Rhodium-catalyzed [2+2+2] cycloaddition of 1,6-diynes with isothiocyanates and carbon disulfide

[STRUCTURE: SEE TEXT] A neutral rhodium(I)/BINAP complex effectively catalyzed a [2+2+2] cycloaddition of 1,6-diynes with isothiocyanates to give bicyclic thiopyranimines in 59-98% isolated yield. The reaction with carbon disulfide also proceeded to give bicyclic dithiopyrones in 74-85% isolated yield.     

Regioselective Synthesis of Polyheterocycles From 4-Cyclohex-2-ENYL-3-Hydroxy-1-Methylquinolin-2(1H)-One

4-Cyclohex-2-enyl-3-hydroxy-1-methylquinolin-2(1H)-one (4) was prepared in 90% yield by the thermal [3,3]sigmatropic rearrangement of 3-cyclohex-2-enyloxy-1-methylquinolin-2(1H)-one (3) in refluxing chloroben-zene for 10 h. Compound (4) was cyclised through a sequence of reactions viz. i) acetylation ii) addition of bromine and iii) treatment of the acetyl dibromo compound (6) with base to give a bicyclic product (7) in 90% yield. Treatment of compound 4 with pyridine hydro-bromide perbromide in dichloromethane at 0–5° C afforded a cyclic product 8 in excellent yield. Compound 4 when treated with cold conc. sulphuric acid at 0–5° C furnished the bicyclic product 12 in 89% yield.     

Recent advances in "formal" ruthenium-catalyzed [2+2+2] cycloaddition reactions of diynes to alkenes

"Formal" and standard RuII-catalyzed [2+2+2] cycloaddition of 1,6-diynes to alkenes gave bicyclic 1,3-cyclohexadienes in relatively good yields. When terminal 1,6-diynes 1 were used, two isomeric bicyclic 1,3-cyclohexadienes 4 or 6 were obtained, depending on the acyclic or cyclic nature of the alkene partner. When unsymmetrical substituted 1,6-diynes 7 were used, the reaction with acyclic alkenes took place regio- and stereoselectively to afford bicyclic 1,3-cyclohexadienes 8. A cascade process that behaves as a "formal" RuII-catalyzed [2+2+2] cycloaddition explained these results. Initially, a Ru-catalyzed linear coupling of 1,6-diynes 1 and 7 with acyclic alkenes occurs to give open 1,3,5-trienes of type 3, which after a thermal disrotatory 6e(-) pi-electrocyclization led to the final 1,3-cyclohexadienes 4 and 8. When disubstituted 1,6-diyne 10 was used with electron-deficient alkenes, new exo-methylene cyclohexadienes 12 arose from a competitive reaction pathway.     

Nickel-catalyzed [3+2+2] cycloaddition of ethyl cyclopropylideneacetate and diynes. Synthesis of 7,6- and 7,5-fused bicyclic compounds

The [3+2+2] cycloaddition reaction of ethyl cyclopropylideneacetate (1) and diynes proceeded in the presence of Ni(0) catalysts, and bicyclic compounds were isolated in good yields. The reaction provided a new approach to 7,6- and 7,5-fused bicyclic compounds.     

New data on the alkylation of cyclic thioureas with á-halocarboxylic acids and their esters. 2. Alkylation of tetrahydropyrimidine-2(1h)-thione and 5,5-dimethyltetrahydropyrimidine-2(1h)-thione

In the absence of bases all the attempted variations for the alkylation of tetrahydropyrimidine-2(1H)-thione with á-halocarboxylic acids gave only the bicyclic product-2-R-6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-one hydrohalide. However the hydrohalide of the “ open” S-ethoxycarbonyl derivative of propyleneisothiourea can be obtained by treatment of tetrahydropyrimidine-2(1H)-thione with ethyl chloro-or bromoacetate in anhydrous acetone at room temperature. Alkylation of 5,5-dimethyltetrahydro-2(1H)-pyrimidinethione with chloro-or bromoacetic acid in anhydrous acetone at room temperature gave the hydrohalide of the “open” S-carboxymethyl derivative of dimethylpropyleneisothiourea. All remaining variations for the alkylation of this substrate with á-halocarboxylic acids or their esters gave only the corresponding bicyclic compounds-the hydrohalide of 2-R-6,6-dimethyl-6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-one-independently of the reaction conditions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 593–604, April, 2006.     

