Synthesis and characterization of ferrocenylgalvinol, a novel d-π redox system

A novel d-π redox molecule bearing ferrocene (Fc) and galvinoxyl (GalO) units as reversible redox active sites has been synthesized and characterized. The molecule shows solvatochromic behavior and changes from a red color in n-hexane (λ_max = 388, 541 nm) to a greenish brown (λ_max = 413, 582 nm) in MeOH. A cyclic voltammogram of 1 under neutral conditions shows a redox process corresponding to Fc/Fc⁺ but not one for GalOH (or GalO⁻)/GalO. Under basic conditions the latter process was observed and it occurred at a lower oxidative potential ( vs Ag/AgCl) than the former process . Thus 1 shows potential as a bilateral multi-redox molecule with pH dependence. Chemical oxidation of 1 under basic conditions (aq KOH, K₃Fe(CN)₆) gives an EPR spectrum with an hfc of 1.2 G attributable to Fc-GalO.     

Addition of diphenylphosphinodithioic acid and thioacetic acid with vinylidenecyclopropanes: reversed regioselectivities

The reaction of vinylidenecyclopropanes 1 with diphenylphosphinodithioic acid produces the adducts 3 in good to high yields in toluene upon heating at 100 °C within 1 h, whereas adducts 5 are obtained in excellent yields in reversed regioselectivity from the reaction of 1 with thioacetic acid under identical conditions. The radical reaction processes have been discussed on the basis of deuterium labeling experiment and the control experiments in the presence of radical inhibitors (TEMPO and BHT) or a proton scavenger (DTBMP).     

AgF-Mediated Homocoupling Reaction of Trialkoxy Aryl Silanes

In this article, we present the direct homocoupling reaction of trialkoxy aryl silanes mediated by AgF in moderate to excellent yields in very mild conditions. It is an important complement for the synthesis of symmetrical biaryls by using homocoupling of trialkoxy silanes. In this reaction, no other catalyst such as Pd or Cu was necessary.

Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for full experimental and spectral details.     

Effects of alpha-Alkoxy Substitution and Conformational Constraints on 6-exo Radical Cyclizations of Hydrazones via Reversible Thiyl and Stannyl Additions

Access to multifunctional hydrazones of relevance to dysiherbaine synthesis studies is described. Subsequent radical cyclizations of multifunctional hydrazones via a Si- and C-linked tethering strategy are shown to function effectively in 6-exo fashion. Conformational constraints are proposed to play a key role in suppressing unproductive premature reduction pathways. The stereochemical outcomes suggest that minimizing the dipole repulsion between neighboring CN and C-O bonds favors a C_α-C(N) dihedral angle placing the CN bond axial within a chairlike transition state, in contrast to the usual Beckwith-Houk model.     

Formation of spiro ketolactones versus alkoxy radical fragmentation-promoted three-atom ring enlarged lactones from cyclic ketones

A dual pathway from readily available 2-allyl-2-carboethoxycycloalkanones 1 provides a new facile stereoselective synthesis either of functionalized spiro ketolactones 4 or of ring enlarged lactones 7 in one-step. Thus, iodination of 5-8-membered 2-allyl-2-carboethoxycycloalkanones 1a-d led, in excellent yields, to spiro ketolactones 4a-d, respectively, as single stereoisomers. On the other hand, iodination of 1a-d under alkoxy radical fragmentation conditions via incipient hemiketals produced the 8-, 9-, 10-, or 11-membered, three-atom ring enlarged, poly-functionalized lactones 7a-c as two stereoisomers and 8 as a single isomer.     

