BF3.OEt2-mediated cycloaddition of O-tert-butyldimethylsilyloximes having olefin moieties: intramolecular cycloaddition of N-borano-nitrones

Treatment of O-tert-butyldimethylsilyloximes having olefin moieties in the molecules with BF3.OEt2 results in efficient generation of N-borano-nitrones, which undergo intramolecular cycloaddition at room temperature to afford N-nonsubstituted cycloadducts after work-up.     

A highly regio- and stereoselective formation of bicyclo[4.2.0]oct-5-ene derivatives through thermal intramolecular [2 + 2] cycloaddition of allenes

Thermal [2 + 2] cycloaddition of allenes with an additional multiple bond is described. By simply heating the allenenes or allenynes having a three-atom tether in an appropriate solvent such as dioxane or DMF, the distal double bond of the allenic moiety regioselectively participates in the cycloaddition to form bicyclo[4.2.0]oct-5-ene derivatives in good to excellent yields. In all the reactions of allenenes, the olefin geometry was completely transferred to the cycloadducts. While the reaction of terminal allenes afforded bicyclic cyclobutane derivatives as a single isomer, the cycloaddition of some internal allenes with axial chirality yielded a diastereomeric mixture of cycloadducts. These results are in good accordance with the stepwise mechanism through a biradical intermediate with a coplanar allyl radical.     

Type 2 intramolecular nitroso Diels-Alder reaction. Synthesis and structure of bridgehead oxazinolactams

[reaction--see text] The type 2 intramolecular Diels-Alder cycloaddition utilizing N-acylnitroso dienophiles provides an efficient entry into bridged oxazinolactams. In contrast to the bimolecular counterpart, the reaction is completely regioselective. Structural characterization of the cycloadducts allows for evaluation of the olefin distortion and the degree of pyramidalization of the bridgehead oxazinolactam.     

1-Methoxycarbonyl-substituiertes 2,3-Dihydropyridin-4(1H)-on (= Methyl-1,2,3,4-tetrahydro-4-oxopyridin-1-carboxylat) als Chromophor für die photochemische [2 + 2]-Cycloaddition

1-Methoxycarbonyl-Substituted 2,3-Dihydropyridin-4(1H)-one(= Methyl 1,2,3,4-Tetrahydro-4-oxopyridine-1-carboxylate) as Chromophore for Photochemical [2 + 2]-Cycloadditions With olefins having an electron-acceptor as well as with olefins having an electron-donor substituent, 1-methoxycarbonyl-substituted dihydropyridinone 12 undergoes [2 + 2] cycloaddition in good preparative yields. The photochemical cycloaddition is highly regioselective. For preparative purposes, the ring junction can be equilibrated to the thermodynamically more stable cis-junction. Only the ‘endo’/‘exo’ selectivity at the C-atom bearing the olefin substituent cannot be controlled. The photodimerization of 12 is the only side reaction. Using a slight excess of the olefin, the photodimerization can be suppressed. The protecting group at the N-atom of the dihydropyridinone can be varied in order to introduce an internal sensitizer, as shown with 1-acyl-substituted compound 29 , which underwent the cycloaddition process even with sunlight.     

A cornucopia of cycloadducts: theoretical predictions of the mechanisms and products of the reactions of cyclopentadiene with cycloheptatriene

The potential cycloaddition reactions between cyclopentadiene and cycloheptatriene have been explored theoretically. B3LYP/6-31G was used to locate the transition states, intermediates, and products for concerted pathways and stepwise pathways passing through diradical intermediates. Interconversions of various cycloadducts through sigmatropic shifts were also explored. CASPT2/6-31G single point calculations were employed to obtain independent activation energy estimates. MM3 was also used to compute reaction energetics. Several bispericyclic cycloadditions in which two cycloadducts are linked by a sigmatropic shift have been identified. B3LYP predicts, in line with frontier molecular orbital predictions, that the [6+4] cycloaddition is the favored concerted pathway, but an alternative [4+2] pathway is very close in energy. By contrast, CASPT2 predicts that a [4+2] cycloaddition is the preferred pathway. B3LYP predicts that the lowest energy path to many of the cycloadducts will involve diradical intermediates, whereas CASPT2 predicts that each of the products of orbital symmetry allowed reactions will be reached most readily by closed shell processes-concerted cycloadditions and sigmatropic shift rearrangements of cycloadducts.     

