Intramolecular Electrophilic Cyclization Research Articles

Regioselectivity of Intramolecular Electrophilic Cyclization of 2-(Alkenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-ones with p-Methoxyphenyltellurium Trichloride

3-Phenyl-2-(prop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one reacted with 4-methoxyphenyltellurium trichloride in a regioselective manner to give angularly fused 1-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-4-oxo-5-phenyl-1,2,4,5,6,7,8,9-octahydrobenzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidinium chloride. Electrophilic cyclization of 2-(prop-2-en-1-ylsulfanyl)- and 2-(2-methylprop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-ones with 4-methoxyphenyltellurium trichloride afforded linearly fused 3-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-2,3,6,7,8,9-hexahydro-5H-benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one hydrochlorides. Regardless of the reactant ratio, the products were isolated as 1:1 complexes with 4-methoxyphenyltellurium trichloride.

Asymmetric Spirocyclization Enabled by Iridium and Brønsted Acid-Catalyzed Formal Reductive Cycloaddition

A catalytic, enantioselective spirocyclization of formanilides or formylindolines and enamides has been developed herein. The reaction proceeds through a sequential iridium-catalyzed hydrosilylatio...

Synthesis of 3‐Substituted Chalcogenophene‐Fused Indoles from 2‐Alkynylindoles

AbstractThe intramolecular electrophilic cyclization of 3‐organoselanyl‐2‐alkynylindoles providing the synthesis of 3‐iodo‐selenophene‐fused indoles is reported herein. The strategy was extended to the preparation of 3‐iodo‐thiophene‐fused indoles in a one‐pot iodine‐promoted thiolation of 2‐alkynylindoles, followed by an electrophilic cyclization sequence. Besides, the synthesis of 3‐butylselanyl‐selenophene‐fused indoles from 3‐butylselanyl‐2‐alkynylindoles was also developed using iron(III) chloride and dibutyl diselenide to promote the cyclization and functionalization of the heterocycle. The identification of the alkyl halide intermediate afforded evidence to the proposed mechanism, which indicated that the reactions proceed through the formation of an iodonium ion, followed by a selenium 5‐endo‐dig cyclization, to afford the indole derivatives. The 3‐iodo‐selenonophene‐fused indoles prepared were applied as substrates in copper‐catalyzed cross‐coupling reactions with thiols to give the Ullmann type products in good yields.magnified image

ELECTROPHILE CYCLIZATION OF N (S, Se)-ALKENYL DERIVATIVES OF PYRIMIDINONE WITH p-METOXYPHENYLTELLURIUM TRICHLORIDE

Pyrimidinone is a component of bioactive natural compounds such as uracil, thymine and cytosine. Pyrimidinone derivatives exhibit antitumor, antiviral and psychotropic properties. The heterocyclization of unsaturated pyrimidinetione derivatives produces condensed azolopyrimidines, which also exhibit a wide range of biological activity. The introduction а tellurium atom into such systems can increase their bioactivity. One of the most convenient and straightforward methods for introducing a tellurium atom is the electrophilic intramolecular cyclization method.The interaction between synthesized for the first time 3-methyl-2-thioxopyrimidin-4-one and p-methoxyphenyltellurium trichloride was carried out in glacial acetic acid at room temperature. It has been established that the electrophilic intramolecular cyclization of N-methallyl 2-thioxopyrimidine-4-one p-methoxyphenyltellurium trichloride takes place with the participation of a sulfur atom with the anelation of the thiazoline cycle to the pyrimidine system. As a result of reaction received 2,7-Dimethyl-2-{[dichloro(4-methoxyphenyl)-telluro]methyl}-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-5-one hydrochloride.The regioselectivity of the process of electrophilic cyclization with aryltelluriumtrichlotide was investigated on 2-S-alkenyl derivatives of 6-methylpyrimidin-4-one. It is shown that the reaction between aryltellurium trichloride and 2-thioalkenyl derivatives of 6-methylpyrimidin-4-one results in the formation of cyclization products with the involvement of a nitrogen atom at the third position of the pyrimidine. It is revealed that tellurofunctionalized thiazolinopyrimidines are formed in the form of complexes with aryltellurium trichloride. To study the effect of chalcogen on the regioselectivity of the process of electrophilic cyclization in reaction with p-methoxyphenyltellurium trichloride, a metalyl selenoether of 6-methylpyrimidin-4-one was used. It has been proved that 2-Se-methallyl N-1,3-unsubstituted pyrimidinone is cyclized by aryltellur trichloride to form a selenazolinopyrimidine system, which in turn allows to obtain potentially biologically active heterocycles with an endocyclic Selenium atom and an exocyclic Tellurium atom. The nature of chalcogen does not affect the direction of electrophilic intramolecular cyclization. The structure of obtained compounds were proved by NMR spectroscopy, IR spectroscopy and elemental analysis.

