Photoinduced Molecular Transformations. Part 142. One-step syntheses of 1H-benz[f]indole-4,9-diones and 1H-indole-4,7-diones by a new regioselective photoaddition of 2-amino-1,4-naphthoquinones and 2-amino-1,4-benzoquinones with alkenes

The 2,3-dihydro-1H-benz[f]indole-4,9-diones 3a–d , h were formed in a one-step reaction in 13–82% yield by an unprecedented [3 + 2] regioselective photoaddition of 2-amino-1,4-naphthoquinone ( 1 ) with various electronrich alkenes 2 (Scheme 1, Table). The [3 + 2] photoadducts derived from 1 with vinyl ethers and vinyl acetate gave 1H-benz[f]indole-4,9-diones 4e , f , i , in 33–72% yield, by spontaneous loss of the corresponding alcohol or AcOH from the resulting adducts; 4i has a kinamycin skeleton. The [3 + 2] photoaddition also took place on irradiation of the differently substituted amino-1,4-benzoquinones 6 , 7 , and 12 and excess alkenes 2 in benzene, giving 1H-indole-4,7-dione derivatives 13 and 14 (Scheme 3), 15a and 16 (Scheme 4), and 18 (Scheme 4), respectively. The initial products in these photoadditions were proved to be hydroquinones, the air oxidation of which yielded the heterocyclic quinones; 2,3-dihydro-2-methoxy-2-methyl-5-phenyl-1H-indole-1,4,7-triyl triacetate ( 19 ) was isolated after treatment of the crude photoaddition mixture obtained from 2-amino-5-phenyl-1,4-benzoquinone ( 7 ) and 2-methoxyprop-1-ene ( 2f ) with Ac₂O and pyridine under N₂. A pathway leading to the annelated hydroquinones involving ionic intermediates arising from an electron transfer in these photoadditions is proposed (Scheme 5).     

Reaction of perfluorinated 1-ethyl-, 1,1-diethyl-, and 1,2-diethylcyclobutabenzenes with pentafluorobenzene in SbF<Subscript>5</Subscript>

Perfluoro(1-ethyl-1,2-dihydrocyclobutabenzene) reacts with pentafluorobenzene in SbF5 to give perfluoro(1-ethyl-2-phenyl-1,2-dihydrocyclobutabenzene). Analogous reaction of a mixture of perfluoro(1,1-diethyl-1,2-dihydrocyclobutabenzene) and perfluoro(1,2-diethyl-1,2-dihydrocyclobutabenzene) leads to the formation (after hydrolysis of the reaction mixture) of perfluorinated 7-phenyl-8,8-diethylbicyclo[4.2.0]octa-1,4,6-trien-3-one, 1,1-diethyl-2-(4-oxocyclohexa-2,5-dienylidene)-1,2-dihydrocyclobutabenzene, and 2-(pent-2-en-3-yl)benzophenone (from the 1,1-isomer) and perfluorinated (E)-1,2-diethyl-1-phenyl-1,2-dihydrocyclobutabenzene, 7,8-diethyl-8-phenylbicyclo[4.2.0]octa-1,4,6-trien-3-one, and 1-[2-(1-phenylprop-1-en-1-yl)-phenyl]propan-1-one (from the 1,2-isomer).     

Synthesis of isocoumarin, 1-isoquinolone and 4(1H)-quinolone derivatives via seleno-intermediates

The reaction of 2-styrylbenzoic acids 2 with N-phenylselenosuccinimide (N-PSS) affords 3-phenyl-iso-coumarin derivatives 3 and 3,4-dihydro-3-phenyl-4-(phenylseleno)isocoumarins 4 via selenolactonization. The reaction of 2-styrylbenzamides 5 and 1-(2-aminophenyl)-3-phenyl-2-peropen-1-one derivatives 11 with N-PSS also resulted in the formation of 1-isoquinolone 6 and 4(1H)-quinolone derivatives 12 , respectively.     

Facile Synthesis of Novel Pentofuranose Analogs of Phospha Sugar Derivatives

Novel pentofuranose analogs of phospha sugar derivatives were synthesized starting from 1-phenyl-2-phospholene 1-oxide ( 1 ). First, the allylic oxidation of 1-phenyl-2-phospholene 1-oxide ( 1 ) with CrO 3 in Ac 2 O-AcOH or 3-hydroxy-1-phenyl-2-phospholene ( 2 ) with MnO 2 afforded 1-phenyl-4-oxo-2-phospholene 1-oxide ( 3 ). The C-5 alkylation of 3 in the presence of NaH by using benzyl bromide or methyl iodide as electrophiles afforded the target title compounds.     

