Annulation of a Methylenecyclopropane with Cyanoalkenes Catalyzed by Lewis Bases.

The annulation of a methylenecyclopropane with acyl cyanoalkenes by using DABCO or quinuclidine as a catalyst to give 2,3-dihydofurans has been developed. A stoichiometric amount of the Lewis bases promoted the isomerization of 2,3-dihydrofurans to furans. 1 H NMR spectra of the reaction in situ revealed that the methylenecyclopropane is opened by the Lewis base to form a reaction intermediate that is added to the cyanoalkenes.

Reductive coupling of allenoates with aldehydes catalyzed by halogenotin hydride.

Hydrostannylation of allenoate 1 with halogenotin hydride (Bu2SnClH) was developed to give allylic stannane (I), which then could react with aldehyde 2. The same coupling gave allylic alcohol 3 under reductive conditions in the presence of a silane and a catalytic amount of Bu2SnClH. This catalytic protocol was applied to the synthesis of lactone 4. The resultant products 3 and 4 were subjected to oxidative conditions to provide oxacycles 5 and 6, respectively.

Synthesis of 5-Membered Sulfur Heterocycles via Tin-Catalyzed Annulation of Mercapto Ketones with Activated Alkenes.

Efficient conversion of α-mercapto ketones 1 with activated alkenes 2 into S-heterocycles was developed with Sn(Oct)2-2MeOH acting as a catalyst. Two types of products, dihydrothiophene 3 and thiolane 4, were obtained. The selectivity of the products was dependent on the reaction temperature and on the rearrangement of the S-heterocycles from 3 to 4 under heating conditions. The dihydrothiophenes 3 were transformed into useful thiolactones 6-8 and thiophene 9.

Catalytic Annulation of Epoxides with Heterocumulenes by the Indium-Tin System.

In the synthesis of five-membered heterocycles by the annulation of epoxides with heterocumulenes such as carbon dioxide and isocyanates, we developed the indium-tin catalytic system and synthesized various cyclic adducts including novel types products under mild reaction conditions.

Catalytic cycloaddition of 2-hydroxy ketones with 1,1-dicyanoalkenes.

A tin-catalyzed reaction of α-hydroxy ketones with 1,1-dicyanoalkenes produced 2-amino-4,5-dihydrofuran-3-nitriles. In the catalytic reaction, tin enolates were generated from α-hydroxy ketones as active catalytic species. The highly basic ability of the Sn-O bonds played an important role in the reactions. This tin-catalyzed reaction was highly atom-economical and required no other metal reagents.

Transition-metal-free coupling reaction of vinylcyclopropanes with aldehydes catalyzed by tin hydride.

Donor-acceptor cyclopropanes are useful building blocks for catalytic cycloaddition reactions with a range of electrophiles to give various cyclic products. In contrast, relatively few methods are available for the synthesis of homoallylic alcohols through coupling of vinylcyclopropanes (VCPs) with aldehydes, even with transition-metal catalysts. Here, we report that the hydrostannation of vinylcyclopropanes (VCPs) was effectively promoted by dibutyliodotin hydride (Bu2 SnIH). The resultant allylic tin compounds reacted easily with aldehydes. Furthermore, the use of Bu2 SnIH was effectively catalytic in the presence of hydrosilane as a hydride source, which established a coupling reaction of VCPs with aldehydes for the synthesis of homoallylic alcohols without the use of transition-metal catalysts. In contrast to conventional catalytic reactions of VCPs, the presented method allowed the use of several VCPs in addition to conventional donor-acceptor cyclopropanes.

Differentiating the aromatic positional isomers of methylbuphedrones and methoxybuphedrones via chemical ionization-mass spectrometry.

Discrimination of aromatic positional isomers of methylbuphedrones and methoxybuphedrones was successfully achieved. Meta isomers were discriminated by chemical ionization-tandem mass spectrometry (CI-MS/MS) using acetonitrile as a reagent gas. Furthermore, all the aromatic positional isomers were discriminated by CI-MS/MS using vinyltrimethylsilane as a reagent gas.

Assay of short-chain carboxylic acids in plasma and urine using gas chromatography after extractive alkylation.

After extractive alkylation combined with plasma deproteinization, we used gas chromatography to assay for short-chain carboxylic acids from formic acid to valeric acid in plasma and urine. It was possible to provide highly sensitive analysis with 0.1-3.4 µg/mL as the limit of detection for plasma and 0.6-8.0 µg/mL for urine, with a correlation coefficient of 1.000 for the linear regression calibration curves. For plasma, deproteinization using ultrafiltration before extractive alkylation resulted in a higher sensitivity for acetic, propionic, butyric, and valeric acids compared with the method without deproteinization. The concentrations of formic acid and acetic acid were determined to be 6 µg/mL and 10 µg/mL, respectively, in the tested plasma, and 22 µg/mL and 32 µg/mL, respectively, in the tested urine. Concentrations from propionic acid to valeric acid were ≤ 1.3 µg/mL. In addition, high concentrations of sulfate, phosphate, hydrogen carbonate, ammonium, and/or sodium ions did not remarkably inhibit the derivatization of carboxylic acids, although hydrogen carbonate ions significantly inhibited that of formic acid.

Improvement of Extractive Alkylation Gas Chromatography of Short-chain Carboxylic Acids in Aqueous Solution.

