Alkyl Species Research Articles

A Copper Catalyst with a Cinchona‐Alkaloid‐Based Sulfonamide Ligand for Asymmetric Radical Oxytrifluoromethylation of Alkenyl Oximes

A copper-catalyzed asymmetric radical oxytrifluoromethylation of alkenyl oxime and Togni's reagent has been successfully developed, thereby providing straightforward access to CF3 -containing isoxazolines bearing α-tertiary stereocenters with excellent yield and enantioselectivity. The key to success is the rational design of cinchona-alkaloid-based sulfonamides as neutral/anionic hybrid ligands to effectively control the stereochemistry in copper-catalyzed reactions involving free alkyl radical species. The utility of this method is illustrated by efficient transformation of the products into useful chiral CF3 -containing 1,3-aminoalcohols.

A Copper Catalyst with a Cinchona‐Alkaloid‐Based Sulfonamide Ligand for Asymmetric Radical Oxytrifluoromethylation of Alkenyl Oximes

AbstractA copper‐catalyzed asymmetric radical oxytrifluoromethylation of alkenyl oxime and Togni's reagent has been successfully developed, thereby providing straightforward access to CF3‐containing isoxazolines bearing α‐tertiary stereocenters with excellent yield and enantioselectivity. The key to success is the rational design of cinchona‐alkaloid‐based sulfonamides as neutral/anionic hybrid ligands to effectively control the stereochemistry in copper‐catalyzed reactions involving free alkyl radical species. The utility of this method is illustrated by efficient transformation of the products into useful chiral CF3‐containing 1,3‐aminoalcohols.

Branched-Selective Hydroformylation of Nonactivated Olefins Using an N-Triphos/Rh Catalyst

We report a catalytic system comprised of nitrogen-centered di- or triphosphine ligands in conjunction with rhodium that is capable of delivering branched aldehydes from terminal olefin substrates which commonly give more linear aldehydes than branched. The incorporation of an apical nitrogen atom into the ligand backbone dramatically improves the reaction rate. Mechanistic and labeling studies suggest the unusual selectivity is due to the irreversible trapping of the Rh–alkyl species along the branched pathway, in comparison to the more reversible linear pathway. A precatalytic equilibrium mixture of rhodium species was observed by high-pressure in situ NMR spectroscopy, suggesting this equilibrium is the catalytic resting state.

A Desulfurative Strategy for the Generation of Alkyl Radicals Enabled by Visible-Light Photoredox Catalysis.

Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible-light photoredox catalysis. A process that involves the generation of N-centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional-group tolerance.

A Desulfurative Strategy for the Generation of Alkyl Radicals Enabled by Visible‐Light Photoredox Catalysis

AbstractHerein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible‐light photoredox catalysis. A process that involves the generation of N‐centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional‐group tolerance.

Benzoimidazole‐Pyridylamido Zirconium and Hafnium Alkyl Complexes as Homogeneous Catalysts for Tandem Carbon Dioxide Hydrosilylation to Methane

AbstractNeutral ZrIV and HfIV alkyl/amido complexes stabilized by a tridentate N ligand that contains a “rolling” heterodentate benzoimidazole fragment have been prepared and characterized. The ultimate nature of the ligand denticity, the electronic properties of the ligand binding pocket and the metal coordination environment are controlled by the protection/deprotection of the benzoimidazole NH group. The metal precursor used [MIV(Bn)4 or MIV(NMe2)4] also has an influence on the final coordination sphere of the complex; indeed, a permanent central pyridine dearomatization occurs in the presence of dimethylamido ancillary groups. DFT calculations on the real system have been used to elucidate the mechanism. Selected alkyl species from this series have been scrutinized for the tandem hydrosilylation of CO2 to CH4 in combination with the strong Lewis acid B(C6F5)3 using a variety of hydrosilanes. A positive effect of the hardness modification of the ligand donor atom set is observed in the catalytic outcomes. Indeed, κ3{N−,N,N−}ZrIV(Bn)2 catalyzes the process to methane selectively with a turnover frequency as high as 272 h−1 (at 96 % substrate conversion) almost twice as much as that claimed for the benchmark κ3{O−,O,O−}ZrIV(Bn)2 complex under similar experimental conditions.