TO THE 70th ANNIVERSARY OF VASYL LENDEL

Vasyl Lendel was born on December 3, 1949 in the Volovets of Transcarpathian region. He has completed secondary education in Svalyava, graduating with honors Svalyava Polytechnic College in 1968. He has continued studies at the Faculty of Chemistry of Uzhhorod State University. He has graduated with honors in higher education in 1973.V.G. Lendel started his work via teaching chemistry at the Svalyava Polytechnic College, and in October 1973 he was invited to take the position of engineer of the Department of Organic Chemistry at UzhSU. In 1974-1977 he studied in graduate school at this department under the supervision of Professor Mygalin Yu.V. In 1977 he has become a head of the laboratories of the Department of Organic Chemistry of Uzhgorod State University.In June 1996, Vasyl Lendel heads the scientific-pedagogical staff of the Department of Organic Chemistry and is appointed to the position of the Dean of the Faculty of Chemistry of Uzh-horod State University, which he holds to this day.V.G. Lendel defends his thesis "Reactions of attachment of selenium tetrahalogens to 1,6-, 1,5-, 1,4-diolefins and their derivatives and properties of adducts obtained" and obtains the degree of candidate of chemical sciences in Taras Shevchenko State University of Kyiv in 1981. Later in 1982 he was elected to the position of assistant of the Department of Organic Chemistry, and in 1985 – Associate Professor of the Department of Organic Chemistry of Uzhhorod State University. He was conferred the academic title of Associate Professor in April 1987. For the cycle of scientific works in 2007 V.G. Lendel was awarded the degree of Doctor of Chemical Sciences.V.G. Lendel is a highly qualified specialist in the field of organic and element-organic chemistry. He heads a scientific school that studies the synthesis, chemical, physical, and biological properties of chalcogen-containing heterocyclic compounds. V.G. Lendel is studying the regio- and stereo-chemistry of electrophilic intra-molecular cyclization of unsaturated acyclic and heterocyclic compounds under the action of such electrophilic reagents as halogens, chalcogen halides. There are three defended PhD theses under his supervision; he fulfilled state budget grants and contractual grants, including foreign scientific projects. He has 624 scientific and teaching works, including about 400 publications in professional scientific journals, of which more than 50 publications are in journals included in science-metric databases. A large number of copyright author certificates and patents testify to the practical importance of his scientific research.He has been awarded the honorary title of "Excellence in Education of Ukraine", "Honored Worker of Higher Education", "Inventor of the USSR", "Honored Worker of Education of Ukraine" for his considerable achievements in work, high professionalism, personal contribution to the development of Ukraine and Transcarpathia. For his merits in scientific and pedagogical work he was awarded the Distinction of President of Ukraine, "Acknowledgment of the President of Ukraine", Anniversary Medal on the occasion of "10th Anniversary of Independence of Ukraine", Honorary Certificate of the Verkhovna Rada of Ukraine, Honorary Certificate of the NAS of Ukraine, Honorary Certificate of the MES of Ukraine, Silver Anniversary Order of the Ukrainian Technological Academy, For Merit industry and art”, the honors and thanks of the Transcarpathian Regional State Administration.

Synthesis of Indole-Fused Polycyclics via Rhodium-Catalyzed Undirected C-H Activation/Alkene Insertion.

A Rh(III)-catalyzed undirected C-H activation/alkene insertion to synthesize diversified indole-fused polycyclics has been developed. Intramolecular electrophilic cyclization generated a 3-indolyl rhodium species that went through an aryl-to-aryl 1,4-rhodium migration to realize the C-H activation. The subsequent [4 + 2] carboannulation or hydroarylation of alkenes could be achieved, respectively, by simply adjusting the additives of the reaction.

Intramolecular Electrophilic Cyclization Approach to 6-Substituted Naphtho[2,1- b]benzofurans: Novel Dual-State Emissive Fluorophores with Blue Emission.

