolines without formation of the tetrahydro derivatives under modified Pictet-Spengler conditions was described. Moreover, a practical application for the synthesis of a natural 1-substituted β-carboline, luzongerine A, isolated from Illigera luzonensis was also successfully carried out utilizing this protocol. The effects of synthetic compounds 11 and 11a on nitric oxide (NO) production in LPS/IFN-γ stimulated RAW 264.7 macrophage cells were evaluated in vitro. They displayed significant dose-dependent inhibition of inducible nitric oxide synthase (iNOS).     

Aza-Michael reaction as an efficient method for the synthesis of first representatives of β-azahetaryl-β-diphenylphosphorylalkanones

Aza-Michael reaction of (E)-4-(diphenylphosphoryl)but-3-en-2-one (1) with a number of mono-and bicyclic nitrogen heterocycles proceeds regioselectively in the absence of catalysts with the formation of corresponding β-azahetaryl β-diphenylphosphoryl ketones; in the case of imidazole, the presence of chiral organic catalysts allows one to increase the yields of the adducts and to obtain them in enantiomerically enriched form.

     

One pot synthesis of novel α,β-dichloro-β-trifluoromethylated enones and their application to the synthesis of trifluoromethylated heterocycles

Trifluoropropynyllithium was reacted with 1 equiv of Weinreb benzamides in THF at −78 to 0 °C, followed by treatment with 4 equiv of trifluoromethanesulfonyl chloride to give α,β-dichloro-β-trifluoromethylated enones 1 in 61-68% yield. The reactions of 1a with substituted amidines or hydrazines in refluxing 1,4-dioxane-CH₃CN afforded trifluoromethylated chloropyrimidines 3 and chloropyrazoles 6 in 58-98% yields. The microwave-assisted coupling reactions of 3 with substituted phenylstannane and allylstannane in refluxing CH₃CN in the presence of Pd(PPh₃)₄ provided the corresponding phenyl and allyl substituted pyrimidines 4 in 89-98% yields.     

Diastereotopic synthesis of 1- and 1,1-substituted 4-phenyl-2,3,4,9-tetrahydro-1H-β-carbolines

A diastereotopic Pictet—Spengler reaction was performed to form previously unknown 1- and 1,1-substituted 4-phenyl--carbolines based on -phenyltryptamine, aldehydes of various structure, and isatins. It has been demonstrated that the predominant diastereomers of the prepared -carbolines have the (R*,R*) configuration. The diasteroselectivity (de) of the reaction varies from 44 to 88%.Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 481–485, November–December, 2004.This revised version was published online in April 2005 with a corrected cover date.     

Highly stereoselective and efficient synthesis of ω-heterofunctional di- and trienoic esters for Horner-Wadsworth-Emmons reaction via alkyne hydrozirconation and Pd-catalyzed alkenylation

In situ OH metalation with ⁱBu₂AlH and hydrozirconation with HZrCp₂Cl of HOCH₂CCH, (E)-HOCH₂CHCHCCH, and HOCH₂CCCH₃ followed by Pd-catalyzed alkenyl-alkenyl coupling with (E)-BrCHCHCO₂Et and (E)-BrCHC(Me)CO₂Et using PEPPSI-IPr (7) as a catalyst provides a highly efficient and selective (?98% all-E) route to ω-hydroxy di- and trienoic acid esters (1a-6a). The corresponding phosphonate esters (1c-4c) of ?98% isomeric purity can be obtained via conventional bromination-phosphonation in >80% yields. As expected, their carbonyl olefination is ca. 85-90% E-selective with alkyl aldehydes but ?98% E-selective with PhCHO and some α,β-unsaturated aldehydes under the conditions used.     

Simple and efficient protocol for the synthesis of benzoxazole,benzoimidazole and benzothiazole heterocycles using Fe(Ⅲ)–Schiff base/SBA-15 as a nanocatalyst

Benzimidazoles, benzoxazoles, and benzothiazoles derivatives were synthesized from condensation of aldehydes and 1,2-phenylenediamine or ortho-aminophenol or ortho-aminothiophenol in the presence of catalytic amount of Fe(Ⅲ)–Schiff base/SBA-15 in water medium. Short reaction times, good to excellent yields, easy availability, reusability, and use of an eco-friendly catalyst are some of the significant attributes of the present method.     