Silica‐Supported Pentamethylcyclopentadienyl Ytterbium(II) and Samarium(II) Sites: Ultrahigh Molecular Weight Polyethylene without Co‐Catalyst

AbstractDesigning highly active supported ethylene polymerization catalysts that do not require a co‐catalyst to generate electrophilic metal alkyl species is still a challenge despite its industrial relevance. Described herein is the synthesis and characterization of well‐defined silica‐supported cyclopentadienyl LnII sites (Ln=Yb and Sm) of general formula [(≡SiO)LnCp*]. These well‐defined surface species are highly activite towards ethylene polymerization in the absence of added co‐catalyst. Initiation is proposed to occur by single electron transfer.

Silica-Supported Pentamethylcyclopentadienyl Ytterbium(II) and Samarium(II) Sites: Ultrahigh Molecular Weight Polyethylene without Co-Catalyst.

Designing highly active supported ethylene polymerization catalysts that do not require a co-catalyst to generate electrophilic metal alkyl species is still a challenge despite its industrial relevance. Described herein is the synthesis and characterization of well-defined silica-supported cyclopentadienyl LnII sites (Ln=Yb and Sm) of general formula [(≡SiO)LnCp*]. These well-defined surface species are highly activite towards ethylene polymerization in the absence of added co-catalyst. Initiation is proposed to occur by single electron transfer.

Theoretical Investigations of Isoprene Polymerization Catalyzed by Cationic Half-Sandwich Scandium Complexes Bearing a Coordinative Side Arm

Density functional theory studies have been conducted for isoprene polymerization catalyzed by the cationic half-sandwich scandium alkyl species containing a methoxy side arm [(C5Me4C6H4OMe-o)Sc(CH2SiMe3)]+ (1) and that containing a phosphine oxide side arm [{C5Me4SiMe2CH2P(O)Ph2}Sc(CH2SiMe3)]+ (2). It has been found that trans-1,4-polymerization of isoprene by species 1 prefers an insertion–isomerization mechanism: (i) an insertion of cis-isoprene into the metal–alkyl bond to give η3-π-anti-form, (ii) anti-syn isomerization of the resulting 1,2-disubstituted allyl complex to yield a syn-allyl form, (iii) repetitive insertion of cis-isoprene into the metal–syn-allyl bond and subsequent anti–syn isomerization. The resulting η3-π-syn-allyl species is suitable for more kinetically favorable cis-monomer insertion. The stability of the key transition state involved in the most feasible pathway could be ascribed to the smaller deformation of cis-isoprene and stronger interaction between the cis-isoprene moiety ...

Iron-Catalyzed Aminative Cyclization/Intermolecular Homolytic Aromatic Substitution Using Oxime Esters and Simple Arenes.

Intermolecular C-H alkylation of simple arenes in the presence of an iron catalyst has been achieved in a cascade manner with an aminative cyclization triggered by N-O bond cleavage of an alkene-tethered oxime ester. Various arenes, including electron-rich and electron-poor arenes, and heteroarenes can be employed in the reaction system. Regioselectivity and radical trapping experiments support the involvement of alkyl radical species, which undergo a homolytic aromatic substitution (HAS) to afford the arylation products.

Cationic half-sandwich rare-earth metal alkyl species catalyzed polymerization and copolymerization of aryl isocyanides possessing polar, bulky, or chiral substituents

Cationic half-sandwich rare-earth metal alkyl species were first used for the coordination–insertion polymerization and copolymerization of aryl isocyanides.

Enantioselective Copper‐Catalyzed Alkylation of Quinoline N‐Oxides with Vinylarenes

AbstractAn asymmetric copper‐catalyzed alkylation of quinoline N‐oxides with chiral Cu–alkyl species, generated by migratory insertion of a vinylarene into a chiral Cu−H complex, is reported. A variety of quinoline N‐oxides and vinylarenes underwent this Cu‐catalyzed enantioselective alkylation reaction, affording the corresponding chiral alkylated N‐heteroarenes in high yield with high‐to‐excellent enantioselectivity. This enantioselective protocol represents the first general and practical approach to access a wide range of chiral alkylated quinolines.

