Dialkyl Acetals Research Articles

Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by the TolBINAP/DMAPEN−Ruthenium(II) Complex: A Significant Effect ofN-Substituents of Chiral 1,2-Diamine Ligands on Enantioselectivity

Asymmetric hydrogenation of acetophenone in the presence of Ru(II) catalysts coordinated by TolBINAP and a series of chiral 1,2-diamines was studied. The sense and degree of enantioselectivity were highly dependent on the N-substituents of the diamine ligands. The N-substituent effect was discussed in detail. Among these catalysts, the (S)-TolBINAP/(R)-DMAPEN-Ru(II) complex showed the highest enantioselectivity. The mode of enantioface selection was interpreted by using transition state models based on the X-ray structure of the catalyst precursor. The chiral catalyst effected the hydrogenation of alkyl aryl ketones and arylglyoxal dialkyl acetals to afford the chiral alcohol in >99% ee in the best cases. Hydrogenation of racemic benzoin methyl ether with the chiral catalyst through dynamic kinetic resolution gave the anti-alcohol (syn:anti = 3:97) in 98% ee, while the reaction of alpha-amidopropiophenones resulted in the syn-alcohols (syn:anti = 96:4 to >99:1) in >98% ee.

Synthesis of 2,5-bis(butylsulfanyl)-2,3-dihydro-4H-pyran-2-carbaldehyde acetals and their unexpected isomerization

2,5-Bis(alkylsulfanyl)-2,3-dihydro-4H-pyran-2carbaldehydes exhibit bacteriostatic effect [1]. 2,5-Bis(butylsulfanyl)-2,3-dihydro-4H-pyran-2-carbaldehyde is known as a strong and safe antiseptic [2]. We examined its reactions with alcohols in order to obtain new potential biologically active derivatives. Unlike 2,5-dialkoxy-2,3-dihydro-4H-pyran-2-carbaldehydes [3] which take up alcohols at the endocyclic double bond, the reaction of sulfur-containing analog I with alcohols in acid medium at room temperature (i.e., under comparable conditions) occurred at the carbonyl group. However, apart from the expected symmetric dialkyl acetal II, diastereoisomeric mixed acetals III and IV were always formed, regardless of the acid taken as catalyst (p-TsOH, HClO4, CF3COOH) or alcohol (MeOH, EtOH); the products are readily detected by gas chromatography–mass spectrometry. To determine the product structure, isomer mixture obtained in the reaction of aldehyde I with methanol were separated by high-performance liquid chromatography (HPLC). The reaction with methanol was selected as model process, taking into account more facile identification of methyl derivatives by NMR spectroscopy. Judging by the intensities of signals from the acetal CH protons at δ 4.27 (IIa), 4.53 (IIIa), and 4.47 ppm (IVa) in the H NMR spectra, the product ratio changed from 2 : 1 : 1 to 1 : 1 : (1–2) in 7–10 days, the conversion of the initial aldehyde being 80–100%. Analysis of the H and C NMR spectra of the first isomer allowed us to identify it as symmetric dimethyl acetal IIa. Formalistically, two other isomers IIIa and IVa result from exchange of OMe and SBu groups in the vicinal acetal and hemithioketal moieties (at the C and C atoms).

ChemInform Abstract: Reductive Coupling of Aromatic Dialkyl Acetals Using the Combination of Zinc and Chlorotrimethylsilane in the Presence of Potassium Carbonate.

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Reductive Coupling of Aromatic Dialkyl Acetals Using the Combination of Zinc and Chlorotrimethylsilane in the Presence of Potassium Carbonate

Abstract The treatment of aromatic acetals with zinc and chlorosilane in the presence of potassium carbonate in toluene brought about facile and effective reductive coupling to give the corresponding coupling products.

Controlling chemoselectivity—application of DMF di- t-butyl acetal in the regioselective synthesis of 3-monosubstituted indolizines

Among a number of DMF dialkyl acetals investigated for the regioselective synthesis of 3-acylindolizines, the di- t-butyl acetal, via its iminium intermediate readily formed in situ, provides the highest chemoselectivity for the intermolecular cyclization of picolinium salts. DMF di- t-butyl acetal was applied to the syntheses of a variety of 3-acylated indolizines including alkyl, aryl, and heteroaryl substituents.

Synthesis of the C9–C21 fragment of debromoaplysiatoxin and oscillatoxins A and D

A highly stereoselective synthesis of the C9–C21 fragment of debromoaplysiatoxin and oscillatoxins A and D has been devised. This new approach relies on the cross coupling of titanium enolates from N-acyl-1,3-thiazolidine-2-thiones and dialkyl acetals and the selective hydrogenolysis of O-benzyl protecting groups.

Pd(II)-Catalyzed Conversion of Styrene Derivatives to Acetals: Impact of (−)-Sparteine on Regioselectivity

[reaction: see text] Pd[(-)-sparteine]Cl(2) catalyzes the formation of dialkyl acetals from styrene derivatives with Markovnikov regioselectivity. The substrate scope of this reaction has been investigated, and initial mechanistic studies indicate that the reaction proceeds through an enol ether intermediate and a Pd-hydride.

