-
Organic Letters Jul 2020Hexafluoroisopropanol (HFIP)-promoted disulfidation and diselenation of C-C unsaturated bonds is reported. Reactions of unactivated alkyne, alkene, and allene,...
Hexafluoroisopropanol (HFIP)-promoted disulfidation and diselenation of C-C unsaturated bonds is reported. Reactions of unactivated alkyne, alkene, and allene, respectively, with disulfides or diselenides in HFIP led to desired products in good to excellent yields (up to 96%). In contrast, other solvents, such as isopropanol and dichloroethane, could not promote the same reaction. This method revealed an example of HFIP-promoted transformations under the mild conditions, which greatly highlighted the unique reactivity of this special solvent.
Topics: Alkenes; Alkynes; Catalysis; Organoselenium Compounds; Propanols; Solvents; Sulfides
PubMed: 32588633
DOI: 10.1021/acs.orglett.0c01834 -
Journal of the American Chemical Society Aug 2019Fluorinated organic molecules are pervasive within the pharmaceutical and agrochemical industries due to the range of structural and physicochemical properties that...
Fluorinated organic molecules are pervasive within the pharmaceutical and agrochemical industries due to the range of structural and physicochemical properties that fluorine imparts. Currently, the most abundant methods for the synthesis of the aryl-CF functionality have relied on the deoxyfluorination of ketones and aldehydes using expensive and poorly atom economical reagents. Here, we report a general method for the synthesis of aryl-CFR and aryl-CFH compounds through activation of the corresponding trifluoromethyl arene precursors. This strategy is enabled by an endergonic electron transfer event that provides access to arene radical anions that lie outside of the catalyst reduction potential. Fragmentation of these reactive intermediates delivers difluorobenzylic radicals that can be intercepted by abundant alkene feedstocks or a hydrogen atom to provide a diverse array of difluoalkylaromatics.
Topics: Alkenes; Alkylation; Carbon; Fluorides; Fluorine; Halogenation; Hydrocarbons, Aromatic; Methylation
PubMed: 31369264
DOI: 10.1021/jacs.9b06004 -
Journal of the American Chemical Society Dec 2016A new class of poly-N-vinylpyrrolidinones containing an asymmetric center at C5 of the pyrrolidinone ring were synthesized from l-amino acids. The polymers, particularly...
A new class of poly-N-vinylpyrrolidinones containing an asymmetric center at C5 of the pyrrolidinone ring were synthesized from l-amino acids. The polymers, particularly 17, were used to stabilize nanoclusters such as Pd/Au for the catalytic asymmetric oxidations of 1,3- and 1,2-cycloalkanediols and alkenes, and Cu/Au was used for C-H oxidation of cycloalkanes. It was found that the bulkier the C5 substituent in the pyrrolidinone ring, the greater the optical yields produced. Both oxidative kinetic resolution of (±)-1,3- and 1,2-trans-cycloalkanediols and desymmetrization of meso cis-diols took place with 0.15 mol % Pd/Au (3:1)-17 under oxygen atmosphere in water to give excellent chemical and optical yields of (S)-hydroxy ketones. Various alkenes were oxidized with 0.5 mol % Pd/Au (3:1)-17 under 30 psi of oxygen in water to give the dihydroxylated products in >93% ee. Oxidation of (R)-limonene at 25 °C occurred at the C-1,2-cyclic alkene function yielding (1S,2R,4R)-dihydroxylimonene 49 in 92% yield. Importantly, cycloalkanes were oxidized with 1 mol % Cu/Au (3:1)-17 and 30% HO in acetonitrile to afford chiral ketones in very good to excellent chemical and optical yields. Alkene function was not oxidized under the reaction conditions. Mechanisms were proposed for the oxidation reactions, and observed stereo- and regio-chemistry were summarized.
Topics: Alkenes; Catalysis; Metal Nanoparticles; Oxidation-Reduction; Pyrrolidinones; Stereoisomerism
PubMed: 27976875
DOI: 10.1021/jacs.6b12113 -
Nature Communications Nov 2017Early-life nourishment exerts long-term influences upon adult physiology and disease risk. These lasting effects of diet are well established but the underlying...
Early-life nourishment exerts long-term influences upon adult physiology and disease risk. These lasting effects of diet are well established but the underlying mechanisms are only partially understood. Here we show that restricting dietary yeast during Drosophila development can, depending upon the subsequent adult environment, more than double median lifespan. Developmental diet acts via a long-term influence upon the adult production of toxic molecules, which we term autotoxins, that are shed into the environment and shorten the lifespan of both sexes. Autotoxins are synthesised by oenocytes and some of them correspond to alkene hydrocarbons that also act as pheromones. This study identifies a mechanism by which the developmental dietary history of an animal regulates its own longevity and that of its conspecific neighbours. It also has important implications for the design of lifespan experiments as autotoxins can influence the regulation of longevity by other factors including diet, sex, insulin signalling and population density.
