Highly enantioselective catalytic [6+3] cycloadditions of azomethine ylides

Under control: Highly functionalized chiral annulated piperidines with eight stereocenters are efficiently obtained by means of a highly enantioselective one-pot [6+3]/[4+2] sequence. This sequence included the first enantioselective [6+3] cycloaddition of azomethine ylides with fulvenes.     

Facile and versatile annulation of the imidazole ring: Single and sequential cyclization reactions of Fischer carbene complexes with 1,4-diazafulvenes

We examined the reactivity of dimethylaminodiazafulvene 1 toward Fischer alkenylcarbene 2 and alkynylcarbene 3 complexes. Diazafulvene 1 reacts with alkenylcarbenes 2 through a formal [6+3] heterocyclization in a regio- and stereoselective manner to afford dihydroimidazo[1,2-a]pyridines 4. Acid-promoted dimethylamine elimination in compound 4 c gives rise to the aromatic imidazo pyridine 5. A likely mechanism for this reaction is a 1,2-nucleophilic addition/[1,2]-shift metal-promoted cyclization sequence. On the other hand, diazafulvene 1 and alkynyl carbenes 3 undergo a [6+2] cyclization to afford pyrrolo[1,2-a]imidazole carbene complex 6 that can be readily oxidized to the corresponding esters 7. When enynylcarbenes 3 e-i are treated with diazafulvene 1, consecutive and diastereoselective [6+2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 8, 9, and 12 that can be appropriately demetallated to the corresponding imidazole-based polyfused systems 10, 11, and 13 respectively. Finally, enynylcarbenes 3 d,f undergo consecutive [6+2]/[5+1] cyclization reactions with diazafulvene 1 and tBuNC, respectively, to yield tetracyclic adducts 14 and 15. All these processes result in high yields and provide a route to the preparation of imidazopyridines and pyrroloimidazoles as well as other polycyclic molecules that contain imidazole groups, which are interesting from a pharmacological and biological point of view.     

Rhodium(III)‐Catalyzed [3+2]/[5+2] Annulation of 4‐Aryl 1,2,3‐Triazoles with Internal Alkynes through Dual C(sp2)H Functionalization

A rhodium(III)‐catalyzed [3+2]/[5+2] annulation of 4‐aryl 1‐tosyl‐1,2,3‐triazoles with internal alkynes is presented. This transformation provides straightforward access to indeno[1,7‐cd]azepine architectures through a sequence involving the formation of a rhodium(III) azavinyl carbene, dual C(sp²)? H functionalization, and [3+2]/[5+2] annulation.     

Rhodium(III)‐Catalyzed [3+2]/[5+2] Annulation of 4‐Aryl 1,2,3‐Triazoles with Internal Alkynes through Dual C(sp2)?H Functionalization

A rhodium(III)‐catalyzed [3+2]/[5+2] annulation of 4‐aryl 1‐tosyl‐1,2,3‐triazoles with internal alkynes is presented. This transformation provides straightforward access to indeno[1,7‐cd]azepine architectures through a sequence involving the formation of a rhodium(III) azavinyl carbene, dual C(sp²) H functionalization, and [3+2]/[5+2] annulation.     

Tandem double intramolecular [4 + 2]/[3 + 2] cycloadditions of nitroalkenes

[reaction: see text]. A new class of tandem [4 + 2]/[3 + 2] cycloadditions of nitroalkenes is described in which both pericyclic processes are intramolecular. Two subclasses of intra [4 + 2]/intra [3 + 2] cycloadditions have been explored in which the dipolarophile is tethered at either C(5) or C(6) of the nitronate. For both families of precursors, the cycloadditions occur in good yield and are found to be highly regio- and stereoselective. This method converts linear polyenes to functionalized polycyclic systems bearing up to six stereogenic centers.     

Tandem double intramolecular [4+2]/[3+2] cycloadditions of nitroalkenes. The fused/bridged mode

A new class of tandem [4+2]/[3+2] cycloadditions of nitroalkenes is described in which both pericyclic processes are intramolecular. Two subclasses of intra [4+2]/intra [3+2] cycloadditions have been explored in which the dipolarophile is tethered at either C(5) or C(6) of the nitronate. For both families of precursors, the cycloadditions occur in good yield and are found to be highly regio- and stereoselective. This method converts linear polyenes to functionalized polycyclic systems bearing up to six stereogenic centers.     

A cascade reaction sequence en route to 7-substituted 2-aminopyrrolo[1,2-a]pyrimidine-4,6-diones and the corresponding acrylic acid derivatives

Reaction of α-bromo ketones with 6-amino-2-methylpyrimidin-4(3H)-one under basic conditions and in the presence of atmospheric oxygen affords novel 7-substituted 2-amino-pyrrolo[1,2-a]pyrimidine-4,6-diones that are readily hydrolyzed to afford the corresponding acrylic acid derivatives. The reaction sequence consists of an initial alkylation, followed by an unexpected condensation, elimination, and oxidation sequence to afford the products. This cascade reaction sequence represents a rapid and unprecedented route to the described small molecules.     

