Radical 4‐exo Cyclizations via Template Catalysis

The mechanism of catalytic 4‐exo cyclizations without gem‐dialkyl substitution was investigated by a comparison of cyclic voltammetry, EPR, and computational studies with previously published synthetic results. The most active catalyst is a super‐unsaturated 13‐electron titanocene(III) complex that is formed by supramolecular activation through hydrogen bonding. The template catalyst binds radicals via a two‐point binding that is mandatory for the success of the 4‐exo cyclization. The computational investigations revealed that formation of the observed trans‐cyclobutane product is not possible from the most stable substrate radical. Instead, the most stable product is formed with the lowest energy of activation from a disfavored substrate in a Curtin–Hammett related scenario.     

Direct arylation of oxazole and benzoxazole with aryl or heteroaryl halides using a palladium-diphosphine catalyst

Through the use of PdCl(dppb)(C₃H₅) as a catalyst, a range of aryl bromides and chlorides undergoes coupling via C-H bond activation/functionalization reaction with oxazole or benzoxazole in good yields. This air-stable catalyst can be used at low loadings with several substrates. Surprisingly, better results in terms of substrate/catalyst ratio were obtained in several cases using electron-excessive aryl bromides than with the electron-deficient ones. This seems to be mainly due to the relatively low thermal stability of some of the 2-arylbenzoxazoles formed with electron-deficient aryl halides. With these substrates, in order to obtain higher yields of product, the reactions had to be performed at a lower temperature (100-120 °C) using a larger amount of catalyst. On the other hand, in the presence of the most stable products, the reactions were performed at 150 °C using as little as 0.2 mol% catalyst. Arylation of benzoxazole with heteroaryl bromides also gave the coupling products in moderate to high yields using 0.2-5 mol% catalyst. With this catalyst, electron-deficient aryl chloride such as 4-chlorobenzonitrile, 4-chloroacetophenone or 2-chloronitrobenzene have also been used successfully.     

Bifunctional catalyst promotes highly enantioselective bromolactonizations to generate stereogenic C-Br bonds

A novel bifunctional catalyst derived from BINOL has been developed that promotes the highly enantioselective bromolactonizations of a number of structurally distinct unsaturated acids. Like some known catalysts, this catalyst promotes highly enantioselective bromolactonizations of 4- and 5-aryl-4-pentenoic acids, but it also catalyzes the highly enantioselective bromolactonizations of 5-alkyl-4(Z)-pentenoic acids. These reactions represent the first catalytic bromolactonizations of alkyl-substituted olefinic acids that proceed via 5-exo mode cyclizations to give lactones in which new carbon-bromine bonds are formed at a stereogenic center with high enantioselectivity. We also disclose the first catalytic desymmetrization of a prochiral dienoic acid by enantioselective bromolactonization.     

Kinetic and spectroscopic studies of the [palladium(Ar-bian)]-catalyzed semi-hydrogenation of 4-octyne

The kinetics of the stereoselective semi-hydrogenation of 4-octyne in THF by the highly active catalyst [Pd{(m,m'-(CF(3))(2)C(6)H(3))-bian}(ma)] (2) (bian = bis(imino)acenaphthene; ma = maleic anhydride) has been investigated. The rate law under hydrogen-rich conditions is described by r = k[4-octyne](0.65)[Pd][H(2)], showing first order in palladium and dihydrogen and a broken order in substrate. Parahydrogen studies have shown that a pairwise transfer of hydrogen atoms occurs in the rate-limiting step. In agreement with recent theoretical results, the proposed mechanism consists of the consecutive steps: alkyne coordination, heterolytic dihydrogen activation (hydrogenolysis of one Pd-N bond), subsequent hydro-palladation of the alkyne, followed by addition of N-H to palladium, reductive coupling of vinyl and hydride and, finally, substitution of the product alkene by the alkyne substrate. Under hydrogen-limiting conditions, side reactions occur, that is, formation of catalytically inactive palladacycles by oxidative alkyne coupling. Furthermore, it has been shown that (Z)-oct-4-ene is the primary reaction product, from which the minor product (E)-oct-4-ene is formed by an H(2)-assisted, palladium-catalyzed isomerization reaction.     