Unusual intramolecular [2 + 2] cycloaddition of allyl and vinylidene C=C bonds under mild conditions: a theoretical analysis

A theoretical analysis allows for the rationalization of the recently reported unusual formation under mild conditions of a cyclobutylidene ring from a diastereoselective [2 + 2] intramolecular cycloaddition of two C=C systems. The reaction takes place by heating in dichloromethane the vinylidene complexes [Ru((eta(5),eta(3)-C(9)H(7))[=C=C(R)H][kappa(1)-(P)-PPh(2)(C(3)H(5))](PPh(3))][BF(4)] (R = Ph, p-Me-C(6)H(4)) (1) yielding the bicyclic alkylidene complexes [Ru((eta(5),eta(3)-C(9)H(7))[kappa(2)-(P,C)-(=CC(R)HCH(2)CHCH(2)-PPh(2)](PPh(3))][BF(4)] (2). The proposed mechanism represents an alternative to the classical Woodward-Hoffmann's supra-antara approach.     

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.     

Syntheses of monocyclic and bicyclic 2,4(1H,3H)-pyrimidinediones and their serotonin 2 antagonist activities

New serotonine 2 (5-HT2) antagonists with a monocyclic or bicyclic 2,4(1H,3H)-pyrimidinedione have been prepared and their activities evaluated. In a series of monocyclic compounds, 1-substituted 5-phenyl-2,4(1H,3H)-pyrimidinedione 14 showed potent in vitro activity, and the corresponding 3-substituted 5-phenyl and 6-phenyl derivatives 3, 8 and 20a also showed moderate activity. In the bicyclic compounds, 3-substituted 5,6,7,8-tetrahydro-2,4(1H,3H)-quinazolinedione 33 exhibited the most potent activity among the compounds prepared in this paper. The in vivo antagonist activity of 33 was comparable to that of ketanserin, a typical peripheral 5-HT2 antagonist.     

Formal and standard ruthenium-catalyzed [2 + 2 + 2] cycloaddition reaction of 1,6-diynes to alkenes: a mechanistic density functional study

"Formal" and standard Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,6-diynes 1 to alkenes gave bicyclic 1,3-cyclohexadienes in relatively good yields. The neutral Ru(II) catalyst was formed in situ by mixing equimolecular amounts of [Cp*Ru(CH3CN)3]PF6 and Et4NCl. Two isomeric bicyclic 1,3-cyclohexadienes 3 and 8 were obtained depending on the cyclic or acyclic nature of the alkene partner. Mechanistic studies on the Ru catalytic cycle revealed a clue for this difference: (a) when acyclic alkenes were used, linear coupling of 1,6-diynes with alkenes was observed giving 1,3,5-trienes 6 as the only initial reaction products, which after a thermal disrotatory 6e-pi electrocyclization led to the final 1,3-cyclohexadienes 3 as probed by NMR studies. This cascade process behaved as a formal Ru-catalyzed [2 + 2 + 2] cycloaddition. (b) With cyclic alkenes, the standard Ru-catalyzed [2 + 2 + 2] cycloaddition occurred, giving the bicyclic 1,3-cyclohexadienes 8 as reaction products. A complete catalytic cycle for the formal and standard Ru-catalyzed [2 + 2 + 2] cycloaddition of acetylene and cyclic and acyclic alkenes with the Cp*RuCl fragment has been proposed and discussed based on DFT/B3LYP calculations. The most likely mechanism for these processes would involve the formation of ruthenacycloheptadiene intermediates XXIII or XXVII depending on the alkene nature. From these complexes, two alternatives could be envisioned: (a) a reductive elimination in the case of cyclic alkenes 7 and (b) a beta-elimination followed by reductive elimination to give 1,3,5-hexatrienes 6 in the case of acyclic alkenes. Final 6e-pi electrocyclization of 6 gave 1,3-cyclohexadienes 3.     

