Ruthenium complexes of thiocinnamaldehydes: synthesis, structure, and [4+2]-cycloaddition reactions

Ruthenium hydrogensulfido complexes [CpRu(P-P)(SH)] ((P-P)=Ph(2)PCH(2)PPh(2) (dppm), Ph(2)PC(2)H(4)PPh(2) (dppe)) were obtained from the corresponding chloro complexes by Cl/SH exchange. Condensation with a range of cinnamaldehydes gave thiocinnamaldehyde complexes [CpRu(P-P)(S=CH-CR(2)=CHR(1))]PF(6) (R(1)=C(6)H(4)X, R(2)=H, Me, X=H, OMe, NMe(2), Cl, NO(2)) as highly-colored crystalline compounds. The thiocinnamaldehyde complexes undergo [4+2]-cycloaddition reactions with vinyl ethers CH(2)=CHOR(3) (R(3)=Et, Bu) and styrenes H(2)C=CHC(6)H(4)Y (Y=H, Me, OMe, Cl, Br, NO(2)) to give complexes of 2,4,5-trisubstituted 3,4-dihydro-2H-thiopyrans as mixtures of two diastereoisomers. The rate of addition of para-substituted styrenes H(2)C=CHC(6)H(4)Y to [CpRu(dppm)(S=CH-CH=CHPh)]PF(6) increases in the series Y=NO(2), Br, Cl, H, Me, OMe, indicating that the cycloaddition is dominated by the HOMO(dienophile)-LUMO(diene) interaction. The strained dienophiles norbornadiene and norbornene also add, giving ruthenium complexes of 3-thia-tricyclo[6.2.1.0(2,7)]undeca-4,9-dienes and 3-thia-tricyclo[6.2.1.0(2,7)]undec-4-enes, respectively. Addition reactions with acrolein, methacrolein, methyl vinyl ketone, acrylic ester, or ethyl propiolate finally yielded ruthenium complexes of 3,4-disubstituted 3,4-dihydro-2H-thiopyrans and 4H-thiopyrans, respectively.     

Functional [6]pericyclynes: synthesis through [14+4] and [8+10] cyclization strategies

Critical analysis of possible strategies for the synthesis of novel carbo-benzene derivatives suggests several [(18-n)+n] routes for the preparation of hexaoxy[6]pericyclyne precursors. Beyond the previously attempted [9+9] symmetrical scheme (n=9), the a priori most selective strategies are those for which n=1, 4, 7, 10, 13, and 16. They involve a cyclizing double-propargylation of a C(18-n) omega-bis-terminal-skipped oligoyne containing (19-n)/3 triple bonds with a C(n) omega-dicarbonyl-skipped oligoyne containing (n-1)/3 triple bonds. To complement the previously used [11+7] strategy, the [14+4] and [8+10] strategies were thus explored. They proved to be efficient, affording seven novel hexaoxy[6]pericyclynes corresponding to six different substitution patterns. These compounds were obtained in 7-15 steps as mixtures of stereoisomers. Thus, by using dibenzoylacetylene as the C(4) electrophile, a [14+4] strategy allowed the synthesis of two hexaphenyl representatives with two or four free carbinol vertices. This approach also afforded tetraphenyl representatives in which the two remaining carbinoxy vertices were substituted with either two alkynyl or one 4-anisyl and one 4-pyridyl groups. By using the hexacarbonyldicobalt complex of butynedial as the C(4) electrophile, a [14+4] strategy also allowed the isolation of a tetraphenylhexaoxy[6]pericyclyne with two adjacent unsubstituted carbinol vertices. A regioisomer with two opposite unsubstituted carbinol vertices was obtained through an [8+10] strategy and its oxidation afforded the corresponding pericyclynedione. Several attempts at synthesizing diphenylhexaoxy[6]pericyclynes with four unsubstituted carbinoxy vertices are described. Only an [8+10] strategy allowed the generation of a fragile diphenylhexaoxy[6]pericyclyne with four adjacent unsubstituted carbinoxy vertices, which could be partly characterized. These results show that the synthesis of the nonsubstituted hexahydroxy[6]pericyclyne, the ring carbo-mer of [6]cyclitol, is a difficult challenge.     