Antioxidant activity of clove oil – A powerful antioxidant source

The number of methods to measure the antioxidants in botanicals, foods, nutraceuticals and other dietary supplements has increased considerably in the last decade. Clove oil is obtained by distillation of the flowers, stems and leaves of the clove tree. In the present paper, clove oil was evaluated by employing various in vitro antioxidant assay such as α,α-diphenyl-β-picryl-hydrazyl free radical (DPPH) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, total antioxidant activity determination by ferric thiocyanate, total reducing ability determination by Fe³⁺–Fe²⁺ transformation method, superoxide anion radical scavenging by riboflavin/methionine/illuminate system, hydrogen peroxide scavenging and ferrous ions (Fe²⁺) chelating activities. Clove oil inhibited 97.3% lipid peroxidation of linoleic acid emulsion at 15 μg/mL concentration. However, under the same conditions, the standard antioxidant compounds such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and trolox demonstrated inhibition of 95.4, 99.7, 84.6 and 95.6% on peroxidation of linoleic acid emulsion at 45 μg/mL concentration, respectively. In addition, clove oil had an effective DPPH scavenging, ABTS⁺ scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe³⁺) reducing power and ferrous ions (Fe²⁺) chelating activities. Also, these various antioxidant activities were compared to BHA, BHT, α-tocopherol and trolox as reference antioxidant compounds.     

Mild,rapid and efficient metal-free synthesis of 2-aryl-4-aryloxyquinolines via direct Csp2O bond formation by using diaryliodonium salts

An efficient ligand- and transition metal-free procedure for the direct C_sp²O bond formation for the arylation of 2-aryl-4-quinolones was developed. The synthesis of the starting quinolones was carried out under our optimized Cu-catalyzed CN bond formation conditions between 2′-bromoacetophenone and benzamide derivatives followed by cyclization. Easily prepared diaryliodonium salts were used as aryl source. Highly functionalized 4-aryloxyquinolines were obtained in a mild and operationally simple protocol, which involves conventional heating and short periods of time. The method shows good to excellent yields and broad toleration of functional groups like fluorine or trifluoromethyl, which are important in medicinal chemistry. The C_sp²O bond formation process herein described for the quinolone functionalization offers an excellent non-toxic alternative to the transition metal-catalyzed reactions that not only can potentially contaminate the final compounds but also can be environmental pollutants.     

Visible-light-induced halogenation of aliphatic CH bonds

Alkyl halides are of particular interests in the areas of pharmaceutical, agrochemical, and material sciences. Direct CH halogenation has been recognized as the most efficient method for the introduction of halogen atoms into organic molecules. This Digest paper highlighted some of the most recent and significant developments in the visible light-promoted halogenation of aliphatic CH bonds.     

Synthesis of cyanofuroxans from 4-nitrofuroxans via CC bond forming reactions

A substitution reaction of 4-nitrofuroxans to prepare 4-cyanofuroxans is described. This substitution reaction was complicated by the reverse reaction and a judicious choice of cyanide source was important to enable this direct synthesis process. The optimized reaction conditions showed an excellent applicability for the synthesis of a range of 4-cyanofuroxans. 3-Cyanofuroxans, known to be thiol-mediated nitric oxide donors, could also be obtained by the thermal or photochemical isomerization of 4-cyanofuroxans. The developed cyanation of furoxans is a rare example of CC bond-forming reaction on a furoxan ring.     

Silver(II) oxide-mediated synthesis of 2,4-diarylquinazolines

A single-pot procedure for the synthesis of 2,4-diarylquinazolines is described which involves a silver oxide-mediated CH activation/CN bond formation process. The generality of this method with respect to substituent effects is presented along with studies leading to process optimization. Mechanistic investigations provide support for the involvement of radical intermediates in the reaction process.     

Palladium-catalyzed direct C2-arylation of free (NH) indoles via norbornene-mediated regioselective CH activation

A palladium-catalyzed direct C2-arylation reaction of free (NH) indoles has been developed. This reaction relies on a norbornene-mediated CH activation process on the indole ring, which features high regioselectivity and excellent functional group tolerance.     

