Ruthenium-catalyzed cyclization of 2-alkyl-1-ethynylbenzenes via a 1,5-hydrogen shift of ruthenium-vinylidene intermediates

Catalytic cyclization of 2-alkyl-1-ethynylbenzene derivatives was implemented by TpRuPPh3(CH3CN)2PF6 (10 mol %) in hot toluene (105 degrees C, 36-100 h) to form 1-substituted-1H-indene and 1-indanone products; such cyclizations proceeded more efficiently for substrates bearing electron-rich benzenes. We propose that the cyclization mechanism involves a 1,5-hydrogen shift of initial metal-vinylidene intermediate.     

A concise synthesis of rooperol and related 1,5-diarylpent-1-en-4-ynes

Two powerful strategies: rapid construction of allylic alkynoates via cyclopropenium ion chemistry and mild, palladium-catalyzed decarboxylative coupling were employed in a concise, 5-steps synthesis of the natural product rooperol. The overall approach allows the preparation of rooperol analogs in as few as 3 steps.     

Ab initio transition structures for 1,5-sigmatropic hydrogen shifts of 1,3-pentadiene and cyclopentadiene

3-21G transition structures for 1,5-sigmatropic hydrogen shifts of 1,3-pentadiene and cyclopentadiene have been located. The CHC angles in the transition structures are 130° and 68°, respectively. The difference in calculated activation energies for the two reactions agrees with the experimental difference.     

Ruthenium-catalyzed [1,n]-metallotropic shift (n = 3, 5) of alkynyl carbene complex intermediates

The ruthenium-catalyzed isomerization of diynes and triynes involving propargyl carboxylate moieties affords dienynes and dienediynes, respectively. The [1,n]-metallotropic shift (n = 3, 5) (carbene walk) of in situ generated alkynyl carbene complexes has been proposed for the catalytic isomerization reaction.     

PtCl2-Catalyzed transannular cycloisomerization of 1,5-enynes: a new efficient regio- and stereocontrolled access to tricyclic derivatives

[reaction: see text] Transannular PtCl(2)-catalyzed cycloisomerizations open a new route to cyclopropanic tricyclic systems. Ketones A or C were efficiently prepared from the same cycloundec-5-en-1-yne precursor B, depending on the substituent at the propargylic position (either benzoate or methoxy).     

Metal-catalyzed chemoselective cycloisomerization of cis-2,4-dien-1-als to 3-cyclopentenones and 4-alkylidene-3,4-dihydro-2H-pyrans

[reaction: see text] PtCl(2) (5 mol %) catalyst effected cycloisomerization of cis-2,4-dien-1-al (1) to 3-cyclopentenone (3) efficiently in hot toluene. In the presence of p-TSA, this PtCl(2) catalysis gave 2-cyclopentenone (5) exclusively because of the secondary isomerization reaction. Although the 1-2 equilibrium state greatly favors aldehyde (1), PdCl(2)(PhCN)(2) (5 mol %) catalyzed cycloisomerization of aldehyde (1) to 4,6,7,8-tetrahydro-3H-isochromene (4) smoothly in hot toluene. A plausible mechanism is proposed on the basis of reaction observation and isotope-labeled experiment.     

Synthesis of 1,5-diphenylpent-3-en-1-yne derivatives utilizing an aqueous B-alkyl Suzuki cross coupling reaction

1,5-Diphenylpent-3-en-1-yne derivatives were isolated in minor quantities from terrestrial plants and exhibited strong anti-inflammatory activity. A cross coupling reaction between B-benzyl-9-BBN and chloroenynes under mild condition was developed resulting in the formation of different 1,5-diphenylpent-3-en-1-yne derivatives with a full control on the E/Z selectivity. Several substrates bearing electron-donating and electron-withdrawing substituents were tolerable under the reaction conditions affording the corresponding products in good yields. This is the first study to report the synthesis of a vast array of novel 1,5-diphenylpent-3-en-1-yne derivatives paving the way for the preparation of tailored derivatives on mass scale necessary for biological studies and drug development.     

Quantum treatment of hydrogen nuclei in primary kinetic isotope effects in a thermal [1,5]-sigmatropic hydrogen (or deuterium) shift from (Z)-1,3-pentadiene

The geometric and kinetic isotope effects (GIE and KIE) for thermal [1,5]-sigmatropic H and D shifts of (Z)-1,3-pentadiene were studied by including the direct quantum effect of the migrating H or D nucleus in the multi-component molecular orbital-Hartree-Fock (MC_MO-HF) method. Based on the results, the C(1)-D bond lengths are 0.007 Angstrom shorter than the C1-H bond lengths in both the reactant (A) and the transition states (TS), whereas other bond lengths resemble those between H and D. The ratio of the rate constant (k(H)/k(D)) of the reaction for the thermal [1,5]-H and D shifts determined using the MC_MO-HF method (8.28) is closer to the experimental value (12.2) than that determined using either the conventional restricted Hartree-Fock (4.10) or restricted M?ller-Plesset second-order perturbation (3.79) methods.     

