Design of an organocatalyst for the enantioselective Diels-Alder reaction with alpha-acyloxyacroleins

We have realized the first enantioselective organocatalytic Diels-Alder reaction between alpha-substituted acroleins, such as alpha-acyloxyacroleins, and not only cyclic but also acyclic dienes. alpha-Acyloxyacroleins are useful as synthetic equivalents of alpha-haloacroleins. The present catalyst could be prepared in situ from pentafluorobenzenesulfonic acid (2.5-3.0 equiv) and chiral triamine (1 equiv) derived from H-l-Phe-l-Leu-N(CH2CH2)2. The enantioselective Diels-Alder reaction of 5-(benzyloxymethyl)cyclopentadiene, cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, and isoprene with alpha-(p-methoxybenzoyloxy)acrolein catalyzed by the above chiral ammonium salt (2.5-20 mol %) at -20-22 degrees C gave the corresponding adducts with 83, 83, 91, 92, and 88% ee, respectively.     

Ruthenium-catalyzed diyne hydrative cyclization: synthesis of substituted 1,3-diene synthons

[reaction: see text]. A novel and versatile strategy for the synthesis of highly functionalized substituted 3-sulfolenes based on [CpRu(CH3CN)3]PF6-catalyzed hydrative cyclization has been developed. A marked ketone directing effect in ruthenium-catalyzed cyclization was observed for the first time. This provides complementary chemoselectivity for the synthesis of 3-sulfolenes and other cyclic enones. The utility of this method has been demonstrated by SO2 extrusion of 3-sulfolenes to afford 1,3-dienes and the subsequent inter- and intramolecular Diels-Alder reaction.     

Nonparallelism between reaction rate and dienophile-catalyst affinity in catalytic enantioselective Diels-Alder reactions

[reaction: see text] The above reaction is much faster with Y = CF(3)CH(2)O than with Y = CH(3)O. However, the methyl ester is a strong inhibitor of the Diels-Alder reaction of the trifluoroethyl ester, since it has a higher affinity for the catalyst 1.     

The first general enantioselective catalytic Diels-Alder reaction with simple alpha,beta-unsaturated ketones

The first general approach to enantioselective catalysis of the Diels-Alder reaction with simple ketone dienophiles has been accomplished. The use of iminium catalysis has enabled enantioselective access to a fundamental Diels-Alder reaction variant that has previously been unavailable using chiral Lewis acid catalysis. A new chiral amine catalyst has been developed that allows a variety of monodentate cyclic and acyclic ketones to successfully participate in enantioselective [4 + 2] cycloadditions. A wide spectrum of cyclic and acyclic diene substrates can also be accommodated in this new organocatalytic transformation. A computational model is provided that is in accord with the sense of enantioinduction observed for all reactions conducted during the course of this study.     

Reactions of gaseous acylium ions with 1,3-dienes: further evidence for polar [4 + 2+] Diels-Alder cycloaddition

A novel reaction of acylium and thioacylium ions, polar [4 + 2(+)] Diels-Alder cycloaddition with 1,3-dienes and O-heterodienes, has been systematically investigated in the gas phase (Eberlin MN, Cooks RG. J. Am. Chem. Soc. 1993; 115: 9226). This polar cycloaddition, yet without precedent in solution, likely forms cyclic 2,5-dihydropyrylium ions. Here we report the reactions of gaseous acylium ions [(CH(3))(2)N-C(+)=O, Ph-C(+)=O, (CH(3))(2)N-C(+)=S, CH(3)-C(+)=O, CH(3)CH(2)-C(+)=O, and CH(2)=CH-C(+)=O] with several 1-oxy-substituted 1,3-dienes of the general formula RO-CH=CH-C(R(1))=CH(2), which were performed to collect further evidence for cycloaddition. In reactions with 1-methoxy and 1-(trimethylsilyloxy)-1,3-butadiene, adducts are formed to a great extent, but upon collision activation they mainly undergo structurally unspecific retro-addition dissociation. In reactions with Danishefsky's diene (trans-1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene), adducts are also formed to great extents, but retro-addition is no longer their major dissociation; the ions dissociate instead mainly to a common fragment, the methoxyacryl cation of m/z 85. This fragment ion is most likely formed with the intermediacy of the acyclic adduct, which isomerizes prior to dissociation by a trimethylsilyl cation shift. Theoretical calculations predict that meta cycloadducts bearing 1-methoxy and 1-trimethylsilyloxy substituents are unstable, undergoing barrierless ring opening induced by the charge-stabilizing effect of the 1-oxy substituents. In contrast, for the reactions with 1-acetoxy-1,3-butadiene, both the experimental results and theoretical calculations point to the formation of intrinsically stable cycloadducts, but the intact cycloadducts are either not observed or observed in low abundances. Both the isomeric ortho and meta cycloadducts are likely formed, but the nascent ions dissociate to great extents owing to excess internal energy. The ortho cycloadducts dissociate by ketene loss; the meta cycloadducts undergo intramolecular proton transfer to the acetoxy group followed by dissociation by acetic acid loss to yield aromatic pyrylium ions. Either or both of these dissociations, ketene and/or acetic acid loss, dominate over the otherwise favored retro-Diels-Alder alternative. The pyrylium ion products therefore constitute compelling evidence for polar [4 + 2(+)] cycloaddition since their formation can only be rationalized with the intermediacy of cyclic adducts.     