A regiospecific synthesis of naphtho[2,1- b]benzofurans with a substituent at the C6 position was achieved via intramolecular 6-endo-dig electrophilic cyclization under acidic conditions to construct the central aromatic C ring. Screening of the synthesized compounds using a high-content imaging system enabled us to discover novel dual state emissive compounds 2{ 1,6}, 2{ 1,8}, and 2{ 4,3}, which are highly emissive with blue emission in their solid states as well as in solution states in most solvents. In addition, the compounds 2{ 4,3}, 2{ 4,12}, and 2{ 5,13} were found to be the most cell permeable in HeLa cells for live cell imaging with negligible phototoxicity.

TELLUROCYCLISATION OF CONDENSED N-ALKENYL DERIVATIVE 4-OXOPYRYMIDINE-2-TION

The derivatives of quinazolines and their fused analogues are promising objects for the rational design of biologically active compounds as prototypes for innovative medicines. This is due to the fact that the quinazoline fragment is a structural unit of many natural alkaloids. Electrophilic intramolecular heterocyclization is a promising method for the synthesis of fused derivatives of quinazoline.This research is devoted to the synthesis of new functionalized unsaturated condensed derivatives of quinazolin-4-one and the study of the regio chemistry of the process of electrophilic heterocyclization under the action of tellurium tetrachloride. The choice of such an electrophilic reagent is due to the fact that in recent years the organic synthesis of chalcogen-containing compounds, in particular, tellurium compounds that exhibit a wide range of biological activity, is increasingly developing.It was established that the electrophilic intramolecular cyclization of 3-alkenyl-2-thioquinazolin-4-one under the action of tellurium tetrachloride in an aqueous acetic acid medium at room temperature takes place with the participation of the alkenyl moiety and the exocyclic sulfur atom in the second position of quinazoline. As a result, thiazolidinequinazoline systems of linear structure were obtained. The structure and composition of the obtained tellurium-containing hydrochlorides has been proved by 1H, 13C NMR spectra and elemental analysis. In the PMR spectrum of hydrochlorides, signals of aliphatic cyclic methylene and methine groups and of the acyclic trichlorotellanylmethyl group are observed, which, together with the signals of aromatic protons, indicates on the formation of thiazolidinequinazolones. The absence of signals characteristic of the C=S group and presence of signals typical for the C-S bond in the 13C NMR spectra are in accord with the proposed structure of the cyclization products.Thus, we investigated the regio chemistry of the electrophilic intramolecular cyclization of 3-alkenyl-2-thioquinazolin-4-one under the action of tellurium tetrachloride. It was proved that the annelation of the thiazolidine cycle takes place with the participation of the sulfur atom in the second position of the pyrimidine, with the formation of tricyclic hydrochlorides of linear structure.

INFLUENCE HALOGEN IN REACTION ARYLTELLUR TRYHALOHENIDE ELECTROPHILIC CYCLIZATION OF N-ALKENYL OF 2-TIOXOBENZO (THIENO)PYRIMIDIN-4-ONES

It is known from the literature that electrophilic heterocyclization of unsaturated substrates under the action of aryltellurium trichlorides is widely used to obtain tellurium-containing polycondensed heterocyclic systems, whereas the use of p -alkoxyphenyltellurium tribromides in such reactions is almost not described. p -Ethoxyphenyltelluriumtribromide was used for study the influence of a halogen in the electrophilic aryltelluronium reagent on products' yields and on the direction of the electrophilic intramolecular cyclization of N-alkenyl-2-thioxobenzo(thieno)pyrimidine-4-ones. It was not possible to obtain this electrophile with the reaction of tellurium tetrabromide with benzene containing electron donating group, so it was synthesized by bromination of the corresponding ditelluride in chloroform medium. The interaction between tellurium-containing electrophile and N-alkenyl-2-thioxobenzo(thieno)pyrimidine-4-ones was carried out in glacial acetic acid at room temperature. It has been established that during aryltellurobromination of 3-allyl-quinazoline-2-thione and N-alkenyl thioxo-thieno-pyrimidinones, the annelation of the thiazoline ring takes place, with the formation of a linear condensed system with an exocyclic aryltellurium fragment – hydrobromides of 3-[dibromo(4-ethoxyphenyl)telluromethyl]-2,3-dihydro-5 H -[1,3]thiazolo[2,3-b]quinazolin-5-one, 2-(dibromo(4-ethoxyphenyl)-telluromethyl)-2,3,6,7,8,9-hexahydro-5 H -benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one and 2-methyl-2-(dibromo(4-ethoxyphenyl)-2,3,6,7,8,9-hexahydro-5 H -benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-5-one. The structure of the products of bromotelluro-cyclization is similar to the structure of products of aryltellurochlorination of the corresponding heterocycles. However, the yields of salts with the exocyclic bromoaryltellurium fragment are smaller compared to chloro- analogs. Lower yields of hydrobromides are associated with lower stability of intermediate bromotelluronium cation compared with chlorotelluronium, which is confirmed by theoretical calculations of Gibbs free energy of interaction of aryldihalidetellanium cation with an unsaturated substrate. Computations were performed using DFT level of theory in PRIRODA 17 program with using of GGA PBE functional and 3ζ basis set. The effect of solvent medium (acetic acid) was taken into account using the COSMO model with PM7 Hamiltonian in MOPAC2016 program. The composition and structure of all obtained compounds are proved by elemental analysis and NMR spectra.

