Catalyst free,visible-light promoted photoaddition reactions between C60 and N-trimethylsilylmethyl-substituted tertiary amines for synthesis of aminomethyl-1,2-dihydrofullerenes

An efficient and benign method for the preparation of aminomethyl-substituted fullerenes has been developed. The process, involving catalyst free, visible-light irradiation of 10% EtOH-toluene solutions containing fullerene C₆₀ and N-trimethylsilylmethyl-substituted amines by using a 20 W compact fluorescent lamp, leads to formation of aminomethyl-substituted fullerene adducts in a highly efficient manner. The photoaddition reaction takes place via a pathway initiated by visible light absorption by C₆₀, followed by SET from the amine to the triplet excited state of C₆₀. Ethanol-promoted desilylation of the resulting a minimum radical then generates the corresponding α-amino radical which couples with the C₆₀ radical anion to form the anion precursor of the fullerene adducts. The new approach using visible-light takes place under mild conditions and it does not require the use of photocatalysts. Thus, the method developed in this effort could broadens the range of functionalized fullerene derivatives that can be readily prepared.     

Iminyl‐Radicals by Oxidation of α‐Imino‐oxy Acids: Photoredox‐Neutral Alkene Carboimination for the Synthesis of Pyrrolines

The visible‐light‐promoted decarboxylation of α‐imino‐oxy propionic acids for the generation of iminyl radicals has been accomplished through the use of Ir(dFCF₃ppy)₂(dtbbpy)PF₆ as a photoredox catalyst. Different from visible‐light‐promoted homolysis and single‐electron reduction of oxime derivatives, this strategy provides a novel catalytic cycle for alkene carboimination through a sequence comprising N‐radical generation, iminyl radical cyclization, intermolecular conjugate addition to a Michael acceptor, and single‐electron reduction to afford various pyrroline derivatives in an overall redox‐neutral process. The indolizidine alkaloid skeleton could be easily constructed from a pyrroline derivative prepared by this synthetic method.     

Radical cyclization of exo-methylene furanose derivatives: an expedient approach to the synthesis of chiral tricyclic nucleosides and benzannulated oxepine derivatives

Tributyltin radical mediated cyclization of the glucose derived exo-methylene furanose derivatives 5a-c led to the highly functionalized cis-fused bicyclic ethers 6a-c. The product could subsequently be transformed to the optically active tricyclic nucleoside analogue 8 or oxepine derivative 9.     

Visible‐Light‐Promoted Trifluoromethylthiolation of Styrenes by Dual Photoredox/Halide Catalysis

Herein, we report a new visible‐light‐promoted strategy to access radical trifluoromethylthiolation reactions by combining halide and photoredox catalysis. This approach allows for the synthesis of vinyl–SCF₃ compounds of relevance in pharmaceutical chemistry directly from alkenes under mild conditions with irradiation from household light sources. Furthermore, alkyl–SCF₃‐containing cyclic ketone and oxindole derivatives can be accessed by radical‐polar crossover semi‐pinacol and cyclization processes. Inexpensive halide salts play a crucial role in activating the trifluoromethylthiolating reagent towards photoredox catalysis and aid the formation of the SCF₃ radical.     

Syntheses of pyrido[1,2-a][1,3,5]triazin-4-one C-deoxyribonucleosides

We achieved the syntheses of new C-deoxyribonucleosides bearing pyrido[1,2-a][1,3,5]triazin-4-one derivatives using palladium-catalyzed Heck-type coupling. Some of these C-deoxyribonucleosides were able to convert to phosphoramidite reagents, which can be used for DNA synthesizer. DNA oligomers including pyrido[1,2-a][1,3,5]triazin-4-one C-deoxyribonucleoside, which had 2-amino group were synthesized, and T_m values with a natural nucleoside were measured.     

