Stereochemistry of the allylation and crotylation reactions of alpha-methyl-beta-hydroxy aldehydes with allyl- and crotyltrifluorosilanes. Synthesis of anti,anti-dipropionate stereotriads and stereodivergent pathways for the reactions with 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes

A new method for the stereoselective synthesis of the anti,anti-dipropionate stereotriad via the reaction of alpha-methyl-beta-hydroxy aldehydes with (Z)-crotyltrifluorosilane (24) is described. These reactions were designed to occur through bicyclic transition states (e.g., 31) in which the silane reagent is covalently bound to the beta-hydroxyl group of the aldehyde and the crotyl group is transferred intramolecularly. This methodology was used to synthesize the C(7)-C(16) segment (58) of zincophorin, which contains a synthetically challenging all-anti stereopentad unit. Surprisingly, 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes react in a stereodivergent manner with 24: 2,3-anti-beta-hydroxy aldehydes give the targeted anti,anti-dipropionate adducts with high selectivity, but the reactions of 2,3-syn-beta-hydroxy aldehydes are poorly selective. The stereodivergent behavior of 2,3-syn- vs 2,3-anti-alpha-methyl-beta-hydroxy aldehydes is also exhibited in their reactions with the allyl- (68) and (E)-crotyltrifluorosilanes (27). Competition experiments performed with beta-hydroxy aldehydes 37a (anti) and the corresponding p-methoxybenzyl (PMB) ether 48, and between aldehyde 39 (syn) and the PMB ether 90, established that the 2,3-anti-beta-hydroxy aldehydes react predominantly through bicyclic transition states while the 2,3-syn aldehydes react predominantly through conventional Zimmerman-Traxler transition states. NMR studies established that both the 2,3-syn and the 2,3-anti aldehydes form stable, pentavalent silicate intermediates (98 and 100) with PhSiF(3), but chelated structures 99 and 101 could not be detected. The activation energies for the competing bicyclic and conventional Zimmerman-Traxler transition states were calculated by using semiemperical methods (MNDO/d). These calculations indicate that the stereodivergent behavior of the 2,3-syn-beta-hydroxy aldehydes and the 2,3-anti-beta-hydroxy aldehydes is due to differences in nonbonded interactions in the bicyclic transition states. Specifically, nonbonded interactions in the bicyclic transition states for the allylation/crotylation reactions of the 2,3-syn-beta-hydroxy aldehydes permits the traditional Zimmerman-Traxler transition states to be preferentially utilized.     

Facile synthesis of highly substituted 3-aminofurans from thiazolium salts, aldehydes, and dimethyl acetylenedicarboxylate

[reaction: see text] A facile preparation of 3-aminofuran derivatives via multicomponent reactions of thiazole carbenes, aldehydes, and dimethyl acetylenedicarboxylate (DMAD) is reported. In this process, the thiazole carbenes, generated in situ from thiazolium salts, reacted with aldehydes and DMAD at -78 to 0 degree C in CH(2)Cl(2) to afford the substituted furans in moderate to good yields. Eight substituted thiazolium salts were employed as carbene precursors in the reaction. Besides aryl aldehydes, alpha,beta-unsaturated aldehydes, aliphatic aldehydes, and arenedial were also investigated and found to be applicable to this reaction.     

Evaluation of solid-phase microextraction methods for determination of trace concentration aldehydes in aqueous solution

A method for trace analysis of a wide range of aldehydes (saturated/unsaturated aliphatic, aromatic aldehydes, including hydroxylated species, and dialdehydes) in an aqueous solution was optimized. An evaluation of three solid-phase microextraction (SPME) techniques (headspace, liquid-phase, and on-fiber derivatization) with o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) aldehyde derivatization was performed focusing on the optimization of the main extraction parameters (temperature and time). The optimized method employed the liquid-phase SPME (D-L-SPME) of derivatized aldehydes at 80 degrees C for 30 min. Limits of detection (LODs) using this optimal method were in the range of 0.1-4.4 microg/L for the majority of aliphatic (saturated, unsaturated), aromatic aldehydes and dialdehydes. Formaldehyde LODs and those of some hydroxylated aromatic aldehydes were between 32 and 55 microg/L. Headspace SPME using an on-fiber derivatization generally showed a lower sensitivity and several compounds were not detected. Another technique, the optimized headspace SPME of aldehydes derivatized in aqueous solution, was not as sensitive as D-L-SPME for hydroxylated aromatic aldehydes. The developed method was used to analyze aqueous particulate matter extracts; this method achieved higher sensitivities than those obtained with US Environmental Protection Agency (EPA) Method 556.     