Rhodium-catalyzed enantioselective [2+2+2] cycloaddition of diynes with unfunctionalized alkenes

A chiral rhodium complex catalyzed an enantioselective [2+2+2] cycloaddition of unsymmetrical diynes with norbornene, and tetracyclic products were obtained in good to excellent ee. The cycloaddition of a symmetrical diyne with styrene derivatives as coupling partners gave bicyclic products in good ee.     

Eight-membered ring construction by [4 + 2 + 2] annulation involving beta-carbon elimination

Cyclobutanones underwent a formal [4 + 2 + 2] annulation reaction with 1,6- and 1,7-diynes in the presence of nickel(0) catalysts to provide bicyclic eight-membered ring ketones. The annulation reaction proceeds through a ring-expansion of oxanickelacycloheptadiene via beta-carbon elimination to form a nine-membered nickelacycle. This reaction employing cyclobutanones as a C4 unit constructs cyclooctadienone cores in one synthetic step.     

Bromenium‐Catalysed Tandem Ring Opening/Cyclisation of Vinylcyclopropanes and Vinylcyclobutanes: A Metal‐Free [3+2+1]/[4+2+1] Cascade for the Synthesis of Chiral Amidines and Computational Investigation

We present a detailed study of a [3+2+1] cascade cyclisation of vinylcyclopropanes (VCP) catalysed by a bromenium species (Br^δ+? X^δ?) generated in situ, which results in the synthesis of chiral bicyclic amidines in a tandem one‐pot operation. The formation of amidines involves the ring‐opening of VCPs with Br? X, followed by a Ritter‐type reaction with chloramine‐T and a tandem cyclisation. The reaction has been further extended to vinylcyclobutane systems and involves a [4+2+1] cascade cyclisation with the same reagents. The versatility of the methodology has been demonstrated by careful choice of VCPs and VCBs to yield bicyclo[4.3.0]‐, ‐[4.3.1]‐ and ‐[4.4.0]amidines in enantiomerically pure form. On the basis of the experimental observations and DFT calculations, a reasonable mechanism has been put forth to account for the formation of the products and the observed stereoselectivity. We propose the existence of a π‐stabilised homoallylic carbocation at the cyclopropane carbon as the reason for high stereoselectivity. DFT studies at B3LYP/6‐311+G** and M06‐2X/6‐31+G* levels of theory in gas‐phase calculations suggest the ring‐opening of VCP is initiated at the π‐complex stage (between the double bond and Br? X). This can be clearly perceived from the solution‐phase (acetonitrile) calculations using the polarisable continuum model (PCM) solvation model, from which the extent of the ring opening of VCP was found to be noticeably high. Studies also show that the formation of zero‐bridge bicyclic amidines is favoured over other bridged bicyclic amidines. The energetics of competing reaction pathways is compared to explain the product selectivity.     

Investigation of the Diels-Alder cycloadditions of 2(H)-1,4-oxazin-2-ones

[Reaction: see text]. A variety of 5-chloro-2(H)-1,4-oxazin-2-ones bearing a range of substituents at their 3- and 6-positions undergo Diels-Alder cycloaddition as a 2-azadiene component with electron-rich, electron-deficient, and electron-neutral dienophiles. These reactions proceed with moderate regio- and stereoselectivity to afford relatively stable and readily isolable bridged bicyclic lactone cycloadducts. Chemical manipulation of these cycloadducts affords highly substituted and functionally rich piperidines. The regio- and stereochemical preferences of the cycloadditions of 5-chloro-2(H)-1,4-oxazin-2-ones are investigated computationally using density functional theory (B3LYP/6-31G).     

