Palladium-catalyzed reaction of 4-cyclopentene-1,3-diol monoacetate with Grignard reagents producing hitherto unreachable cis-1,2-isomers

Reaction of 4-cyclopentene-1,3-diol monoacetate with RMgCl (R = alkyl, aryl) in the presence of a palladium catalyst proceeded with retention of configuration to give cis-1,2-regioisomers as the major products.     

A new reagent system for installation of an aryl group onto the monoacetate of 4-cyclopentene-1,3-diol

Among the three types of reagents from PhMgX (X=Br, Cl) and CuCN for phenylation of 4-cyclopentene-1,3-diol monoacetate, PhMgCl/CuCN (cat.) and Ph₂Cu(CN)(MgCl)₂ in THF afforded the trans-1,4-isomer efficiently (82-87% yields, 91-93% regioselectivity). Similarly, o- and p-RC₆H₄MgCl (R=Me, OMe, CH₂CH) in combination with CuCN furnished good to excellent reactivity and regioselectivity. As an application, a three-step synthesis of dihydromultifidene was accomplished successfully.     

Reinvestigation of palladium-catalyzed allylation of the monoacetate of 4-cyclopentene-1,3-diol and synthesis of the coronafacic acid ethyl ester

A larger quantity of a β-keto ester that is 1.5–1.7 equiv more than the base (t-BuOK, NaH) was found to be essential in securing sufficient yields of the products in the palladium-catalyzed allylic substitution of the monoacetate of 4-cyclopentene-1,3-diol with β-keto esters. This requirement also works well for substitutions with the TBS ether of the monoacetate and the monoacetate of 2-cyclohexene-1,4-diol. As an application, the coronafacic acid ethyl ester was synthesized as an optically active form.     

Scope and limitation of organocuprates, and copper or nickel catalyst-modified Grignard reagents for installation of an alkyl group onto cis-4-cyclopentene-1,3-diol monoacetate

Alkylation of the title compound 1 was investigated with two types of reagents. One is a copper reagent derived from R(T)MgX (X = Cl, Br) and CuX (X = CN, I) and the other is R(T)MgX in the presence of a copper or a nickel catalyst. First, butylation was studied with BuCu(CN)(MgX), Bu(2)Cu(CN)(MgX)(2), BuMgX/CuCN (10 mol %), BuCu (derived from BuMgCl and CuI), and BuMgCl/CuI (10 mol %) in THF or Et(2)O. We found that trans 1,4-isomer 2a and/or trans 1,2-isomer 3a were produced exclusively with these reagents and that the stoichiometry of BuMgX/CuX and the choice of solvent were critical to attain high regioselectivity and efficient yield. Reaction with Bu(2)Cu(CN)(MgCl)(2) and BuMgCl/CuX (X = CN, I; 10 mol %) both in THF produced 2a with 93-94% regioselectivity in 87-92% yields. On the other hand, BuCu(CN)(MgX) in THF, Bu(2)Cu(CN)(MgX)(2) in Et(2)O, and BuMgX/CuCN (10 mol %) in Et(2)O furnished 3a in good yields with >90% selectively, irrespective of X of BuMgX. In the nickel-catalyzed butylation of 1 with BuMgCl, NiCl(2)(dppp) among NiCl(2)(tpp)(2), NiCl(2)(dppf), and NiCl(2)(dppp) furnished the best result to produce 2a. The CuCN-based protocol was then applied to other alkyl Grignard reagents, which include Me, Et, (CH(2))(3)Ph, c-C(6)H(11), (CH(2))(6)OMOM, (CH(2))(9)CH=CH(2), and CH(2)Ph as the alkyl group (R(T)). In addition, the Mitsunobu inversion of 2a and 3a afforded the corresponding cis isomers stereoselectively with AcOH as an acid at -78 degrees C in toluene for 2a and with 4-(NO(2))C(6)H(4)COOH in THF at r.t. for 3a. No racemization during the alkylation was confirmed by the reaction using (1R,3S)-1 (>99% ee) to produce (1S,4S)-2a and (1S,2S)-3a, respectively.     

