Electronic regioselectivity in the reactions of pyridinium ylides with tetracyanoethylene

Highly regioselective reactions of pyridinium ylides with tetracyanoethylene occur via an Ad_N-E mechanism to form Z-isomers of 3-aroyl-3-(1-pyridinio)-1,1,2-tricyano-2-propenides-1, corresponding in structure to 1,4-ylides with maximum charge separation. If the unsaturated nitrite starting material contains a nucleofugal group 1,2-elimination predominates over 1,3-elimination.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1087–1094, August, 1991.     

Preparation of new nitrogen-bridged heterocycles. 49. A new access to thieno[3,4-b]indolizine derivatives

The title compounds, together with 3-vinylindolizine-1-carbonitriles (4-56%), were prepared in 1-18% yields from the S-alkylation of pyridinium 1-[3-ethoxycarbonyl-1-[cyanomethylthio(thiocarbonyl)]]all ylides with alkyl halides, followed by treatment of the resulting pyridinium salts with a base and then a dehydrogenating agent. In several reactions of pyridinium salts obtained from reaction of the allylides with benzylic halides, trace amounts of bis[1-cyano-9-(ethoxycarbonyl)thieno[3,4-b]indolizin-3-yl] disulfides with an interesting superimposed structure were also isolated. The structures of these compounds were confirmed by X-ray analyses.     

Preparation of 2‐Amino‐1,3‐butadienes as N‐Pyridine Derivatives

2‐Amino‐1,3‐butadienes as pyridine derivatives have been prepared from corresponding dihydrothiazolo[3,2‐a]pyridinium salts in reactions with a strong base. The pyridinium salts were prepared from pyridine‐2(1H)‐thiones and trans‐1,4‐dibromo‐2‐butene by a vicinal and chemoselective formation of 3‐vinyldihydrothiazolo[3,2‐a]pyridinium salts. A strong base was used for selective proton removal from the vinyl‐substituted 3‐position. A subsequent ring opening provided 2‐substituted 1,3‐butadienes with the azine appended at the annular nitrogen. Simple S‐alkylation yielded a corresponding azinium salt, thereby introducing electrophilic character to the 1,3‐butadiene system. Hydrolysis of the sulfide function provided the corresponding pyridin-2(1H)‐one attached to the 1,3‐butadiene in the 2‐position.     

Electrochemical reductions of substituted pyridinium 2-pyridylcarbonylmethylides,their Pt(II) complexes,and substituted n-(2-pyridylcarbonyl)methylpyridinium perchlorates

The title pyridinium salts and pyridinium ylide-platinum(II) complexes have been reduced through a one-electron process at more positive potentials by 0.3 $\text{\$}\text{?}$0.6 V than the corresponding ylides. Both the reduced pyridinium salts and Pt(II)-ylide complexes reacted with dioxygen, followed by elimination of the N-methylene and ylide protons to form pyridinium ylides and Pt(II)-pyridinium ylide complexes containing the three-coordinate ylide carbon atom, respectively.     

Etude de la reactivite d'ylures de sulfonium et de pyridinium stabilises par un groupement cyanoformyle

The sulfonium and pyridinium ylides stabilized by a cyanoformyl group, in an acidic medium, lead to sulfonium and pyridinium salts which are equivalents of pyridinium or sulfonium ketene salts. This originality has been used to prepare new stabilized ylides, or derivatives of substituted arylacetic acids or 4-hydroxy thiazoles.     

Regio- and stereoselectivity of the reactions of pyridinium and picolinium salts and ylids with nitriles containing a nucleofugic group

The reaction of pyridinium, 2-picolinium, and 3-picolinium ylids with tetracyanoethylene, ethoxymethylenemalononitrile, and (dimethylthio)methyl-enecyanamide in the presence of organic bases proceeds regio- and stereo-selectively to give substituted pyridinium 1,4-ylids, 2-(2-propen-1-ylidene)-1,2-dihydropyridines, and 5-(1-pyridino)pyrimidin-4-olates, respectively. The reaction of 1-phenacylpyridinium bromide and tetracyanoethylene leads to 1-phenacylpyridinium tricyanoethenolate.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 939–942 April, 1990.     