Asymmetric direct aldol reaction catalyzed by an L-prolinamide derivative: considerable improvement of the catalytic efficiency in the ionic liquid

The asymmetric direct aldol reactions of a wide scope of aldehydes with unmodified ketones in the presence of 20 mol%(S,S,S)-pyrrolidine-2-carboxylic acid (2'-hydroxyl-1',2'-diphenyl-ethyl)-amine (1) were performed in ionic liquids; aldol products with 91 to >99% ees for aromatic aldehydes and 99% ees for alphatic aldehydes were offered by the present procedure.     

Diastereoselective synthesis of polysubstituted tetrahydropyrans and thiacyclohexanes via indium trichloride mediated cyclizations.

Polysubstituted tetrahydropyrans and thiacyclohexanes were synthesized in high yields with excellent diastereoselectivities via indium trichloride mediated cyclizations between homoallyl alcohols and mercaptans with aldehydes. In the case of tetrahydropyran products, the stereochemistry of the product was found to be directly correlated with the geometry of the homoallyl alcohols; whereas the cross-cyclization of aldehydes with trans-homoallyl alcohols generated (up-down-up) 2,3,4-trisubstituted tetrahydropyran products exclusively, the reaction of aldehydes with cis-homoallyl alcohols provided mainly (up-up-up) 2,3,4-trisubstituted products. When a trisubstituted homoallyl alcohol was used, its cross-cyclization with aldehydes generated (up-down-up-down-up) pentasubstituted tetrahydropyran derivatives with simultaneous controlling of five stereogenic centers. On the other hand, a cyclization-decyclization equilibrium was observed in the formation of thiacyclohexanes. The reaction of both cis- and trans-homoallyl mercaptans with aldehydes provided the same major diastereomers.     

5-Amino-4-sulfanylphthalhydrazide as a chemiluminescence derivatization reagent for aromatic aldehydes in liquid chromatography

5-Amino-4-sulfanylphthalhydrazide (ASPH) was synthesized as a chemiluminescence derivatization reagent for aromatic aldehydes in liquid chromatography (LC). Benzaldehyde, 4-tolualdehyde, 4-chlorobenzaldehyde, 4-formylbenzoic acid, 4-hydroxybenzaldehyde and vanillin were used as model compounds to optimize the derivatization conditions. This reagent, ASPH, reacts selectively with aromatic aldehydes in the presence of sodium sulfite and disodium hydrogenphoshite in acidic medium at 100 degrees C to give the corresponding highly chemiluminescent 2-arylbenzothiazole derivatives. The resulting derivatives generated intense chemiluminescence by reaction with hydrogen peroxide and potassium hexacyanoferrate(III) in alkaline solution. The ASPH derivatives of aromatic aldehydes were separated by reversed-phase liquid chromatography with isocratic elution, and detected chemiluminometrically after mixing with oxidizing agents. The detection limits (signal-to-noise ratio = 3) for aromatic aldehydes are in the range 0.2-4.0 fmol for a 20-microl injection volume. Currently, the method is not effective for aliphatic aldehydes because of interfering LC peaks.     