Allylstannane photoadditions to iminium salts. Efficiencies of sequential electron transfer destannation versus desilylation pathways

Electron transfer induced, photoadditions of allyltins to 1-methyl-2-phenyl-1-pyrrolinium perchlorates have been probed. The quantum efficiencies of these processes are larger that for photoaddition of the corresponding allylsilane.     

Pd-catalyzed cross-coupling reactions of halogenated 1-phenylpyrazol-3-ols and related triflates

1-Phenyl-1H-pyrazol-3-ol was used as a versatile synthon for the preparation of various 1-phenyl-1H-pyrazole derivatives substituted at C-3 and C-4 of the pyrazole nucleus and at the phenyl ring para-position. Treatment of 1-phenyl-1H-pyrazol-3-ol with triflic anhydride in the presence of base gave 3-trifloyloxy pyrazole, while bromination and iodination yielded the corresponding halogenated derivatives. The obtained scaffolds were used in carbon-carbon bond forming Pd-catalyzed cross-coupling reactions to yield (het)aryl- and carbo-functionally substituted 1-phenyl-1H-pyrazoles.     

Catalytic Potential of Pyrazolone Based Dioxidomolybdenum(VI) Complexes for Multicomponent Biginelli Reactions,Epoxidation of Olefins and Oxidative Bromination of Phenol Derivatives

Three different types of dioxidomolybdenum(VI) complexes of 4-acetyl-3-methyl-1-phenyl-5-pyrazolone (Hmp, I )), 3-methyl-1-phenyl-4-propionyl-5-pyrazolone (Hpp, II ), 4-butyryl-3-methyl-1-phenyl-5-pyrazolone (Hbutp, III ), and 4-isobutyryl-3-methyl-1-phenyl-5-pyrazolone (isobutp, IV ) have been isolated and characterized by various spectroscopic (FT-IR, UV/Vis, ¹H and ¹³C NMR) techniques, thermal analysis and single crystal X-ray analysis. These complexes adopt a distorted six-coordinate octahedral geometry where ligands act as bidentate, coordinating through the two O atoms. These complexes have been used as catalysts to explore a single pot multicomponent (benzaldehyde or its derivatives, urea/thiourea and ethyl acetoacetate/phenyl acetoacatate) Biginelli reaction producing biologically active 3,4-dihydropyrimidin-2-(1H)-one and 3,4-dihydropyrimidin-2-(1H)-thione based biomolecules under solvent-free conditions. Presence of H₂O₂ improves the yield of dihydropyrimidin-2-(1H)-one but it acts as poison for the later molecule. Epoxidation of internal and terminal alkenes mainly resulted in the formation of the corresponding epoxide. The catalytic oxidative bromination of thymol, a reaction facilitated by vanadium dependent haloperoxidases, resulted in the formation of three product namely 2-bromothymol, 4-bromothymol and 2,4-bromothymol. Other phenol derivatives have also been brominated effectively.     

Synthesis, reactions and biological evaluation of some new naphtho[2,1-b]furan derivatives bearing a pyrazole nucleus

Vilsmeier formylation of 2-(1-phenylhydrazonoethyl)naphtho[2,1-b]furan (2) gave 3-naphtho[2,1-b]furan-2-yl-1-phenyl-1H-pyrazole-4-carbaldehyde (3), which was reacted with C- and N-nucleophiles to afford naphthofuranpyrazol derivatives 4-8. Treatment of 2-[(3-(naphtho[2,1-b]furan-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene]-malononitrile (4a) with reactants having active hydrogen and Et?N gave the corresponding pyrazoline, pyran and chromene addition product derivatives 10, 12 and 13, consisting of three different connected heterocyclic moieties. Reaction of 1-((3-(naphtho[2,1-b]furan-2-yl)-1-phenyl-1H-pyrazol-4-yl) methylene)-2-phenylhydrazone (6b) with AcONa and ethyl bromoacetate or chloroacetone afforded the thiazolidinone and methylthiazole derivatives 14 and 15, respectively. In addition, intramolecular cyclization of 6d with Ac?O afford the corresponding 1,3,4-thiadiazol-2-yl acetamide derivative 16. The structures of the synthesized compounds were confirmed by IR, 1H-NMR/13C-NMR and mass spectral studies. Compound 14 showed promising effects against the tested Gram positive and negative bacteria and fungi.     