Transition-metal-free synthesis of 1,4-benzoxazepines via [4+3]-cycloaddition of para-quinone methides with azaoxyallyl cations

A formal[4+3]-cycloaddition reaction of ortho-hydroxyphenyl-substituted para-quinone methides(p-QMs)with in-situ generated azaoxyallyl cations is reported.The reaction occurs under very mild reaction conditions(transition-metal free,room temperature,cheap inorganic base)and provides a very efficient route to a series of biologically important 1,4-benzoxazepine derivatives in good to excellent yields.     

[4 + 2]-cycloaddition of alkyl vinyl ethers to 3-aroylpyrrolo-[2,1-c][1,4]benzoxazine-1,2,4-triones

Russian Journal of Organic Chemistry -     

On the [4+2]-cycloaddition reaction of levoglucosenone with piperylene

The Diets-Alder reaction of levoglucosenone with piperylene catalyzed by ZnCl₂ proceeds regio- and stereoselectively to give thesin-cis-adduct3; the thermal reaction yields an epimeric mixture of compound3 withsin-trans-adduct4 in the ratio of 4 : 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2584–2585, October, 1996.     

Stereoselective synthesis of tetrahydropyrans via formal [4 + 2]-cycloaddition: a comparison of allylsilane and crotylsilane

The reaction of a series of beta-(triethylsilyloxy)aldehydes with several allylsilanes and crotyldimethylphenylsilane is described. Aldehydes possessing an alpha-stereocenter afforded tetrahydropyrans as mixtures of two diastereomers with allylsilane, but only a single diastereomer was observed in the case of crotylsilanes. The reaction time for crotylsilanes was longer than that for allylsilanes likely due to the increased steric hindrance. Allylsilanes afforded tetrahydropyrans in 34-67% yields, and crotylsilanes provided products in 0-62% yields.     

Enantioselective formal synthesis of (+)-precapnelladiene by chiral copper-catalyzed asymmetric [2+2]-cycloaddition reaction

Enantioselective short formal synthesis of (+)-precapnelladiene (1) was achieved from a bicyclo[3.2.0]heptane derivative, which was prepared enantioselectively by chiral copper-catalyzed [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one with phenylthioacetylene developed by us.     

Unsaturated germanes and stannanes in the synthesis of nitrogen-containing heterocycles by [2+3]-cycloaddition

Literature data and the results of fundamental investigations on synthetic methods and chemical reactions of the products of 1,3-dipolar additions to unsaturated germanes and stannanes are reviewed.Dedicated to Professor A. Katritzky on his seventieth birthday.Latvian Institute of Organic Synthesis, Riga LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1155–1169, September, 1998.     

Expeditious synthesis of imidazo[1,2-c]pyrimidines via a [4+1]-cycloaddition

A new and versatile synthesis of imidazo[1,2-c]pyrimidines via a [4+1]-cycloaddition is described. The reported novel synthetic approach leads to pharmacologically interesting scaffolds containing three points of potential diversity, which previously were not accessible under conventional conditions. In addition, this novel synthetic procedure is amenable to the assembly of libraries with this interesting core structure.     

Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement cascade

A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has been developed and is based on an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium-catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].     

High-pressure [2 + 4]-cycloaddition of dimethylmaleic anhydride to 3,4-dimethoxyfuran; synthesis of dimethoxycantharidin preliminary communication

As an active diene (more active than furan itself), 3,4-dimethoxyfuran ( 1 ) affords with many dienophiles the respective cycloadducts in a high yield [2]. It has recently been found that under thermal conditions 1 easily reacts with maleic anhydride and its monomethyl derivative, but not with dimethylmaleic anhydride ( 2 ) [3]. This is probably due to steric hindrance resulting from the location of two methyl groups on the double bond of the dienophile. Since all Diels-Alder reactions in particular those with steric hindrance are pressure-sensitive [4]. we resolved to perform the title reaction under conditions of static high pressure.     