Topics: Alkenes; Animals; Animals, Genetically Modified; Diet; Drosophila melanogaster; Female; Housing, Animal; Insulin; Larva; Lipid Metabolism; Longevity; Male
PubMed: 29123106
DOI: 10.1038/s41467-017-01740-9 -
Angewandte Chemie (International Ed. in... Sep 2018Spirocyclic ethers can be found in bioactive compounds. This copper-catalyzed enantioselective alkene carboetherification provides 5,5-, 5,6- and 6,6-spirocyclic...
Spirocyclic ethers can be found in bioactive compounds. This copper-catalyzed enantioselective alkene carboetherification provides 5,5-, 5,6- and 6,6-spirocyclic products containing fully substituted chiral carbon centers with up to 99 % enantiomeric excess. This reaction features the formation of two rings from acyclic substrates, 1,1-disubstituted alkenols functionalized with either arenes, alkenes, or alkynes, and clearly constitutes a powerful way to synthesize chiral spirocyclic ethers.
Topics: Alkenes; Alkynes; Catalysis; Copper; Crystallography, X-Ray; Ethers; Molecular Conformation; Propanols; Spiro Compounds; Stereoisomerism
PubMed: 30117646
DOI: 10.1002/anie.201808554 -
Nature Sep 1999Attempts to fabricate mechanical devices on the molecular level have yielded analogues of rotors, gears, switches, shuttles, turnstiles and ratchets. Molecular motors,...
Attempts to fabricate mechanical devices on the molecular level have yielded analogues of rotors, gears, switches, shuttles, turnstiles and ratchets. Molecular motors, however, have not yet been made, even though they are common in biological systems. Rotary motion as such has been induced in interlocked systems and directly visualized for single molecules, but the controlled conversion of energy into unidirectional rotary motion has remained difficult to achieve. Here we report repetitive, monodirectional rotation around a central carbon-carbon double bond in a chiral, helical alkene, with each 360 degrees rotation involving four discrete isomerization steps activated by ultraviolet light or a change in the temperature of the system. We find that axial chirality and the presence of two chiral centres are essential for the observed monodirectional behaviour of the molecular motor. Two light-induced cis-trans isomerizations are each associated with a 180 degrees rotation around the carbon-carbon double bond and are each followed by thermally controlled helicity inversions, which effectively block reverse rotation and thus ensure that the four individual steps add up to one full rotation in one direction only. As the energy barriers of the helicity inversion steps can be adjusted by structural modifications, chiral alkenes based on our system may find use as basic components for 'molecular machinery' driven by light.
Topics: Alkenes; Molecular Conformation; Molecular Motor Proteins; Motion; Phenanthrenes; Temperature; Ultraviolet Rays
PubMed: 10490022
DOI: 10.1038/43646 -
Organic Letters Oct 2020The copper-catalyzed enantioselective intramolecular hydroalkoxylation of unactivated alkenes for the synthesis of tetrahydrofurans, phthalans, isochromans, and...
The copper-catalyzed enantioselective intramolecular hydroalkoxylation of unactivated alkenes for the synthesis of tetrahydrofurans, phthalans, isochromans, and morpholines from 4- and 5-alkenols is reported. The substrate scope is complementary to existing enantioselective alkene hydroalkoxylations and is broad with respect to substrate backbone and alkene substitution. The asymmetric induction and isotopic labeling studies support a polar/radical mechanism involving enantioselective oxycupration followed by C-[Cu] homolysis and hydrogen atom transfer. Synthesis of the antifungal insecticide furametpyr was accomplished.
Topics: Alkenes; Antifungal Agents; Benzofurans; Catalysis; Copper; Ethers, Cyclic; Furans; Hydrogen; Insecticides; Molecular Structure; Pyrazoles; Stereoisomerism
PubMed: 32496794
DOI: 10.1021/acs.orglett.0c01691 -
Angewandte Chemie (International Ed. in... May 2014A metal-free, Lewis acid promoted intramolecular aminocyanation of alkenes was developed. B(C6F5)3 activates N-sulfonyl cyanamides, thus leading to a formal cleavage of...
A metal-free, Lewis acid promoted intramolecular aminocyanation of alkenes was developed. B(C6F5)3 activates N-sulfonyl cyanamides, thus leading to a formal cleavage of the N-CN bonds in conjunction with vicinal addition of sulfonamide and nitrile groups across an alkene. This method enables atom-economical access to indolines and tetrahydroquinolines in excellent yields, and provides a complementary strategy for regioselective alkene difunctionalizations with sulfonamide and nitrile groups. Labeling experiments with (13)C suggest a fully intramolecular cyclization pattern due to the lack of label scrambling in double crossover experiments. Catalysis with Lewis acid is realized and the reaction can be conducted under air.
