Rhodium‐Catalyzed Asymmetric Arylation of β,γ‐Unsaturated α‐Ketoamides for the Construction of Nonracemic γ,γ‐Diarylcarbonyl Compounds

A highly regio‐ and enantioselective rhodium‐catalyzed 1,4‐addition of arylboronic acids to β,γ‐unsaturated α‐ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic γ,γ‐diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline‐2‐carboxylamide.     

Novel polymer-supported β-diketonate nickel catalysts for α-olefin activation

Styrene–divinylbenzene resins were used for the synthesis of different polymer-bound β-diketones, obtained by anchoring the chelating group through either the central or the lateral position. The heterogenized diketone ligand was subsequently reacted with Ni(COD)₂ analogously to the corresponding homogeneous catalysts active in α-olefin oligomerization. The heterogenized catalysts showed a good activity only when the central position of the chelate moiety was free. Heterogenization caused a significant change of selectivity: olefin oligomerization was accompanied by the formation of a large amount of polymeric products. This behavior is discussed in terms of steric effects caused by the bulky polymeric ligand. © 1998 John Wiley & Sons, Ltd.     

Asymmetric γ‐Allylation of α,β‐Unsaturated Aldehydes by Combined Organocatalysis and Transition‐Metal Catalysis

The first asymmetric regio‐ and diastereodivergent γ‐allylation of cyclic α,β‐unsaturated aldehydes based on combined organocatalysis and transition‐metal catalysis is disclosed. By combining an aminocatalyst with an iridium catalyst, both diastereomers of branched allylated products can be achieved in moderate to good yields and excellent regio‐ and stereoselectivities. Furthermore, by replacing the iridium catalyst with a palladium catalyst, the linear allylated products are formed in good yields and excellent regio‐ and enantioselectivities. The developed method thus provides selective access to all six isomers of the γ‐allylated product in a divergent fashion by choosing the appropriate combination of organocatalyst, transition‐metal catalyst, and ligand.     

Catalytic,Conjugate Reduction‐Aldol Addition Reaction of β′‐Oxoalkyl α,β‐Unsaturated Carboxylates

Intramolecular conjugate reduction‐aldol addition reactions of β′‐oxoalkyl α,β‐unsaturated carboxylates were performed in the presence of copper catalysts generated in situ from copper salts, phosphine ligands and silanes. Moderate to good yields and high diastereoselectivities were obtained in 15 min to 3 h using bis[(2‐diphenylphosphino)phenyl] ether as the ligand.     

Unprecedented μ-η2:η2-Pyrazolate Coordination in [{Yb(η2-tBu2pz)(μ-η2:η2-tBu2pz)(thf)}2]

A higher degree of coordination saturation is attainable through the unusual coordination mode in the title compound 1 , in which the central pyrazolate groups function both as chelating and as bridging ligands. There is some asymmetry in the bridging, and the N atoms of each μ-η²:η²-pyrazolato ligand are 0.07–0.11 Å closer to one of the two Yb centers.     

Ligand‐Controlled α‐ and β‐Arylation of Acyclic N‐Boc Amines

The palladium‐catalyzed ligand‐controlled arylation of α‐zincated acyclic amines, obtained by directed α‐lithiation and transmetalation, is described. Whereas PtBu₃ gave rise to α‐arylated Boc‐protected amines, more flexible N‐phenylazole‐based phosphine ligands induced major β‐arylation through migrative cross‐coupling.     

Ligand‐Enabled γ‐C(sp3)−H Olefination of Free Carboxylic Acids

We report the ligand‐enabled C?H activation/olefination of free carboxylic acids in the γ‐position. Through an intramolecular Michael addition, δ‐lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium‐catalyzed activation of free carboxylic acids in the γ‐position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.     

Stable Peptides Instead of Stapled Peptides: Highly Potent αvβ6‐Selective Integrin Ligands

The αvβ6 integrin binds the RGD‐containing peptide of the foot and mouth disease virus with high selectivity. In this study, the long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub‐nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins. Computational studies were performed to disclose the molecular bases underlying the high binding affinity and receptor subtype selectivity of this peptide. Finally, the utility of the ligand for use in biomedical studies was also demonstrated here.     

Cu‐Catalyzed Diastereo‐ and Enantioselective Reactions of γ,γ‐Disubstituted Allyldiboron Compounds with Ketones

A catalytic diastereo‐ and enantioselective method for the preparation of complex tertiary homoallylic alcohols containing a vicinal quaternary carbon stereogenic center and a versatile alkenylboronic ester is disclosed. Transformations are promoted by 5 mol % of a readily available copper catalyst bearing a bulky monodentate phosphoramidite ligand, which is essential for attaining both high dr and er. Reactions proceed with a wide variety of ketones and allylic 1,1‐diboronate reagents, which enables the efficient preparation of diverse array of molecular scaffolds.     