Realization of anti-SN2' selective allylation of 4-cyclopentene-1,3-diol monoester with aryl- and alkenyl-zinc reagents

Anti-SN2' mode of allylation of the monoester of 4-cyclopentene-1,3-diol with aryl and alkenyl anions was achieved, for the first time, with the MeOCH2CO2- group as a leaving group to which R-ZnBr and CuCl (as a catalyst) were best fitted. The aryl groups successfully installed were Ph, o- and p-MeC6H4, o-MOMOC6H4, o-MeOC6H4, and p-F-C6H4, while cis and trans alkenyl groups were attached with retention of the olefinic stereochemistries.     

New reagent system for attaining high regio- and stereoselectivities in allylic displacement of 4-cyclopentene-1,3-diol monoacetate with aryl- and alkenylmagnesium bromides

[Reaction: see text] Low regioselectivity of RMgBr (R = aryl, alkenyl) in the CuCN-catalyzed reaction with 4-cyclopentene-1,3-diol monoacetate is improved by addition of LiCl or MgCl2 to a similar extent as previously obtained with RMgCl (>90:10). The limitation encountered in the preparation of RMgCl no longer exists in the present method using RMgBr. The method is utilized in the synthesis of AH-13205, a selective EP2-receptor agonist.     

Vibrational spectrum and assignment of 4-cyclopentene-1,3-dione

The IR and Raman spectra of 4-cyclopentene-1,3-dione have been studied. A complete assignment of the observed bands is proposed on the basis of the usual criteria (contours of the IR bands in the vapour phase and depolarization state of the Raman bands). For the planar species the assignment is confirmed by a normal-coordinate calculation.     

Synthesis of 2-ferrocenylidene-4-cyclopentene-1,3-diones

A squarate-based synthesis of 2-ferrocenylidene-4-cyclopentene-1,3-diones is described. When refluxed in dioxane at 100 °C, heated with silica gel as a solvent free grinded solid mixture at 125 °C or stirred with silica gel in ethyl acetate at room temperature, 4-ferrocenylethynyl-4-hydroxy-2-cyclobutenones, prepared from ethynylferrocene and 3-cyclobutene-1,2-diones, afforded 2-ferrocenylidene-4-cyclopentene-1,3-diones as the major or single product of the reaction. In some cases, ferrocenyl quinones also resulted from these reactions as the minor products. The major or exclusive formation of 2-ferrocenylidene-4-cyclopentene-1,3-diones is attributed to the radical-stabilizing ability of the ferrocenyl group.     

Copolymerization of 4-cyclopentene-1,3-dione with p-chlorostyrene and vinylidene chloride

The copolymerization of 4-cyclopentene-1,3-dione (M₂) with p-chlorostyrene and vinylidene chloride is reported. The copolymers were prepared in sealed tubes under nitrogen with azobisisobutyronitrile initiator. Infrared absorption bands at 1580 cm.^?1 revealed the presence of a highly enolic β-diketone and indicated that copolymerization had occurred. The copolymer compositions were determined from the chlorine analyses and the reactivity ratios were evaluated. The copolymerization with p-chlorostyrene (M₁) was highly alternating and provided the reactivity ratios r₁ = 0.32 ± 0.06, r₂ = 0.02 ± 0.01. Copolymerization with vinylidene chloride (M₁) afforded the reactivity ratios r₁ = 2.4 ± 0.6, r₂ = 0.15 ± 0.05. The Q and e values for the dione (Q = 0.13, e = 1.37), as evaluated from the results of the vinylidene chloride case, agree closely with the previously reported results of copolymerization with methyl methacrylate and acrylonitrile and confirm the general low reactivity of 4-cyclopentene-1,3-dione in nonalternating systems.     

Acceleration of the corrosion reaction of magnesium by Fenton reagents

Abstract

Magnesium alloys have attracted increased attention for a variety of applications, chief among which are alternative energy and medical implants. The use of biodegradable implants in the complex system of the human body, in which myriad reactions occur, must consider the potential effects of the body’s natural chemical reactions on implant corrosion rates. The aim of this study was to elucidate the synergistic effects of pure Mg and Mg alloys on the Mg corrosion reaction with reagents that participate in the Fenton reaction. We corroborated our results with six different measurement methods (hydrogen evolution rate [HER], gas chromatography [GC], potentiodynamic polarization, inductively coupled plasma [ICP] spectrometry, Auger electron spectroscopy [AES], and scanning electron microscope [SEM]). The results point out that the corrosion and hydrogen evaluation rates of Mg were elevated by the addition of Fenton reagents, divalent iron and hydrogen peroxide, to a saline solution. In the context of Mg-based alloy medical implant development and use, this observation is significant.     