Mono and double polar [4 + 2(+)] Diels-Alder cycloaddition of acylium ions with O-heterodienes

Gas-phase reactions of acylium ions with alpha,beta-unsaturated carbonyl compounds were investigated using pentaquadrupole multiple-stage mass spectrometry. With acrolein and metacrolein, CH(3)-C(+)(double bond)O, CH(2)(double bond)CH-C(+)(double bond)O, C(6)H(5)-C(+)(double bond)O, and (CH(3))(2)N-C(+)(double bond)O react to variable extents by mono and double polar [4 + 2(+)] Diels-Alder cycloaddition. With ethyl vinyl ketone, CH(3)-C(+)(double bond)O reacts exclusively by proton transfer and C(6)H(5)-C(+)(double bond)O forms only the mono cycloadduct whereas CH(2)(double bond)CH-C(+)(double bond)O and (CH(3))(2)N-C(+)(double bond)O reacts to great extents by mono and double cycloaddition. The positively charged acylium ions are activated O-heterodienophiles, and mono cycloaddition occurs readily across their C(+)(double bond)O bonds to form resonance-stabilized 1,3-dioxinylium ions which, upon collisional activation, dissociate predominantly by retro-addition. The mono cycloadducts are also dienophiles activated by resonance-stabilized and chemically inert 1,3-dioxonium ion groups, hence they undergo a second cycloaddition across their polarized C(double bond)C ring double bonds. (18)O labeling and characteristic dissociations displayed by the double cycloadducts indicate the site and regioselectivity of double cycloaddition, which are corroborated by Becke3LYP/6-311++G(d,p) calculations. Most double cycloadducts dissociate by the loss of a RCO(2)COR(1) molecule and by a pathway that reforms the acylium ion directly. The double cycloadduct of the thioacylium ion (CH(3))(2)N-C(+)(double bond)S with acrolein dissociates to (CH(3))(2)N-C(+)(double bond)O in a sulfur-by-oxygen replacement process intermediated by the cyclic monoadduct. The double cycloaddition can be viewed as a charge-remote type of polar [4 + 2(+)] Diels-Alder cycloaddition reaction.     

Oxidative Diels-Alder reaction of 2, 5-dihydroxybenzoic acid with 1, 3-cyclopentadiene

The electrochemical oxidation of 2,5-dihydroxybenzoic acid (1) has been studied in the presence of 1,3-cyclopentadiene (2) as a diene in water/ethanol (40/60, v/v) mixture using cyclic voltammetry and controlled-potential coulometry. A plausible mechanism for the oxidation of 1 in the presence of 2 is presented. Compound 1 was converted into bis-adduct 5 via electrooxidation, Diels-Alder reaction of 2 to anodically generated 3,6-dioxocyclohexa-1,4-dienecarboxylic acid (1ox), decarboxylation reaction, electrooxidation and Diels-Alder reaction. The electrochemical synthesis of 5 was performed in a onepot reaction, without toxic reagents, at a carbon electrode in a simple cell using an environmentally friendly method.     

A novel route for synthesizing esters and polyesters from the Diels-Alder adduct of levopimaric acid and acrylic acid

A novel route for the esterification of the Diels-Alder adduct between abietic acid, in its isomer form of levopimaric acid, and acrylic acid was established. The high purity Diels-Alder adduct was prepared starting from rosin acids. When the adduct was subjected to a condensation reaction in the presence of a cyclic carbonate ester and of an efficient amine catalyst, hydroxyalkyl esters were obtained. The corresponding linear polyesters were synthesized by the advanced polycondensation of the above intermediates at high temperature, under vacuum, and in the presence of some adequate polyesterification catalysts. In the work 1,3-dioxolan-2-one as cyclic carbonate ester, triethylamine as esterification catalyst, and toluene-4-sulfonic acid monohydrate or tetrabutyl titanate as polycondensation catalysts, were preferred for exemplifications. The polyesters were soluble in dimethylacetamide, trichloromethane, tetrahydrofuran, 1,1,2,2-tetrachloroethane, or 1,4-dioxane. The thermal and electric studies showed that the polymers were substances with good thermal stability and high dielectric properties.     