Synthesis of substituted disulfonyl-containing polycyclic azines with the bridgehead nitrogen atom. Effects of the structure of 3-substituted pyridinium ylides on the regioselectivity of their reactions with <Emphasis Type="Italic">E</Emphasis>-1,2-di(alkylsulfonyl)-1,2-dichloroethenes

Heating the substituted pyridinium and isoquinolinium salts with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes in either chloroform or acetone in the presence of three-fold excess of Et₃N gave high yields of substituted 1,2-di(alkylsulfonyl)indolizines and 1,2-di(alkylsulfonyl) pyrrolo[2,1-a]isoquinolines, respectively. Effects of the structure of 3-substituted pyridinium ylides on the regioselectivity of their reaction with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes were revealed. It was shown that the presence of electron-releasing and electron-withdrawing substituents in the pyridinium ylide favors the formation of 8-substituted and 6-substituted 1,2-(dialkylsulfonyl)indolizines, respectively.     

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment

We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp³) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing—rather than thermolyzing—these reagents.     

Synthesis and characterization of bromonium ylides and their unusual ligand transfer reactions with N-heterocycles

Stable aliphatic bromonium ylides (RfSO2)2C--Br+C6H4-p-CF3 (Rf = CF3, CF3(CF2)3) have been synthesized and structurally characterized for the first time. X-ray crystallographic analyses indicated a ylide structure with an sp2 hybridization of the ylide carbanions and with little double-bond character for the ylidic bond. The bromonium ylides selectively undergo transfer of the aryl group to nitrogen heterocycles, such as pyridines, yielding N-arylpyridinium salts. This is in a marked contrast to the reaction of the iodonium ylides, which produces pyridinium ylides through transylidations.     

Etude des reactions des diazoderives avec les cycloimmonium ylures-I : Action des sels de diazonium sur quelques pyridinium - ylures

The synthesis of cycloimmonium salts of the type $\text{7}$, $\text{8}$ and the corresponding cycloimmonium ylides $\text{9}$, $\text{10}$ are reported. In the reaction with diazonium salts $\text{11}$, $\text{12}$ the pyridinium monosubstituted carbanion ylides $\text{9}$, $\text{10}$ give the pyridinium disubstituted carbanion ylides $\text{17}$ – $\text{20}$. These are new types of isolable stable ylides. The synthesis involves the formation “in situ” of ylides $\text{9}$, $\text{10}$ which are bonded by their nucleophile ylide carbon atom to the nitrogen atom in diazonium salts. The intermediat formation of cycloimmonium salts $\text{13}$ – $\text{16}$ must be accepted. The structures of all compounds presented in this paper have been established by using elementary analysis, IR and ¹H-RMN spectra.     

Intramolecular photocyclization of N-[(2-haloaryl)methyl]pyridinium and n-(arylmethyl)-2-halopyridinium salts

Various N-[(2-haloaryl)methyl]pyridinium, N-(arylmethyl)-2-halopyridinium and N-(2-halobenzyl)iso-quinolinium salts have been synthesized and their intramolecular photocyclization reactions studied. Upon irradiation the aqueous solution of N-[(2-haloaryl)methyl]pyridinium, and N-arylmethyl-2-halopyridinium salts 1, 2 were cyclized to give isoindolium salts. In contrast to the pyridinium salts 1, 2 , the aqueous solution of N-(2-halobenzyl)isoquinolinium salts 3 appear not to undergo photocyclization. N-Benzyl-2-chloropyridinium salts 1c is more reactive than N-(2-chlorobenzyl)pyridinium salt 1a in the photocyclization. N-(2-Chlorobenzyl)-2-chloropyridinium salt 1d is three times more reactive than 1c . A mechanism of π-complex formation of the halogen moiety of the pyridinium ring with the phenyl ring is suggested for the reactive pyridinium salt. The triplet energy of the isoquinolinium salts 3 is tool low to photocyclize.     