Selenophilic reaction of organolithium and magnesium reagents with phosphinoselenoic chlorides

The reaction of phosphinoselenoic chlorides 1 with various organolithium and magnesium reagents was studied. Sequential reaction of phosphinoselenoic chlorides 1 with organolithium and magnesium reagents and elemental selenium gave two types of products, phosphine selenides 2 and phosphinodiselenoic acid esters 3 . The esters 3 appeared to be formed via the selenophilic reaction of organolithium and magnesium reagents with the chlorides 1 . Molecular orbital calculations were carried out for model compounds H₂P(E)Cl (E = O, S and Se) to determine their electronic structures. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:185–191, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20091     

Levopimaric acid derived 1,2-diamines and their application in the copper-catalyzed asymmetric Henry reaction

Levopimaric acid, a readily available starting material, was used in efficient syntheses of new enantiopure diamines and Schiff bases with good yields. The synthetic procedure is based on the fumaropimaric acid monomethyl ester conversion into the optically pure trans-1,2-diamine via a Curtius rearrangement. New diamines were studied as ligands in the copper-catalyzed asymmetric Henry reaction.     

Aldimines of 5-aminouracil as reagents in 1,3-dipolar cycloaddition reaction

Abstract  

The condensation of 5-aminouracil with aromatic aldehydes gave the appropriate C-arylimines, which were used in [2+3] cycloaddition with nitrile oxides derived from 4-substituted benzaldoximes. As a result of the dipolar cycloaddition reaction several hitherto unknown 5-(3,5-diphenyl-1,2,4-oxadiazol-4(5H)-yl)pyrimidine-2,4(1H,3H)-diones have been obtained in satisfactory yields.     

The kinetics of the reaction between magnesium and EBT

The kinetics of the reaction between Mg²⁺ and Eriochrome-Black-T (EBT) has been investigated in the pH range between 7.05 and 9.0, in the presence of 12% ethanol. The reaction is found to consist of two parallel paths, one involving the tervalent unprotonated ligand, and one its monoprotonated form. The rate constant for the unprotonated ligand has a “normal” value, whereas that for the protonated form is much lower. The numerical value of the rate constant for the unprotonated ligand obtained from results at a magnesium concentration of 10^?3M and a pH up to 9.0 is, however, inconsistent with that obtained from results at [Mg²⁺] = (1 to 4) × 10^?3M and pH up to 8.1. This can be explained, at least partially, if we assume the intermediate MgHD to lose its proton not only to H₂O, but also to other bases present in the solution.     

Chemoenzymatic synthesis of glycosylated enantiomerically pure 4-pentene 1,2- and 1,3-diol derivatives

1-Dimethylthexylsiloxy-2-chloroacetoxy-4-pentene 2 and 1-dimethylthexylsiloxy-3-chloroacetoxy-4-pentene 3 were saponified with Pseudomonas lipase to give (R)-1-dimethylthexylsiloxy-4-pentene-2-ol (ee=99%) and (S)-2 (ee=99%) and (S)-1-dimethylthexylsiloxy-4-pentene-3-ol (ee=99%) and (R)-3 (ee=98%), respectively. All enantiomers were chemically transformed into the corresponding enatiomerically pure 2-benzoyloxy-4-pentene-1-ols 8 and 3-benzoyloxy-4-pentene-1-ols 14, respectively. Mannosylation of (R)-8 and (S)-14 with 2,3,4,6-tetra-O-benzoyl-a-d-mannopyranosyl trichloroacetimidate afforded the corresponding mannopyranosides.     

On the mechanism of the copper-catalyzed cyclopropanation reaction

The selectivity-determining step in enantioselective copper-catalyzed cyclopropanation with diazo compounds has been studied by experimental and computational methods. The addition of the very reactive metallacarbene intermediate in an early transition state to the substrate alkene is concerted but strongly asynchronous, with substantial cationic character on one alkene carbon in the neighborhood of the transition state. Evidence from isotope effects and Hammett studies supports the nature of the transition state. Formation of a metallacyclobutane intermediate by a [2+2] addition is kinetically disfavored. Ligand-substrate interactions influencing the enantio- and diastereoselectivity have been identified, and the preferred orientation of the alkene substrate during the addition is suggested.