Huisgen's 1,3-Dipolar Cycloadditions to Fulvenes Proceed via Ambimodal [6+4]/[4+2] Transition States

Huisgen's 1960 announcement of the concept of 1,3-dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry.     

Huisgen's 1,3‐Dipolar Cycloadditions to Fulvenes Proceed via Ambimodal [6+4]/[4+2] Transition States

Huisgen's 1960 announcement of the concept of 1,3‐dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry.     

Multicomponent domino [4+2]/[3+2] cycloadditions of nitroheteroaromatics: an efficient synthesis of fused nitrogenated polycycles

Activation by high pressure allows 3-nitroindole and 3-nitropyrrole derivatives to behave as electron-poor heterodienes in multicomponent domino [4+2]/[3+2] cycloaddition processes. The primary [4+2] inverse demand cycloaddition appears to be completely endo selective, while the subsequent [3+2] process shows a total facial selectivity, setting the stereochemistry at ring junction, and an endo/exo selectivity depending on the nature of the heterocycle. In two operations, a polycyclic diamine featuring a quaternary center at ring junction is efficiently generated.     

Chemical Behaviour of Zirconium Oxychloride Octahydrate and Acetic Acid in Precursor Solution for Zirconia Film Formation on Glass

Precursor solutions for zirconia films on soda lime silica glass substrate were prepared from zirconium oxychloride octahydrate (ZOO) and acetic acid (HOAC) maintaining the mol ratios, [HOAC]/[ZOO] = 2, 4, 6, 8 and 10. A characteristic UV absorption band at ～280 nm in the ～120 h aged precursor solutions was identified for acetate group of the zirconium acetato complexed species. The presence of acetate ligand coordinated with either ZrOOH+ or [Zr4(OH)8]8+ or with both was predicted by the studies of UV spectra of aged solutions and FTIR spectra of unbaked films on silicon wafer. Dipping technique was followed for film formation. Thicknesses and refractive indices of the baked (450° ± 5°C) films were in the ranges 1818 ± 20 Å and 1.702–1.762 respectively. The positive SIMS experiment on two typical films baked at 450° ± 5°C derived from the precursors with [HOAC]/[ZOO] = 2 and 6, detected the ionic species, Zr+, ZrO+, ZrO2+, Na+, Ca+, Fe+, H+ while the negative SIMS detected O- and Cl-. The relative contents of the ionic species with respect to Zr+ were dependent on the acid content of the precursors. Reflection (%) of the baked films in the UV region was also dependent on the acid content of the precursors. Electron diffraction pattern of the typical baked film derived from the precursor with [HOAC]/[ZOO] = 2 exhibited meta-stable cubic phase of zirconia and the grains were found to be elongated (aspect ratio, 2.00–2.33).     

Cp2TiCl-catalyzed radical chemistry: living styrene polymerizations from epoxides, aldehydes, halides, and peroxides

Four different Cp₂TiCl-activated radical sources (1,4-butanediol diglycidyl ether, benzaldehyde, (1-bromoethyl)benzene, and benzoyl peroxide) were investigated as initiators in the Cp₂TiCl-catalyzed living radical polymerization of styrene (St). The effect of reaction variables was investigated over a wide range of values ([St]/[I]=50/1-400/1, [I]/[Cp₂TiCl₂]=1/0.5-1/4, [Cp₂TiCl₂]/[Zn]=1/0.5-1/3 and T=40-130 °C). A linear dependence of molecular weight on conversion was observed for each initiator, but larger initiator efficiencies and lower polydispersities were obtained upon increasing [Cp₂TiCl₂] and [Zn] and decreasing temperature. The optimum conditions are initiator dependent but broadly correspond to [St]/[I]/[Cp₂TiCl₂]/[Zn]=[50-200]/[1]/[2-3]/[4-6] at 70-90 °C. The most robust initiators are aldehydes followed by peroxides, epoxides, and finally halides.     

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.     

A computational study on the kinetics and mechanism for the unimolecular decomposition of o-nitrotoluene

The kinetics and mechanism for the unimolecular decomposition of o-nitrotoluene (o-CH(3)C(6)H(4)NO(2)) have been studied computationally at the G2M(RCC, MP2)//B3LYP/6-311G(d, p) level of theory in conjunction with rate constant predictions with RRKM and TST calculations. The results of the calculations reveal 10 decomposition channels for o-nitrotoluene and its six isomeric intermediates, among them four channels give major products: CH(3)C(6)H(4) + NO(2), C(6)H(4)C(H)ON (anthranil) + H(2)O, CH(3)C(6)H(4)O (o-methyl phenoxy) + NO, and C(6)H(4)C(H(2))NO + OH. The predicted rate constants in the 500-2000 K temperature range indicate that anthranil production, taking place initially by intramolecular H-abstraction from the CH(3) group by NO(2) followed by five-membered ring formation and dehydration, dominates at temperatures below 1000 K, whereas NO(2) elimination becomes predominant above 1100 K and CH(3)C(6)H(4)O formation by the nitro-nitrite isomerization/decomposition process accounts for only 5-11% of the total product yield in the middle temperature range 800-1300 K. The branching ratio for CH(2)C(6)H(4)NO formation by the decomposition process of CH(2)C(6)H(4)N(O)OH is negligible. The predicted high-pressure-limit rate constants with the rate expression of 4.10 x 10(17) exp[-37000/T] s(-1) for the NO(2) elimination channel and 9.09 x 10(12) exp[-25800/T] s(-1) for the H(2)O elimination channel generally agree reasonably with available experimental data. The predicted high-pressure-limit rate constants for the NO and OH elimination channels are represented as 1.49 x 10(14) exp[-30000/T] and 1.31 x 10(15) exp[-38000/T] s(-1), respectively.     