ELECTROPHYLIC HETEROCYCLIZATION OF 5-METHYL-6-TIOXOPYRAZOLO[3,4-d]PYRIMIDINE-4-ON

Derivatives of pyrazolo[3,4-d]pyrimidine have valuable biological activity. The structural fragment of pyrazolopyrimidines is widely used to develop new effective pharmaceuticals. A new promising direction in the construction of polycyclic systems based on pyrazolopyrimidine is the method of electrophilic intramolecular heterocyclicization.The halogenation of 5-methyl-6-thioxopyrazolo[3,4-d]pyrimidin-4-one was carried out in acetic acid medium at room temperature with twice the excess of halogen. It was found that halogenation (with bromine and iodine) of 5-methyl-6-thioxopirazolo[3,4-d]pyrimidin-4-one results the annelation of the thiazolinic cycle with the formation of linear polynuclear systems of a salt-like structure. 7-Halogenomethyl-7-methyl-1,4,6,7-tetrahydropyrazolo[3,4-d][1,3]thiazolo[3,2-a]pyrimidin-4-one was obtained via the action of sodium sulfite in the DMSO-water medium.To study the effect of the nature of the electrophilic reagent on the direction of the electrophilic intramolecular cyclization of 5-methyl-6-thioxopyrazolo[3,4-d]pyrimidin-4-one the p-methoxyphenyltetrachloride was used (tested). Electrophilic heterocyclization take place under similar conditions (room temperature, glacial acetic acid medium), with the formation of the tricyclic system with an exocyclic aryltellurium moiety – 7-(dichloro-(4-methoxyphenyl) telluromethyl)-7-methyl-1,4,6,7-tetrahydropyrazolo[3,4-d][1,3]thiazolo[3,2-a]pyrimidin-4-one. Thus, the direction of electrophilic intramolecular cyclization of 5-methyl-6-thioxopyrazolo[3,4-d]pyrimidine-4-one using as electrophilic agents of halogens (bromine, iodine) and p-methoxyphenyltetrachloride does not depend on the nature of the electrophile and takes place with the participation of the exocyclic sulfur atom in the second position of the pyrimidine and lead to the formation of a condensed system of linear structure – halogenomethyl or aryl telluromethyl derivatives of pyrazolo[3,4-d][1,3]thiazolo[3,2-a]pyrimidin-4-one. The composition and structure of all synthesized compounds were proved by elemental analysis and 1H-NMR spectra.

The synthesis and structural functionalization of 6-substituted 2,3-dihydroimidazo[2,1-b] [1,3]thiazol-5-ones

Aim. To extend the synthetic limits of the reaction of the electrophilic intramolecular cyclization (EIC) on the examples of 5,5-disubstituted and 5-yliden substituted 3-allyl-2-thiohydantoins and the directed structural modification of 2-halogenomethyl-2,3-dihydroimidazo[2,1-b][1,3]thiazole-5-ones obtained. Results and discussion. It has been found that the cyclization of 5,5-disubstituted and 5-yliden substituted 3-allyl-2-thiohydantoins under the effect of polyphosphoric acid (PPA), bromine and iodine is an effective method for the synthesis of new 2,3-dihydroimidazo[2,1-b][1,3]thiazole-5-ones. The reaction of the nucleophilic substitution of their 2-halogenomethyl representatives was used to obtain a number of sulfur-containing derivatives and azides. The latter were tested in the reaction of [3+2]-cycloaddition with N-phenylmaleinimide and propargyl alcohol. Experimental part. A series of 2-substituted 2,3-dihydroimidazo[2,1-b][1,3]thiazole-5-ones was synthesized by the reaction of 5,5-disubstituted and 5-yliden substituted 3-allyl-2-thiohydantoins with PPA and halogens with the yields of 66-96 %. A directed modification of the halogenomethyl group of imidazotiazolones produced a series of sulfur-containing derivatives and azides with the yields of 63-93 %. The azides synthesized were used in the [3+2]-cycloaddition reaction with N-phenylmaleinimide and propargyl alcohol leading to 1,2,3-triazoloderivatives with the yields of 51-85 %; their structure was confirmed by the complex spectral analysis. Conclusions. A convenient method for the synthesis of 2-halogenomethyl-substituted imidazo[2,1-b][1,3] thiazoles, which are effective reagents for the directed structural modification by sulfur- and nitrogen-containing functional groups, has been developed.

