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Chemistry, An Asian Journal Oct 2022Addition reactions of ketene silyl acetals with alkenes that do not have an electron-withdrawing group are generally difficult because the nucleophilicity of ketene...
Addition reactions of ketene silyl acetals with alkenes that do not have an electron-withdrawing group are generally difficult because the nucleophilicity of ketene silyl acetals and the electrophilicity of alkenes are not sufficient. Herein, we report photocatalytic addition reactions of ketene silyl acetals with alkenes that proceed through formation of α-carbonyl radicals. In the presence of an appropriate protic additive, the reactions proceeded smoothly under blue-light irradiation to afford the desired products in moderate to high yields.
Topics: Acetals; Alkenes; Ethylenes; Ketones
PubMed: 35878061
DOI: 10.1002/asia.202200647 -
Chemistry (Weinheim An Der Bergstrasse,... Jul 2022Au-catalyzed hydroamination proceeds well for alkynes but not alkenes. We report gas-phase binding energies of alkenes and alkynes to a cationic Au center, which...
Au-catalyzed hydroamination proceeds well for alkynes but not alkenes. We report gas-phase binding energies of alkenes and alkynes to a cationic Au center, which indicate that differences in binding are not the origin of the disparate chemical behavior. We further report the synthesis and characterization of 2-aminoalkylgold complexes, which would be the intermediates in a hypothetical Au-catalyzed hydroamination of styrene. The reactivity of the well-characterized and isolable complexes reveals that protonation or alkylation of the 2-aminoalkylgold complexes results in amine elimination in solution, and in the gas phase, indicating that the failure of Au-catalyzed alkene hydroamination derives from a non-competitive protodeauration step. We analyze possible transition states for the protodeauration, and identify an insufficiently strong Au-proton interaction as the reason that the transition states lie too high in energy to compete.
Topics: Alkenes; Alkynes; Amination; Amines; Catalysis
PubMed: 35319803
DOI: 10.1002/chem.202200332 -
Organic & Biomolecular Chemistry Oct 2022β-Amino carbonyl substructures are privileged motifs in natural products and active pharmaceutical compounds. Here, we report a photoinduced metal-free and highly...
β-Amino carbonyl substructures are privileged motifs in natural products and active pharmaceutical compounds. Here, we report a photoinduced metal-free and highly regioselective intermolecular carboimination method the simultaneous introduction of amino and carbonyl groups into the CC double bond in one step, providing straightforward, green and general access to both β-amino acid and β-amino ketone motifs from readily available alkene feedstocks. The mild reaction conditions, excellent functional group tolerance and product diversity should make this a broadly applicable carboimination approach of very broad interest to organic and medicinal chemists.
Topics: Alkenes; Amino Acids; Biological Products; Ketones; Metals; Pharmaceutical Preparations
PubMed: 36128897
DOI: 10.1039/d2ob01474b -
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 Dec 2014CONSPECTUS: The vicinal fluorofunctionalization of alkenes is an attractive transformation that converts feedstock olefins into valuable cyclic fluorinated molecules for...
CONSPECTUS: The vicinal fluorofunctionalization of alkenes is an attractive transformation that converts feedstock olefins into valuable cyclic fluorinated molecules for application in the pharmaceutical, agrochemical, medical, and material sectors. The challenges associated with asymmetric fluorocyclizations induced by F(+) reagents are distinct from other types of halocyclizations. Processes initiated by the addition of an F(+) reagent onto an alkene do not involve the reversible formation of bridged fluoronium ions but generate acyclic β-fluorocationic intermediates. This mechanistic feature implies that fluorocyclizations are not stereospecific. A discontinuity exists between the importance of this class of fluorocyclization and the activation modes currently available to implement successful catalysis. Progress toward fluorocyclization has been achieved by investing in neutral and cationic [NF] reagent development. The body of work on asymmetric fluorination using chiral cationic [NF](+) reagents prepared by fluorine transfer from the dicationic [NF](2+) reagent Selectfluor to quinuclidines, inspired the development of asymmetric F(+)-induced fluorocyclizations catalyzed by cinchona alkaloids; for catalysis, the use of N-fluorobenzenesulfonimide, which is less reactive than Selectfluor, ensures that the achiral F(+) source remains unreactive toward the alkene. These organocatalyzed enantioselective fluorocyclizations