Structural determination of mannopeptimycin cyclic acetals

In structure–activity relationship (SAR) studies on mannopeptimycin antibiotics, mannopeptimycin α(1) was acetalized by reacting with certain dialkyl acetals under acidic conditions. The major products of these reactions were determined to be cyclic acetals at the 4,6-positions of the terminal mannose (Man-B), by exemplary spectroscopic analyses of two typical acetalization products 2 and 3.

Structure of pyridynes and pyridyne N-oxides and their cycloaddition to ketene dialkyl acetals

The structure of pyridine, pyridine N-oxide, 2-pyridyne, 3-pyridyne, 2-pyridine N-oxide and 3-pyridyne N-oxide have been calculated at the Becke3LYP/6-311(d,p) level of theory. The regioselectivity of the [2+2] cycloaddition of the 3,4-pyridyne to the dimethoxyethylene to give azabenzocyclobutenone dimethyl acetal is in accordance with a biradical pathway.

A Simple, Efficient and General Procedure for Acetalization of Carbonyl Compounds and Deprotection of Acetals under the Catalysis of Indium(III) Chloride

AbstractIndium(III) chloride efficiently catalyzes the protection of a variety of aldehydes and ketones to their corresponding 1,3‐dioxolanes and dialkyl acetals in refluxing cyclohexane. On the other hand, deprotection of acetals is also achieved in refluxing aqueous methanol under the catalysis of indium(III) chloride.

Development of Novel Carbon—Carbon Bond Forming Reactions Using Zirconocene Complex

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and Chemical Properties of 1-Aryl-substituted Pyrimido[5,4-b]indoles

The class of isomeric pyrimidoindoles and their derivatives contain many compounds possessing biological activity of various types, including analgesic [1, 2], vasodilating [3], antihypoxant [4], antiinflammatory [5], inotropic [6], etc. Recently, it was also established that some derivatives of pyrimido[5,4-b]indoles are capable of inhibiting NO synthases — enzymes catalyzing the oxidation of L-arginine into citrulline and nitric oxide [7]. A number of NO synthase blockers have been found among the compounds containing amidine fragments – for example, imino derivatives of various heterocycles, including substituted pyrimidines [8]. Nitric oxide (NO) is capable of penetrating by means of simple diffusion through almost all biological membranes. For this reason, a large release of this biologically-active mediator gives rise to numerous (frequently, serious) pathological states. Such disorders include septic shock, neurodegenerative diseases, and various inflammatory processes. In order to avoid NO overproduction in the organism, it is necessary to use NO synthase inhibitors. This study was aimed at the synthesis and characterization of new 1-aryl-substituted pyrimido[5,4-b]indoles containing amidine fragments — potential NO synthase inhibitors. Methods most widely used for the synthesis of pyrimido[5,4-b]indoles are based on the cyclization of 3-aminoindole-2-carboxylic acid derivatives via reactions with “single-carbon” components such as dimethylformamide dialkyl acetals [9] and isocyanates [10, 11]. Recently [12, 13], we obtained a series of 1-aryl-2-oxo1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole-4-oxides (Ia – Id) and transformed a seven-member cycle of 4-oxide Ia into a six-member cycle under the action of PCl3 with the formation of 2-oxo-1-phenyl-3-formyl-2,3,4,5-tetrahydro-1H-pyrimido[5, 4-b]indole (IIa) [12]. In this study, by analogy with the above transformation of oxide Ia, we have also decreased the diazepine cycle of compounds Ib – Id and obtained the corresponding 1H-pyrimido[5,4-b]indoles (IIb – IId). The H NMR spectra of compounds IIb – IId exhibit doubling of most signals due to amide isomerism. The appearance of singlets at = 8.35, 8.46, and 8.82 – 8.85 ppm is indicative of the presence of N–CHO groups in these compounds. The physicochemical characteristics and parameters of the H NMR spectra of the newly synthesized compounds are presented in Tables 1 and 2. It should be noted that the transformation of 6-methyl-substituted 4-oxide of [1,4]diazepino[6,5-b]indole Id proceeds much more difficultly (a mixture of oxide Id and PCl3 is boiled for 4 h) than the analogous conversion of unsubstituted 4-oxides Ib and Ic, for which the reaction is completed within 10 min. We have also studied the transformations of 2-oxo-1phenyl-2,5-dihydro-1H-pyrimido[5,4-b]indole (III) obtained by boiling 3-formylpyrimidoindole IIa with piperidine in methanol. This reaction involves deformylation and subsequent aromatization of the pyrimidine ring

Palladium‐Catalyzed Heck Reaction on 1‐Alkoxy‐1,3‐dienes: A Regioselective γ‐Arylation of α,β‐Unsaturated Carbonyl Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Development of Novel Carbon-Carbon Bond Forming Reactions Using Zirconocene Complex