The adequacy of the observed kinetic order in catalyst and the differential selectivity patterns to the hypothesis of the cooperative mechanism of catalysis of the Suzuki—Miyaura reaction

The generally accepted mechanism of the Suzuki—Miyaura reaction suggests a sequential activation of the substrate (aryl halide) and the reagent (arylboronic acid) by a palladium catalyst with the formation of unsymmetric biaryl as a result of a single turnover of the catalytic cycle, i.e., it is linear from the kinetic point of view. At the same time, the use of an unconventional kinetic approach based on the analysis of the differential selectivity of the reaction, rather than the regularities of catalytic activity, indicates the inadequacy of the linear mechanism, that is consistent with the hypothesis of a nonlinear (the so-called cooperative) mechanism of catalysis, in which the product is formed as a result of the substrate and reagent activation by two different palladium-containing intermediates in two parallel catalytic cycles. The experimentally observed low kinetic orders of the Suzuki—Miyaura reaction with respect to the concentration of the palladium catalyst precursor under the ligand-free conditions of catalysis are also consistent with the cooperative mechanism and can be due to the changes in the relative amount of the catalyst in two parallel catalytic cycles and/or to the process of catalyst deactivation.

     

8-endo versus 7-exo cyclization of alpha-carbamoyl radicals. A combination of experimental and theoretical studies

Atom transfer radical cyclization reactions of N-(4-pentenyl)iodoacetamides were investigated. The reactions were efficiently promoted by BF3.OEt2. For N-alkenyl-substituted iodoamides, excellent regioselectivity in favor of 8-endo cyclization was observed, while both 7-exo and 8-endo cyclization products were formed with the 8-endo cyclization preferred in the cases of N-(2-allylphenyl)-substituted iodoamides. Density functional theory calculations at the B3LYP/6-31G level revealed that both the s-trans and the s-cis conformational transition structures were feasible for the 8-endo cyclization of N-alkenyl-substituted alpha-carbamoyl radicals while 7-exo transition structures were much less stable. For the cyclization of N-(2-allylphenyl)-substituted alpha-carbamoyl radicals, the transition structures for 8-endo and 7-exo cyclizations were of comparable energy. These results were in excellent agreement with the experimental observations.     

Asymmetric hydrogenations one by one: differentiation of up to three beta-ketocarboxylic acid derivatives based on Ruthenium(II)-binap catalysis

Noyori-type reductions of pairs of beta-ketoamides and beta-ketoesters with elemental hydrogen (4 bar) proceeded substrate by substrate. When Et(2)NH(2) (+)[{RuCl(S)-binap}(2)](mu-Cl)(3)(-) was employed as a catalyst in a methanol or ethanol solution, the substrates were reduced at room temperature in the order beta-ketopyrrolidide > or = beta-ketopiperidide > or = beta-keto(N,N-diethylamide) > beta-keto(alkyl esters) > beta-keto(oligofluoroalkyl esters). This is the first time that beta-ketoamides have been reduced asymmetrically (91 to >98 % ee) under such mild conditions. Monitoring the concentrations of these beta-ketocarboxyl acid derivatives and their respective hydrogenation products over the course of time showed that the most electron-rich substrate is captured by the catalyst preferentially and exothermically; whether this occurs reversibly or irreversibly remains to be determined. The hydrogenation product is subsequently formed. The last transformation includes the rate-determining step. The combination of these events explains why starting from appropriate mixtures of substrates a "first-choice substrate" reacted from early on while the "second-choice substrate" stayed virtually untouched over an extended period of time and reacted no earlier than after the "first-choice substrate" had disappeared. From then onward, however, the "second-choice substrate" also reacted relatively rapidly.     

