Monoamine Oxidase-Catalyzed Oxidative Rearrangement of trans,trans-1-(Aminomethyl)-2-methoxy-3-phenylcyclopropane

trans,trans-1-(Aminomethyl)-2-methoxy-3-phenylcyclopropane (3) was synthesized in three steps from (Z)-beta-methoxystyrene and ethyl diazoacetate. Compound 3 was shown to be a substrate and inactivator of mitochondrial beef liver monoamine oxidase (MAO) with a partition ratio of 1428. MAO-catalyzed oxidation of 3 produces one major metabolite, isolated and identified by GCOSY, GHMQC, and GHMBC NMR techniques to be trans,trans-2-methoxy-3-phenyl-1-N-[(3-phenyl-N-pyrrolyl)methyl]cyclopropane (7). A mechanism, supported by a model reaction, is proposed for the formation of this metabolite.     

Activation/driving force relationships for cyclopropylcarbinyl --> homoallyl-type rearrangements of radical anions

By using direct and indirect electrochemical methods, rate constants (ko) for cyclopropane ring opening of radical anions derived from the one-electron reduction of trans-1-benzoyl-2-phenylcyclopropane, trans-1-benzoyl-2-vinylcyclopropane, 2-methylenecyclopropyl phenyl ketone, spiro[anthracene-9,1'-cyclopropan-10-one], 3-cyclopropylcyclohex-2-en-1-one, and 3-(1-methylcyclopropyl)cyclohex-2-en-1-one were determined. Qualitatively, rate constants for ring opening of these (and other cyclopropyl- and cyclobutyl-containing radical anions) can be rationalized on the basis of the thermodynamic stability of the radical anion, the ability of substituents on the cyclopropyl group to stabilize the radical portion of the distonic radical anion, and the stability of the enolate portion of the distonic radical anion. On the basis of this notion, a thermochemical cycle for estimating deltaG(o) for ring opening was presented. For simple cyclopropyl-containing ketyl anions, a reasonable correlation between log(ko) and deltaG(o) was found, and stepwise dissociative electron transfer theory was applied to rationalize the results. Activation energies calculated with density functional theory (UB3LYP/6-31+G*) correlate reasonably well with measured log(ko). The derived log(ko) and deltaG(o) and log(ko) vs E(a) plots provide the basis for a "calibration curve" to predict rate constants for ring opening of radical anions derived from carbonyl compounds, in general.     

Divergent oxidative rearrangements in solution and in a zeolite: distal vs proximal bond cleavage of methylenecyclopropanes

Irradiation of 9,10-dicyanoanthracene (DCA) or p-chloranil in the presence of E-1-benzylidene-2-phenylcyclopropane (E-5) in CH(2)Cl(2) causes E-5 to undergo methylenecyclopropane rearrangement. An adduct, Z-7, between DCA and 5 firmly supports the involvement of a bifunctional trimethylenemethane radical cation. In contrast, incorporation of E-5 into HZSM-5 produces trans,trans-1,4-diphenyl-1,3-butadiene radical cation sequestered in the HZSM-5 interior, tt-8(.+)@HZSM-5, identified by ESR and diffuse reflectance spectroscopy. In addition, low yields of tt-8, its cis,trans-isomer (ct-8), and 1-phenyl-1,2-dihydronaphthalene (9) were isolated from the supernatant solution. The sharp contrast between the photoinduced electron-transfer reaction with photosensitizers in solution and the spontaneous reaction with redox-active acidic zeolite offers the prospect of further zeolite-induced regiodivergent reactions in a range of additional substrates.     

Copper-catalyzed enantioselective intramolecular conjugate addition/trapping reactions: synthesis of cyclic compounds with multichiral centers

The Cu-catalyzed enantioselective conjugate addition of dialkylzinc to bis-alpha,beta-unsaturated carbonyl compounds followed by the intramolecular trapping of the zinc enolate in the presence of chiral phosphoramidite ligands was investigated. Cyclic and heterocyclic compounds with multichiral centers were formed as a mixture of two diastereomers with excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to 94 % ee, ee=enantiomeric excess). The stereochemistry was determined to be trans,trans for the major products and trans,cis for the minor products. The absolute configuration of the cyclic compounds was assigned by comparison with the analogous adduct derived from trans-3-nonen-2-one and Et(2)Zn or the adduct obtained through conjugate addition of Me(2)Zn to trans-1-phenyl-non-2-en-1-one. Further transformation of these cyclic products into more complex compounds is under investigation in our laboratory.     