Novel heterotricyclic systems: 2,6-dioxa- and 2-oxa-6-thia-10-azatricyclo-[5.2.1.04,10] deeanes; 2,6-dioxa-11-azatricyclo[5.3.1.04,11] undecane; and 9,13-dioxa-14-azatetracyclo[6.5.1.02,7.011,14]tetradeca-2,4,6-triene

The acid-catalyzed condensation of 2-amino-1,3-propanediols and 1,4-diketones under water-azeotroping conditions has led to the first synthesis of the new tent-like, essentially strain-free heterotricyclic system, 2,6-dioxa-10-azatricyclo[5.2.1.0^4,10]decane. Over thirty new compounds containing this system are reported. In cases where the aminodiol is unsubstituted or bears a phenyl substituent a mixture of the tricycle and the isomeric pyrrole resulted. These observations indicate alternative pathways in the Knorr-Paal condensation which lead to one, or the other, or both of these products. A scheme postulating common intermediates is presented. Examples of three additional, related, novel heteropolycyclic systems synthesized in analogous fashion are also reported.     

Click chemistry in CuI-zeolites: the Huisgen [3 + 2]-cycloaddition

[reaction: see text] CuI-exchanged solids based on zeolite materials were investigated for the first time as catalysts in organic synthesis. The catalytic potential of these materials was evaluated in the Huisgen [3 + 2]-cycloaddition. Five CuI-exchanged zeolites were examined and CuI-USY proved to be a novel and efficient heterogeneous ligand-free catalyst for this "click chemistry"-type transformation.     

Regioselective [4 + 2]-cycloaddition of styrene to 4-isopropoxalyl-1H-pyrrole-2,3-diones

Russian Journal of Organic Chemistry -     

Studies on the synthesis of (+/-)-stenine: a combined intramolecular [4 + 2]-cycloaddition/rearrangement cascade

Several cyclic 2-(methylthio)-5-amidofurans containing tethered unsaturation were prepared via the reaction of dimethyl(methylthio)sulfonium tetrafluoroborate (DMSTF) with beta-alkoxy-gamma-dithiane lactams. Thermolysis of these furans resulted in an intramolecular Diels-Alder reaction (IMDAF). The resulting oxa-bridge cycloadducts underwent a subsequent 1,2-methylthio shift to form tricyclic lactams in high yield. Furan 9, annealed to an azepine ring, underwent the IMDAF reaction at or below room temperature. Conformational effects imposed by the placement of a carbonyl group within the tether, combined with a rotational bias about the C(2)-N bond, enhances the rate of the IMDAF reaction of the seven-ring system so that it occurs readily at 25 degrees C. The feasibility of using the cascade sequence in the context of a total synthesis of the Stemona alkaloid (+/-)-stenine was explored. The eventual synthesis of (+/-)-stenine was carried out by an intramolecular Diels-Alder reaction of a 2-amido-5-methylthio-substituted furan containing a trans-pent-3-enoic acid methyl ester side chain in order to create the desired azepinoindole skeleton. This was followed by a series of reductions to set the syn-anti stereochemical relationship at the incipient ring fusion sites present in stenine. All six stereocenters at the azepinoindole core were derived in high stereoselectivity from the functionality present in the rearranged cycloadduct 10. Compound 10 was converted to stenine in 11 additional steps via a sequence that features a Crabtree's-catalyst directed hydrogenation, iodolactonization, and a Keck allylation.     