Separation of α‐ from β‐arylalanines by nickel nitrilotriacetate chromatography

A method is described to separate α‐ from β‐arylalanines by ligand exchange chromatography on a nickel nitrilotriacetate agarose column with UV monitoring of the effluent. Separate mixtures containing an α‐ and β‐arylalanine pair (1 mg of each) were individually loaded onto the nickel resin pre‐equilibrated with the mobile phase at room temperature, and the amino acids were eluted from the column with a gradient from pH 12.0–8.0. The β‐arylalanines eluted first, followed by the α‐isomers. The four α/β‐amino acid pairs tested were well separated with baseline resolution. An aliquot of each fraction was chemically treated to derivatize the amino acids to their N‐acyl methyl ester analogs, and their identities were confirmed by GC/MS analysis. The sample recovery was quantitative (>98%), and the column matrix was very resilient, as demonstrated by consistent separation of the solutes after ～100 preparative cycles.     

catena‐Poly[[(tetrahydrofuran‐κO)potassium]‐μ‐(η5:η5)‐2,3,4,5‐tetramethyl‐1‐n‐pentylcyclopentadienyl]

The title compound, [K(C₁₄H₂₃)(C₄H₈O)]_n, comprises zigzag chains of alternating bridging 2,3,4,5‐tetramethyl‐1‐n‐pentylcyclopentadienyl ligands and potassium ions, with an ancillary tetrahydrofuran ligand in the coordination environment of potassium. The coordination polymer strands so formed extend by 2₁ screw symmetry in the b‐axis direction. The chemically modified cyclopentadienyl ligand, with a tethered n‐pentyl group, was synthesized from 2,3,4,5‐tetramethylcyclopent‐2‐enone by a Grignard reaction.     

Modeling η5‐C5Me4SiMe3 with η3‐C3H5 for DFT study of a tetranuclear yttrium polyhydrido complex [(η5‐C5Me4SiMe3)YH2]4

π‐Allyl (η³‐C₃H₅), a four‐electron donor, was used as a ligand model to replace η⁵‐C₅Me₄SiMe₃ in DFT calculations on the tetranuclear yttrium polyhydrido complex (η⁵‐C₅Me₄SiMe₃)₄Y₄H₈ containing a Y₄H₈ tetrahedral core structure, which may separate the four π‐allyl groups and hence suppress the allyl ligand coupling during the computation. In terms of the calculated core geometry, isomerization energy barrier, charge population, and frontier orbital features of the complex, the η³‐C₃H₅ ligand model is comparable to η⁵‐C₅H₅. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Direct Catalytic Asymmetric Aldol Reaction of α‐Alkoxyamides to α‐Fluorinated Ketones

α‐Oxygen‐functionalized amides found particular utility as enolate surrogates for direct aldol couplings with α‐fluorinated ketones in a catalytic manner. Because of the likely involvement of open transition states, both syn‐ and anti‐aldol adducts can be accessed with high enantioselectivity by judicious choice of the chiral ligands. A broad variety of alkoxy substituents on the amides and aryl and fluoroalkyl groups on the ketone were tolerated, and the corresponding substrates delivered a range of enantioenriched fluorinated 1,2‐dihydroxycarboxylic acid derivatives with divergent diastereoselectivity depending on the ligand used. The amide moiety of the aldol adduct was transformed into a variety of functional groups without protection of the tertiary alcohol, showcasing the synthetic utility of the present asymmetric aldol process.     

Catalytic Asymmetric Epoxidation of α,β‐Unsaturated Esters with Chiral Yttrium–Biaryldiol Complexes

The full details of the asymmetric epoxidation of α,β‐unsaturated esters catalyzed by yttrium complexes with biaryldiol ligands are described. An yttrium–biphenyldiol catalyst, generated from Y(OiPr)₃–biphenyldiol ligand–triphenylarsine oxide (1:1:1), is suitable for the epoxidation of various α,β‐unsaturated esters. With this catalyst, β‐aryl α,β‐unsaturated esters gave high enantioselectivities and good yields (≤99 % ee). The reactivity of this catalyst is good, and the catalyst loading could be decreased to as little as 0.5–2 mol % (the turnover number was up to 116), while high enantiomeric excesses were maintained. For β‐alkyl α,β‐unsaturated esters, an yttrium–binol catalyst, generated from Y(OiPr)₃–binol ligand–triphenylphosphine oxide (1:1:2), gave the best enantioselectivities (≤97 % ee). The utility of the epoxidation reaction was demonstrated in an efficient synthesis of (?)‐ragaglitazar, a potential antidiabetes agent.     