Exploring Gold Catalysis in a 1,6-Conjugate Addition/Domino Electrophilic Cyclization Cascade: Synthesis of Cyclohepta[ b]indoles.

An effective method for the construction of the structurally complex fused cyclohepta[ b]indole core has been developed through an intermolecular 1,6-conjugate addition of indoles to 2-alkynyl p-quinone methides followed by an intramolecular electrophilic cyclization under oxophilic and alkynophilic gold catalysis.

The proton-initiated cyclization of N-alkylamides of styrylacetic acids. The synthesis of 5-arylpirrolidine-2-ones

Aim. To study the effect of the structural parameters of styrylacetic acid amides on the course of the reaction of the electrophilic intramolecular cyclization under the action of polyphosphoric acid and search the rational approaches to obtain N-unsubstituted 5-arylpyrrolidine-2-ones. Results and discussion. The literature sources related to the main methods of synthesis, as well as the biological activity of 5-arylpyrrolidine-2-ones, have been analyzed and systematized. The regiochemistry of the cyclization of N-unsubstituted and N-alkyl amides of styrylacetic acids has been studied using polyphosphoric acid (PPA). Experimental part. It has been found that N-unsubstituted styrylacetic acid amides when heating at 100 °C in PPA are cyclized to 5-arylpyrrolidine-2-ones with the yields of 44-58 %. For N-tert-butylamides with donor substituents in the styrenic moiety of the molecule the cyclization under similar conditions is accompanied with elimination of the N-alkyl fragment resulting in N-unsubstituted 5-arylpyrrolidine-2-ones with the yields of 50-95 %. Lactamization of N-benzylamide and N-isopropylamides under the action of PPA proceeds with formation of 1-alkyl-5-arylpyrrolidine-2-ones. Conclusions. It has been found that the proton-initiated cyclization of N-unsubstituted and N-tert-butylamides of styrylacetic acid with donor substituents in the styrene fragment in polyphosphoric acid when heating at 100 °C is a preparative convenient method for the synthesis of 1-unsubstituted 5-arylpyrrolidine-2-ones. A similar reaction of N-benzyl (isopropyl) amides leads to the preferential formation of 1-alkyl-5-arylpyrrolidine-2-ones.

A Dihydrodinaphthoheptacene.

We report the first example of a dihydrodinaphthoheptacene derivative and the mechanistic investigations of the regioselective electrophilic intramolecular cyclization reaction involved in the synthesis. The structural, electrochemical, and photophysical properties have been investigated.

Noval Route through O-C Bond Formation for the Synthesis of Diastereomeric 2, 4-Disubstituted Pyrano [2, 3-B] Quinolines from 3Formyl-2-Quinolones via Intramolecular Electrophilic Cyclization

Noval Route through O-C Bond Formation for the Synthesis of Diastereomeric 2, 4-Disubstituted Pyrano [2, 3-B] Quinolines from 3Formyl-2-Quinolones via Intramolecular Electrophilic Cyclization

Fused pyrimidine systems: XVII. Arylsulfenylation of 5-allylpyrimidine-4(3H)-one derivatives. Synthesis of arylsulfanyl-substituted 5,6-dihydrofuro[2,3-d]- and 6,7-dihydro-5H-pyrano[2,3-d]pyrimidines

5-Allylpyrimidine-4-ones react with arylsulfenyl chlorides in dichloromethane with the formation of 5-[(2-arylsulfanyl)-3-chloropropyl]-pyrimidine-4-ones that under the action of sodium acetate undergo cyclization into 6-arylsulfanyl-6,7-dihydro-5H-pyrano[2,3-d]pyrimidines. At performing similar reactions in nitromethane an intramolecular electrophilic cyclization occurs affording 6-[(arylsulfanyl)methyl]-5,6-dihydrofuro[2,3-d]pyrimidines.