Dicobaltoctacarbonyl-mediated synthesis of tricyclic 5,6-diydropyran-2-one derivatives via tandem cycloaddition reaction between cis-epoxyalkynes, a tethered olefin, and carbon monoxide

Cobalt carbonyl complex Co2(CO)8 implemented an intramolecular carbonylation of cis-epoxyalkynes to generate Co2(CO)6-stabilized gamma-lactonyl allene species. For 1,1,2-trisubstituted epoxyalkynes, this Co2(CO)6-allene species reacted with a tethered olefin to give [2+2]-cycloadducts, and with CO and a tethered olefin to produce [2+2+1]-cycloadducts. These resulting cycloadducts have a 5,6-diydropyran-2-one core fused with a cyclobutane and a cyclopentanone ring, respectively. For 1,2-disubstituted cis-epoxyalkyne and 1,1,2-trisubstituted cis-epoxyalkynes bearing a heteroatom constituent, cyclization of the corresponding epoxyalkyne with a tethered alkene is invariably accompanied by incorporation of CO to produce a [2+2+1]-cycloadduct, even in the absence of CO. We have prepared various 1,1,2-trisubstituted and 1,2-disubstituted cis-epoxyalkynes to generalize such cycloaddition pathways. Attempt to use an organic promoter to perform these tandem cycloadditions was unsuccessful because of a competing Pauson-Khand reaction. Cyclization of a 1,2-disubstituted epoxyalkyne with a tethered diene was achieved successfully in one case, but the yield was low (25%).     

Intramolecular nitrone cycloaddition reaction on carbohydrate-based precursors: application in the synthesis of spironucleosides and spirobisnucleosides

A simple synthesis of chiral spironucleosides and spirobisnucleosides is described. Intramolecular 1,3-dipolar nitrone cycloaddition reaction of d-glucose-derived precursors having olefin at C-3 and nitrone at C-5, C-1, or C-2 (in nor-series) furnished bisisoxazolidinospirocycles 4-7, 11, and 12 in good yields. Reductive ring opening of the isoxazolidine moieties in 4-6 followed by construction of a nucleoside base upon the generated amino groups smoothly yielded spirobisnucleosides 17 and 18 and spironucleosides 20 and 21.     

Quantum mechanical inspection of the Diels-Alder approach to biaryls mechanism

The Diels-Alder reaction of substituted cyclohexadienes with substituted phenylacetylenes offers an attractive alternative for the synthesis of biaryl compounds via a two-step cycloaddition/cycloelimination pathway. Quantum mechanical calculations using B3LYP and M06-2X density functional methods for the reaction of 2-chloro-6-nitrophenylacetylene with 1-carbomethoxy-cyclohexadiene show the reaction proceeds by a stepwise diradical [4+2] cycloaddition followed by concerted [2+4] cycloelimination of ethylene. [2+2] cycloadducts are also the result of stepwise addition. [2+2] cycloadducts isomerize to [4+2] cycloadducts via diradical pathways, which involve the same diradical intermediate in cycloaddition. There is also a competitive conrotatory ring opening followed by trans-cis double bond isomerization pathway of the [4.2.0] bicycle (the [2+2] cycloadduct) to give the cis,cis,cis-1,3,5-cyclooctatriene.     

Rhodium N-heterocyclic carbene-catalyzed [4 + 2] and [5 + 2] cycloaddition reactions

[reactions: see text] A rhodium complex of N-heterocyclic carbene (NHC) has been developed for intra- and intermolecular [4 + 2] and intramolecular [5 + 2] cycloaddition reactions. This is the first use of a transition-metal NHC complex in a Diels-Alder-type reaction. For the intramolecular [4 + 2] cycloaddition reactions, all the dienynes studied were converted to their corresponding cycloadducts in 91-99% yields within 10 min. Moreover, up to 1900 turnovers have been obtained for the intramolecular [4 + 2] cycloaddition at 15-20 degrees C. For the intermolecular [4 + 2] cycloadditions, high yields (71-99%) of the corresponding cycloaddition products were obtained. The reaction time and yield were highly dependent upon the diene and the dienophile. For the intramolecular [5 + 2] cycloaddition reactions, all the alkyne vinylcyclopropanes studied were converted to their corresponding cycloadducts in 91-98% yields within 10 min. However, the catalytic system was not effective for an intermolecular [5 + 2] cycloaddition reaction.     