Stereoselective cascade reactions that incorporate a 7-exo acyl radical cyclization

[reaction: see text] Radical cascades that feature a 7-exo acyl radical cyclization followed by a 6-exo or 5-exo alkyl radical cyclization proceed with very good yields and diastereoselectivities. Two stereocenters are created by the reaction, and a single isomeric product was obtained from each of the five substrates examined. The relative configurations of the products are consistent with cyclizations occurring via chairlike or pseudochairlike transition states.     

Kinetic and theoretical study of 4-exo ring closures of carbamoyl radicals onto C=C and C=N bonds

Carbamoyl radicals were generated from oxime oxalate amides, and the kinetics of their 4-exo cyclizations onto C=C and C=NO bonds, leading to beta-lactam-containing species, were studied by EPR spectroscopy. DFT computations with model carbamoyl radicals predicted 4-exo ring closures onto C=NO bonds to be facile, especially when tert-butyl substituents were present. The reverse ring-opening reactions were predicted to have much higher activation energies. Experimental evidence also favored slow reverse ring opening.     

Free radical cyclization in molecular aggregates

The cyclization of free radicals has been investigated in micelles and multilamellar lipid bilayer vesicles. The substrate for cyclization is the amphipathic bromohydrin 7-bramo-octadec-11-ene-8-ol, 1. The radical is generated from 1 in aqueous micelles or vesicles by $\text{NaBH}{}_4\text{Bu}{}_3\text{SnCl}$. Four diastereomeric cyclopentanol products are formed in the 5-exo cyclization and the distribution of these products depends on the solvent and aggregate. Product distributions for cyclization in all media which have an aqueous/organic interface are significantly different from product distributions obtained for reactions in homogeneous media.     

Homogeneous and biphasic autoxidation of tetralin catalyzed by transition metal salts and complexes

The biphasic autoxidation of tetralin was carried out using various Co, Ni and Mn complexes as catalysts. Cobalt–N,N′-dimethylethylenediamine complex, which is amphiphilic and surface-active, was found to be most effective; it could be easily recovered in a compact emulsion layer after the reaction and could be reused with no apparent loss of activity. The biphasic reaction differs from the homogeneous counterpart in that (1) little hydroperoxide product is formed, (2) there is lesser sensitivity to product inhibition and a greater degree of conversion and (3) there is an easier catalyst recovery and substrate recycle.     

Regiochemical control in intramolecular cyclization of methylene-interrupted epoxydiols

[reaction: see text] Methylene-interrupted epoxydiols have multiple regiochemical routes for cyclization. The 5-exo process is the most prevalent under acidic conditions. However, the regioselectivity can be controlled by the appropriate choice of acid promoter and pendant groups adjacent to the epoxide. The 5-exo product is obtained exclusively without the presence of a carbocation-stabilizing pendant group. Alkenyl and thiophenyl groups adjacent to the epoxide alter the regioselectivity and enable access to the 5-endo tetrahydrofuran and 6-endo tetrahydropyran products.     

Linear-selective hydroformylation of vinyl ether using Rh (acac)(2,2′-bis{(di[1H-indol-1-yl]phosphanyl)oxy}-1,1′-binaphthalene) – Possible way to synthesize 1,3-propanediol

Three bidentate phosphoramidite ligands were synthesized, characterized, and employed in Rh-catalyzed hydroformylation of vinyl ethers. The complex Rh(acac)(2,2′-bis{(di[1H-indol-1-yl]phosphanyl)oxy}-1,1′-binaphthalene} (acac = acetylacetone) (Rh- L4 ) was also synthesized and characterized. Rh- L4 showed good regioselectivity for the hydroformylation of vinyl ethers under mild reaction conditions: 2 MPa of syngas, 1:1 (H₂/CO) substrate/catalyst molar ratio 1000:1, and 60 °C. The linear selectivity was up to 98%, and in most cases was about 80%, with no hydrogenation product formation observed, which could be a potential way to synthesize 1,3-propanediol. A mechanism study including density functional theory computational analysis showed that both Rh–H and CO insertion steps in the hydroformylation of vinyl ether were linear-preferred in our catalyst system.     