Lewis acid-catalyzed intermolecular [4 + 2] cycloaddition of 3-alkoxycyclobutanones to aldehydes and ketones

Intermolecular [4 + 2] cycloaddition between 3-alkoxycyclobutanones and aldehydes or ketones by the activation with boron trifluoride etherate is reported. The carbonyl compounds are inserted into the less substituted C2-C3 bond of the cyclobutanone ring of 6-alkyl-2-oxabicyclo[4.2.0]octan-7-ones to afford 1-alkyl-5,7-dioxabicyclo[4.4.0]decan-2-one derivatives regioselectively (>99:1) and diastereoselectively. On the other hand, [4 + 2] cycloaddition of 3-ethoxy-2,2-dialkylcyclobutanones at low temperature proceeds at the more substituted C2-C3 bond to yield 3,3-dialkyl-6-ethoxy-2,3,5,6-tetrahydro-4H-pyran-4-one derivatives with high regioselectivities. This [4 + 2] cycloaddition is developed into a one-pot synthesis of tri- or tetrasubstituted dihydro-gamma-pyrones from 3-ethoxycyclobutanones which are readily prepared from acid chloride and ethyl vinyl ether. The two regioselectivities observed in ring-opening of cyclobutanones can ascribe to thermodynamic stabilities of zwitterionic intermediates generated from tetrahydropyran-fused cyclobutanones and 3-ethoxycyclobutanones.     

Lewis Acid-Catalyzed Intramolecular [2 + 2] Cycloaddition of alpha-Ester-Substituted Conjugated Dienyl- and Trienylphosphonates. New Synthesis of Functionalized Cyclic Terpenoids

alpha-Ester-substituted 1,3-dienylphosphonates 7 and 8, prepared by the Knoevenagel condensation, underwent intramolecular [2 + 2] cycloaddition in the presence of Lewis acid to form bicyclo[4.2.0] (26-57% yield) and bicyclo[3.2.0]skeleton (14-38% yield), respectively. Similar treatment of homologous 1,3-dienylphosphonate 11 and 1,3,5-trienylphosphonate 12 resulted in the formation of ionone derivatives (30-94% yield). The intramolecular cycloaddition reaction was applicable to several conjugated dienes bearing an ester group.     

Methoxy-substituted stilbenes, styrenes, and 1-arylpropenes: photophysical properties and photoadditions of alcohols

The photochemistry of trans-stilbene and four methoxy-substituted stilbene derivatives has been investigated in a variety of solvents. The fluorescence of all five trans isomers was quenched by 2,2,2-trifluoroethanol (TFE). Upon irradiation of the five substrates in TFE, the products derived from photoaddition of the solvent were detected. Nuclear magnetic resonance spectroscopy of the products formed by irradiation in TFE-OD indicated that the proton and nucleophile are attached to two adjacent atoms of the original alkene double bond. Irradiation of the corresponding methoxy-substituted styrenes and trans-1-arylpropenes in TFE produced the analogous solvent adducts. The photoaddition of TFE proceeded with the general order of reactivity: styrenes > trans-1-arylpropenes > trans-stilbenes. Transient carbocation intermediates were observed following laser flash photolysis of the stilbenes in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The results are consistent with a mechanism that involves photoprotonation of the substrates by TFE or HFIP, followed by nucleophilic trapping of short-lived carbocation intermediates. Compared to the other stilbene derivatives, trans-3,5-dimethoxystilbene displayed a large quantum yield of fluorescence and a low quantum yield of trans-cis isomerization in polar organic solvents. The unique photophysical properties of trans-3,5-dimethoxystilbene are attributed to formation of a highly polarized charge-transfer excited state (mu(e) = 13.2 D).     

Photoreactive polyamides having m- or 1-type dimer moiety derived from 4-(3-oxo-3-phenyl-1-propenyl)benzoic acid derivatives

Photoreactive polyamides having m- or 1 -type cyclobutane moiety were prepared via a topochemical photodimerization of 4-(3-oxo-3-phenyl-1-propenyl)benzoic derivatives,⁴ followed by polycondensation of cyclobutane dicarboxylate derivatives with diamines. From the spectral studies of resulted polyamides compared with the corresponding reference diamides, it was concluded that both types of polyamides were depolymerized photochemically to give the same type of amide derivative having chalcone moiety with a small amount of undefined side reaction. The cyclobutane ring of the m-dimer from 4-(3-oxo-3-phenyl-1-propenyl)benzoic acid in crystal is severely twisted presumably because of the enhanced steric repulsions between two pairs of adjacent substituents. The higher quantum yield of the m-dimer for the photocleavege, compared with that of the 1 -dimer, has been interpreted in terms of such steric repulsions by the strained structure of the m-dimer.     