Polymer-mediated extraction of the fluorescent compounds derived by Hantzsch reaction with dimedone for the sensitive determination of aliphatic aldehydes in air

An extraction method based on the thermo-responsive precipitation of a water-soluble polymer, poly(N-isopropylacrylamide) [PNIPAAm], was applied to the concentration of dimedone (5,5-dimethylcycrohexane-1,3-dion) derivatives for the highly sensitive determination of aldehydes in air. Aliphatic aldehydes including formaldehyde, acetaldehyde, propanal, 1-butanal, 1-heptanal, and 1-hexanal in air were well solubilized into the aqueous solution of dimedone and ammonium acetate by mixing the solution and air sample in a polyvinyl fluoride bag. Fluorescent derivatives of aldehydes that had formed by the Hantzsch reaction with dimedone were concentrated by polymer-mediated extraction. The recoveries of the fluorescent compounds increased with increasing the carbon number of aldehyde and were more than 80% for the derivatives from aldehydes having more than three carbon atoms under the optimal conditions. Microgram per m3 (sub-ppb) levels of the aliphatic aldehydes, propanal, 1-butanal, 1-heptanal, and 1-hexanal, in ambient air were successfully determined by HPLC separation with fluorometric detection. The sampling volume and time required were only 1l and 20 s, respectively.     

Z-selective synthesis of alpha,beta-unsaturated amides with triphenylsilylacetamides

With the purpose of developing a method of preparing Z-alpha,beta-unsaturated amides, the Peterson reaction of the (triphenylsilyl)acetamide Ph(3)SiCH(2)COX (1, X = NBn(2); 3, X = NMe(2)) with various aldehydes was examined. The reaction of aromatic aldehydes gave selectivities up to >97:3. It was found that the selectivity was a function of the electronic nature of the aromatic ring and higher Z selectivity was attained with electron-rich aldehydes. With aliphatic aldehydes selectivities up to 92:8 were achieved, and unlike with analogous phosphorus reagents, less sterically hindered aldehydes gave higher Z selectivity. Also, 3, which has a smaller amide group than 1, tended to give rise to higher selectivity. A comparison with the reaction of trimethylsilyl analogues revealed the significance of the phenyl substituents on the silyl group.     

A simple, rapid and sensitive method for determination of aldehydes in human blood by gas chromatography/mass spectrometry and solid-phase microextraction with on-fiber derivatization

Aldehydes are considered potential markers for enhanced oxidative stress and have been proposed as a diagnostic measure of cancer status. Do to their volatility and activity, it is very difficult to accurately measure aldehydes in human blood. In the present work, gas chromatography/mass spectrometry (GC/MS) and solid-phase microextraction (SPME) with on-fiber derivatization was developed for determination of aldehydes in human blood. O-(2,3,4,5,6-Pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) in aqueous solution was first adsorbed by a SPME fiber, and then the aldehydes in blood samples were headspace extracted by the SPME fiber and rapidly derivatized with PFBHA on the SPME fiber. Finally, the oximes formed were desorbed and detected by GC/MS in electron ionization (EI) mode. Validation of the present method was carried out, and the method was applied to quantitative analysis of the aldehydes in lung cancer blood. The results demonstrated that GC/MS and SPME with on-fiber derivatization is a simple, rapid, sensitive and solvent-free method for the determination of aldehydes in human blood.     

Reactions of substituted (1,3-butadiene-1,4-diyl)magnesium, 1,4-bis(bromomagnesio)butadienes and 1,4-dilithiobutadienes with ketones, aldehydes and PhNO to yield cyclopentadiene derivatives and N-Ph pyrroles by cyclodialkenylation

1,4-Dilithiobutadiene derivatives 1, 1,4-bis(bromomagnesio)butadiene derivatives 2 and metallacyclic (1,3-butadiene-1,4-diyl)magnesium reagents 3 were prepared and their reactions with ketones, aldehydes, and PhNO were investigated. Multiply substituted cyclopentadienes and N-Ph pyrroles were formed by unprecedented reaction conditions. The carbonyl group of aldehydes and ketones was deoxygenated during the reaction and behaved formally as a one-carbon unit; the N==O moiety of PhNO was cleaved to afford N-Ph pyrrole derivatives. Furthermore, different reactivities among these three types of reagents 1, 2 and 3 were revealed. The 1,4-dilithium reagents 1 readily reacted with both aldehydes and ketones; the 1,4-dimagnesium reagents 2 reacted with aldehydes, but not ketones; the metallacyclopentadiene reagents of magnesium 3 showed higher reactivity and did react with ketones.     