甲烷氧化偶联W-Mn催化剂的制备及表征

本文详细报道了制备因素对Na-W-Mn—O/SiO_2催化剂反应性能的影响,并用O_2-TPD,XRD,FT-IR,LRS等方法对催化剂进行了表征。结果表明,该催化剂的最佳组成是Mn 0.32wt％—Na_2WO_4 4wt％/SiO_2,由混浆法制备的催化剂具有较好的稳定性,连续反应30 h后,其甲烷转化活性和C_2烃收率均保持不变。催化剂的结构研究表明,Na_2WO_4与SiO_2发生了相互作用,形成有Si参与的表面钨氧物种,该催化剂具有较好的催化活性与表面钨氧物种的形成相关联,Mn的加入,可能大大提高了该催化剂中表面晶格氧的浓度,从而加快了CH_4的活化速度。     

Stable Lewis acid chelate of a bis(imido) tungsten compound and implications for alpha-olefin dimerisation catalysis: a DFT study

Dimerisation of alpha-olefins by a catalyst system comprising of a bis(imido) tungsten compound and a Lewis acid component has been investigated by density functional theory employing a catalyst model that closely mimics the real system together with ethylene chosen as a prototypical substrate. This study disclosed that the Lewis acid preferably forms four-membered chelates by bridging across tungsten-imido linkages. Complexation at one imido group is predicted as the favourable, stable mode of Lewis acid association onto a bis(imido) tungsten(VI) compound. The computational analysis revealed that the cocatalyst affects the energetics of the several steps to a different extent. Formation of the five-membered tungstanacycle and the further growth is moderately influenced, this is in contrast to its profound influence on metallacycle degradation. AlClMe2 chelation of both tungsten-imido groups is seen as being most effective in smoothing the energetics of the dimer-generating route. The predicted energy profile of the most accessible pathway, however, is at odds with observed catalytic abilities. This study indicates that the removal of one imido ligand by the Lewis acid is a viable process, thereby suggesting that mono(imido) tungsten compounds are effective in dimerisation catalysis of the reported catalyst system.     

5-Exo versus 6-endo cyclization of primary aminyl radicals: an experimental and theoretical investigation

The cyclization of neutral primary pent-4-enylaminyl radicals was investigated experimentally and theoretically. Unlike the corresponding secondary aminyl radicals, primary pent-4-enylaminyl radicals underwent efficient cyclization to afford the pyrrolidine and/or piperidine products in good to high yields. While the simple pent-4-enylaminyl radical gave predominately the 5-exo cyclization product, 4-chloropent-4-enylaminyl radicals led to the formation of the corresponding 6-endo cyclization products in excellent regioselectivity. Theoretical calculations revealed that the 5-exo cyclization rate of primary aminyl radicals is about 3-4 orders of magnitude higher than that of secondary aminyl radicals.     

Mechanism of the transition-metal-catalyzed hydroarylation of bromo-alkynes revisited: hydrogen versus bromine migration