Opening of the four-membered ring in perfluorinated 1-alkyl-2-phenyl- and 1-aryl-1,2-dihydrocyclobutabenzenes in the system I<Subscript>2</Subscript>-SbF<Subscript>5</Subscript>

Reactions of perfluorinated 1-phenyl-, 1-(2-ethylphenyl)-, 1-(4-ethylphenyl)-, 1-methyl-2-phenyl-, and 1-ethyl-2-phenyl-1,2-dihydrocyclobutabenzenes with iodine in antimony pentafluoride at 130°C, followed by hydroysis of the reaction mixture, resulted in the formation of perfluorinated 2-methyl-, 2-ethyl-2′-methyl-, 4-ethyl-2′-methyl-, 2-ethyl-, and 2-propylbenzophenones via opening of the four-membered ring in the initial cyclobutabenzene at the C¹–C² bond. The presence of hydrogen fluoride facilitates the process and promotes profound transformations leading to anthracene derivatives.     

Synthesis of three-dimensional fused and spirocyclic oxygen-containing cyclobutanone derivatives

An approach to fused and spirocyclic oxygen-containing cyclobutanone derivatives based on ketene [2+2] cycloaddition with vinyl ethers is described. Using alicyclic chloroanhydrides as ketene sources as well as cyclic vinyl ethers in the reaction resulted in the formation of three-dimensional conformationally restricted building blocks of interest to medicinal chemistry and organic synthesis. In particular, 2-oxaspiro(bicyclo[3.2.0]heptane-7,1′-cycloalkane)-6-ones and 2-oxaspiro(bicyclo[4.2.0]octane-8,1′-cycloalkane)-6-ones were obtained. The procedure involves readily available and inexpensive starting materials and allows construction of complex molecular architectures on a large scale in a single run.     

Synthesis of 2-imino-4-vinyl-2,5-dihydrofuran-3-carboxamides and some their chemical transformations

2-Imino-2,5-dihydrofuran-3-carboxamides containing 2-phenyl- and 2-furylvinyl substituents in position 4 of the furan ring were synthesized by condensation of 2-imino-4-methyl-2,5-dihydrofuran-3-carboxamides with the corresponding aldehydes. Acid hydrolysis of 4-(2-arylvinyl)-2-imino-2,5-dihydrofuran-3-carboxamides gave 4-(2-arylvinyl)-2-oxo-2,5-dihydrofuran-3-carboxamides, and their condensation with malononitrile resulted in the formation of 2-dicyanomethylidene derivatives.     

Synthesis and herbicidal activity evaluation of novel β-carboline derivatives

Based on the original structure of harmine, several novel 1,2,3,4-tetrahydro-β-carboline, β-carboline and 1-substituted-β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were designed and synthesized to investigate the structure-activity relationship of their analogues. All of the compounds were characterized by infrared (IR), proton and carbon nuclear magnetic resonance (1H-NMR, 13C-NMR), and mass spectroscopy (MS). The bioassay tests showed that N'-benzylidene-1-phenyl-β-carboline-3-carbohydrazide (C(25)H(18)N(4)O, m.w. 390.4) (c2) and N'-(4-trifluoromethyl-benzylidene)-1-phenyl-β-carboline-3-carbohydrazide (C(26)H(17)N(4)OF(3), m.w. 458) (d2) exhibited good inhibitory activity against dicotyledonous and monocotyledonous weeds, with EC(50) values of 4.83 μM and 14.25 μM, respectively.     

Photoaddition Reactions of 5-Fluoro-4,4-dimethyl-2-cyclopentenone

The photoaddition of 5-fluoro-4,4-dimethyl-2-cyclopentenone ( 4 ) to 2,3-dimethyl-2-butene leads specifically (in cyclohexane) and selectively (in acetonitrile) to the formation of the oxetanes 16 . The title compound is compared in its behaviour to the analogous 6-fluoro-4,4-dimethyl-2-cyclohexenone ( 1 ) and both α'-fluoro-4,4-dimethyl-2-cycloalkenones in turn are compared to the corresponding 2-cycloalkenones ( 6 and 3 ) and 4,4-dimethyl-2-cycloalkenones ( 5 and 2 ). The quantum yield for the addition of these enones to 2,3-dimethyl-2-butene and to cyclopentene are discussed.     