Novel ene trimerization of 1-phenylcyclopropene

1-Phenylcyclopropene (1) was synthesized by treatment of 1,1,2-tribromo-2-phenylcyclopropane (2) with 2.5 equiv of methyllithium followed by protonation. Compound 1 underwent ene dimerization to form ene dimer 5 followed by ene reaction with monomer 1 (enophile) to give an ene trimer 6. Both of these two ene reactions derived endo transition states. In the meantime, the [2+2] adduct, trans-1,2-diphenylbicyclo[3.1.0.0(2,4)]hexane (7), was also formed. When the adduct 7 was heated at THF refluxing temperature, 1,2-diphenylcyclohexa-1,4-diene (8) was obtained. Compound 8 was treated with DDQ to yield o-diphenylbenzene.     

Conjugate addition of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a cationic rhodium complex

[reaction: see text] A novel, additive-free, and clean conjugate addition reaction of organosiloxanes to alpha,beta-unsaturated carbonyl compounds catalyzed by a cationic rhodium complex in water-containing solvent has been developed. A plausible reaction mechanism involving the additive-free transmetalation step between the rhodium complex and the silicon reagent is proposed.     

A computational study on addition of Grignard reagents to carbonyl compounds

The mechanism of stereoselective addition of Grignard reagents to carbonyl compounds has been investigated using B3LYP density functional theory calculations. The study of the reaction of methylmagnesium chloride and formaldehyde in dimethyl ether revealed a new reaction path involving carbonyl compound coordination to magnesium atoms in a dimeric Grignard reagent. The structure of the transition state for the addition step shows that an interaction between a vicinal-magnesium bonding alkyl group and C=O causes the C-C bond formation. The simplified mechanism shown by this model is in accord with the aggregation nature of Grignard reagents and their high reactivities toward carbonyl compounds. Concerted and four-centered formation of strong O-Mg and C-C bonds was suggested as a polar mechanism. When the alkyl group is bulky, C-C bond formation is blocked and the Mg-O bond formation takes precedence. A diradical is formed with the odd spins localized on the alkyl group and carbonyl moiety. Diradical formation and its recombination were suggested to be a single electron transfer (SET) process. The criteria for the concerted polar and stepwise SET processes were discussed in terms of precursor geometries and relative energies.     

New "green" approaches to the synthesis of pyrazole derivatives

A novel approach to the synthesis of pyrazole derivatives from tosylhydrazones of alpha,beta-unsaturated carbonyl compounds possessing a beta-hydrogen is proposed, exploiting microwave (MW) activation coupled with solvent free reaction conditions. The cycloaddition was studied on three ketones (trans-4-phenyl-3-buten-2-one, beta-ionone and trans-chalcone). The corresponding 3,5-disubstituted-1H-pyrazoles were obtained in high yields and after short reaction times. In order to simplify and point out the green chemistry features of the method, a further improvement was achieved under the same catalytic conditions with a "one pot" synthesis of these heterocyclic compounds, starting directly from their carbonyl precursors via tosylhydrazones generated in situ. For an exhaustive study, the dielectric properties of the solid reaction mixtures were also measured, in order to obtain input data for the numerical simulation of their heating behaviour in the single mode MW cavity which was used for experimental work. In order to supply a valid methodology and tool for measuring the environmental impact, a comparative study between the synthetic route proposed and the classical synthetic route has been carried out.     

12-(酰氧亚氨基)-1,15-十五内酯的合成及结构表征

以α-硝基环十二酮为原料,与丙烯醛加成、扩环并经Nef反应合成了12-氧代-1,15-十五内酯,再经成肟和酰化及硅胶柱层析分离分别得到12-(酰氧亚氨基)-1,15-十五内酯的顺式及反式异构体.结构经IR,¹HNMR及元素分析确证.通过对个别化合物的单晶X射线分析,结合¹HNMR数据,分别确定了它们的Z,E构型.结果表明,12-氧代-1,15-十五内酯成肟时对顺、反异构体的形成缺少明显的选择性,而目标化合物环骨架的优势构象为[23434],羰基和肟基位于两个不同的角碳位置.     

Catalytic olefination of carbonyl compounds. A new versatile method for the synthesis of alkenes

The review is devoted to a new catalytic olefination reaction (COR) discovered by the authors. This is the reaction between N-unsubstituted hydrazones of carbonyl compounds with dihalides CHal₂XY in the presence of copper(i) chloride to give substituted alkenes. Catalytic olefination is versatile. Variation of the carbonyl and olefinating components opens up the way for the synthesis of various classes of unsaturated compounds including those containing functional groups. The reaction mechanism is discussed and a catalytic cycle describing the process is proposed. A model for estimating and predicting the reactivity of halogen-containing compounds in the COR is developed. The relationship between the structure of the carbonyl substrates and their behavior in the title reaction is elucidated.     