Thermal and metal-catalyzed cyclization of 1-substituted 3,5-dien-1-ynes via a [1,7]-hydrogen shift: development of a tandem aldol condensation-dehydration and aromatization catalysis between 3-en-1-yn-5-al units and cyclic ketones

This work investigates the feasibility of thermal and catalytic cyclization of 6,6-disubstituted 3,5-dien-1-ynes via a 1,7-hydrogen shift. Our strategy began with an understanding of a structural correlation of 3,5-dien-1-ynes with their thermal cyclization efficiency. Thermal cyclization proceeded only with 3,5-dien-1-ynes bearing an electron-withdrawing C(1)-phenyl or C(6)-carbonyl substituent, but the efficiencies were generally low (20-40% yields). On the basis of this structure-activity relationship, we conclude that such a [1,7]-hydrogen shift is characterized by a "protonic" hydrogen shift, which should be catalyzed by pi-alkyne activators. We prepared various 6,6-disubstituted 3,5-dien-1-ynes bearing either a phenyl or a carbonyl group, and we found their thermal cyclizations to be greatly enhanced by RuCl(3), PtCl(2), and TpRuPPh(3)(CH(3)CN)(2)PF(6) catalysts to confirm our hypothesis: the C(7)-H acidity of 3,5-dien-1-ynes is crucial for thermal cyclization. To achieve the atom economy, we have developed a tandem aldol condensation-dehydration and aromatization catalysis between cycloalkanones and special 3-en-1-yn-5-als using the weakly acidic catalyst CpRu(PPh(3))(2)Cl, which provided complex 1-indanones and alpha-tetralones with yields exceeding 65% in most cases. The deuterium-labeling experiments reveal two operable pathways for the metal-catalyzed [1,7]-hydrogen shift of 3,5-dien-1-ynes. Formation of alpha-tetralones d(4)-56 arises from a concerted [1,7]-hydrogen shift, whereas benzene derivative d(4)-9 proceeds through a proton dissociation and reprotonation process.     

1,3-Dipolar cycloadditions of diazoalkanes to pyridazine derivatives. Thermal 1,5-sigmatropic rearrangement of methyl groups in 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazine derivatives

Thermal 1,5-sigmatropic rearrangements of one of the methyl group attached at position 3 of 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazin-4(5H)-ones 1–3 taking place either in a clock-wise or anti-clockwise direction gave N₂-methylated products 4–6 and C_3a-methylated products 7– 9 . The -7(6)-one derivative 10 and -4,7(5H,6H)-dione derivative 12 gave only N₂-methylated products 11 and 13 respectively, and 1,2-dihydro derivative 14 produced after elimination of methane, 15 .     

A theoretical study of the reaction between cyclopentadiene and protonated imine derivatives: a shift from a concerted to a stepwise molecular mechanism

The reaction between cyclopentadiene and protonated pyridine-2-carboxaldehyde imine derivatives has been studied by using Hartree-Fock (HF) and B3LYP methods together with the 6-31G basis set. The molecular mechanism is stepwise along an inverted energy profile. This results from the protonation on both nitrogen atoms of the imine group and the pyridine framework. The first step corresponds to the nucleophilic attack of cyclopentadiene on the electron-poor carbon atom of the iminium cation group to give an acyclic cation intermediate, and the second step is associated with the ring closure of this intermediate via the formation of a C-N single bond yielding the final cycloadduct. Two reactive channels have been characterized corresponding to the endo and exo approach modes of the cyclopentadiene to the iminium cation. The role of the pyridium cation substituent and the nitrogen position (ortho, meta, and para) along the reaction pathway has been also considered. Solvent effects (dichloromethane) by means of a continuum model have been taken into account to model the experimental environment.     

Novel synthesis of 3-(3,3,3-trifluoroprop-1-en-2-yl)furans via stereoselective processing and palladium-catalyzed cycloisomerization

The 3,3,3-trifluoroprop-1-en-2-yl-substituted furans (4) were synthesized via palladium-catalyzed cyclization-isomerization of 1,1,1-trifluoro-2-[(tert-butyldimethylsilyloxy)methyl]-3-alkynylbut-2-en-1-ols (3), which were readily obtained from 1,1,1-trifluoro-2-[(tert-butyldimethylsilyloxy)methyl]-3,3-dibromoprop-2-ene (1) in three steps.     

Gold and Brønsted acid catalyzed isomerization of [3]cumulenols and [3]cumulenones: efficient syntheses of 1,5-dien-3-ynes and furan derivatives

An attractive method for assembling π-conjugated dienynes with high stereoselectivity was achieved by dehydration reaction of TMS-substituted [3]cumulenols catalyzed by TsOH·H₂O. On the other hand, cycloisomerizations of the corresponding [3]cumulenones catalyzed by gold(I) complexes afford vinyl furans through activation of the cumulenic double bond via a π-complex, and during the process, deprotonation from an alkyl group on cumulene terminus takes place to induce the isomerization.     