Intramolecular Diels–Alder reaction for the synthesis of tetracyclic carbazoles and isocanthines

One pot intramolecular Diels–Alder reaction has been efficiently used as a new route for the synthesis of four tetracyclic carbazoles and four isocanthine analogues where a dialdehyde is utilised as a common intermediate for both the scaffolds. Biological activity was evaluated for some molecules, which demonstrated moderate activity against HeLa cervical cancer cell lines.     

Intramolecular palladium-catalysed enolate arylation of 2- and 3-iodoindole derivatives for the synthesis of β-carbolines, γ-carbolines, and pyrrolo[3,4-b]indoles

The palladium-catalysed intramolecular α-arylation of carbonyl compounds with amino-tethered 2- and 3-iodoindoles provides a useful methodology for the synthesis of indolo-b-fused nitrogen heterocycles. A variety of substituted tetrahydro β- and γ-carbolines, and pyrrolo[3,4-b]indoles, have been prepared by means of this palladium-catalysed annulation process.     

An efficient synthesis of styryl 1,3,4-thiadiazoles using Lawesson’s reagent and Propylphosphonic anhydride-precursors for bis heterocycles

The compounds styryl 1,3,4-thiadiazoles were prepared adopting one and two step methodologies to optimize the yield of the products. The two-step methodology via benzohydrazide followed by treatment with Lawesson’s reagent in the presence of Propylphosphonic anhydride and triethylamine produced styryl 1,3,4-thiadiazoles in excellent yields. The olefin moiety in these compounds is utilized to develop pyrazole and isoxazole rings by 1,3-dipolar cycloaddition methodology followed by oxidation.     

Suzuki–Miyaura cross-coupling reaction of aryl and heteroaryl pinacol boronates for the synthesis of 2-substituted pyrimidines

Suzuki–Miyaura cross-coupling reaction with 2-heteroarylboronic acids is generally challenging due to these acids easy decomposition. To overcome this problem, we developed a coupling method that uses 2-heteroaryl pinacol boronates in the presence of 1.0 mol % Pd(OAc)₂ and 2.0 mol % S-Phos with 4 equiv amount of LiOH in dioxane and H₂O at 80 °C for 30 min. This developed method allowed for the synthesis of a wide variety of 2-heteroaryl pyrimidines from 2-chloropyrimidyl derivatives in high yields, and is also useful in the preparation of various biaryl derivatives from heteroaryl chlorides.     

Methods for the synthesis of chiral sulfur heterocycles and their application in the asymmetric Baylis–Hillman reactions

Enantiomerically pure (2S,6S)-2,6-diphenyltetrahydro-2H-thiopyran, (2S)-2-phenyltetrahydro thiophene, and (2S)-2-phenyltetrahydro-2H-thiopyran were prepared in 70–72% yields and with 86–99% ee via cyclization of the corresponding dimesylate in an S_N2 cyclization reaction using sodium sulfide nonahydrate. The results on the application of various chiral sulfides in asymmetric Baylis–Hillman reactions are also described.     

Efficient synthesis of 3-arylbutadiene sulfones using the Heck–Matsuda reaction

An efficient and practical method for a scalable synthesis of 3-arylbutadiene sulfones deals with the ligand-free Heck–Matsuda reaction of sulfolene with aryldiazonium tetrafluoroborates followed by triethylamine-promoted double bond shift.     

Copper-catalyzed oxidative coupling of carboxylic acids with formamides for the synthesis of α,β-unsaturated amides

A novel and efficient protocol for the synthesis of α,β-unsaturated amides has been developed using catalytic amount of Cu(OAc)₂ and TBHP as an available oxidant. Oxidative coupling of various unsaturated carboxylic acids with N,N-disubstituted formamides was examined to furnish the desired products in good yields.     

Study on the alkylation reaction of guanine and N-acetylguanine and the synthesis of 1''''-C alkylated carba-DHPG analogues

The alkylation reaction of guanine and N-acetylguanine with model compounds such as isopropyl bromide or 4-heptyl tosylate were studied. The reaction conditions such as temperature, solvent, base, and catalyst were examined for their effects on the reaction rate, and the yield and regioselectivity of the coupling reaction. The highest yield was obtained by using DMSO as the solvent. The reaction proceeded in a homogenous manner to give higher yield of 9-N and 7-N substituted product in a mole ratio of 1:1. The ratio could be raised to 2:1 if dibenzo-18-crown-6 was used as a catalyst. Using the above procedure, three carba-DHPG analogues bearing different 1'-C alkyl side chains were synthesized.