Lipidomic profiling of plasma in a healthy Singaporean population to identify ethnic specific differences in lipid levels and associations with disease risk factors

BackgroundPlasma lipids (i.e., cholesterol, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and triglycerides) are linked to a range of metabolic diseases, including heart disease and diabetes. Plasma lipid species have similarly been associated with the same diseases. However, neither abundance profiling of plasma lipid species in healthy populations, nor differences between ethnic groups has not been reported. MethodsIn this study, we have profiled over 280 lipid species using liquid chromatography–tandem mass spectrometry, independently across two sites, in 359 healthy Singaporean individuals of Chinese (n = 122), Indian (n = 120) and Malay (n = 117) ethnicity. ResultsWe found variations in abundance (defined as % coefficient of variation) of plasma lipid species that fluctuated between 13 and 120%. Analysis of covariance (ANCOVA) identified differences between ethnic groups, particularly among alkyl and alkenylphosphatidylethanolamine species, as well as in two species of sphingosine-1-phosphate (i.e., d18:0 and d18:1), which were elevated in the Chinese group. Regression analysis identified ethnic-specific differences in the association of plasma lipids and lipid species with age, gender and body mass index (BMI). Chinese and Malay groups showed a positive association of glycerolipids (i.e., diglycerides (DG), triglycerides (TG)) and cholesteryl esters (CE) with BMI, but this was not seen in the Indian group. Furthermore, Indian and Malay groups showed a positive association between the abundance of sphingolipids and age, which was absent in the Chinese group. ConclusionsThis study provides baseline characterisation of the natural biological variation of plasma lipid species in three healthy ethnic groups, and identifies important differences in plasma lipid levels and their association with known disease risk factors.

The controls on the composition of biodegraded oils in the deep subsurface – Part 4. Destruction and production of high molecular weight non-hydrocarbon species and destruction of aromatic hydrocarbons during progressive in-reservoir biodegradation

This study extends the analysis of previously well studied biodegraded crude oil case history sample sets. The analytical window is extended into the high molecular weight, aromatic hydrocarbon and non-hydrocarbon fraction of crude oils, using a 12T ultra-high resolution mass spectrometer (FTICR-MS).Biodegradation is pervasive across compound groups and extent of degradation appears dependent on compound abundance and hence availability. Oil constituents with molecular weights up to m/z 600 (carbon number 44) are affected by in-reservoir biodegradation. Apart from special, specific compound groups possibly related to the active reservoir biomass, all hydrocarbon and single heteroatom-containing compound classes are depleted by biodegradation. Production of various highly alkylated species indicate that transformation of crude oil components often involves derivatization and preservation rather than just complete destruction of high molecular weight compounds. Whereas one case study shows good correlation between depletion of S1 species and a strong increase in SO2 species, a nitrogen enriched oil suite shows an analogous trend in the transformation of N1 species to the corresponding NO2 species. Increase in O2 species are seen in both sample sets indicating partial oxidation is a major overall process in in-situ reservoir biodegradation. These variations are important geochemically but also impact transport, interfacial and corrosion properties of oils.Nitrogen isotope systematics indicate that nitrogen-containing compounds might act as nitrogen nutrient sources or mainly as carbon sources for the microorganisms causing in-situ reservoir biodegradation depending level of biodegradation. Distributions of some heterocyclic species add a very biodegradation resistant parameter set, to the petroleum geochemists arsenal.

Engaging Radicals in Transition Metal-Catalyzed Cross-Coupling with Alkyl Electrophiles: Recent Advances

Transition metal-catalyzed cross-coupling reactions have created an epoch in modern synthetic organic chemistry, offering a variety of insights into retrosynthetic tactics for synthesizing targeted complex molecules in medicine and materials-based applications. Despite numerous types of combinations of nucleophiles, electrophiles, and transition metal catalysts available for the cross-coupling reactions, construction of covalent bonds that include sp3-hybridized carbon(s) remains a challenge because of the inherent diverse reactivity of the alkyl species (i.e., alkyl halides and alkyl metals) involved in the catalytic cycle. Methods for leveraging alkyl radicals have recently emerged, which will aid in the realization of this goal. This perspective highlights and discusses recent advances in transition metal-catalyzed cross-coupling reactions that engage alkyl radicals for C(sp3)–N and C(sp3)–Si bond formation with alkyl halides as well as use of carboxylic acid derivatives as surrogates of alkyl halides ...