Formal [4 + 4]-, [4 + 3]-, and [4 + 2]-cycloaddition reactions of donor–acceptor cyclobutenes,cyclopropenes and siloxyalkynes induced by Brønsted acid catalysis

Brønsted acid catalyzed formal [4 + 4]-, [4 + 3]-, and [4 + 2]-cycloadditions of donor–acceptor cyclobutenes, cyclopropenes, and siloxyalkynes with benzopyrylium ions are reported. [4 + 2]-cyclization/deMayo-type ring-extension cascade processes produce highly functionalized benzocyclooctatrienes, benzocycloheptatrienes, and 2-naphthols in good to excellent yields and selectivities. Moreover, the optical purity of reactant donor–acceptor cyclobutenes is fully retained during the cascade. The 1,3-dicarbonyl product framework of the reaction products provides opportunities for salen-type ligand syntheses and the construction of fused pyrazoles and isoxazoles that reveal a novel rotamer-diastereoisomerism.

Brønsted acid catalysis realizes formal [4 + 4]-, [4 + 3]-, and [4 + 2]-cycloadditions of donor–acceptor cyclobutenes, cyclopropanes, and siloxyalkynes with benzopyrylium ions.

Medium-sized rings are the core skeletons of many natural products and bioactive molecules,¹ and a growing number of strategies have been developed for their synthesis.² Because of their enthalpic and entropic advantages, ring expansion is a highly efficient methodology for these constructions.^3–6 For example, Sun and co-workers have developed acid promoted ring extensions of oxetenium and azetidinium species formed from siloxyalkynes with cyclic acetals and hemiaminals (Scheme 1a).⁴ Takasu and co-workers have reported an elegant ring expansion with a palladium(ii) catalyzed 4π-electrocyclic ring-opening/Heck arylation cascade with fused cyclobutenes (Scheme 1b).⁵ Each transformation is initiated by the formation of fused bicyclic units followed by ring expansion or rearrangement to give medium-sized rings.Open in a separate windowScheme 1Cycloaddition/ring expansion background and this work.Strategies for the formation of fused bicyclic compounds rely on cycloaddition of dienes or dipoles with unsaturated cyclic compounds⁷ and, if the reactant cyclic compound is strained and chiral, the resulting bicyclic compound is activated toward ring opening that results in retention of chirality. We have recently reported access to donor–acceptor cycloalkenes by [3 + n] cycloaddition that have the prerequisites of unsaturated cyclic compounds suitable for cycloaddition.⁸ Donor–acceptor (D–A) cyclopropenes⁹ and cyclobutenes¹⁰ have sufficient strain in the resulting bicyclic compounds to undergo ring opening. We envision that the selection of a diene or dipolar reactant and suitable reaction conditions could realize cycloaddition and subsequent ring expansion. Benzopyrylium species,^11,12 which are generated by metal or acid catalysis, have attracted our attention. We anticipated that their high reactivity would overcome the conventional unfavorable kinetic and/or thermodynamic factors that typically impede medium-sized ring formation. From a mechanistic perspective, benzopyrylium species are often formed by transition metal catalyzed reactions with 2-alkynylbenzaldehydes.¹¹ Recently, the reaction between 1H-isochromene acetal and Brønsted acid catalyst forms the 2-benzopyrylium salts that could react with functional alkenes to give same cycloaddition products.¹² Consequently, we believed that the [4 + 2]-cyclization between benzopyrylium species and donor–acceptor cyclobutenes, cyclopropenes, or siloxyalkynes would give bridged oxetenium intermediates, which contain high strain energy that should provide the driving force for ring expansion. The “push and pull” electronic effect of donor–acceptor functional groups facilitates deMayo-type ring-opening of the cyclobutane or cyclopropane skeletons (Scheme 1c).¹³Here we report bis(trifluoromethanesulfonyl)imide (HNTf₂) catalyzed formal [4 + 4]-, [4 + 3]- and [4 + 2]-cycloaddition reactions of D–A cyclobutenes, cyclopropenes, and siloxyalkynes with benzopyrylium salts. Polysubstituted benzo-cyclooctatrienes, benzocycloheptatrienes and 2-naphthols, are produced in good to excellent yields and selectivities. Complete retention of configuration occurs using chiral cyclobutenes, and opportunities for further functionalization are built into these constructions.Initially, we conducted transition metal catalyzed reactions with 2-alkynylbenzaldehyde intending to produce the corresponding benzopyrylium ion and explore the possibility of cycloaddition/ring opening with donor–acceptor cyclobutene 2a. Use of Ph₃PAuCl/AgSbF₆, Pd(OAc)₂ and Cu(OTf)₂, which were efficient catalysts in previous transformations,¹¹ gave only a trace amount of cycloaddition product (Fig. 1). Spectral analysis showed that mostly starting material remained (Fig. 1-i and ii). Increasing the reaction temperature led only to decomposition of 2-alkynylbenzaldehyde (Fig. 1-iv) or donor–acceptor cyclobutene 2a (Fig. 1-iv).Open in a separate windowFig. 1Reaction of 2-alkynylbenzaldehyde with donor–acceptor cyclobutene 2a.From these disappointments we turned our attention to 1H-isochromene acetal 1a as the benzopyrylium ion precursor. Various Lewis acid catalysts were employed with limited success, but we were pleased to observe the formation of the desired formal [4 + 4]-cycloaddition benzocyclooctatriene product 3aa, albeit in low yields (Table 1, entries 1–6). Selection of the Brønsted super acid HNTf₂ (ref. 14) proved to be the most promising, producing 3aa in 40% yield (Table 1, entry 7). Increasing the amount of D–A cyclobutene 2a by 30% gave a much higher yield of 3aa (Table 1, entry 8 vs. 7). Optimization of the stoichiometric reaction between 1a and 2a by increasing the reaction temperature from rt to 35 °C led to the formation of the desired product in 76% isolated yield (Table 1, entry 9 vs. 8). However, a further increase in the reaction temperature (Table 1, entry 10) or reducing the catalyst loading to 5 mol% did not improve the yield of 3aa (Table 1, entry 11).Optimization of reaction conditions^a