吡哆胺对1,4-二羰基化合物清除机理的密度泛函理论研究

吡哆胺（PM）能够清除生物体新陈代谢过程中产生的活性二羰基化合物,此类化合物能与体内的氨基酸作用生成有毒的吡咯类化合物。本文用密度泛函理论B3LYP方法在6-31G*基组水平上,研究了PM与OPA反应的机理。计算结果表明,该反应可通过两个连续的步骤完成。首先,通过竞争反应生成一个四氢吡咯类化合物;随后,该化合物经过平行反应脱水生成最终产物。理论上,反应过程中还有可能生成亚胺类化合物,但计算结果表明其为副反应。最后,本文讨论了空间位阻效应对反应性质的影响。所有计算结果与实验结果非常吻和。     

Conjugate addition of organocopper reagents to n-tosylated α, β-unsaturated amides

N-Tosylated α, β-unsaturated amides and lactams undergo facile conjugate addition with R²CuLi or RMgX/CuI (cat.). Stereoselective synthesis of trans-β,γ-dialkyl-γ-lactams can be achieved by this procedure. The resulting N-tosylamide moiety is further transformed to alcohol and several carbonyl compounds by way of reduction or nucleophillic displacement.     

Synthesis of trans-1, trans-2, trans-3, and trans-4 bisadducts of C60 by regio- and stereoselective tether-directed remote functionalization

The double Bingel reaction of fullerene C60 with bismalonates attached to a Tr?ger base derived tether afforded trans-1, trans-2, trans-3, and trans-4 bisadducts with excellent regioselectivity. In particular, enantiomerically pure bisadducts with inherently chiral trans-2 or trans-3 addition patterns were prepared starting from enantiomerically pure bismalonates. The absolute configuration of the trans-2 and trans-3 bisadducts was established from their CD spectra. The excellent diastereoselectivity in the double additions to give the trans-2 bisadducts is particularly remarkable given the large distance between the two reacting bonds in opposite hemispheres of the fullerene that is spanned by the tether. Now, all inherently chiral double addition patterns are readily available by tether-directed functionalization using appropriate chiral, nonracemic spacers.     

α－羰基烯酮环二硫代缩醛化学（Ⅺ）──α－羰基烯酮环二硫代缩醛类化合物与Reformatsky试剂的加成反应初步研究

报道了标题化合物和Ｒｅｆｏｒｍａｔｓｋｙ试剂［Ｅｔｈｙｌ（ｂｒｏｍｏｚｉｎｃｉｏ）ａｃｅｔａｔｅ］的加成反应。实验表明，该加成反应能否进行和α－羰基烯酮二硫代缩醛类化合物中缩醛基结构密切相关．结合晶体结构数据和构象分析可以推测，当缩醛基的两个烷硫基处在（或近于）同一平面上时，因满足了两个硫原子和Ｒｅｆｏｒｍａｔｓｋｙ试剂形成络合物的电子要求，底物被活化而易发生加成反应；反之，两个烷硫基难于处在同一平面上时，加成反应难以进行。     

Ruthenium-catalyzed regioselective deuteration of alcohols at the β-carbon position with deuterium oxide

A convenient method for regioselective H/D exchange between D(2)O and alcohols at the β-carbon position using the catalytic system [(p-cymene)RuCl(2)]/ethanolamine/KOH is described. This method is applicable for deuteration of both primary and secondary alcohols. The H/D exchange reactions proceed through an oxidation/modification/reduction reaction sequence. Alcohols are first temporarily oxidized to carbonyl compounds by the hydrogen transfer catalyst. The carbonyl compounds then undergo deuteration at the carbon adjacent to the carbonyl group by keto-enol tautomerization in the presence of D(2)O and a catalytic amount of base. The deuterated carbonyl compounds are then reduced to produce deuterated alcohols. In support of the reaction mechanism, a well-defined bimetallic ruthenium complex was isolated from the reaction of [{(p-cymene)RuCl(2)}(2)] with ethanolamine. The activity of this complex is similar to that of [{(p-cymene)RuCl(2)}(2)]/ethanolamine.     