Synthesis of α,α-disubstituted amino acids based on tandem reaction of dehydroamino acid derivatives

The formation of all-substituted sp³-hybridized carbon-center was investigated via tandem reaction of dehydroamino acid derivatives. The diethylzinc-promoted reaction of dehydroamino acid derivatives with acid anhydride or π-allyl palladium complex proceeded smoothly to afford α,α-disubstituted amino acids via a radical and anionic carbon-carbon bond-forming processes. The tandem reductive reaction of N-phthaloyl dehydroalanine also proceeded effectively by using Bu₃SnH and Pd(PPh₃)₄.     

Convenient synthesis of (E)-5-aminoallyl-2′-deoxycytidine and some related derivatives

Preparation via the Heck reaction of 5-(E)-(3-trifluoroacetamidoallyl)-2′-deoxycytidine (3a) and some N4-formamidine protected derivatives is reported. Difficulties with coupling N-allyl-trifluoroacetamide to 5-iodo-2′-deoxycytidine were overcome by using Pd₂(dba)₃ as catalyst and temporary dimethylformamidine protection of the N4-amine of the nucleoside. Compound 3a was isolated with 60% overall yield by crystallization.     

Stereoselective synthesis of tri- and tetrasubstituted oxepanes via n-Bu3SnH mediated 7-endo-trig vinyl radical cyclisation

A stereoselective 7-endo-trig cyclisation of homopropargyl and phenyl homopropargyl derivatives of Baylis-Hillman adducts using n-Bu₃SnH/AIBN mediated vinyl radical cyclisation affords tri- and tetrasubstituted oxepanes, respectively, in good yields.     

Redox system for perfluoroalkylation of arenes and α-methylstyrene derivatives using titanium oxide as photocatalyst

Photoirradiation of titanium oxide (TiO₂) excites the electrons from the valence band to the conduction band, leaving holes in the valence band. Using these holes and electrons, it is possible to perform one-electron oxidations and reductions. We developed a method for the photocatalytic perfluoroalkylation of aromatic rings such as benzene and its derivatives, naphthalene and benzofuran with perfluoroalkyl iodide by the combination of reduction and oxidation reactions with TiO₂. Perfluoroalkyl iodide was reduced to a perfluoroalkyl radical by the excited electrons in the conduction band of TiO₂, and the resulting radical reacted with an aromatic ring to form an arenium radical that was successively oxidized to a cation by the holes in the valence band of TiO₂. Similarly, the photocatalytic reaction of α-methylstyrene with perfluoroalkyl iodide afforded perfluoroalkylated α-methylstyrene, in which the perfluoroalkyl group is on a methyl carbon.     

Acetyl derivatives of nucleoside 5′-triphosphates,I

Acetyl derivatives of nucleoside 5′-phosphates and nucleoside 5′-triphosphates (both ribo and deoxyribo series) were prepared by accomplishing partial (O-) and full (N, O-) acetylation of the basic compounds with acetic anhydride in pyridine medium.     

Total syntheses of chaetocin and ent-chaetocin

The first total synthesis of chaetocin (1), a potent histone methyltransferase inhibitor, is described in detail. Key reactions were radical bromination for α-oxidation of the diketopiperazine ring, and reductive radical coupling for construction of the dimeric core structure. Stereoselective construction of the disulfide bridges was achieved via substitution reaction with H₂S. The total synthesis of 1 was accomplished in nine steps starting from known d-amino acid derivatives. Total synthesis of non-natural ent-chaetocin (ent-1) was also achieved via the established synthetic route, starting from l-amino acid derivatives.     

Efficiency of alkoxyl radical product formation from 5-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones

In a comparative study, reactions between 5-(p-methoxyphenyl)-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones and appropriate mediators (BrCCl₃, Bu₃SnH) provided higher yields of alkoxyl radical products (δ-bromohydrins, cyclic ethers, carbonyl compounds) than respective transformations of 5-phenyl- and 5-methyl-substituted derivatives. The unusual selectivity of applied thiohydroxamates to furnish products of O-alkylation, even upon treatment with soft carbon electrophiles, and the marked propensity of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones to crystallize, facilitated preparation and purification of the new family of alkoxyl radical precursors in a noteworthy manner.     