Organocatalytic SOMO reactions of copper(I)-acetylide and alkylindium compounds with aldehydes

The derivatisation of aldehydes in their α-position is an important facet of organic synthesis. Organocatalytic radical reactions afford α-functionalised aldehydes via a SOMO activation pathway. New organo-SOMO reactions of aldehydes with copper(I)-acetylide and alkylindium reagents are detailed. These reactions proceed well under the catalysis of chiral imidazolidinones. The corresponding functionalised aldehydes were obtained with acceptable yields, but with only low enantiomeric ratios.     

Synthesis of alpha-heteroarylpropanoic acid via asymmetric hydroformylation catalyzed by Rh(I)-(R,S)-BINAPHOS and the subsequent oxidation

The asymmetric hydroformylation of vinyl heteroarenes (vinylfurans and vinylthiophenes) was investigated by using Rh(I)-BINAPHOS derivatives as a catalyst. The hydroformylation of vinylthiophenes 1 gave the corresponding branched aldehydes 2 with high enantiopurities as major products. Oxidation of the aldehydes 2 successfully afforded alpha-heteroarylpropanoic acids 4 in good yields. In addition, the aldehydes 2 were reduced to alcohols 5 without loss of enantiomeric excess.     

Synthesis of 2-Aryl Benzothiazoles via K(2)S(2)O(8)-mediated Oxidative Condensation of Benzothiazoles with Aryl Aldehydes

Nontransition metal-catalyzed synthesis of 2-aryl benzothiazoles was achieved through K(2)S(2)O(8)-mediated oxidative condensation of benzothiazoles with aryl aldehydes. The same transformation can also be effected when the aryl aldehydes were replaced with phenylglyoxylic acids.     

Simultaneous derivatization/preconcentration of volatile aldehydes with a miniaturized fiber-packed sample preparation device designed for gas chromatographic analysis

A novel in-needle sample preparation device has been developed for the determination of volatile aldehydes in gaseous samples. The needle device is designed for the gas chromatographic (GC) analysis of aldehydes and ketones commonly found in typical in-house environments. In order to prepare the extraction device, a bundle of polymer-coated filaments was longitudinally packed into a specially designed needle. Derivatization reactions were prompted by 2,4-dinitrophenylhydrazine (NDPH) included in the needle, and so the aldehydes and ketones were derivatized to the corresponding hydrazones and extracted with the extraction needle. A reproducible extraction needle preparation process was established, along with a repeatable derivatization/extraction process that ensures the successful determination of aldehydes. The storage performance of the extraction needle was also evaluated at room temperature for three days. The results demonstrate the successful application of the fiber-packed extraction device to the preparation of a gaseous sample of aldehydes, and the future possibility of applying the extraction device to the analysis of in-house environments.     

Determination of low-aliphatic aldehyde derivatizatives in human saliva using polymer monolith microextraction coupled to high-performance liquid chromatography

In this study, a polymer monolith microextraction (PMME) using a poly (methacrylic acid-ethylene glycol dimethacrylate) (MAA-EGDMA) monolith in conjunction with high-performance liquid chromatography (HPLC) was developed for the determination of 2,4-dinitrophenylhydrazine (DNPH) derivatives of several aldehydes in human saliva. The conditions for the labeling reactions of aldehydes with DNPH and followed extraction of the derivatives were optimized. The precision, recovery and detection limits were evaluated with spiked saliva. The limits of detection ranged from 0.43 to 1.40 μg/L. The inter-and intra-day relative standard deviations were less than 10%. The proposed method was successfully applied to the determination of aldehydes in saliva samples from a non-smoker, a passive smoker and a heavy smoker.     

