Cycloaddition reactions of benzothiete with azomethines

A new synthetic route to 3,4-dihydro-2H-1,3-benzothiazines 5 has been developed by the regiospecific cycloaddition of Schiff bases 4 and benzothiete 1 , which is primarily opened by heating to the corresponding o-quinoidal form 2 .     

Cycloaddition of electron-deficient olefins to norbornadiene in the presence of nickel bisphosphine systems

[2+2+2] Cycloaddition of electron-deficient olefins to norbornadiene in the presence of nickel bisphosphine catalysts was studied. The influence of the bisphosphine structure on the regio- and stereoselectivity of the reaction as well as on the yields of the reaction products was investigated. New evidence for the influence of chiral bisphosphine ligands on the enantioselectivity of the reaction was obtained.     

[4+2] Cycloaddition reactions of 4-sulfur-substituted 2-pyridones with electron-deficient dienophiles

[4+2] Cycloaddition reactions of 4-(phenylthio)-1-tosyl-2-pyridone (6a) and 4-(phenylsulfonyl)-1-tosyl-2-pyridone (6b) with electron-deficient dienophiles 7 (N-methylmaleimide, N-phenylmaleimide, and methyl acrylate) gave new isoquinuclidine products 8-10. The N-tosyl group of 6a and 6b was also efficiently converted to N-alkyl derivatives 6c-f, which showed different stereoselectivity toward reactions with dienophiles 7. Several other dienophiles 15 (dimethyl acetylenedicarboxylate, methyl vinyl ketone, ethyl vinyl ether, and methyl methacrylate) were found not to react with 6a or 6b, but led to the formation of tosyl migration products 4-(phenylthio)-O-tosyl-pyridinol (16a) and 4-(phenylsulfonyl)-O-tosyl-2-pyridinol (16b), respectively. The reactivity, regioselectivity, and stereoselectivity of the cycloaddition reactions were also compared with semi-empirical calculations.     

Cycloaddition reactions of 1-lithio-1,3-dienes with aromatic nitriles affording multiply substituted pyridines, pyrroles, and linear butadienylimines

Fully or partially substituted 1-iodo- or 1-bromo-1,3-dienes could be readily lithiated using t-BuLi or n-BuLi to afford their corresponding 1-lithio-1,3-diene derivatives in quantitative yields. When these in situ generated lithium reagents were treated with organonitriles, depending on the substitution patterns of the butadienyl skeletons, substituted pyridines, pyrroles, and/or linear butadienyl imines were formed in good to excellent yields via N-lithioketimine intermediates. In the cases of 1,2,3,4-tetrasubstituted and 2,3-disubstituted 1-lithio-1,3-dienes, pyridine derivatives or linear butadienyl imines were generally formed depending on the reaction temperatures. When 1,2,3,4-tetrasubstituted 4-halo-1-lithio-1,3-dienes and 1,2-disubstituted 1-lithio-1,3-dienes were treated with organonitriles, pyrrole derivatives or linear butadienyl imines were obtained. Competition between 5-exo and 6-endo cyclization was found to be responsible for the formation of either pyrroles or pyridines. Selective elimination of RLi from the lithiated cyclic N-containing intermediates was observed. The order of elimination was found to be LiCl > Me3SiLi > LiH.     

Cycloaddition reaction of 2-azadienes derived from beta-amino acids with electron-rich and electron-deficient alkenes and carbonyl compounds. Synthesis of pyridine and 1,3-oxazine derivatives

Functionalized keto-enamines 6 were obtained by nucleophilic addition of enol ethers to the imine moiety of 2-azadienes derived from dehydroaspartic esters 4. Reactions of 2-azadiene 4c containing three electron-withdrawing substituents (CO(2)R) with enol ethers 5 in the presence of lithium perchlorate led to the formation of tetrahydropyridine derivatives 7 in a regio- and stereoselective fashion. 2H-[1,3]-oxazines 10 and pyridine derivatives 12 and 13 were obtained by heterocycloaddition reactions of electron-poor azadienes 4d-g containing two electron-withdrawing substituents (4-O(2)N-C(6)H(4), CO(2)R) in positions 1 and 4 with carbonyl derivatives (ethyl glyoxalate 9a and diethyl ketomalonate 9b) and the electron-deficient olefin tetracyanoethylene 11.     

Synthesis and characterization of electron-deficient pentacenes

[structure: see text]. Halogen functional groups on pentacene can be used both as synthetic handles for further functionalization as well as to tune the pi-stacking in these systems. The halogenated pentacene derivatives described here (X = Br, X' = H, and X = X' = F) are all stable and soluble, with reduction potentials significantly lower than that of the parent functionalized pentacene (X = X' = H). The bromopentacenes could be further elucidated to pentacene nitriles, further decreasing the acene's reduction potential, while the charge-carrier mobility in the fluorinated systems was shown to scale with the degree of fluorine substitution.     