Novel zirconium-mediated carbon-carbon bond-forming reactions were developed. The allylic, gamma-alkoxyallylic, allenyl, and gamma, gamma-dialkoxyallylic zirconium species can be prepared from corresponding ethers under mild conditions through the addition of a zirconocene-butene complex to the carbon-carbon multiple bond of the ethers and subsequent beta-elimination of the alkoxyl group. The gamma,gamma-dialkoxyallylic zirconium species reacts with carbonyl compounds at the beta-position of the zirconium atom like a ketene dialkyl acetal in the presence of stoichiometric amounts of Lewis acid and gave cyclopropane and/or cyclobutane derivatives. Intramolecular reaction of allylic zirconium species with acetal also develops as a ring contraction reaction of carbohydrates and morpholine derivatives. This method is useful for the construction of chiral highly functionalized carbocycles and pyrrolidines. The intramolecular ester transfer reaction through the zirconium-mediated coupling reaction of alkenyl carbamates gave gamma-aminobutyric acid derivatives and pyrrolidine-3-carboxylic acids.

Palladium-catalyzed Heck reaction on 1-alkoxy-1,3-dienes: a regioselective gamma-arylation of alpha,beta-unsaturated carbonyl compounds.

[reaction: see text] alpha,beta-Unsaturated acetals afford, in the presence of the LIC-KOR superbase, 1-alkoxybuta-1,3-dienes. These substrates cross couple with aryl derivatives in the presence of Pd catalyst (Heck conditions) in a regio- and stereoselective mode. With dialkyl acetals, the reaction affords arylated dienes; on the other hand, in the case of 1,3-dioxane derivatives, the final outcome of the process formally corresponds to the direct gamma-arylation reaction of the starting alpha,beta-unsaturated material.

Structure of substituted o-benzynes and their cycloaddition to ketene dialkyl acetals

The cycloaddition of substituted arynes to ketene dialkyl acetals to give benzocyclobutenone dialkyl ketals has been studied. Fifteen new derivatives of benzocyclobutene have been described. Theoretical structures of 18 substituted arynes have been calculated at the Becke3LYP/6-311G(d,p) level. The LUMO energies of 3- or 4-substituted arynes have been nicely correlated with the Hammett σ m values. In order to determine the relative stability of the benzynes, the energies of aryne formation from corresponding subtituted benzenes (via 1,2-didehydrogenation reactions) have been calculated. The mechanism of the addition of benzyne to ketene dialkyl acetal has been discussed and a biradical pathway may account for the regioselectivity of the reaction.

Synthesis of [5′‐13C]Ribonucleosides and 2′‐Deoxy[5′‐13C]ribonucleosides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Effect of alkyl group size on the mechanism of acid hydrolyses of benzaldehyde acetals.

Hydrolyses of benzaldehyde acetals, PhCH(OR)(2), are specific hydrogen-ion catalyzed when R = methyl, n-butyl, but with secondary and tertiary alkyl derivatives, R = i-propyl, s-butyl, t-butyl, t-amyl, hydrolyses are general-acid catalyzed. The Brønsted alpha values for both secondary and tertiary alkyl groups are in the range: alpha = 0.57-0.61. A simple iterative procedure was developed to estimate the individual rate constants for general-acid catalysis by the diacid and monoacid forms of succinic acid buffer. Plots of log k(obs) (at [buffer] = 0 M) against pH are linear for the secondary and tertiary acetals, and plots of log k(H) for the H(3)O(+)-catalyzed reaction, (13)C and (1)H chemical shifts, and (1)J(CH) coupling constants against the Charton steric parameter, nu, for alkoxy groups are linear. The second-order rate constant, k(H), increases about 100-fold on going from R = Me to R = t-amyl, indicating the significant role of steric effects on reactivity. Steric effects upon (13)C NMR chemical shifts and coupling constants indicate that increasing the bulk of the alkoxy moiety increases the electron density at the carbon reaction center, which accelerates hydrolysis. Analysis of the Jencks-More-O'Ferrall free energy diagram for the reaction provides support for concerted proton transfer and C-O bond breaking in the transition state for hydrolyses of benzaldehyde acetals with secondary and tertiary alkyl groups in contrast to specific hydrogen catalysis with R = Me and n-Bu. All our results are consistent with rate-determining acid hydrolysis of benzaldehyde dialkyl acetals to hemiacetal intermediates that breakdown rapidly to benzaldehyde.

First [2 + 2]‐Cycloaddition of a 3,4‐Didehydropyridine and a Ketene Dialkyl Acetal.

AbstractFor Abstract see ChemInform Abstract in Full Text.

First [2+2]-cycloaddition of a 3,4-didehydropyridine and a ketene dialkyl acetal

The 3- or 4-halopyridines and a ketene dialkyl acetal were shown to permit the synthesis of pyrido[ b]cyclobutene derivatives. This finding constitutes the first published report of cycloadditions involving an olefin and a 3,4-pyridyne partner. The reaction is totally regioselective and the structure of the cycloadduct is determined unambiguously by NMR experiments.