1,3,5,7-四甲基-8-丙酰肼-二氟化硼-二吡咯甲烷柱前衍生高效液相色谱测定白酒中的脂肪醛

以合成的1,3,5,7-四甲基-8-丙酰肼-二氟化硼-二吡咯甲烷(BODIPY-丙酰肼)作为柱前荧光衍生试剂,用于高效液相色谱分离荧光法检测甲醛、乙醛、丙醛、丁醛、戊醛、己醛、庚醛、辛醛、壬醛、癸醛、十一醛、十二醛等12种脂肪醛.通过对衍生条件和分离条件进行优化,建立了测定脂肪醛的HPLC/FD新方法.衍生反应以H3P...     

Stereocontrolled synthesis of acyclic 1,3-diols via condensation of tungsten-syn-pi-pentadienyl complexes with aldehydes. A new Prins reaction via s-trans-diene cationic intermediates

In the presence of BF(3).Et(2)O, condensation of CpW(CO)(2)(syn-pi-2-methoxycarbonylpentadienyl) with aldehydes generated tungsten-eta(4)-trans-diene cation in cold toluene, and hydrolysis of this salt afforded tungsten-pi-allyl-anti-1,3-diols in good yields. This new synthesis of anti-1,3-diols represents an atypical Prins reaction that is applicable to normal aldehydes. The anti/syn ratios of 1,3-diols increased with an increase in the size of the aldehydes. These anti-1,3-diols were transformed into various complex oxygen heterocycles based on two demetalations: (1) conversion to an allyl cation followed by nucleophilic attack and (2) condensation with aldehydes via its CpW(NO)Cl derivative, to give functionalized alpha-methylene butyrolactones. A semi-emperical calculation was performed to deduce the transition-state structure to rationalize the anti-stereoselectivity.     

Studies on the synthesis of 2-(2-arylvinyl)thieno[2,3-d]pyrimidines and 5-(2-arylvinyl)triazolothieno[3,2-e]pyrimidines

Synthesis of 2-(2-arylvinyl)thienopyrimidines, by the acid catalyzed condensation of nitriles with thiophene o-aminocarbonyl compounds, the condensation of aldehydes with thiophene o-aminoamides, the base catalyzed condensation of aldehydes with 2-methylthienopyrimidines and by the Wittig condensation of 2-thieno-pyrimidinylmethylphosphonium salts with aldehydes is described. Isomeric 5-methyltriazolothienopyrimidines were found to react, under basic condition, with aldehydes yielding 5-(2-arylvinyl)triazolo[2,3-c]thieno-pyrimidines. While 5-styryltriazolo[4,3-c] isomers resisted acid catalysed isomerization, they were found to isomerize to triazolo[2,3-c]pyrimidines under base catalysis.     

Ruthenium-catalyzed oxidative cleavage of olefins to aldehydes.

Three oxidation protocols have been developed to cleave olefins to carbonyl compounds with ruthenium trichloride as catalyst (3.5 mol %). These methods convert olefins that are not fully substituted to aldehydes rather than carboxylic acids. While aryl olefins were cleaved to aromatic aldehydes in excellent yields by using the system of RuCl3-Oxone-NaHCO3 in CH3CN-H2O (1.5:1), aliphatic olefins were converted into alkyl aldehydes with RuCl3-NaIO4 in 1,2-dichloroethane-H2O (1:1) in good to excellent yields. It is noteworthy that terminal aliphatic olefins were cleaved to the corresponding aldehydes in excellent yields by using RuCl3-NaIO4 in CH3CN-H2O (6:1).     

Highly enantioselective phenylacetylene additions to both aliphatic and aromatic aldehydes

The readily available and inexpensive BINOL in combination with Ti(O(i)Pr)(4) is found to catalyze the reaction of an alkynylzinc reagent with various types of aldehydes including aliphatic aldehydes, aromatic aldehydes, and other alpha,beta-unsaturated aldehydes to generate chiral propargyl alcohols with 91-99% ee at room temperature. No previous chiral catalysts have exhibited such a broad scope of enantioselectivity with respect to the type of aldehydes for this reaction. [reaction: see text]