Electrochemical iodofluorination of electron-deficient olefins

Electron-deficient olefins like α,β-unsaturated ester, amide, and phosphonate reacted with iodonium cation species generated by the anodic oxidation of iodide anion in Et₃N-5HF/CH₃NO₂ to form corresponding iodofluorinated compounds in good to moderate yields. The reaction proceeds at room temperature under air atmosphere and constant current conditions. The iodofluorinated products were shown to be useful fluorine-containing building blocks.     

Partial reduction of electron-deficient pyridines

The partial reduction of electron-deficient pyridines is described herein. Mono- and disubstituted pyridines can be transformed into functionalized dihydropyridines using either Birch reduction conditions or sodium/naphthalene in THF. The compounds formed by these high-yielding reductive alkylation protocols have potential as synthetic intermediates, and we have shown that bicyclo compounds containing 6,5, 6,6, and 6,7 ring systems can be prepared in one step via a base-promoted cylization.     

Oximes and nitriles of cardenolides

The influence of the oximation of cardenolides and the production of 10-cyanocardenolides on their biological activity has been studied. The prefered conformation of strophanthidin 19-aldoxime has been established; it has chelate fragment as the result of the orientation in the same direction of the nitrogen atom of the oxime group and the hydroxy groups at C-3 and C-5.All-Union Scientific-Research Institute of the Chemistry and Technology of Drugs, Khar'kov. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 608–612, September–October, 1983.     

Photodifluoramination of nitriles

Gas phase irradiation of N₂F₄(NF₂) in the presence of trifluoroacetonitrile, ¹⁵N-trifluoroacetonitrile, or acetonitrile resulted in the formation of products that correspond to perfluorination of the unsaturation or to conversion of the substrate to a saturated fluorocarbon. The proposed mechanism involves atomic fluorine attack on the nitrile and subsequent rearrangement of the resulting N,N-difluorohydrazone, R₂C(F)NNF₂, to an alkylfluorodiazene R₂C(F)-N=N-F. Decomposition of diazenes accounts for the observed products.     

Electrochemical fluoro-selenenylation of electron-deficient olefins

Electrochemical fluoro-selenenylation of electron-deficient olefins like α,β-unsaturated ester, carboxylic acid, amide, and phosphonate was successfully carried out by the anodic oxidation of diphenyl diselenide in the presence of olefins in Et₃N·5HF/CH₃NO₂. The anodically generated benzeneselenenyl fluoride [PhSeF] equivalent was stable in the electrolytic solution, which resulted in the efficient fluoro-selenenylation. The fluoro-selenenylation products were shown to be potential useful fluoro-building blocks.     

Phosphine-catalyzed bishydrophosphorylation of electron-deficient alkynes

Tertiary phosphines (n-Bu₃P, Ph₃P) efficiently catalyze the vicinal bis-addition of dialkyl phosphites and diaryl phosphine oxides to alkynoates though the tandem α-umpolung/β-Michael addition. This reaction offers a simple metal-free method for gram-scale preparation of practically useful bisphosphonates and bisphosphine oxides under mild conditions with high atom economy and selectivity.     

Symmetrical electron-deficient materials incorporating azaheterocycles

To investigate the potential of di- and tri-azaheterocycles as building blocks for pi-conjugated materials with high electron affinity, linear oligomers incorporating pyrazine and a C(3)-symmetric discotic molecule based on triazine were synthesized. The tridodecyloxyphenyl end-capped ethynylene pyrazinylene oligomers showed remarkable solvatochroism in absorption and emission in solution. The oligomers containing one and two pyrazine rings displayed liquid crystallinity in the solid state. The largest ethynylene pyrazinylene oligomer containing three pyrazine rings had the lowest first reduction potential at -1.08 V. The triazine-derived discotic molecule exhibited UV/Vis and fluorescence behavior comparable to that of the linear oligomers and featured a first reduction potential at -1.49 V, somewhat lower than expected.     

Ruthenium-catalyzed cross-metathesis between diallylsilanes and electron-deficient olefins

Diallysilanes can be selectively coupled with electron-deficient olefins under cross-metathesis (CM) conditions using the Hoveyda-Grubbs catalyst to produce mono- and/or bis-CM compounds in good yield. The formation of the mono- and the bis-CM compounds depends on the nature of the electron-deficient olefin.     

Platinum-catalyzed selective hydration of hindered nitriles and nitriles with acid- or base-sensitive groups

Hindered tertiary nitriles can be hydrolyzed under neutral and mild conditions to the corresponding amides using platinum(II) catalysts with dimethylphosphine oxide or other secondary phosphine oxides (SPOs, phosphinous acids) as ligands. We have found that this procedure also works well for nitriles with acid- or base-sensitive groups, which is unprecedented in terms of yield and selectivity. The catalyst loading can be as low as 0.5 mol %. Amides are isolated as the only product in high yield, and no further hydrolysis to the corresponding acids takes place. Reactions are carried out at 80 degrees C but take place even at room temperature. When enantiopure secondary phosphine oxide ligands are used in the hydrolysis of racemic nitriles, no kinetic resolution is observed, presumably due to racemization of the ligand during the reaction.