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Abstract: Among the bisphosphine ligands, we have previously developed C n -TunePhos (n =1–6) as a family of ligands with tunable bite angles. The increase in spacer –CH2– groups in this family of ligands causes changes in ligand dihedral angle, which in turn causes P–Pd–P bite angle variation. Pd-catalyzed asymmetric alkylations and cycloadditions have been tested with C n -TunePhos ligands. This study aims at a possible correlation between ligand bite angles with enantioselectivity of the Pd-catalyzed asymmetric products. [Copyright &y& Elsevier]

A series of new chiral mono- or bidentate phosphorus ligands were efficiently prepared through a key intermediate (S)-4-chloro-4,5-dihydro-3H-4-phosphacyclohepta[2,1-a;3,4-a′]binaphthalene and its derivatives. These ligands were applied in the Rh-catalyzed asymmetric hydrogenation of α-dehydro amino acids, enol acetates, itaconates, and enamides. Good to excellent enantioselectivities were obtained (up to 99.5% ee). [Copyright &y& Elsevier]

Palladium-catalyzed homocoupling reaction of aryl boronic acids has been developed using a protocol similar to the well-documented crosscoupling reaction. α-Halocarbonyl compounds are applied to initiate the reaction via oxidative addition to a palladium(0) species. The resulting palladium enolate halide can promote the double transmetallation. Reductive elimination generates the desire homocoupling product. [Copyright &y& Elsevier]

Abstract: A new six-membered bis(azaphosphorinane) ligand has been readily prepared starting from an inexpensive chiral epoxide; excellent enantioselectivities (up to over 99% ee) have been achieved in the Rh-catalyzed asymmetric hydrogenations of β-dehydroamino acid derivatives and α-arylenamides. [Copyright &y& Elsevier]

[Display omitted] The asymmetric hydrogenation of imines has been well-established; however, the asymmetric hydrogenation of oximes and oxime ethers with the retention of N O bonds remains a significant challenge in the realm of asymmetric hydrogenation, due to the low reactivity and the difficulty in control of stereoselectivity. Catalytic asymmetric hydrogenation of oximes or oxime ethers represents one of the most direct and efficient method for the construction of chiral hydroxylamines, which are key structural motifs in a wide range of bioactive compounds and pharmaceuticals. This review describes the recent progress in the development of catalytic asymmetric hydrogenation of oximes and oxime ethers. We hope that this review will inspire the development of new synthetic strategies for the asymmetric synthesis of chiral hydroxylamines. [ABSTRACT FROM AUTHOR]

The bisphosphine ligand 1c is highly efficient and selective for the asymmetric hydroformylation (AHF) of dihydrofuran and pyrrolines. The AHF of 2,3-dihydrofuran yielded the 2-carbaldehyde in up to 93% ee. The remarkable highest regioselectivity of 2,5-dihydrofuran was obtained to date up to 499 β-isomer/α-isomer with ligand 1c . Furthermore, the highest 96% and 92% ee values were accomplished using the same catalytic system in the AHF of N -Boc pyrroline 11 and 14 . [ABSTRACT FROM AUTHOR]

Abstract: A new type of chiral phosphine–quinoline ligand bearing a spiro[4,4]-1,6-nonadiene scaffold was designed and synthesized. Its cationic iridium complex has been characterized by X-ray diffraction analysis and evaluated in the catalytic asymmetric hydrogenation of alkene and imine derivatives, giving the corresponding hydrogenation products with high activity albeit moderate enantioselecitivity. [ABSTRACT FROM AUTHOR]

Abstract: A new class of C 1-symmetric bisphosphine ligands with three hindered quadrants have been obtained through facile synthesis from chiral BINOL derivatives. Their rhodium complexes have exhibited high enantioselectivities (up to 98% ee) in the asymmetric hydrogenation of various unsaturated prochiral olefins, providing an efficient catalytic system for the enantioselective synthesis of chiral amino acids and amines. [Copyright &y& Elsevier]

Abstract: A series of new diphosphite ligands have been easily prepared from BINOL derivatives; moderate enantioselectivities (up to 80% ee) and excellent regioselectivities (b/l up to 98/2) have been achieved in the Rh-catalyzed asymmetric hydroformylation of vinyl acetate. [Copyright &y& Elsevier]

Abstract: Rhodium complexes of functionalized bisphospholane ligands (S,S,S,S-Me-ketalphos) 1 and (R,S,S,R-Me-ketalphos) 2 have been used as catalyst precursors for the asymmetric hydrogenation of several different types of functionalized olefins and have achieved high enantioselectivities. [Copyright &y& Elsevier]

Abstract: A three component reaction of aryl aldehydes and malononitrile with ethyl 2,3-butadienoate catalyzed by triphenylphosphine has been developed. The reaction furnishes highly functionalized cyclopentenes in moderate to good yields in a one-pot process. [Copyright &y& Elsevier]