Kinetics and mechanisms of the redox reaction of hexaaquotitanium(III) and the ethylenediamine tetraacetato titanium(III) complex by aqueous solutions of bromine

At 25°C, I = 1.0 M (CF₃SO₃⁻Li⁺+CF₃SO₃H), [H⁺] = 0.034–0.274 M and λ = 453 nm, the rate equation for the oxidation of Ti(H₂O), ₆³⁺ by bromine was found to be: −d/[Br₂]T/dt=kK/[Br₂][Ti^III]/[H⁺]+K+kK/[Br₃⁻][Ti^III]/[H⁺+K, where k = 9.2 × 10⁻³ M ⁻¹ s ⁻¹ and K = 4.5 × 10⁻³ M. At [H⁺] = 1.0 M, [Br⁻] = 0.05–0.4 M, the apparent second-order rate constant decreases as [Br⁻] increases.

The pH-dependence of the oxidation of Ti^III-edta by bromine is interpreted in terms of the change in identity of the Ti^III-edta species as the pH of the reaction medium changes. The second-order rate constants were fitted using a non-linear least-square computer program with (1/k₀^edta)² weighting into an equation of the form: k₀^edta =k₁+k₂K₁[H⁺]⁻¹+k₃K₁K₂[H⁺]^−2/1+K₁[H⁺[H⁺⁻¹+K₁K₂[H⁺]⁻², with K₁ and K₂ fixed as earlier determined at 9.55 × 10⁻³ and 2.29 × 10⁻⁹ M, respectively, for the oxidation of bromine. k₁=k₂=(3.1±0.32)×10³M⁻¹s⁻¹ k₃=(2.3±0.45)×10⁶N⁻¹s⁻¹.

It is proposed that these electron transfer reactions proceed by univalent changes with the production of Br₂^.− as a transient intermediate. An outer-sphere mechanism is proposed for these reactions. The homonuclear exchange rate for Ti^III-edta+Ti^IV-edta is estimated at 32 M⁻¹ s⁻¹.     

Asymmetric synthesis of rubiginones A(2) and C(2) and their 11-methoxy regioisomers

Convergent enantioselective syntheses of angucyclinone-type natural products rubiginones A(2) (2) and C(2) (1) and their 11-methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1-vinylcyclohexene 4. Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe(3) on (SS)-[(p-tolylsulfinyl)methyl]-p-quinol (9) and the elimination of the beta-hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels-Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C-2 or C-3 of the dienophiles 5 or 6, derived from 5-methoxy-1,4-naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C-1 oxidation.     

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.     

Total synthesis of sordaricin

[structure: see text] The total synthesis of sordaricin, the diterpene aglycone of an important class of antifungal compounds, is described. Two approaches were explored, the first of which utilized a possible biogenetic intramolecular [4 + 2] cycloaddition to form the complete carbon skeleton of the target molecule. A second approach using a tandem cycloreversion/intramolecular [4 + 2] cycloaddition sequence is also detailed.     

Two-coordinate d9 complexes. synthesis and oxidation of NHC nickel(I) amides

Reaction of the d9-d9 Ni(I) monochloride dimer, [(IPr)Ni(mu-Cl)]2 (1), with NaN(SiMe3)2 and LiNHAr (Ar = 2,6-diisopropylphenyl) gives the novel monomeric, 2-coordinate Ni(I) complexes (IPr)Ni{N(SiMe3)2} (2) and (IPr)Ni(NHAr) (3). Reaction of 2 with Cp2Fe+ results in its 1-e- oxidation followed by beta-Me elimination to give a base-stabilized iminosilane complex [(IPr)Ni(CH3){kappa1-N(SiMe3)=SiMe2.Et2O}][BArF4] (6). Oxidation of 3 gives [(IPr)Ni(eta3-NHAr)(THF)][BArF4] (4), which upon loss of THF affords dimeric [(IPr)Ni(N,eta3:NHC6iPr2H3)]2[BArF4]2 (5).     

A novel chromium(0)-promoted four-component cycloaddition reaction

[formula: see text] Reaction of (eta 6-thiepin-1,1-dioxide)tricarbonylchromium(0) with excess terminal alkynes under photoactivation conditions affords novel pentacyclic adducts formally derived from a sequential [6 pi + 2 pi]/[6 pi + 2 pi]/[2 sigma + 2 pi] cycloaddition process.