Asymmetric Synthesis of Bicyclic Pyrazolidinones through Alkaloid-Catalyzed [3+2]-Cycloadditions of Ketenes and Azomethine Imines

A versatile asymmetric synthesis of bicyclic pyrazolidinones through alkaloid-catalyzed formal [3+2]- and [3+2+2]-cycloadditions of ketenes with azomethine imines is described. The methodology was found to be tolerant of ketene and a variety of monosubstituted ketenes (R=alkyl, OAc). The products were formed in good to excellent yields (71–99 % for 24 examples, 39 examples in all), with good to excellent diastereoselectivity in many cases (dr 3 : 1 to 27 : 1 for 22 examples), and with excellent enantioselectivity for most examples (≥93 % ee for 34 products). In the case of most disubstituted ketenes, the reaction proceeded through a [3+2+2]-cycloaddition to form structurally interesting bicyclic pyrazolo-oxadiazepinediones with moderate diastereoselectivity (dr up to 3.7 : 1) and as racemic mixtures (3 examples). The method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.     

Iridium complex-catalyzed [2+2+2] cycloaddition of alpha,omega-diynes with monoynes and monoenes

[reaction: see text] [Ir(cod)Cl]2/DPPE was found to be a new catalyst for the cycloaddition of alpha,omega-diynes with monoynes to give polysubstituted benzene derivatives in high yields. Internal monoynes as well as terminal monoynes could be used. The reaction tolerates a broad range of functional groups such as alcohol, amine, alkene, ether, halogen, and nitrile. The reaction of 1,6-octadiyne derivatives with 1-alkynes gives ortho products and meta products. The regioselectivity could be controlled by the choice of ligand. The reaction with DPPE was meta selective, with meta selectivity of up to 82%. The reaction with DPPF was ortho selective, with ortho selectivity of up to 88%. We propose a mechanism to account for this regioselective cycloaddition. [Ir(cod)Cl](2)/DPPE also catalyzed the cycloaddition of alpha,omega-diynes with 2,5-dihydrofuran to give bicyclic cyclohexadiene derivatives. The reaction with 2,3-dihydrofuran and n-butyl vinyl ether gave benzene derivatives instead of cyclohexadiene derivatives. We also propose a mechanism to account for this novel aromatization that includes cleavage of the C-O bond.     

Cobalt(I)-mediated [2 + 2 + 2] cyclization of allenediynes toward a diastereoselective approach to 11-aryl steroid skeletons

[reaction: see text] An 11-aryl steroid skeleton has been built in one step with a simultaneous introduction of the substituents at both C11 and C10 in 48% overall yield from a trans-allenediyne, whereas a formal Alder ene reaction leading to a bicyclic yne-trienic compound becomes the major process from the cis-allenediyne.     

New monoacylhydrazidate-coordinated Mn2+ and Pb2+ compounds

By the simple hydrothermal self-assembly, four new monoacylhydrazidate-coordinated compounds [Mn(APTH)(2)(H(2)O)] 1, [Pb(APTH)(2)]·0.25H(2)O 2, [Pb(2)(EPDH)(4)(H(2)O)] 3 and [Pb(MPDH)(2)] 4 (APTH = 3-aminophthalhydrazidate, EPDH = 5-ethylpyridine-2,3-dicarboxylhydrazidate, MPDH = 6-methylpyrinde-2,3-dicarboxylhydrazidate) were obtained. It is noteworthy that APTH was derived from the in situ reduction reaction of NPTH (3-nitrophthalhydrazide) with N(2)H(4)·H(2)O as the reducer, whereas EPDH and MPDH were derived respectively from the in situ acylation reactions of epdca and mpdca (epdca = 5-ethylpyridine-2,3-dicarboxylic acid, mpdca = 6-methylpyridine-2,3-dicarboxylic acid) with N(2)H(4)·H(2)O. The photoluminescence analysis indicates that compounds 3 and 4 possess luminescence properties with maximum emissions at 531 nm for 3, and 600 nm for 4, respectively. The density functional theory (DFT) calculations indicate that the emission for compound 3 can be ascribed to a combination of the intra-ligand and inter-ligand charge transfers, while the emission for compound 4 is assigned to the intra-ligand charge transfer.     

