Regioselective Coupling of Different Conjugate Esters by Magnesium Metal Reduction: A Route to Unsymmetrical Adipic Acid Esters.

A novel tactic to synthesize unsymmetrical 3-aryladipic acid esters has been developed via magnesium-promoted reductive coupling of ethyl cinnamates with methyl acrylate. In the present methodology, 3-aryladipic acid derivatives were prepared with good functional group tolerance and a wide substrate scope under very mild reaction conditions in good yields. The application of this reaction to dienic acid esters led to the successful control of the reaction to give 5-aryl-oct-3-enedioic acid esters with high regioselectivity.

Degradation of three ß-O-4 lignin model compounds via organic electrolysis and elucidation of the degradation mechanisms.

Woody biomass comprising cellulose, hemicellulose, and lignin has been the focus of considerable attention as an alternative energy source to fossil fuel for various applications. However, lignin has a complex structure, which is difficult to degrade. Typically, lignin degradation is studied using ß-O-4 lignin model compounds as lignin contains a large number of ß-O-4 bonds. In this study, we investigated the degradation of the following lignin model compounds via organic electrolysis: 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol 1a, 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)-1,3-propanediol 2a, and 1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-1,3-propanediol 3a. The electrolysis was conducted for 2.5 h at a constant current of 0.2 A using a carbon electrode. Various degradation products such as 1-phenylethane-1,2-diol, vanillin, and guaiacol were identified upon separation via silica-gel column chromatography. The degradation reaction mechanisms were elucidated using electrochemical results as well as density functional theory calculations. The results suggest that the organic electrolytic reaction can be used for the degradation reaction of a lignin model with ß-O-4 bonds.

Magnesium-Promoted Reductive Carboxylation of Aryl Vinyl Ketones: Synthesis of γ-Keto Carboxylic Acids.

Direct reductive carboxylation of easily prepared aryl vinyl ketones under the atmosphere of carbon dioxide led to the selective formation of γ-keto carboxylic acids in 38-86% yields. The reaction is characterized by the carbon-carbon bond formation of carbon dioxide at the ß-position of enone, with the use of magnesium turnings that can be easily handled as the reducing agent and the eco-friendly reaction conditions such as no pressuring, no lower or higher reaction temperature, and short reaction time. This protocol showed a wide substrate scope and provided a useful and convenient alternative to access biologically important γ-keto carboxylic acids.

Regioselective Silylations of Propargyl and Allyl Pivalates through Ca-Promoted Reductive C(sp3)-O Bond Cleavage.

A practical protocol for the regioselective preparation of 3-phenylpropargylsilanes and 3-phenylallylsilanes in yields of 36-77 and 48-86%, respectively, from readily accessible 3-phenylpropargyl and 1-phenylallyl pivalates was developed through reductive C(sp3)-O bond cleavage. This method represents the first example of the direct application of vastly abundant calcium granules to a reductive coupling reaction. A broad range of propargylsilanes and allylsilanes are simply prepared using easy-to-handle pivalates and chlorotrimethylsilane under mild catalyst-free and additive-free conditions.

Reductive 3-Silylation of Benzofuran Derivatives via Coupling Reaction with Chlorotrialkylsilane.

Reductive silylation of benzofurans with an electron-withdrawing group by a magnesium metal and the subsequent oxidative rearomatization by DDQ gave the selective formation of less reported 3-silylated benzofurans in moderate to good yields under mild reaction conditions with wide substituent scope. The silyl group introduced on the five-membered ring by the reductive coupling could survive with no elimination throughout the oxidation process. The silylated heteroaromatic skeleton is useful as an intermediate in organic synthesis, and its practical utility was also demonstrated by several transformation reactions.

Construction of a CF3-Containing Benzofurofuranone Skeleton from Coumarins via Reductive Coupling and Acid-Mediated Ring Contraction.