Tetronamides as latent acyclic vinylogous amides in formal aza-[3 + 3] cycloaddition reactions with alpha,beta-unsaturated iminium salts. An unexpected rearrangement and an approach to synthesis of substituted piperidines

A detailed account regarding formal aza-[3 + 3] cycloaddition reactions of tetronamides with alpha,beta-unsaturated iminium salts is described here. This investigation uncovers regioisomeric cycloadducts that were not found in previous studies involving this formal cycloaddition and an unexpected rearrangement that led to pyridines and dihydropyridines. Both stereochemical and regiochemical issues raised in this study provide further mechanistic insights into this cycloaddition. With careful control of reaction temperatures, the desired formal cycloadducts are obtained. Ensuing transformation of these cycloadducts into functionalized piperidines establishes the concept of employing tetronamides as latent acyclic vinylogous amides for the formal aza-[3 + 3] cycloaddition.     

Synthesis of multiply functionalized benzenes via ruthenium-catalyzed cycloaddition of diiododiynes

Highly functionalized benzenes were precisely synthesized via multi-step processes consisting of ruthenium-catalyzed [2+2+2] cycloaddition of diiododiynes with an ethynylboronate or terminal alkynes, and subsequent chemo- and regio-selective palladium-catalyzed C-C bond-forming reactions of the resulting cycloadducts. The sequential cycloaddition/coupling process was applied to the synthesis of oligo(p-phenylene ethynylene)s.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

Intramolecular [2+2+2] cycloaddition reactions of yne-ene-yne and yne-yne-ene enediynes catalysed by Rh(I): experimental and theoretical mechanistic studies

N-tosyl-linked open-chain yne-ene-yne enediynes 1 and 2 and yne-yne-ene enediynes 3 and 4 have been satisfactorily synthesised. The [2+2+2] cycloaddition process catalysed by the Wilkinson catalyst [RhCl(PPh(3))(3)] was tested with the above-mentioned substrates resulting in the production of high yields of the cycloadducts. Enediynes 1 and 2 gave standard [2+2+2] cycloaddition reactions whereas enediynes 3 and 4 suffered β-hydride elimination followed by reductive elimination of the Wilkinson catalyst to give cycloadducts, which are isomers of those that would be obtained by standard [2+2+2] cycloaddition reactions. The different reactivities of these two types of enediyne have been rationalised by density functional theory calculations.     

Cycloaddition of 2(1H)-pyridones having a methoxycarbonyl group to 1,3-butadiene derivatives

The cycloaddition of 4-methoxycarbonyl-2(1H)-pyridones to silyloxydienes gave isoquinolone derivatives in reasonable yields. Furthermore, the cycloaddition of 6-methoxycarbonyl-2(1H)-pyridones to 2,3-dimethyl-1,3-butadiene produced cycloadducts (isoquinolone and quinolone derivatives) and double cycloadducts (phenanthridone derivatives). The activation energies using Gaussian 98 with RHF/3-21G level of 4- and 6-methoxycarbonyl-2(1H)-pyridones coincided with the experimental facts.     

The first report of unusual flipping of the cycloadducts from 1,3-dipolar cycloaddition of 3,4,5,6-tetrahydropyridine N-oxide to N-cinnamoyl piperidines

A series of cycloadducts possessing unusual flipping modes have been isolated from the 1,3-dipolar cycloaddition of 3,4,5,6-tetrahydropyridine N-oxide to piperidides of cinnamic acid and para-substituted cinnamic acids and these were analyzed by X-ray crystallography to reveal novel solid-state structures. The presence of two different flippomers arising due to flipping of the six/five bicyclic ring was confirmed both in solid state and in solution. This is the first observation of 1,3-dipolar cycloadducts having two different flippomers arising due to flipping of the isoxazolidine ring.     