Design of a functional protein for molecular recognition: specificity of ligand binding in a metal-assembled protein cavity probed by 19f NMR

A metal-assembled homotrimeric coiled coil based on the GCN4-p1 sequence has been designed that noncovalently binds hexafluorobenzene and other similar ligands in a hydrophobic cavity, created by making the core substitution Asn16Ala ([Fe(bpyGCN4-N16A)3]2+). The KD of binding of hexafluorobenzene with [Fe(bpyGCN4-N16A)3]2+ was observed to be 1.1(9) x 10(-4) M by diffusion NMR experiments. A control coiled coil with the core substitution Asn16Val ([Fe(bpyGCN4-N16V)3]2+) exhibited a significantly weaker association with hexafluorobenzene, providing evidence that even in the absence of structural data, benzene-like ligands bind in the cavity created by the Asn16Ala substitution. 19F NMR was employed to observe hexafluorobenzene binding and to monitor titrations with competing hydrophobic and polar ligands similar in size and shape to hexafluorobenzene. All hydrophobic ligands bound with greater affinity than the polar ligands in the hydrophobic core, although the cavity seems to be somewhat flexible in terms of the sizes of molecules it can accommodate. Thus 19F NMR has proved to be a useful spectral tool to probe molecular recognition in a hydrophobic cavity of a metal-assembled coiled coil.     

Chemistry of acyl(imidoyl)ketenes. 8*. Thermolysis of 3-alkoxycarbonyl- 5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]- quinoxaline-1,2,4-triones. Structure of 2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)- 2,4-di(ethoxycarbonyl)-6-phenyl-2,3,5,6-tetrahydro- 1h-pyrido[1,2-a]quinoxaline-1,3,5-trione

3-Alkoxycarbonylmethylene-1-phenyl-1,2,3,4-tetrahydro-2-quinoxalones, obtained by the interaction of dialkyl esters of oxaloacetic acid and N-phenyl-o-phenylenediamine, react with oxalyl chloride with the formation of 3-alkoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones. Alkoxycarbonyl(2-oxo-1-phenyl-1,2-dihydro-3-quinoxalinyl)ketenes, generated on thermal decarbonylation of the latter, are stabilized by participation in a [4+2] cyclodimerization reaction with the formation of 2,4-di(alkoxycarbonyl)-2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-6-phenyl-2,3,5,6-tetrahydro-1H-pyrido[1,2-a]quinoxaline-1,3,5-triones. The crystal and molecular structure of the di(ethoxycarbonyl) derivative have been investigated by X-ray structural analysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1501–1506, October, 2004.     

Steric control of the excited-state intramolecular proton transfer in 3-hydroxyquinolones: steady-state and time-resolved fluorescence study

3-Hydroxyquinolones (3HQs), similarly to their 3-hydroxychromone analogs, undergo excited state intramolecular proton transfer (ESIPT) resulting in dual emission. In the ground state, 2-phenyl-3HQ derivatives are not flat due to a steric hindrance between the 2-phenyl group and the 3-OH group that participates in the ESIPT reaction. To study the effect of this steric hindrance on the ESIPT reaction, a number of 3HQ derivatives have been synthesized and characterized in different organic solvents by steady-state and time-resolved fluorescence techniques. According to our results, 2-phenyl-3HQ derivatives undergo much faster ESIPT (by nearly 1 order of magnitude) than their 2-methyl-3HQ analogs. Moreover, 1-methyl-2-phenyl-3HQ having a strongly twisted 2-phenyl group undergoes a two- to three-fold slower ESIPT compared to 2-phenyl-3HQ. These results suggest that the flatter conformation of 2-phenyl-3HQ, which allows a close proximity of the 2-phenyl and 3-OH groups, favors a fast ESIPT reaction. The absorption and fluorescence spectra of the 3HQ derivatives additionally confirm that the steric rather than the electronic effect of the 2-phenyl group is responsible for the faster ESIPT reaction. Based on the spectroscopic studies and quantum chemical calculations, we suggest that the 2-phenyl group decreases the rotational freedom of its proximal 3-OH group in the more planar conformation of 2-phenyl-3HQ. As a result, the conformations of 3HQ, where the 3-OH group orients to form an intramolecular H-bond with the 4-carbonyl group, are favored over those with a disrupted intramolecular H-bond. Therefore, the 2-phenyl group sterically favors the intramolecular H-bond and thus accelerates the ESIPT reaction. This conclusion provides a new understanding of the ESIPT process in 3-hydroxyquinolones and related systems and suggests new possibilities for the design of ESIPT based molecular sensors and switchers.