Topics: Alkenes; Amines; Cyanides; Hydrolysis
PubMed: 24719371
DOI: 10.1002/anie.201310983 -
Accounts of Chemical Research Apr 2020Nickel complexes exhibit distinct properties from other group 10 metals, including a small nuclear radius, high paring energy, low electronegativity, and low redox...
Nickel complexes exhibit distinct properties from other group 10 metals, including a small nuclear radius, high paring energy, low electronegativity, and low redox potentials. These properties enable Ni catalysts to accommodate and stabilize paramagnetic intermediates, access radical pathways, and undergo slow β-H elimination. Our research program investigates how each of these fundamental attributes impact the catalytic properties of Ni, in particular in the context of alkene functionalization.Alkenes are versatile functional groups, but stereoselective carbofunctionalization reactions of alkenes have been underdeveloped. This challenge may derive from the difficulty of controlling selectivity via traditional two-electron migratory insertion pathways. Ni catalysts could lead to different stereodetermining steps via radical mechanisms, allowing access to molecular scaffolds that are otherwise difficult to prepare. For example, an asymmetric alkene diarylation reaction developed by our group relies upon the radical properties of Ni(III) intermediates to control the enantioselectivity and give access to a library of chiral α,α,β-triarylethane molecules with biological activity.Mechanistic studies on a two-component reductive 1,2-difunctionalization reaction have shed light on the origin of the cross-electrophile selectivity, as C sp and C sp electrophiles are independently activated at Ni(I) via two-electron and radical pathways, respectively. Catalyst reduction has been identified to be the turnover-limiting step in this system. A closer investigation of the radical formation step using a (Xantphos)Ni(I)Ar model complex reveals that Ni(I) initiates radical formation via a concerted halogen-abstraction pathway.The low redox potentials of Ni have allowed us to develop a reductive, selective diene cyclization, wherein a classic two-electron mechanism operates on a Ni(I)/Ni(III) platform, accounting for the chemo- and stereoselectivity. This reaction has found applications in the efficient synthesis of pharmaceutically relevant molecules, such as 3,4-dimethylgababutin.The tendency of Ni to undergo one-electron redox processes prompted us to explore dinuclear Ni-mediated bond formations. These studies provide insight into Ni-Ni bonding and how two metal centers react cooperatively to promote C-C, C-X, and N-N bond forming reductive elimination.Finally, isolation of β-agostic Ni and Pd complexes has allowed for X-ray and neutron diffraction characterization of these highly reactive molecules. The bonding parameters serve as unambiguous evidence for β-agostic interactions and help rationalize the slower β-H elimination at Ni relative to Pd. Overall, our research has elucidated the fundamental properties of Ni complexes in several contexts. Greater mechanistic understanding facilitates catalyst design and helps rationalize the reactivity and selectivity in Ni-catalyzed alkene functionalization reactions.
Topics: Alkenes; Catalysis; Cyclization; Free Radicals; Kinetics; Nickel; Stereoisomerism
PubMed: 32237734
DOI: 10.1021/acs.accounts.0c00032 -
Journal of Biotechnology Jul 2024Industrial biotechnology and biocatalysis can provide very effective synthetic tools to increase the sustainability of the production of fine chemicals, especially... (Review)
Review
Industrial biotechnology and biocatalysis can provide very effective synthetic tools to increase the sustainability of the production of fine chemicals, especially flavour and fragrance (F&F) ingredients, the market demand of which has been constantly increasing in the last years. One of the most important transformations in F&F chemistry is the reduction of CC bonds, typically carried out with metal-catalysed hydrogenations or hydride-based reagents. Its biocatalytic counterpart is a competitive alternative, showcasing a range of advantages such as excellent chemo-, regio- and stereoselectivity, ease of implementation, mild reaction conditions and modest environmental impact. In the present review, the application of biocatalysed alkene reductions (from microbial fermentations with wild-type strains to engineered isolated ene-reductase enzymes) to synthetic processes useful for the F&F industry will be described, highlighting not only the exquisite stereoselectivity achieved, but also the overall improvement when chirality is not involved. Multi-enzymatic cascades involving CC bioreductions are also examined, which allow much greater chemical complexity to be built in one-pot biocatalytic systems.
Topics: Biocatalysis; Flavoring Agents; Perfume; Biotechnology; Alkenes; Oxidation-Reduction
PubMed: 38761886
DOI: 10.1016/j.jbiotec.2024.05.006