Peri-selective photocycloadditions of methyl 2-pyrone-5-carboxylate with unsaturated cyclic ethers

Photosensitized cycloaddition reaction of methyl 2-pyrone-5-carboxylate ( 1 ) with 2,3-dihydrofuran gave cis- exo- and cis-endo-[2 + 2] cycloadducts across the C₃-C₄ double bond in 1 , and a [4 + 2] cycloadduct which was different in addition-orientation from the Diels-Alder adducts. Each [2 + 2] cycloadduct was obtained by the use of sensitizers having different triplet energies. Photosensitized reactions of 1 with 3,4-dihydro-2H-pyrans afforded cis-endo-[2 + 2] cycloadducts, respectively. The photocycloaddition mechanism was also explained from the excited state of 1 calculated by means of MNDO-Cl method.     

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.     

Solvent and Substituent Effects in the Periselectivity of the Staudinger Reaction between Ketenes and alpha,beta-Unsaturated Imines. A Theoretical and Experimental Study

The outcome of the cycloaddition between activated ketenes and alpha,beta-unsaturated imines has been investigated both experimentally and theoretically. Our results indicate that activated monosubstituted ketenes yield exclusively [2 + 2] cycloadducts. Disubstituted activated ketenes yield [2 + 2] and/or [4 + 2] cycloadducts. In one case, an unexpected piperidin-2-one has been obtained, although its relative abundance with respect to the corresponding [2 + 2] or [4 + 2] cycloadducts can be minimized by the proper choice of experimental conditions. The ability of different ab initio and semiempirical methods to account for these results has been tested. The best agreement between theory and experiment is achieved at the MP2/6-31G level of theory, with solvent effects taken into account. The semiempirical hamiltonian AM1, at the RHF level, tends to overestimate the stability of the transition structures leading to six-membered cycloadducts, whereas 3 x 3CI-HE/AM1 and CASSCF(2,2)/6-31G methods tend to overestimate the stability and the biradical character of the transition structures leading to [2 + 2] cycloadducts.     

Trapping of 1,8-biradical intermediates by molecular oxygen in photocycloaddition of naphthyl-N-(naphthylcarbonyl)carboxamides; formation of novel 1,8-epidioxides and evidence of stepwise aromatic cycloaddition.

The photocycloaddition reaction of naphthyl-N-(naphthylcarbonyl)carboxamides (1) was examined under argon and oxygen atmospheres. In addition to the [2 + 2] and [4 + 4] cycloadducts, 3 and 4, respectively, novel 1,8-epidioxides (5) were formed under oxygen atmosphere. The transient absorption at lambda max of 360 nm with the lifetime of 360 ns was observed by laser flash photolysis of 1c and was interpreted as the absorption of biradical intermediate 2. On the basis of the anti stereochemistry of 5, which was different from that of the major [4 + 4] cycloadducts, syn-4, it was deduced that equilibrium between biradical intermediates syn-2 and anti-2 would exist. Retro [2 + 2] cycloaddition of 3 was responsible for the efficient trapping of the biradical intermediate with molecular oxygen. The photocycloaddition of the anthryl derivatives, 9-anthryl-N-(methylethyl)-N-(naphthylcarbonyl)carboxamides (7), afforded the [4 + 4] cycloadducts (8) exclusively in a quantitative yield even under oxygen atmosphere. The absence of trapping with molecular oxygen was interpreted to be due to the lack of retro [4 + 4] cycloaddition of 8.     

Ruthenium-catalyzed [2+2] cycloadditions of bicyclic alkenes and ynamides

Ruthenium-catalyzed [2+2] cycloadditions between bicyclic alkenes and ynamides were investigated. The ynamide moiety was found to be compatible with the ruthenium-catalyzed cycloaddition conditions giving the corresponding cyclobutene cycloadducts in moderate to good yields (up to 97%). Diastereoselective cycloaddition utilizing chiral cyclic ynamides were also examined and a low to moderate level of asymmetric induction was observed.