Design of chiral bis-phosphoric acid catalyst derived from (R)-3,3'-di(2-hydroxy-3-arylphenyl)binaphthol: catalytic enantioselective Diels-Alder reaction of α,β-unsaturated aldehydes with amidodienes

Chiral bis-phosphoric acid 1 was designed to identify a new class of structural features in chiral Br?nsted acid catalysts. X-ray diffraction analysis revealed the single atropisomer 1, bearing S axial chirality at 3,3'-biaryl substituents on (R)-binaphthyl and intramolecular hydrogen bonding between the two phosphoric acid moieties. The newly designed bis-phosphoric acid 1 was evaluated in the Diels-Alder reaction of α,β-unsaturated aldehydes 4 with 1-N-acylamino-1,3-butadienes 3. After systematic variation of the catalyst substituents, as well as the N-acyl substituents of 1,3-butadiene, the use of an N-Cbz amidodiene 3a in the presence of bis-phosphoric acid 1e with a 2,4,6-tri-isopropylphenyl group was found to be optimal to yield the 1S,6R enantiomeric product 5aa in a Diels-Alder reaction of acrolein (4a). Application of this method to substituted substrates was found to be an efficient approach to the enantioselective synthesis of 3- and 3,6-substituted cyclic formylcarbamates 5. The specific character as well as the utility of 1e was further established by comparing its enantioselectivity, absolute stereochemistry, and catalytic efficiency with those of mono-phosphoric acid 2.     

Synthesis of unsymmetrical annulated 2,2'-bipyridine analogues with attached cycloalkene and piperidine rings via sequential Diels-Alder Reaction of 5,5'-bi-1,2,4-triazines

Synthesis of bisfunctionalized unsymmetrical 2,2'-bipyridines 8 or their sulfonyl derivatives 12a,b are described. They were prepared via the Diels-Alder reaction of 1-methyl-4-pyrrolidin-1-yl-1,2,3,6-tetrahydropyridine (6) with 3,3'-bis(methyl- sulfanyl)-5,5'-bi-1,2,4-triazine (1). The reaction leads to the single cycloaddition product 7 which undergoes Diels-Alder reaction with cyclic enamines 2a,b to give unsymmetrical 2,2'-bipyridine derivatives 8, consisting of the two different heterocyclic units: cycloalkeno[c]pyridine and 2,6-naphthyridine.     

Chiral 1,1'-binaphthyl-2,2'-diammonium salt catalysts for the enantioselective Diels-Alder reaction with alpha-acyloxyacroleins

[reaction: see text] A diammonium salt of chiral 1,1'-binaphthyl-2,2'-diamine and trifluoromethanesulfonimide (Tf(2)NH) shows excellent catalytic activity and enantioselectivity for the Diels-Alder reaction of alpha-acyloxyacroleins with cyclic dienes. For example, in the presence of 5 mol % of the ammonium catalyst, the Diels-Alder reaction of alpha-(cyclohexanecarbonyloxy)acrolein with cyclopentadiene proceeded in EtCN at -75 degrees C to give the adducts in 88% yield with 92% exo and 91% ee. This catalyst can be easily prepared in situ by mixing the commercially available chiral diamine and Tf(2)NH.     

Theoretical study on the Diels-Alder reaction between 2-methylacrolein and cyclopentadiene catalyzed by a cationic oxazaborolidine Lewis acid

The reaction mechanism of the Diels-Alder reaction between 2-methylacrolein and cyclopentadiene catalyzed by a cationic oxazaborolidine Lewis acid has been characterized using density functional theory calculations. The solvent effect on the studied reaction is taken into account by optimizing all stationary points in CH(2)Cl(2) using the polarizable-continuum model. Our calculations show that the presence of this cationic oxazaborolidine catalyst changes the molecular mechanism of the studied reaction from concerted to stepwise, and lowers the activation barrier by more than 10.0 kcal/mol. A comparison of the results obtained for four different reaction channels reveals that the studied reaction is energetically favorable to occur along the exo/s-cis channel, which reasonably explains the stereoselectivity of the title reaction observed in related experiments. The electronic effect of this cationic oxazaborolidine complex in catalyzing the title reaction is found to be very similar to that of the commonly used Lewis acid BF(3).     