Synthesis of 4,5-dihydrofuran derivatives. Stereochemical study of the reactions of 1,3-alkadienes with β-dicarbonyl compounds

4,5-Dihydrofuran derivatives were obtained by the reaction of cis- and trans-1,3-alkadienes with carbonyl compounds in the presence of the manganese (III) acetate/copper (II) acetate oxidizing system. It was observed that in the case of cis-1,3-alkadienes, in contrast to trans-1,3-alkadienes, inversion of the cis double bond, the degree of which depends on the structures of the unsaturated and carbonyl components of the reaction, occurs. It was shown that the reaction of cis-1,3-dodecadiene with diethyl malonate leads to the corresponding 1,4-addition product.Communic,ation 119 from the series Reactions of unsaturated compounds. See [1] for Communication 118.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 308–314, March, 1985.     

Photocatalytic Enantioselective Hydrosulfonylation of α,β-Unsaturated Carbonyls with Sulfonyl Chlorides

This research explores the enantioselective hydrosulfonylation of various α,β-unsaturated carbonyl compounds via the use of visible light and redox-active chiral Ni-catalysis, facilitating the synthesis of enantioenriched α-chiral sulfones with remarkable enantioselectivity (exceeding 99 % ee). A significant challenge entails enhancing the reactivity between chiral metal-coordinated carbonyl compounds and moderate electrophilic sulfonyl radicals, aiming to minimize the background reactions. The success of our approach stems from two distinctive attributes: 1) the Cl-atom abstraction employed for sulfonyl radical generation from sulfonyl chlorides, and 2) the single-electron reduction to produce a key enolate radical Ni-complex. The latter process appears to enhance the feasibility of the sulfonyl radical's addition to the electron-rich enolate radical. An in-depth investigation into the reaction mechanism, supported by both experimental observations and theoretical analysis, offers insight into the intricate reaction process. Moreover, the versatility of our methodology is highlighted through its successful application in the late-stage functionalization of complex bioactive molecules, demonstrating its practicality as a strategy for producing α-chiral sulfones.     

Analysis of an unprecedented mechanism for the catalytic hydrosilylation of carbonyl compounds

This work details an in-depth evaluation of an unprecedented mechanism for the hydrosilylation of carbonyl compounds catalyzed by (PPh3)2Re(O)2I. The proposed mechanism involves addition of a silane Si-H bond across one of the rhenium-oxo bonds to form siloxyrhenium hydride intermediate 2 that reacts with a carbonyl substrate to generate siloxyrhenium alkoxide 4, which, in turn, affords the silyl ether product. Compelling evidence for the operation of this pathway includes the following: (a) isolation and structural characterization by X-ray diffraction of siloxyrhenium hydride intermediate 2, (b) demonstration of the catalytic competence of intermediate 2 in the hydrosilylation reaction, (c) 1H and 31P{1H} NMR and ESI-MS evidence for single-turnover conversion of 2 into 1, (d) observation of intermediate 2 in the working catalyst system, and (e) kinetic analysis of the catalytic hydrosilylation of carbonyl compounds by 1.     

Computational study on the reaction mechanism of hydrosilylation of carbonyls catalyzed by high-valent rhenium(V)-di-oxo complexes

Density functional theory (DFT) calculations have been performed to elucidate the reaction mechanism of hydrosilylation of carbonyl compounds catalyzed by high-valent rhenium(V)-di-oxo complexes ReO2I(PR3)2 (R = Me, Ph). The calculations suggest that the most favorable mechanism involves the rate-determining dissociative [2 + 2] addition of the Si-H bond across a Re=O bond to form a Re(V) hydrido siloxy intermediate; this is followed by carbonyl coordination, reduction of the carbonyl, rearrangement, and final intramolecular nucleophilic attack from the alkoxy group to the silyl center (dissociative retro-[2 + 2] addition). It was also found that the additional oxo ligand in the ReO2I(PR3)2 complexes promotes the [2 + 2] addition across the rhenium-oxo bond both kinetically and thermodynamically, as compared to the neutral rhenium(V)-mono-oxo complex ReOCl3(PMe3)2. The effect of different silanes on the [2 + 2] addition barriers is also studied.     

New reactivity patterns in activated indoles with 2-methyl substituents

The synthesis and reactive properties of two new 3-aryl-2-methyl-4,6-dimethoxyindoles are reported. These compounds show typical electrophilic substitution and addition reactions at C7, but not oxidative dimerisation because of the reactivity of the 2-methyl group. This methyl group can be effectively oxidised to a carbaldehyde by selenium dioxide, but formation of 7,7′-diindolylselenides also occurs.