In the analysis of short-chain carboxylic acids such as formic acid and acetic acid in aqueous solution using extractive alkylation gas chromatography, tetrahexylammonium bromide (THAB) as a phase-transfer catalyst (PTC) causes a high intensity and broad peaks in the gas chromatogram, and interfere with the detection of carboxylic acid derivatives. By an easy treatment of the extractive alkylation solution with perchloric acid and n-hexane, it is possible to remove more than 95% of THAB, and to provide good gas chromatogram with a little admixture of carboxylic acid derivatives. The desensitization was 16% at the maximum, the contamination of the glass insert in gas chromatograph and liquid phase in column by THAB was minimized, and trouble in continuous measurement could be avoided.

Synthesis of oxazolidinones initiated by regio- and diastereo-controlled crotylation of alpha-dicarbonyl compounds.

A one-pot synthesis of oxazolidinones was initiated via the allylation of alpha-dicarbonyl compounds, accompanying regio- and diastereo-controlled carbon-carbon bond formation on the side chains of the oxazolidinones.

Direct use of 1,3-dienes for the allylation of ketones via catalytic hydroindation.

In this study, in situ catalytically generated allylic indium from 1,3 dienes and InCl2H was developed for use in the allylation of ketones. This protocol resulted in the unprecedented establishment of a successive combining of quaternary C-C bonds, which could then be applied to many types of ketones. Other branched 1,3 dienes and vinyl cyclopropanes, could also be coupled with ketones in a reaction where CuH would not be applicable.

Regio- and stereoselective hydrostannation of allenes using dibutyliodotin hydride (Bu2SnIH) and successive coupling with aromatic halides.

Regio- and stereoselective hydrostannation of allenes by using di-n-butyliodotin hydride (Bu2SnIH) was accomplished to give alpha,beta-disubstituted vinyltins, which induced the synthesis of multi-substituted alkenes in a one-pot procedure.

Catalytic Annulation of Diethyl Methylenecyclopropane-1,1-dicarboxylate with 1,1-Dicyanoalkenes.

The catalytic annulation of methylenecyclopropane 1 with 1,1-dicyanoalkenes 2 using a Mg-Sn catalytic system was developed. Selective formation of cyclopentylidenemalonates 3 and spiro[2,3]hexane-1,1-dicarboxylates 4 was accomplished via the choice of a proper solvent and an effective catalytic system.

Transition-Metal-Free Reductive Coupling of 1,3-Butadienes with Aldehydes Catalyzed by Dibutyliodotin Hydride.

In this study, the Bu2SnIH-catalyzed direct coupling of 1,3-dienes with aldehydes was developed. This reaction could be suitable for coupling without the use of transition-metal catalysts. Many types of aldehydes were applied to this reaction. The addition of MeOH promoted the catalytic cycle.

Generation of allylic indium by hydroindation of 1,3-dienes and one-pot reaction with carbonyl compounds.

A hydroindation of 1,3-dienes by dichloroindium hydride (HInCl2) generates allylic indiums that react with carbonyl or imine moieties in a one-pot treatment. The former reaction proceeds in a radical manner, and the latter is ionic allylation. Moreover, both reactions require no additives such as radical initiators, Lewis acids, or transition metal catalysts.

High chelation control of three contiguous stereogenic centers in the Reformatsky reactions of indium enolates with alpha-hydroxy ketones: unexpected stereochemistry of lactone formation.

[reaction: see text] A boat-type of chelated bicyclic transition state involving highly diastereoselective construction of three contiguous stereogenic centers in the Reformatsky reaction of indium enolates with alpha-alkoxy/hydroxy ketones is proposed. alpha-Hydroxy ketones with indium enolates furnished highly diastereoselective lactones, while alpha-alkoxy ketones gave acyclic esters in moderate selectivities. X-ray structure analyses of key products unequivocally revealed the unexpected stereochemistry of products and the reaction pathway.

The reductive amination of aldehydes and ketones by catalytic use of dibutylchlorotin hydride complex.

The reductive amination of aldehydes or ketones using Ph(2)SiH(2) or PhSiH(3) has been effectively promoted by the direct use of Bu(2)SnClH-pyridine N-oxide as a catalyst; this method has advantages in terms of its mild conditions and wide application to various carbonyls and amines, including aliphatic examples.

Inter- and intramolecular radical couplings of ene-ynes or halo-alkenes promoted by an InCl3/MeONa/Ph2SiH2 system.

[reaction: see text] An effective generation of indium hydride (HInCl(2)) under nonacidic conditions is achieved by transmetalation between Ph(2)SiH(2) and InCl(2)OMe. The presented system achieves the titled coupling reactions in a radical manner. In particular, the nonacidic character enables the applications to acid-sensitive inter- and intramolecular ene-yne couplings.

Catalytic [3 + 2] Cycloaddition through Ring Cleavage of Simple Cyclopropanes with Isocyanates.

The catalytic synthesis of γ-butyrolactams was established via [3 + 2]-cycloaddition of cyclopropanes with isocyanates. An organotin iodide ate complex, MgBr(+)[Bu2SnBrI2](-), was employed as an effective catalyst. Simple cyclopropanes that lack aryl or vinyl substituents were useful precursors. Even acyl cyclopropanes were applicable. The hybrid characteristics of a tin complex, acidic MgBr(+) with nucleophilic tin iodide, was responsible for the catalytic reaction.