A comprehensive mechanistic study of the InCl(3)-, AuCl-, and PtCl(2)-catalyzed cycloisomerization of the 2-(haloethynyl)biphenyl derivatives of Fürstner et al. was carried out by DFT/M06 calculations to uncover the catalyst-dependent selectivity of the reactions. The results revealed that the 6-endo-dig cyclization is the most favorable pathway in both InCl(3)- and AuCl-catalyzed reactions. When AuCl is used, the 9-bromophenanthrene product could be formed by consecutive 1,2-H/1,2-Br migrations from the Wheland-type intermediate of the 6-endo-dig cyclization. However, in the InCl(3)-catalyzed reactions, the chloride-assisted intermolecular H-migrations between two Wheland-type intermediates are more favorable. These Cl-assisted H-migrations would eventually lead to 10-bromophenanthrene through proto-demetalation of the aryl indium intermediate with HCl. The cause of the poor selectivity of the PtCl(2) catalyst in the experiments by the Fürstner group was predicted. It was found that both the PtCl(2)-catalyzed alkyne-vinylidene rearrangement and the 5-exo-dig cyclization pathways have very close activation energies. Further calculations found the former pathway would lead eventually to both 9- and 10-bromophenanthrene products, as a result of the Cl-assisted H-migrations after the cyclization of the Pt-vinylidene intermediate. Alternatively, the intermediate from the 5-exo-dig cyclization would be transformed into a relatively stable Pt-carbene intermediate irreversibly, which could give rise to the 9-alkylidene fluorene product through a 1,2-H shift with a 28.1 kcal mol(-1) activation barrier. These findings shed new light on the complex product mixtures of the PtCl(2)-catalyzed reaction.     

Thermodynamic and strain effects in the competition between 5-exo-dig and 6-endo-dig cyclizations of vinyl and aryl radicals

Electronic and structural factors controlling the competition between 5-exo-dig and 6-endo-dig cyclizations of sp2-radicals were analyzed using a combination of available experimental data and computation. Although the stereoelectronically favored 5-exo pathways usually has the lower activation energy, formation of a new aromatic ring not only makes the 6-endo process favorable thermodynamically in conjugated systems but also lowers its activation barrier to the extent where the 5-exo/6-endo selectivity is controlled by subtle factors such as the different sensitivity of the two pathways to strain effects in polycyclic systems. In particular, the stronger sensitivity of the 5-exo pathway to strain leads to a crossover in selectivity. The 6-endo cyclization is kinetically favored in smaller (and strained) cycles, whereas the 5-exo cyclization has lower barriers in the larger rings.     

镁-钛系聚乙烯高效催化剂的机理研究

本文对一种典型的反应法制聚乙烯高效催化剂的各步反应产物进行了研完:第一步氯化镁加乙醇反应,生成醇合物MgCl₂·nC₂H₅OH,其作用是将氯化镁晶格破坏;第二步加烷基铝,第三步加四氯化钛,其作用是与醇合物中的醇反应使之溶解,重新生成高分散的氯化镁微晶,活性组份钛化合物高度分散在氯化镁微晶表面上,故催化剂具有高活性。用这种反应法制得的高效催化剂,载体分散度高,内部孔隙多,有利于传质,因而比一般研磨法制得的高效催化剂聚合收率高。X光衍射发现在其他一些聚乙烯高效催化剂中也存在微晶MgCl₂,说明它们的高活性机理是类似的。     

The Mechanism of NO Bond Cleavage in Rhodium‐Catalyzed CH Bond Functionalization of Quinoline N‐oxides with Alkynes: A Computational Study

Metal‐catalyzed C?H activation not only offers important strategies to construct new bonds, it also allows the merge of important research areas. When quinoline N‐oxide is used as an arene source in C?H activation studies, the N?O bond can act as a directing group as well as an O‐atom donor. The newly reported density functional theory method, M11L, has been used to elucidate the mechanistic details of the coupling between quinoline N?O bond and alkynes, which results in C?H activation and O‐atom transfer. The computational results indicated that the most favorable pathway involves an electrophilic deprotonation, an insertion of an acetylene group into a Rh?C bond, a reductive elimination to form an oxazinoquinolinium‐coordinated Rh^I intermediate, an oxidative addition to break the N?O bond, and a protonation reaction to regenerate the active catalyst. The regioselectivity of the reaction has also been studied by using prop‐1‐yn‐1‐ylbenzene as a model unsymmetrical substrate. Theoretical calculations suggested that 1‐phenyl‐2‐quinolinylpropanone would be the major product because of better conjugation between the phenyl group and enolate moiety in the corresponding transition state of the regioselectivity‐determining step. These calculated data are consistent with the experimental observations.