Selectivity between N-1 and N-7 nucleosides: regioselective synthesis of BMK-Y101, a potent cdk7 and 9 inhibitor

BMK-Y101 is a new pyrrolo[2,3-d]pyrimidine-based potent cdk7 and 9 inhibitor, which is characterized by an intriguing structural feature of N-1 nucleoside, departing from previously reported N-7 nucleoside Cdk inhibitor, xylocydine. Though N-1 nucleosides have appeared in the literature, they have often been considered as kinetic products and thus intermediates of N-7 glycosylation. In the course of the synthetic studies of xylocydine derivatives, we have developed a highly regioselective method to obtain the N-1 nucleoside. The origin of the selectivity is apparently based on the reactivity of the silylated nucleobase and the stability of the resulting N-1 nucleoside. The choice of BSA as a silylating agent was critical in securing the N-1 nucleoside, BMK-Y101. On the other hand, proper selection of reaction conditions promoting transglycosylation provides an efficient route to N-7 nucleosides.     

Evaluation of chemiluminescence reagents for selective detection of reactive oxygen species

In order to evaluate the chemiluminescence (CL) reagents for selective detection of reactive oxygen species (ROS), we comprehensively measured the CL responses of 20 CL reagents (three luminol derivatives, two imidazopyrazinone derivatives, eight lophine derivatives, six acridinium ester derivatives and lucigenin) against six types of ROS (superoxide anion: O₂⁻, hydroxyl radical: OH, hydrogen peroxide: H₂O₂, hypochlorite anion: ClO⁻, singlet oxygen: ¹O₂, and nitric oxide: NO). As a result of the screening, it was found that nine CL reagents selectively detected O₂⁻ while one CL reagent selectively detected OH. However, no CL reagent had selectivity on the detection of H₂O₂, ClO⁻, ¹O₂ and NO. Our screening results could help to select the most suitable CL reagent for selective determination of different ROS.As an application study, 4-methoxyphenyl-10-methylacridinium-9-carboxylate (MMAC), one of the acridinium ester derivatives, showed high selectivity on the detection of O₂⁻, and thus was applied to the assay of superoxide dismutase (SOD) activity. The dynamic range and detection limit of the developed CL assay were 0.1-10 and 0.06 U mL⁻¹, respectively. Significant correlation (r = 0.997) was observed between the results by the CL assay using MMAC and the spectrophotometric assay using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt.     

Gas-Phase Fragmentations of Anions Derived from N-Phenyl Benzenesulfonamides

In addition to the well-known SO₂ loss, there are several additional fragmentation pathways that gas-phase anions derived from N-phenyl benzenesulfonamides and its derivatives undergo upon collisional activation. For example, N-phenyl benzenesulfonamide fragments to form an anilide anion (m/z 92) by a mechanism in which a hydrogen atom from the ortho position of the benzenesulfonamide moiety is specifically transferred to the charge center. Moreover, after the initial SO₂ elimination, the product ion formed undergoes primarily, an inter-annular H₂ loss to form a carbazolide anion (m/z 166) because the competing intra-annular H₂ loss is significantly less energetically favorable. Results from tandem mass spectrometric experiments conducted with deuterium-labeled compounds confirmed that the inter-ring mechanism is the preferred pathway. Furthermore, N-phenyl benzenesulfonamide and its derivatives also undergo a phenyl radical loss to form a radical ion with a mass-to-charge ratio of 155, which is in violation of the so-called “even-electron rule.”