Cyclization of β-hydroxyalkylphosphine oxides - Mechanism elucidation using experimental and DFT methods

β-Hydroxyalkylphosphine oxides undergo an intramolecular electrophilic cyclization reaction in strongly acidic media. The main product in cases where rearrangement of the starting β-carbocation is possible possesses the benzophosphorinane skeleton. To gain insight into the mechanism of this transformation, both experimental methods and DFT calculations have been used. The data show a clear dependence of the selectivity of the reaction on both the amount and the concentration of the acid. NMR experiments provided some insight into the transformation of the substrate whereas DFT calculations explain the preferential formation of benzophosphorinane skeleton.

Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: VIII. Cyclization of 4-aryl-N-(thiophen-3-yl)but-3-enamides by the action of polyphosphoric acid and chlorosulfanylarenes

Intramolecular cyclization of 4-aryl-N-(thiophen-3-yl)but-3-enamides on heating in polyphosphoric acid afforded 8-aryl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones and 5-aryl-1-(thiophen-3-yl)pyrrolidin-2-ones. Cyclofunctionalization of the title compounds with (chlorosulfanyl)benzene and 4-(chlorosulfanyl)-toluene led to the formation of 8-aryl-7-arylsulfanyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones or their mixtures with 5-aryl-4-arylsulfanyltetrahydrofuran-2-ones. 1-(Chlorosulfanyl)-4-nitrobenzene reacted with 4-(4-methylphenyl)-N-(thiophen-3-yl)but-3-enamide and 4-(4-fluorophenyl)-N-(thiophen-3-yl)but-3-enamide to give 5-(4-methylphenyl)-4-(4-nitrophenylsulfanyl)-1-(thiophen-3-yl)pyrrolidin-2-one and 5-(4-fluorophenyl)-4-(4-nitrophenylsulfanyl)tetrahydrofuran-2-one, respectively.

Dimethyl Sulfoxide and N-Iodosuccinimide Promoted 5-exo-dig Oxidative Cyclization of Yne-Tethered Ynamide: Access to Pyrrolidones and Spiro-pyrrolidones.

An unprecedented metal-free dimethyl sulfoxide (DMSO) and N-iodosuccinimide mediated regioselective 5-exo-dig oxidative cyclization of an in situ generated enol equivalent of amides from ynamides bearing internal alkynes is demonstrated. The reaction allows easy access to functionalized pyrrolidone skeletons. Pyrrolidones having 3-o-biaryl motifs successfully undergo intramolecular electrophilic cyclization with the α,β-unsaturated olefin, furnishing spiro-pyrrolidone motifs. A one-pot sequential 5-exo-dig cyclization of the yne-tethered ynamides, followed by electrophilic cyclization of the pyrrolidone, is presented. The role of DMSO in the transformation is clarified, and a tentative reaction pathway is proposed.

Polycyclic systems with the pyridopyrimidine and pteridine nuclei

The literary sources relating to the methods for obtaining polycyclic compounds with pyridopyrimidine and pteridine subunits have been systematized and analyzed. The synthetic potential of two main approaches to the processes of formation of these types of structures has been revealed: 1) annelation of the fused pyrimidine rings to the pyridine or diazine nuclei; 2) cyclization based on functional derivatives of fused pyrimidines. It has been shown that the core structures for implementation of the first approach are usually amino(iso)nicotinic acids, heteroaromatic halogen acids, isotiocyanatopyridine carboxylates, 1H-pyrido[2,3-d][1,3]oxazine-2,4-diones and 2-amino derivatives of pyridines or diazines. The convenient tools for formation of a fused pyrimidine ring such as the cross-coupling reaction by Buchwald-Hartwig through amination of haloarenes, the radical cascade cyclization of N-acylcyanamides and the intramolecular reaction of aza-Wittig have been described. The second approach focuses on the cycle formation processes involving hydrazinopyrimidines, 2-aminopyridopyrimidines and 2-thioxopyridopyrimidones. It has been noted that the electrophilic intramolecular cyclization under the action of halogenarylchalcogenides and mineral acids is an important factor for the directed synthesis of polycyclic systems based on alkenyl fused pyridopyrimidones or pteridones. In this review a considerable attention is paid to structures that exhibit pronounced biological effects.