Stereocontrol in radical Mannich equivalents for aminosugar synthesis: haloacetal and 2-(phenylthio)vinyl tethered radical additions to α-hydroxyhydrazones

Studies of stereocontrol in two types of radical equivalents of Mannich addition reactions offer new insights for application to aminosugar synthesis. In the first method, haloacetal addition (Ueno-Stork reaction) is extended to dihydroxyhydrazones, leading to an adduct with the unexpected 3-epi-l-daunosamine configuration. A neighboring α-benzyloxy substituent causes a dramatic reversal of stereocontrol compared with hydrazones where this substituent is absent; vicinal dipole repulsion is proposed to account for the diastereoselectivity. In the second method, radical addition-cyclization with thiophenol and treatment with fluoride leads to diastereoselective group transfer from a silicon-tethered ethynyl group to the CN bond of hydrazones, affording anti-hydrazino alcohols with a trans-2-(phenylthio)vinyl substituent. The one-pot process occurs under neutral, tin-free radical conditions, and offers stereocontrol which is complementary to the haloacetal method. Synthetic utility of the radical Mannich concept is demonstrated in a brief asymmetric synthesis of N-trifluoroacetyl-l-daunosamine from achiral precursors.     

Tris(trimethylsilyl)silyl versus tris(trimethylsilyl)germyl: Radical reactivity and oxidation ability

A comparison of the tris(trimethylsilyl)silyl I and tris(trimethylsilyl)germyl II radical reactivity is provided. Their formation as well as their reactivity encountered in a large variety of chemical processes (addition to double bond, halogen abstraction, peroxyl radical formation…) is examined by laser flash photolysis, quantum mechanical calculations and electron spin resonance (ESR) experiments. The starting compound (TMS)₃GeH is more reactive than (TMS)₃SiH toward the t-butoxyl, the t-butylperoxyl and the phosphinoyl radicals. A similar behavior is noted for an aromatic ketone triplet state. II exhibits a lower absolute electronegativity: accordingly, the addition to electron rich alkenes is less efficient than for I. Radical II is also found less reactive for both the peroxylation and the halogen abstraction reactions. The rearrangement of is slower than for ; this is related to the respective exothermicity of the processes.     

Recent advance in radical fluoroalkylation with sulfinate salts

In the last few years, the incorporation of a fluoroalkyl moiety into an organic molecule has been extensively studied. Especially, radical fluoroalkylation, involving the formation of CC and Cheteroatom bonds, presents its valuable synthetic potential to achieve fluoroalkylated compounds. This digest paper highlights recent progress on fluoroalkylation with sulfinate salts, and focuses on radical tri-/di-/monofluoromethylation during the last five years.     

High-performance liquid chromatography with post-column 2,2′-diphenyl-1-picrylhydrazyl radical scavenging assay: Methodological considerations and application to complex samples

An improved post-column 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay for the screening of antioxidants in complex matrices was developed. Experimental parameters believed to be influential to DPPH response were studied in a univariate approach. Optimum conditions were found to be: 5 × 10⁻⁵ M DPPH reagent prepared in a 75% methanol: 25% 40 mM citric acid-sodium citrate buffer (pH 6) solution, degassed with nitrogen; reaction coil of 2 m × 0.25 mm i.d. PEEK tubing; detection at 521 nm; analysis at room temperature. The analytical utility of this protocol was evaluated by screening for antioxidants in thyme and green tea, in comparison with two commonly employed methodologies.     

Silver-mediated radical aryltrifluoromethylthiolation of activated alkenes by S-trifluoromethyl 4-methylbenzenesulfonothioate

Herein, we describe the preparation of trifluoromethylthiol-substituted oxindoles by silver-mediated aryltrifluoromethylthiolation of activated alkenes, using S-trifluoromethyl 4-methylbenzenesulfonothioate as a F₃CS radical source and showing that the reagent availability, mild conditions, and broad functional group compatibility of this transformation make it a viable alternative strategy of constructing C_sp3SCF₃ bonds.