Short, enantioselective total synthesis of aflatoxin B2 using an asymmetric [3+2]-cycloaddition step

A highly enantioselective [3+2]-cycloaddition reaction of 2,3-dihydrofuran with 1,4-benzoquinones using a chiral oxazaborolidinium triflimidate as catalyst has been developed which allows rapid access to a variety of chiral phenolic tricycles (enantiomeric excesses ranging from 91 to 98%). The utility of this new methodology is demonstrated by a short synthesis of the important pentacyclic natural product, aflatoxin B2. This exploratory study indicates that an even broader application of these catalysts to enantioselective cycloadditions may be possible.     

Oscillations of reactivity in the [2+4]-cycloaddition of methyl acrylate to furan

The kinetics of [2+4]-cycloaddition of methyl acrylate to furan (Diets—Alder reaction) were studied at 70°C and 907 MPa,i.e., under conditions where the solvent (benzene) exists in the solid state. It was found that the reactivity exhibits oscillations with astronomic time and that its averaging leads to reaction rate constants, which are close to those expected from the calculations, carried out using the known reaction and activation volume effects and the reactivity at a pressure close to the atmospheric pressure.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2450–2455, October, 1996.     

One-pot diastereoselective synthesis of tetrahydroepimino-benzo[b]azocines through sequential [3+2]-cycloaddition and Staudinger-aza-Wittig reactions

The one-pot synthesis of tetrahydro-epiminobenzo[b]azocines through a sequential 1,3-dipolar cycloaddition and intramolecular Staudinger-aza-Wittig reaction sequence is reported. This methodology provides a new and efficient approach for medium-sized and bridged nitrogen heterocyclic molecules.     

[7+2]- and [11+2]-cycloaddition reactions of diazo-azoles with isocyanates to azolo[5,1-d] [1,2,3,5] tetrazine-4-ones

Diazo-azoles react as 1,7- or 1,11-dipoles with isocyanates to form the hitherto unknown pyrazolo[5,1-d] [1,2,3,5]tetrazine-4-ones, [1,2,3,5]tetrazino[5,4-b]indazole-4-ones and [1,2,3]triazolo[5,1-d][1,2,3,5]tetrazine-4-ones in a [7+2]- or [11+2]-cycloaddition reaction.