George A. Olah (1927-2017).

George A. Olah (1927-2017).

Well-Defined Molybdenum Oxo Alkyl Complex Supported on Silica by Surface Organometallic Chemistry: A Highly Active Olefin Metathesis Precatalyst.

The well-defined silica-supported molybdenum oxo alkyl species (≡SiO-)MoO(CH2tBu)3 was selectively prepared by grafting of MoO(CH2tBu)3Cl onto partially dehydroxylated silica (silica700) using the surface organometallic chemistry approach. This surface species was fully characterized by elemental analysis and DRIFT, solid-state NMR, and EXAFS spectroscopy. This new material is related to the active species of industrial supported MoO3/SiO2 olefin metathesis catalysts. It displays very high activity in propene self-metathesis at mild (turnover number = 90 000 after 25 h). Remarkably, its catalytic performance outpaces those of the parent imido derivative and its tungsten oxo analogue.

Aquathermolysis of Natural Bitumen under Supercritical Conditions in the Presence of Ferrospheres

The influence of a catalytic additive – magnetic ferrospheres – on the product composition of cracking of natural bitumen from Ashal'chinskoe oilfield (4.6 wt % of fractions with IBP 200 °C) was studied. The reaction was achieved in an autoclave in the presence of a hydrogen donor (water). The addition of 10 wt % of ferrospheres was shown to favor the tar destruction and to increase the yield of light boiling fractions. The coke formation was decelerated during bitumen aquathermolysis under supercritical conditions. In aquathermolysis with ferrospheres at 500 °C, the yield of fractions IBP 360 °C increase by 12.5 %, while gas and coke yields decreased by 14.4 and 3.9 wt %, respectively, against the yields during bitumen cracking. The data on structure and group analysis of tars and asphaltenes indicate considerable destruction of the alkyl and naphthene species during aquathermolysis. Application of aquathermolysis allows heavy hydrocarbon feedstock to be processed using inexpensive and effective additives to improve considerably the conversion ratio.

Well-defined silica supported bipodal molybdenum oxo alkyl complexes: a model of the active sites of industrial olefin metathesis catalysts.

A well-defined, silica-supported molybdenum oxo alkyl species, ([triple bond, length as m-dash]SiO-)2Mo([double bond, length as m-dash]O)(CH2tBu)2, was prepared by the selective grafting of Mo([double bond, length as m-dash]O)(CH2tBu)3Cl onto a silica partially dehydroxylated at 200 °C using a rigorous surface organometallic chemistry approach. The immobilized bipodal surface species, partly resembling the active species of industrial MoO3/SiO2 olefin metathesis catalysts, exhibited excellent functional group tolerance in conjunction with its high activity in homocoupling, self and ring closing olefin metathesis.

Development of Novel Hydrophobic Pharmacophores Based on Three-dimensional Molecular Architectures and Elements Chemistry.

Hydrophobic interaction, as well as polar interactions such as hydrogen bonding and electrostatic interaction, plays an essential role in the interaction between biologically active compounds and their target molecules. Therefore, the application of novel hydrophobic structures other than simple hydrocarbons or aromatic rings is expected to be useful in the development of biologically active compounds with distinctive chemical and pharmacological properties. In this study, we developed various bioactive compounds bearing a boron cluster, silicon-containing or germanium-containing functionalities as novel hydrophobic structures. Regarding the boron cluster-based compounds, we developed highly potent nonsteroidal androgen receptor (AR) antagonists, progesterone receptor (PR) antagonists, and non-secosteroidal vitamin D receptor (VDR) agonists. Regarding the Group 14 elements, we systematically determined hydrophobicity parameters of various trialylmethyl, trialkylsilyl and trialkylgermyl substituents, and revealed that silicon and germanium containing compounds exhibited higher hydrophobicity than the corresponding carbon analogues, with a difference in log P value of approximately 0.6, independent of the alkyl species. We also revealed that sila- and germa-substitution of carbon could enhance their biological activity. Furthermore, we demonstrated that silyl substructures could function as mimetics of cis-diatomic substructures. These results are expected to expand the chemical space of hydrophobic pharmacophores and thus contribute to the development of novel and distinctive drug candidates.