Stereoselective synthesis of and atropisomerism in 4-pyridyl-3-(1-pyridinio)-3,4-trans-1,2,3,4-tetrahydropyridines and their transformation products

A series of 2-oxo-4-pyridyl-3-(1-pyridinio)-5-cyano-3,4-trans-1,2,3,4-tetrahydropyridine-6-6-olates were prepared by condensation of pyridinium ylides with α,β-unsaturated carbonyl compounds or more conveniently by a three-component condensation of pyridinium ylides, pyridine aldehydes, and ethyl cyanoacetate 3 and/or 6 . This analogues of the above tetrahydropyridines were prepared in a similar way starting from suitable substrates. Spectroscopic data revealed that the reaction leads to trans-isomers around the C³-C⁴ bond and is atroposelective. The conformation of and tautomerism in the tetrahydropyridines are discussed in the light of ¹H NMR data. The reaction of 5-cyano-3-(3-methyl-1-pyridinio)-2-oxo-4-(3-pyridyl)-1,2,3,4-tetrahydropyridine-6-thiolate 10c with phenacyl bromide was found to give 3-hydroxy-5-oxo-7-(3-pyridyl)-6-(3-methyl-1-pyridinio)-3-phenyl-8-cyano-6,7-trans-2,3,6,7-tetrahydrothiazol[3,2a]pyridine bromide, the crystal and molecular structure of which has been determined by X-ray crystallographic analysis.     

Regio- and stereoselective synthesis of tetrahydroindolysines,tetrahydropyridin-6-olates,and cyclopropanes from pyridinium ylides and unsaturated nitriles

The regio- and stereoselectivity of the reactions of pyridinium ylides with unsaturated nitriles are dependent on the electronic nature of the substituent in position 3 of the pyridine ring. The reaction of 1-carbamoylmethylide-3-cyanopyridinium with arylmethylenemalononitriles or arylmethylcyanoacetic esters proceeds regio- and stereoselectively with the formation of substituted 2-aryl-3-carbamoyl-6-cyano-2,3-trans- or 2,3-cis-1,2,3,8a-tetrahydroindolysines. The condensation of pyridinium 1-carbamoylmethylide with arylmethylenecyanoacetic ether leads to 4-aryl-2-oxo-3-(1-pyridinio)-5-cyano-3,4-trans-1,2,3,4-tetrahydropyridin-6-olates. The reaction of pyridinium (3-methylpyridinium) 1-carbamoylmethylide with arylmethylenemalononitriles results in the formation of 2-aryl-1,1-dicyano-3-carbamoyl-3-(1-pyridinio)- or (3-methyl-1-pyridinio)-1-propanides, which undergo stereoselective 1,3-transelimination with the formation of 3-aryl-1,1-dicyano-2-carbamoylcyclopropanes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 146–155. January, 1991.     

The Synthesis and Reactions of 1-(2-Propynyl)pyidinium Salts

The synthesis of 1-(2-propynyl)pyridinium salts 3 described. Compounds 3 react with a second pyridine molecule, in the presence of the corresponding hydrochloride, to form products of type 4, Certain bases cause the 1-(2-propynyl)pyridinium salts 3 to rearrange into 1-propadienylpyridinium salts. 5 . Diethylamine converts compounds 3 into 1-acetonylpyridinium salts 8 . Moreover, treatment of 3 or 5 with sodium methoxide gives enol ether sof type 9, which can be hydrolyzed to teh ketones 8 . Addition of bromine to some of teh unsaturated compounds is also reported.     

Stereochemistry of the reaction of pyridinium ylides with α,Β-unsaturated nitriles

Regioselective and stereoselective methods were developed for the synthesis of 4-aryl-2-oxo-3-(1-pyridinio)-5-cyano-3,4-trans-1,2,3,4-tetrahydropyridin-6-olates from pyridinium ylides and ,-unsaturated nitriles. The compounds were also obtained by the condensation of aromatic aldehydes, cyanoacetamide, and pyridinium ylides. It was established that these reactions take place through the corresponding Michael adducts, which undergo heterocyclization in the form of the anti conformers to substituted 3,4-trans-1,2,3,4-tetrahydropyridin-6-olates.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 363–369, March, 1990.     