can be applied to indoles to install the fluorine on a quaternary benzylic stereogenic carbon center and to afford fluorinated analogues of natural products featuring the hexahydropyrrolo[2,3-b]indole or the tetrahydro-2H-furo[2,3-b]indole skeleton. In an alternative approach, the poor solubility of dicationic Selectfluor bis(tetrafluoroborate) in nonpolar solvent was exploited with anionic phase transfer catalysis as the operating activation mode. Exchange of the tetrafluoroborate ions of Selectfluor with bulky lipophilic chiral anions (e.g., TRIP and derivatives) brings into solution the resulting chiral Selectfluor reagent, now capable of asymmetric fluorocyclization. This strategy is best applied to a subset of substrates bearing a nucleophilic pendent group (benzamide is best) capable of hydrogen bonding for association with the chiral phosphate catalyst. These contributions focused on fluoroheterocyclization involving either O- or N-nucleophiles. As for other halocyclizations, alkenes armed with π C-nucleophiles represent the most demanding class of substrates for asymmetric F(+)-induced electrophilic fluorination-cyclization. Successful implementation required the design of new chiral Selectfluor reagents featuring stereogenicity on the DABCO core. These reagents, accessible from chiral vicinal diamines, allowed the synthesis of unusual chiral fluorine-containing tetracyclic compounds, some composed of carbon, hydrogen, and fluorine exclusively. The challenges associated with F(+)-induced fluorocarbocyclizations prompted methodologists to consider chemistry where the Csp(3)-F bond formation event follows a catalyst-controlled cyclization. An exciting development built on in the area of transition metal π-cyclization of polyenes leading to cationic metal-alkyl intermediates. When intercepted by oxidative fluorodemetalation with a F(+) source, the resulting products are complex polycyclic structures emerging from an overall catalytic cascade fluorocarbocyclization. Complementing F(+)-based reactions, examples of fluorocyclizations with fluoride in the presence of an oxidant were reported. Despite some exciting developments, the field of asymmetric fluorocyclizations is in its infancy and undoubtedly requires new activation modes, catalysts, as well as F(+) and F(-) reagents to progress into general retrosynthetic approach toward enantioenriched fluorocycles. Numerous opportunities emerge, not least the use of a latent fluorine source as a means to minimize background fluorination.
Topics: Alkenes; Catalysis; Cyclization; Fluorine; Molecular Structure; Oxidation-Reduction
PubMed: 25379791
DOI: 10.1021/ar500282z -
Journal of the American Chemical Society Jul 2022Despite the frequent occurrence of γ-branched amines in bioactive molecules, the direct catalytic asymmetric synthesis of this structural motif containing a remote...
Despite the frequent occurrence of γ-branched amines in bioactive molecules, the direct catalytic asymmetric synthesis of this structural motif containing a remote stereocenter remains an important synthetic challenge. Here, we report an amide-directed, rhodium-catalyzed highly diastereo- and enantioselective hydroboration of unactivated internal alkenes. This method provided facile access to enantioenriched amines containing β,γ-vicinal stereocenters. The application of this strategy to the synthesis of bioactive molecules was demonstrated. Computational studies indicated that migratory insertion of the alkene into rhodium hydride controls the enantioselectivity.
Topics: Alkenes; Amides; Amines; Catalysis; Molecular Structure; Rhodium; Stereoisomerism
PubMed: 35830595
DOI: 10.1021/jacs.2c05993 -
Angewandte Chemie (International Ed. in... Sep 2022We report herein the three-component radical addition reaction of SF Cl, alkene and diazo compounds for the selective formation of α-alkyl-α-SF carbonyl compounds. The...
We report herein the three-component radical addition reaction of SF Cl, alkene and diazo compounds for the selective formation of α-alkyl-α-SF carbonyl compounds. The three-component addition reaction proceeded through the first reaction of SF radical with the diazo compound followed by the addition of the in situ generated carbon radical to alkene. The synthetic useful α-allyl-α-SF carbonyl compounds were successfully prepared when allyl trimethylsilanes were used as the alkene substrates. Furthermore, the three-component adducts formed from SF Cl, α-diazoacetophenones and vinyl acetates were converted into pentafluorosulfanylfurans. This transformation provided a practical and efficeint method for the synthesis of pentafluorosulfanylfurans.
Topics: Acetates; Alkenes; Azo Compounds; Carbon; Chlorides; Halogens
PubMed: 35942876
DOI: 10.1002/anie.202208860 -
Nature Dec 2017Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in...
Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity-namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products-and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem. Here we show that through cross-metathesis reactions involving E- or Z-trisubstituted alkenes, which are easily prepared from commercially available starting materials by cross-coupling reactions, many desirable and otherwise difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to 98 per cent E or 95 per cent Z). The utility of the strategy is demonstrated by the concise stereoselective syntheses of biologically active compounds, such as the antifungal indiacen B and the anti-inflammatory coibacin D.
Topics: Alkenes; Anti-Inflammatory Agents; Antifungal Agents; Catalysis; Chemistry Techniques, Synthetic; Indoles; Stereoisomerism
PubMed: 29293209
DOI: 10.1038/nature25002 -
Journal of the American Chemical Society Jun 2022We report a total synthesis of the alkaloid myrioneurinol enabled by the recognition of hidden symmetry within its polycyclic structure. Our approach traces...
We report a total synthesis of the alkaloid myrioneurinol enabled by the recognition of hidden symmetry within its polycyclic structure. Our approach traces myrioneurinol's complex framework back to a symmetrical diketone precursor, a double reductive amination of which forges its central piperidine unit. By employing an inexpensive chiral amine in this key desymmetrizing event, four stereocenters of the natural product including the core quaternary stereocenter are set in an absolute sense, providing the first asymmetric entry to this target. Other noteworthy strategic maneuvers include utilizing a bicyclic alkene as a latent -1,3-bis(hydroxymethyl) synthon and a topologically controlled alkene hydrogenation. Overall, our synthesis proceeds in 18 steps and ∼1% yield from commercial materials.
Topics: Alkaloids; Alkenes; Amination; Heterocyclic Compounds, 4 or More Rings; Stereoisomerism
PubMed: 35699935
DOI: 10.1021/jacs.2c04487 -
Journal of the American Chemical Society Sep 2017Mechanistic studies of the copper-catalyzed asymmetric hydroboration of vinylarenes and internal alkenes are reported. Catalytic systems with both DTBM-SEGPHOS and...
Mechanistic studies of the copper-catalyzed asymmetric hydroboration of vinylarenes and internal alkenes are reported. Catalytic systems with both DTBM-SEGPHOS and SEGPHOS as the ligands have been investigated. With DTBM-SEGPHOS as the ligand, the resting state of the catalyst, which is also a catalytic intermediate, for hydroboration of 4-fluorostyrene is a phenethylcopper(I) complex ligated by the bisphosphine. This complex was fully characterized by NMR spectroscopy and X-ray crystallography. The turnover-limiting step in the catalytic cycle for the reaction of vinylarenes is the borylation of this phenethylcopper complex with pinacolborane (HBpin) to form the boronate ester product and a copper hydride. Experiments showed that the borylation occurs with retention of configuration at the benzylic position. β-Hydrogen elimination and insertion of the alkene to reform this phenethylcopper complex is reversible in the absence of HBpin but is irreversible during the catalytic process because reaction with HBpin is faster than β-hydrogen elimination of the phenethylcopper complex. Studies on the hydroboration of a representative internal alkene, trans-3-hexenyl 2,4,6-trichlorobenzoate, which undergoes enantio- and regioselective addition of HBpin catalyzed by DTBM-SEGPHOS, KOtBu, and CuCl, also was conducted, and these studies revealed that a DTBM-SEGPHOS-ligated copper(I) dihydridoborate complex is the resting state of the catalyst in this case. The turnover-limiting step in the catalytic cycle for hydroboration of the internal alkene is insertion of the alkene into a copper(I) hydride formed by reversible dissociation of HBpin from the copper dihydridoborate species. With SEGPHOS as the ligand, a dimeric copper hydride was observed as the dominant species during the hydroboration of 4-fluorostyrene, and this complex is not catalytically competent. DFT calculations provide a view into the origins of regio- and enantioselectivity of the catalytic process and indicate that the charge on the copper-bound carbon and delocalization of charge onto the aryl ring control the rate of the alkene insertion and the regioselectivity of the catalytic reactions of vinylarenes.
Topics: Alkenes; Boron; Catalysis; Copper; Crystallography, X-Ray; Kinetics; Ligands; Magnetic Resonance Spectroscopy; Molecular Structure
PubMed: 28787137
DOI: 10.1021/jacs.7b07124