Enantioselective multicomponent synthesis of fused 6-5 bicyclic 2-butenolides by a cascade heterobicyclisation process

The successive coupling of an alkoxy(aryl/heteroaryl)carbene complex of chromium with either a ketone or an imide lithium enolate and then a 3-substituted (H, TMS, PhCH(2), PhCH(2)CH(2), Me) propargylic organomagnesium reagent has afforded novel hydroxy-substituted bicyclic [4.3.0]-γ-alkylidene-2-butenolides with three modular points that has allowed the efficient introduction of molecular complexity, including a homopropargylic alcohol core. The selective formation of these five- or six-component heterobicyclisation products is the result of the regioselective integration of the Grignard reagent as a propargyl fragment followed by a cascade CO/alkyne/CO insertion, ketene trapping and elimination sequence. By using lithium enolates of chiral N-acetyl-2-oxazolidinones and the corresponding propargylic organocerium reagents, both enantiomers of these bicyclic heterocycles were efficiently prepared with very high enantiomeric purity. Architecturally, these fused bicyclic butenolides are characterised by a highly unsaturated and oxygenated core and they exhibit strong blue fluorescence in solution.     

Reflected shock tube studies of high-temperature rate constants for OH + C2H2 and OH + C2H4

The reflected shock tube technique with multi-pass absorption spectrometric detection of OH-radicals at 308 nm (corresponding to a total path length of approximately 4.9 m) has been used to study the reactions, OH + C(2)H(2)--> products (1) and OH + C(2)H(4)--> C(2)H(3) + H(2)O (2). The present optical configuration gives a S/N ratio of approximately 1 at approximately 0.5-1.0 x 10(12) radicals cm(-3). Hence, kinetics experiments could be performed at [OH](0) = approximately 4-20 ppm thereby minimizing secondary reactions. OH was produced rapidly from the dissociations of either CH(3)OH or NH(2)OH (hydroxylamine). A mechanism was then used to obtain profile fits that agreed with the experiment to within <+/-5%. The derived Arrhenius expressions, in units of cm(3) molecule(-1) s(-1) are: k(1) = (1.03 +/- 0.24) x 10(-10) exp(-7212 +/- 417 K/T) for 1509-2362 K and k(2) = (10.2 +/- 5.8) x 10(-10) exp(-7411 +/- 871 K/T) for 1463-1931 K. The present study is the first ever direct measurement for reaction (1) at temperatures >1275 K while the present results extend the temperature range for (2) by approximately 700 K. These values are compared with earlier determinations and with recent theoretical calculations. The calculations agree with the present data for both reactions to within +/-10% over the entire T-range.     

Study on the reactivity of oxabicyclic alkenes in ruthenium-catalyzed [2+2] cycloadditions

The ruthenium-catalyzed [2+2] cycloadditions of various bicyclic alkenes with an alkyne have been investigated. The presence of the oxygen in the bridgehead of the bicyclic alkene significantly enhanced the rate of the ruthenium-catalyzed [2+2] cycloadditions. The presence of a C1-substituent on the oxanorbornadiene decreased the rate of the cycloaddition and electron-withdrawing C1-substituents were found to be more reactive than electron-donating C1-substituents in the Ru-catalyzed [2+2] cycloaddition. The nature of the substituent on the benzene ring of oxabenzonorbornadienes showed little effect on the rate of the cycloaddition.