Magnesium-promoted reductive introduction of a trifluoroacetyl group to coumarin in the presence of ethyl trifluoroacetate and the subsequent treatment with trifluoroacetic acid led to simple access to a trifluoromethylated benzofurofuranone at 8a-position with a high regio- and stereoselectivity. Trifluoromethylated or difluoromethylated benzofurofuranone derivatives were also prepared from coumarins including naturally occurring ones only in two successive steps, which might have potential bioactivity in medicinal chemistry.

Catalyst-Free and Solvent-Controlled Reductive Coupling of Activated Vinyl Triflates with Chlorotrimethylsilane by Magnesium Metal and Its Synthetic Application.

Vinylsilanes were directly prepared from the corresponding vinyl triflates under magnesium-promoted reductive conditions in THF with no transition metal catalyst, and gem-bis-silylated compounds were obtained in NMP. Investigation of the redox potential of starting materials and products suggested that reductive coupling reactions of vinyl triflates might be controlled by the reduction potential. A variety of gem-bis-silylated compounds and 3-silyladipic acid esters were easily synthesized in only two steps from vinyl triflates in high yields.

Synthesis of 4-(Trifluoromethyl)cyclopentenones and 2-(Trifluoromethyl)furans by Reductive Trifluoroacetylation of Ynones.

Reductive introduction of a fluorine-containing carbon block to readily available conjugated ynones, followed by intramolecular cyclization, successfully gave the corresponding trifluoromethylated cyclopentenones or trifluoromethylated furans in good yields through a simple two-step protocol. The key compound in carbon-carbon bond formation by magnesium-promoted reduction is ethyl trifluoroacetate, which has been rarely used as a fluorine-containing carbon source, especially to electron-deficient carbon atoms in organic synthesis.

[Preparation and characterization of (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl thiamine sulfides].

A new type of S-protected thiol-type thiamines (prodrugs), which have a (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl group recognized as a biologically safe promoiety, were designed, prepared, and confirmed to show higher serum thiamine levels after oral administration to rats than after that of thiamine itself and bisbentiamin as standards. Thus it was shown that the promoiety should be also used for improvement of poor oral absorption of drugs with a mercapto group, in addition to the absorption of drugs with carboxyl, amino, and hydroxyl groups.

Zn-promoted regioselective and sequence-selective one-pot joining reaction of three components: alkyl iodides, alpha,beta-unsaturated esters (or nitriles), and acylating agents.

One-pot treatment of alkyl iodides, alpha,beta-unsaturated esters (or nitriles), and acylating agents such as nitriles or acid anhydrides in the presence of Zn metal at room temperature in the same reaction system brought about a regioselective and sequence-selective three-component joining reaction involving first C-alkylation at the beta-position and second C-acylation at the alpha-position of alpha,beta-unsaturated esters (or nitriles) to afford the corresponding alpha,alpha-dialkylketoesters (or alpha,alpha-dialkylketonitriles) in moderate to good yields. [reaction: see text]

Novel one-pot vicinal double C-acylation of styrenes and methacrylates by electroreduction.

[reaction: see text] Electroreduction of styrenes or alkyl methacrylates in the presence of aliphatic acid anhydrides or N-acylimidazoles with an undivided cell equipped with zinc electrodes as the anode and the cathode brought about novel one-pot vicinal double C-acylation to afford the corresponding 1,4-diketones in satisfactory yields.

Enantioselective electrochemical oxidation of enol acetates using a chiral supporting electrolyte.

Anodic oxidation of 1-acetoxy-3,4-dihydronaphthalene (1) and alpha-acetoxy-beta-alkylstyrenes (3) at -78 degrees C in a mixed solvent of acetonitrile (CH(3)CN), tetrahydrofuran (THF), and acetic acid (AcOH) containing (S)-tetraethylammonium camphorsulfonate as a chiral supporting electrolyte brought about enantioselective formation of the corresponding 2-acetoxy-1-tetralones (2) and (R)-2-acetoxy-1-phenyl-1-alkanone (4) with maximum enantiomeric excess (ee) of 44% and 21%, respectively. Introduction of a 7-methoxy group into 1 and increase in bulkiness of a beta-alkyl group in 3 resulted in improvement of enantioselectivity of the reactions.