Skeletal remodeling of chalcone-based pyridinium salts to access isoindoline polycycles and their bridged derivatives

Simultaneous deconstructive ring-opening and skeletal reconstruction of an inert, aromatic pyridinium ring is of great importance in synthetic communities. However, research in this area is still in its infancy. Here, a skeletal re-modeling strategy was developed to transform chalcone-based pyridinium salts into structurally intriguing polycyclic isoindolines through a dearomative ring-opening/ring-closing sequence. Two distinct driving forces for the deconstruction of the pyridinium core were involved in these transformations. One was the unprecedented harnessing of the instability of in situ generated cyclic β-aminoketones, and the other was the instability of the resultant N,N-ketals. The desired isoindoline polycycles could undergo the Wittig reaction with various phosphorus ylides to achieve structural diversity and complexity. Notably, by tuning the Wittig conditions by addition of one equivalent of base, an additional bridged ring was introduced. A plausible mechanism was proposed on the basis of control experiments and theoretical calculations.

A novel skeletal remodeling strategy to transform chalcone-based pyridinium salts into structurally intriguing polycyclic isoindolines was achieved through a dearomative ring-opening/ring-closing sequence.     

The effect of 4-substituents on the stability of pyridinium dicarbethoxymethylides

The effect of 4-substituents on the stability of pyridinium dicarbethoxymethylides, as determined by pK_a measurements, is found to correlate well with their effect on the stability of similarly substituted pyridine 1-oxides. Displacements in chemical shift in the ylides, particularly of the α-protons, are also found to correlate well with substituent effects. Intramolecular charge-transfer transitions in the electronic spectra, characteristic of pyridinium ylides, are reported.     

Stereoselective synthesis and tautomeric conversions of pyridyl-substituted 3,4-trans-1,2,3,4-tetrahydropyridines

Condensation of pyridinium ylides with pyridylmethylenecyanoacetic ester or pyridylmethylenecyanothioacetamide proceeds stereoselectively to form substituted 4-pyridyl-3-(1-pyridinio)-3,4-trans-1,2,3,4-tetrahydropyridine-6-(olates)thiolates. Substituted 2-(oxo)thio-4-(4-pyridyl)-3-(1-pyridinio)-3,4-trans-1,2,3,4-tetrahydropyridine-6-(olates)thiolates in DMSO-d₆ solution exist in tautomeric equilibrium with 4-(4-pyridinio)-3-(1-pyridinio)-1,4-dihydropyridine-2,6-(diolates)-dithiolates.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1630–1637, July, 1991.     

Synthesis and anti-inflammatory activities of some N-[pyridyl(phenyl)carbonylamino]-tert-butyl/phenyl-1,2,3,6- tetrahydropyridines

Nucleophilic attack of tert-butyl/phenylpyridines 3 on 1-chloro-2,4-dinitrobenzene 4 results in the formation of tert-butyl/phenyl substituted 2,4-dinitrophenylpyridinium chlorides 5. Benzoyl hydrazide and pyridyl acid hydrazides 6 were reacted with the pyridinium chlorides 5 furnishing the 2,4-dinitroanilino derivatives 7, which were subsequently hydrolyzed with water: p-dioxane to yield N-[pyridyl(phenyl)carbonylimino]-tert-butyl/phenylpyridinium ylides 8. The title compounds 9, N-[pyridyl(phenyl)carbonylamino]-tert-butyl/phenyl-1,2,3,6- tetrahydropyridines, were obtained by sodium borohydride reduction of the pyridinium ylides 8. The anti-inflammatory activities of compounds 9a-p were determined using the carrageenan-soaked sponge model of inflammation in Sprague Dawley rats. All compounds tested showed moderate to good anti-inflammatory effects compared to indomethacin. Compounds 9b, 9c and 9p were the most active analogs of the group in this model.     

Synthesis of some N-[pyridyl(phenyl)carbonylamino]-alkyl-1,2,3,6-tetrahydropyridines

Alkyl substituted 2,4-dinitrophenylpyridinium chlorides 3 are formed by the nucleophilic substitution of 1-chloro-2,4-dinitrobenzene with alkyl pyridines. Reaction of pyridyl acid hydrazides or benzoyl hydrazides 4 with the pyridinium chlorides 3 furnish the isolable 2,4-dinitroanilino derivatives 5 which undergo hydrolysis when refluxed in water:p-dioxane mixture (1:4 v/v) to yield the pyridinium ylides 6 . Sodium borohydride reduction of 6 in absolute ethanol at 0° for 4 hours result the formation of the title compounds 7 in moderate to excellent yields.