Synthesis, characterization, and aqueous properties of new amphiphilic copolymer with fluorocarbon groups

A series of amphiphilic copolymers with fluorocarbon groups (Poly(AMPS-co-FS), PAMFS) were synthesized by the radical copolymerization of sodium 2-acryamido-2-methylpropanesulfonate (AMPS) and styrene derivatives with a fluorocarbon side chain (FS). The structures and molecular characteristics of PAMFS were confirmed by ¹H-NMR, ¹⁹F-NMR, elemental analysis, and static light scattering. The aggregation behavior of the copolymer in aqueous solution was studied by surface tension, electrical conductivity, dynamic laser light scattering, transmission electron microscopy, and fluorescence measurements at different conditions. The results indicated that the surface activity of PAMFS is dependent on the content of fluorocarbon groups in the copolymer structure. The surface tension (γ _cmc) and critical micelle concentration of PAMFS decrease with the increase of sodium chloride concentration. The copolymers formed micelle-like aggregates and the fluorocarbon groups exhibited a strong tendency for intermolecular association.     

Line dependence of CIDEP polarizations for the p-benzosemiquinone,radical

Time-resolved steady state experiments were performed on six prominent hf-lines of the p-benzosemiquinone radical (PBQH) dissolved in ethylene glycol using an improved experimental technique. For the same six lines T₁ and _T2 were determined experimentally. Initial and radical pair polarizations as well as the second order chemical decay constant β were obtained by simulating each of the time-resolved curves using a new procedure. It was found that both the initial polarization P_a^∞(I) and β were the same within experimental accuracy for all six lines in four different experiments. The radical pair polarization P_a*, however, varied within the experimental accuracy in the manner predicted qualitatively from the theory for a second order termination reaction. Light attenuation experiments with both pulsed and continuous light confirmed these results. The magnitude of P_a^∞ (I) may be interpreted in terms of the microscopic theory for the photo-activated triplet mechanism, whereas the magnitude of P_a* appears to be too high by a factor of four to six as compared to the microscopic theory for the radical pair mechanism.     

Phototransformations of azetidine radical cations stabilized in freonic matrices

It has been established that transformations of azetidine radical cations observed in freonic matrices under the action of light with λ = 436 nm (T = 77 K) are associated with C-N bond cleavage which corresponds to the cyclic form yielding a mixture of open distonic C-centered radical cations of the following structure: ·CH₂CH₂CH=NH ₂ ⁺      

Solvent‐Free One‐Step Photochemical Hydroxylation of Benzene Derivatives by the Singlet Excited State of 2,3‐Dichloro‐5,6‐dicyano‐p‐benzoquinone Acting as a Super Oxidant

Photoinduced hydroxylation of neat deaerated benzene to phenol occurred under visible‐light irradiation of 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ), which acts as a super photooxidant in the presence of water. Photocatalytic solvent‐free hydroxylation of benzene derivatives with electron‐withdrawing substituents such as benzonitrile, nitrobenzene, and trifluoromethylbenzene used as neat solvents has been achieved for the first time by using DDQ as a super photooxidant to yield the corresponding phenol derivatives and 2,3‐dichloro‐5,6‐dicyanohydroquinone (DDQH₂) in the presence of water under deaerated conditions. In the presence of dioxygen and tert‐butyl nitrite, the photocatalytic hydroxylation of neat benzene occurred with DDQ as a photocatalyst to produce phenol. The photocatalytic reactions are initiated by oxidation of benzene derivatives with the singlet and triplet excited states of DDQ to form the corresponding radical cations, which associate with benzene derivatives to produce the dimer radical cations, which were detected by the femto‐ and nanosecond laser flash photolysis measurements to clarify the photocatalytic reaction mechanisms. Radical cations of benzene derivatives react with water to yield the OH‐adduct radicals. On the other hand, DDQ ^{. ?} produced by the photoinduced electron transfer from benzene derivatives reacts with the OH‐adduct radicals to yield the corresponding phenol derivatives and DDQH₂. DDQ is recovered by the reaction of DDQH₂ with tert‐butyl nitrite when DDQ acts as a photocatalyst for the hydroxylation of benzene derivatives by dioxygen.