Diels-Alder反应中的次级轨道效应

利用概念密度泛函理论下的局域软度和广义局域软度,结合局域硬软酸碱(HSAB)原理,研究环戊二烯与CH2=CHCOCnH2n+1之间的Diels-Alder反应的立体选择性,其中活性因子均是由ABEEMσπ模型获得.与以往不同的是,除了将主要参与反应的4个原子作为反应中心之外,还将产生次级轨道效应(SOI)的2个原子也作为参与反应的一部分.得到的结果表明,所有反应的立体选择性均与实验结果取得了很好的一致性,由此提出了一种定量快速处理包含次级轨道效应的Diels-Alder反应的立体选择性的方法.     

First kinetic evidence for the CH/π and π/π solute-solvent interaction of C60 in the Diels-Alder reaction with cyclohexadiene

The first CH/π solute-solvent interaction of C(60) was evidenced by the kinetic solvent effects in the Diels-Alder reaction with 1,3-cyclohexadiene based on the evaluation of linear free energy relationship of log k(2) with empirical solvent polarity and basicity parameters, E(T)(30) and D(π), respectively.     

New synthetic approach to substituted isoindolo[2,1-a]quinoline carboxylic acids via intramolecular Diels-Alder reaction of 4-(N-furyl-2)-4-arylaminobutenes-1 with maleic anhydride

Acylation of substituted 4-(furyl-2)-4-arylaminobut-1-enes with maleic anhydride provided 2-allyl-6-carboxy-4-oxo-3-aza-10-oxatricyclo[5.2.1.0^1,5]dec-8-enes in high yield under mild reaction conditions. The Diels-Alder adducts are formed via an initial amide formation followed by a stereoselective intramolecular [4+2] exo-cycloaddition reaction. Treatment of the tricyclic compounds with phosphoric acid at high temperatures (70-120 °C) promoted cyclic ether opening, intramolecular cyclization and aromatization to give the corresponding tetracyclic compounds, 5,6,6a,11-tetrahydro-10-carboxyisoindolo[2,1-a]quinolines, in moderate yields. The influence of the acid and the reaction temperature on the cyclization reactions are also discussed.     

Efficient three-component synthesis of tetrahydrothieno[3,2-f]quinolines

An efficient one-pot method for the synthesis of tetrahydrothieno[3,2-f]quinolines is described, using the imino Diels-Alder reaction between ethyl-5-aminobenzothiophene-2-carboxylate, aromatic aldehydes and cyclic enol ethers. Furthermore, hydroxyalkyl-substituted tetrahydrothieno[3,2-f]quinolines were synthesized in good yields, by performing the same imino Diels-Alder reaction in absence of aldehydes. The intramolecular aza-Diels-Alder reaction of 5-aminobenzothiophene with o-(allyloxy)benzaldehyde was also performed resulting in the fully oxidized thienoquinoline derivative.     

Catalytic enantioselective Diels-Alder reaction via a chiral indium(III) complex

[reaction: see text] A chiral indium complex has been developed to effect high enantioselectivities in catalyzing enantioselective Diels-Alder reaction. The cycloaddition of a variety of cyclic and open-chained dienes to 2-methacrolein and 2-bromoacrolein resulted in good yields and excellent enantioselectivities (up to 98% ee).     

Reactivity and stereoselectivity of the Diels-Alder reaction using cyclic dienophiles and siloxyaminobutadienes

Several bicyclic compounds were synthesized by the Diels-Alder reaction using aminodiene and a cyclic dienophile. The stereochemistries of the obtained adducts were determined by X-ray crystallography or NMR analysis. The stereoselectivity of this Diels-Alder reaction was based on the interaction of molecular orbitals between the diene and dienophile. The reactivities of these Diels-Alder reactions were estimated, and the generality of this reaction is discussed.     

Intramolecular ionic Diels-Alder reactions of alpha-acetylenic acetals

The intramolecular ionic Diels-Alder reaction of alpha-acetylenic acetals as a precursor of the propargyl cation has been investigated in the presence of Lewis acids and in protic acids. The reaction of diene-tethered alpha-acetylenic acetals (1-2) with formic acid yielded the regioselective intramolecular ionic Diels-Alder reaction products, bicyclodienal (9) and bicyclodienone (11) derivatives, in good yields.     

乙醇在碳载Pt纳米薄膜电极上吸附和氧化过程研究——II.酸性介质中EQCM和原位FTIR反射光谱

运用电化学循环伏安 ,石英晶体微天平 (EQCM )和原位FTIR反射光谱等方法研究了酸性介质中乙醇在碳载纳米Pt膜电极上吸附和氧化行为 .结果表明 ,乙醇的电氧化与溶液酸碱性及电极表面氧物种有密切的关系 ,并指出乙醇电催化氧化是通过解离吸附产物和反应中间体双途径机理进行的 .在实验条件下 ,经原位FTIR反射光谱检测 ,解离吸附产物为CO ,反应中间体主要有CH3COOH和CH3CHO等物种 .