Diastereoselective synthesis of (E)-1-trimethylsilyl-3-en-1-ynes by palladium-catalyzed cross-coupling reaction between trimethylsilylethynylzinc chloride and stereoisomeric mixtures of 1-bromo-1-alkenes

In the stereospecific palladium-catalyzed cross-coupling reaction of triimethylsilyl-ethynylzinc chloride, (B)-1-bromo-1-alkenes react preferentially in the presence of the corresponding (Z)-stereoisomers.     

Synthesis of pyrroles from 1-dialkylamino-3-phosphoryl(or phosphanyl)allenes through 1,5-cyclization of conjugated azomethine ylide intermediates

1-Dialkylamino-1,3-diaryl-3-diphenylphosphanylallenes 3a-e are thermally converted into a-annulated 3,5-diarylpyrroles 6a-f and [a]-annulated benzo[c]azepines 7a,b,d. These transformations are likely to include conjugated azomethine ylide intermediates that can undergo either a 1,5- or a 1,7-electrocyclization. The periselectivity is markedly shifted toward 1,5-cyclization when the diphenylphosphanyl substituent is replaced by the diphenylphosphoryl group. Thus, 1-dialkylamino-3-(diphenylphosphoryl)allenes 4a-f yield pyrroles 6 exclusively and with improved yields, unless the 3-aryl substituent in the allene is too electron-rich (e.g., benzodioxol-5-yl, 4f --> 7f). The preparation and thermal transformation of aminoallenes 4 over three or four steps can be conducted as a one-pot procedure, thus providing a convenient synthesis of [a]-annulated 3,5-diarylpyrroles from enaminoketones.     

Ruthenium-catalyzed transformation of 3-benzyl but-1-ynyl ethers into 1,3-dienes and benzaldehyde via transfer hydrogen

TpRuPPh(3)(CH(3)CN)(2)PF(6) catalyzed the transformation of various 3-benzyl but-1-ynyl ethers into dienes and benzaldehyde at a catalyst loading of 5 mol %. This process represents an atypical pattern of transfer hydrogenation. This catalytic reaction can be applied to various derivatives of 2-ethynyl tetrahydrofurans and pyrans to cleave their ether rings and gives diene and tethered aldehyde functionalities, respectively.     

Syntheses of substituted benzosiloles and siloles by diisobutylaluminium hydride-promoted cyclization of 1-silyl-2-(2-silylethynyl)benzenes and 1,4-disilylalk-3-en-1-ynes

An efficient method for preparing substituted benzosiloles and unsymmetrically substituted siloles by intramolecular C-Si bond formation has been developed. The reaction of 1-methoxysilyl-2-[2-(trimethylsilyl)ethynyl]benzenes with 1.5 equiv of diisobutylaluminium hydride (DIBAL-H) gave benzosiloles in good to high yields. Similarly 4-methoxysilyl-1-silylalk-3-en-1-ynes were cyclized to multisubstituted siloles. Mechanistic study of this transformation uncovered that the methoxysilyl group was initially converted into the corresponding hydrosilyl group by the action of DIBAL-H, and that the resultant hydrosilanes underwent the DIBAL-H-promoted cyclization to benzosiloles. When 1-hydrosilyl-2-[2-(trimethylsilyl)ethynyl]benzenes were used as substrates, a substoichiometric amount of DIBAL-H was enough for the cyclization. The DIBAL-H-promoted transformation could be applied to regio-defined synthesis of unsymmetrically substituted siloles from 4-hydrosilyl-1-silylalk-3-en-1-ynes. This pre-installation approach provides a straightforward access to multisubstituted siloles with complete regioselection.     

The skeletal rearrangement of gold- and platinum-catalyzed cycloisomerization of cis-4,6-dien-1-yn-3-ols: pinacol rearrangement and formation of bicyclo[4.1.0]heptenone and reorganized styrene derivatives

With gold and platinum catalysts, cis-4,6-dien-1-yn-3-ols undergo cycloisomerizations that enable structural reorganization of cyclized products chemoselectively. The AuCl3-catalyzed cyclizations of 6-substituted cis-4,6-dien-1-yn-3-ols proceeded via a 6-exo-dig pathway to give allyl cations, which subsequently undergo a pinacol rearrangement to produce reorganized cyclopentenyl aldehyde products. Using chiral alcohol substrates, such cyclizations proceed with reasonable chirality transfer. In the PtCl2-catalyzed cyclization of 7,7-disubstituted cis-4,6-dien-1-yn-3-ols, we obtained exclusively either bicyclo[4.1.0]heptenones or reorganized styrene products with varied substrate structures. On the basis of the chemoselectivity/structure relationship, we propose that bicyclo[4.1.0]heptenone products result from 6-endo-dig cyclization, whereas reorganized styrene products are derived from the 5-exo-dig pathway. This proposed mechanism is supported by theoretic calculations.