Ligand‐Controlled Direct γ‐C−H Arylation of Aldehydes

The first example of Pd^II‐catalyzed γ‐C(sp³)?H functionalization of aliphatic and benzoheteroaryl aldehydes has been developed using a transient ligand and an external ligand, concurrently. A wide array of γ‐arylated aldehydes were readily accessed without preinstalling internal directing groups. The catalytic mechanism was studied by performing deuterium‐labelling experiments, which indicated that the γ‐C(sp³)?H bond cleavage is the rate‐limiting step during the reaction process. This reaction could be performed on a gram scale, and also demonstrated its potential application in the synthesis of new mechanofluorochromic materials with blue‐shifted mechanochromic properties.     

Silyl Ligand Mediated Reversible β‐Hydrogen Elimination and Hydrometalation at Palladium

The mechanism and origin of the facile β‐hydrogen elimination and hydrometalation of a palladium complex bearing a phenylene‐bridged PSiP pincer ligand are clarified. Experimental and theoretical studies demonstrate a new mechanism for β‐hydrogen elimination and hydrometalation mediated by a silyl ligand at palladium, which enables direct interconversion between an ethylpalladium(II) complex and an η²‐(Si‐H)palladium(0) complex without formation of a square‐planar palladium(II) hydride intermediate. The flexibility of the PSiP pincer ligand enables it to act as an efficient scaffold to deliver the hydrogen atom as a hydride ligand.     

The synthesis of some complexed ketones or sulfones by oxidation of η-arene-η-cyclopentadienyliron cations or η-arenedi-η-cyclopentadienyliron dications

Di-η⁵-cyclopentadienyliron complexed dications of 9,10-dihydroanthracene, xanthene, thioxanthene and diphenylmethane derived from ligand exchange reactions but without their prior isolation were oxidized with KMnO₄ to give, respectively, the dications of anthraquinone, xanthone, thioxanthone and benzophenone, isolated as their dihexafluorophosphate salts. Cyclopentadienyliron complexes of arenes containing a sulfide function were oxidized by m-chloroperbenzoic acid to the corresponding complexed sulfones, and sulfones prepared in this way include the hexafluorophosphate salt of the η⁶-p-tolysulfonylbenzene, thioxanthene-10,10-dioxide, 9,9-dimethylthioxanthene-10,10-dioxide or dibenzothiophene-9,9-dioxide-η⁵-cyclopentadienyliron cation.     

Highly Enantioselective Synthesis of 1,2,3‐Substituted Cyclopropanes by Using α‐Iodo‐ and α‐Chloromethylzinc Carbenoids

Herein, we report the enantio‐ and diastereoselective formation of trans‐iodo‐ and trans‐chlorocyclopropanes from α‐iodo‐ and α‐chlorozinc carbenoids by using a dioxaborolane‐derived chiral ligand. The synthetically useful iodocyclopropane building blocks were derivatized by an electrophilic trapping of the corresponding cyclopropyl lithium species or a Negishi coupling to give access to a variety of enantioenriched 1,2,3‐substituted cyclopropanes. The synthetic utility of this method was demonstrated by the formal synthesis of an HIV‐1 protease inhibitor. In addition, the related stereoselective bromocyclopropanation was also investigated. New insights about the relative electrophilicity of haloiodomethylzinc carbenoids are also presented.     

Ligand‐Enabled Arylation of γ‐C−H Bonds

Pd^II‐catalyzed arylation of γ‐C(sp³)?H bonds of aliphatic acid‐derived amides was developed by using quinoline‐based ligands. Various γ‐aryl‐α‐amino acids were prepared from natural amino acids using this method. The influence of ligand structure on reactivity was also systematically investigated.     

Cu/Pd Synergistic Dual Catalysis: Asymmetric α‐Allylation of an α‐CF3 Amide

Despite the burgeoning demand for fluorine‐containing chemical entities, the construction of CF₃‐containing stereogenic centers has remained elusive. Herein, we report the strategic merger of Cu^I/base‐catalyzed enolization of an α‐CF₃ amide and Pd⁰‐catalyzed allylic alkylation in an enantioselective manner to deliver chiral building blocks bearing a stereogenic carbon center connected to a CF₃, an amide carbonyl, and a manipulable allylic group. The phosphine complexes of Cu^I and Pd⁰ engage in distinct catalytic roles without ligand scrambling to render the dual catalysis operative to achieve asymmetric α‐allylation of the amide. The stereoselective cyclization of the obtained α‐CF₃‐γ,δ‐unsaturated amides to give tetrahydropyran and γ‐lactone‐fused cyclopropane skeletons highlights the synthetic utility of the present catalytic method as a new entry to non‐racemic CF₃‐containing compounds.