Abstract: A new series of chiral ferrocenyl bis-phosphine ligands have been synthesized. Elements of planar and central chirality have been incorporated into a ferrocene backbone through sulfinyl, sulfonyl and sulfenyl groups at the ortho-position to the phosphines. The effectiveness of these ligands has been demonstrated in Rh-catalyzed hydrogenations and Pd-catalyzed allylic alkylations. [Copyright &y& Elsevier]

Abstract: A new class of conformationally rigid phosphino-oxazoline ligands 3 were synthesized via an efficient ortho-substitution of phenyl glycinol as the key step. Divergent synthetic routes for easy ligand modulation, as well as a procedure suitable for scale-up synthesis, were established. The catalytic potential of ligands 3 has been demonstrated in the highly enantioselective Ir-catalyzed hydrogenation of alkenes and Pd-catalyzed allylic substitution and intermolecular Heck reactions. [Copyright &y& Elsevier]

Abstract: A kinetic resolution process of Rh-catalyzed intramolecular Alder-ene reaction is described along with the studies of the substrate scope and stereochemistry of this remarkably efficient process. 3,4,5-Trisubstituted γ-lactones were synthesized in high enantioselectivity (>99% ee) and efficiency. The formal asymmetric syntheses of (−)-blastmycinolactol and (+)-blastmycinone, degradation products of the macrocyclic dilactone (+)-antimycin, were reported to address the applications of this methodology. [Copyright &y& Elsevier]

A new BIPHEP-type ligand with phenyl groups at the 3,3′-positions, o-Ph-MeO-BIPHEP 3 was prepared. This ligand afforded excellent enantioselectivities when used in the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives. The strong influence of o-phenyl groups of the ligand on the enantioselectivities of the reaction has been demonstrated by a comparison with its parent ligand MeO-BIPHEP. [Copyright &y& Elsevier]

Several DIOP derivatives have been developed as efficient ligands for Rh and Ir-catalyzed asymmetric hydrogenations. The conformational mobility of the backbone in this type of ligand plays an important role in governing both the reactivity and enantioselectivity. Isolation of pure pre-catalyst is another key factor to obtain high catalytic activity. [Copyright &y& Elsevier]

A new chiral ruthenium complex 6, featured with an N,O-mixed polydentate ligand, was synthesized and characterized. This ruthenium complex showed high efficiency in catalytic cyclopropanations of alkenes with diazoacetates. High trans/cis selectivity and enantioselectivity (up to 96%) were achieved with the readily accessible ethyl diazoacetate as the reagent. [Copyright &y& Elsevier]

Abstract: Synthesis of chiral cyclic β-amino ketones has been first reported via Ru-catalyzed asymmetric hydrogenation. High enantioselectivities were achieved by using (S)-C3-TunePhos chiral ligand (up to 94% ee). [Copyright &y& Elsevier]

Abstract: Highly electron-donating bis(trialkylphosphine) TangPhos and its corresponding ruthenium complexes provided high enantioselectivities for the hydrogenation of β-keto esters. Up to 99.8% and 99.5% ee have been achieved in hydrogenation of β-alkyl and β-aryl substituted β-keto esters, respectively. Asymmetric hydrogenation of ethyl 4-chloro acetoacetate in 98.2% ee is also reported. [Copyright &y& Elsevier]

Two novel phosphine-phosphite (S,R)-o-BINAPHOS and phosphine-phosphinite (S)-o-BIPNITE ligands based on ortho phenyl substituted (S)-BINOL have been synthesized. Extremely high enantioselectivity (over 99% ee in most cases) has been achieved for the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives. [Copyright &y& Elsevier]

NMR studies of the catalyst, deuteration experiments, mass spectrometry, and isolation and characterization of intermediates, allow us to propose an outer-sphere mechanism for the Iridium-catalyzed asymmetric hydrogenation of N -alkyl-2-arylpyridinium salts. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs) infect a broad range of hosts, including humans and various animals, with a tendency to cross the species barrier, causing severe harm to human society and fostering the need for effective anti-coronaviral drugs. GS-441524 is a broad-spectrum antiviral nucleoside with potent anti-CoVs activities. However, its application is limited by poor oral bioavailability. Herein, we designed and synthesized several conjugates via covalently binding NSAIDs to 5′-OH of GS-441524 through ester bonds. The ibuprofen conjugate, ATV041 , exhibited potent in vitro anti-coronaviral efficacy against four zoonotic coronaviruses in the alpha- and beta- genera. Oral-dosed ATV041 resulted in favorable bioavailability and rapid tissue distribution of GS-441524 and ibuprofen. In MHV-A59 infected mice, ATV041 dose-dependently decreased viral RNA replication and significantly reduced the proinflammatory cytokines in the liver and the lung at 3 dpi. As a result, the MHV-A59-induced lung and liver inflammatory injury was significantly alleviated. Taken together, this work provides a novel drug conjugate strategy to improve oral PK and offers a potent anti-coronaviral lead compound for further studies. [Display omitted] • Ibuprofen and nucleotide analog GS-441524 conjugates (ATV041) were designed and demonstrated broad anti-CoV activities. • ATV041 successfully improved the oral PK profile and tissue distribution relative to GS-441524 which has poor oral PK. • Oral ATV041 reduced viral loads, alleviated tissue damage and virus-induced inflammation in MHV-A59 mice. [ABSTRACT FROM AUTHOR]

Cephalotaxine-type alkaloids (CTAs), represented by homoharringtonine (HHT, 1), display potent efficacy against different types of leukemia cells. In this study, a method for hydrogenation of β-substituted itaconic acid monoesters with chiral Ru[DTBM-SegPhos](OAc) 2 was developed. This metal-catalyzed asymmetric hydrogenation enabled the convenient semisynthesis of novel cephalotaxine derivatives with chiral 2′-substituted-succinic acid 4-mono-methyl esters as side chains. The preliminary structure-activity relationship (SAR) of the compounds' antineoplastic activities was studied. Eventually, we discovered compound 10b with potent antineoplastic activities against leukemia and broadly anticancer activities against a panel of cancer cells. Our study provided a highly enantioselective process enabling the semisynthesis of cephalotaxine derivatives, which are interesting for further study on a scientific basis. [Display omitted] • Novel cephalotaxine derivatives were designed and semi-synthesized. • Asymmetric hydrogenation of β-substituted itaconic acid was developed as a key step. • 10b exhibited broad anti-leukemia activity and reduced the expression of oncoproteins. [ABSTRACT FROM AUTHOR]

Asymmetric hydrogenation of 4-substituted cyclic enamido esters catalyzed by a rhodium–TangPhos complex provides an efficient method for the synthesis of chiral 4-substituted oxazolinones with excellent yields and good enantioselectivities. The products are valuable chiral building blocks and the applications as chiral auxiliaries and pharmaceuticals are well-known. [ABSTRACT FROM AUTHOR]

Abstract: The rhodium-catalyzed asymmetric hydrogenation of β-acetylamino acrylonitriles was investigated by using monophosphine and bisphosphine ligands. It was found that an Rh-QuinoxP∗ complex exhibited high enantioselectivities for β-aryl substituted β-acetylamino acrylonitriles and the Rh-JosiPhos CyPF-t-Bu complex was proven to be effective for the hydrogenation of tetrasubstituted olefins from cyclic β-acetylamino acrylonitriles. [Copyright &y& Elsevier]

Abstract: A series of spirocyclic phosphoramidite ligands 6–9 with different substituents on the amine moiety were synthesized from the chiral spirocyclic diol (R)-5 . These monodentate ligands have been applied in copper-catalyzed conjugate addition of diethylzinc to cyclic enones. Excellent enantioselectivities (up to 99% ee) can be achieved by the use of ligand (R,S,S)-9 bearing stereochemically matched structure derived from the C 2-symmetric (S,S)-bis(α-methylbenzyl)amine. [Copyright &y& Elsevier]

Abstract: A new electron-rich TunePhos type ligand has been synthesized; excellent enantioselectivities (up to 99% ee) have been achieved in Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid methyl esters and dimethyl itaconate. [Copyright &y& Elsevier]

Abstract: Rhodium-catalyzed hydroformylation of 1,5-hexadiene to corresponding dialdehydes was investigated using tetraphosphorus ligands. These ligands showed a high regioselectivity for linear aldehydes (linear to branch ratio up to 98%) in very good yield (up to 87%). It was found that the introduction of the substituents at the ortho position of the biphenyl moiety has little effect on the regioselectivity and the electron-donating substituents retard the reaction somewhat. [Copyright &y& Elsevier]

Abstract: Axially 4,4′-di-tert-butyl TunePhos-type chiral diphosphine ligand was designed and synthesized by means of central-to-axial chirality transfer. Up to 99% and 98% ee have been achieved in Ru-catalyzed hydrogenation of β-alkyl and β-aryl-substituted β-keto esters, respectively. [Copyright &y& Elsevier]

Abstract: Rh- or Ru-catalyzed highly enantioselective hydrogenation of N-phthaloyl enamides is presented. Electron-rich TangPhos and DuanPhos are found to be effective ligands for Rh-catalyzed hydrogenation of α-aryl enamides and up to 99% ee has been achieved. In contrast, for the hydrogenation of α-alkyl enamide, the Ru-C3-TunePhos complex is more effective and up to 69% ee can be observed. This work is the first report of the hydrogenation of N-phthaloyl enamides. [Copyright &y& Elsevier]

A practical synthesis of 2-amino-2′-hydroxy-1,1′-binaphthyl (NOBIN) was realized from BINOL through a single step. Its facile purification procedure makes the process amenable for large scale synthesis of NOBIN. [Copyright &y& Elsevier]