Biferrocene-Based Diphosphine Ligands: Synthesis and Application of Walphos Analogues in Asymmetric Hydrogenations.
ABSTRACT: A total of four biferrocene-based Walphos-type ligands have been synthesized, structurally characterized, and tested in the rhodium-, ruthenium- and iridium-catalyzed hydrogenation of alkenes and ketones. Negishi coupling conditions allowed the biferrocene backbone of these diphosphine ligands to be built up diastereoselectively from the two nonidentical and nonracemic ferrocene fragments (R)-1-(N,N-dimethylamino)ethylferrocene and (S Fc)-2-bromoiodoferrocene. The molecular structures of (S Fc)-2-bromoiodoferrocene, the coupling product, two ligands, and the two complexes ([PdCl2(L)] and [RuCl(p-cymene)(L)]PF6) were determined by X-ray diffraction. The structural features of complexes and the catalysis results obtained with the newly synthesized biferrocene-based ligands were compared with those of the corresponding Walphos ligands.
Project description:Essentially complete atropdiastereoselectivity was realized in the preparation of biaryl diphosphine dioxide by asymmetric intramolecular Ullmann coupling and oxidative coupling with central-to-axial chirality transfer. A bridged C(2)-symmetric biphenyl phosphine ligand possessing additional chiral centers on the linking unit of the biphenyl groups was synthesized. No resolution step was required for the preparation of the enantiomerically pure chiral ligand. These findings offer a general and practical tool for the development of previously uninvestigated atropdiastereomeric biaryl phosphine ligands. The diphosphine ligand was found to be highly effective in the asymmetric hydrogenation of alpha- and beta-ketoesters, 2-(6'-methoxy-2'-naphthyl)propenoic acid, beta-(acylamino)acrylates, and enol acetates.
Project description:In transition metal-catalyzed asymmetric synthesis, enantioselectivity strongly depends on the structures of chiral ligands, so the development of new chiral ligands is crucial. Here, an efficient and highly enantioselective palladium-catalyzed intramolecular hydroarylation has been developed, and a new kind of N-heterocycles, 1H-pyrazolo[5,1-a]isoindol-2(8H)-ones containing a quaternary stereocenter, was prepared in high yields and excellent enantiomeric excess values. The reaction was effectively catalyzed by palladium-diphosphine complexes with numerous functional group tolerance, in which the newly developed axially chiral cyclic diphosphine ligands played key roles in the reactivity and enantioselectivity of the substrates. We believe that the cyclic diphosphine ligands with adjustable dihedral angles will find wide application in asymmetric synthesis.
Project description:The development of efficient redox-photosensitizers based on the earth-abundant metal ions as an alternative toward noble- and/or rare-metal based photosensitizers is very desirable. In recent years, heteroleptic diimine-diphosphine Cu(I) complexes have been well investigated as one of the most remarkable candidates because of their great potentials as efficient photosensitizers. Here, we investigated the effects of the structure of the diphosphine ligands on the photosensitizing abilities using a series of Cu(I) complexes bearing 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (dmpp) and various diphosphine ligands in order to explore the suitable structure for the photosensitizing reactions. The number of methylene chains between the two phosphorous atoms in the diphosphine ligands was systematically changed from two to four, and the relationship between the length of the carbon chains and the photosensitizing abilities were investigated by conducting photocatalytic CO2 reduction with the Cu(I) complexes as photosensitizers. Turnover frequencies of the CO2 reduction drastically increased with increasing the length of the carbon chains. The systematic study herein reported suggests that the large P-Cu-P angles should be one of the most important factors for enhancing the photosensitizing abilities.
Project description:Two representative Walphos analogues with an achiral 2,2?-biferrocenediyl backbone were synthesized. These diphosphine ligands were tested in the rhodium-catalyzed asymmetric hydrogenation of several alkenes and in the ruthenium-catalyzed hydrogenation of two ketones. The results were compared with those previously obtained on using biferrocene ligands with a C 2-symmetric 2,2?-biferrocenediyl backbone as well as with those obtained with Walphos ligands. The application of one newly synthesized ligand in the hydrogenation of 2-methylcinnamic acid gave (R)-2-methyl-3-phenylpropanoic acid with full conversion and with 92% ee. The same ligand was used to transform 2,4-pentanedione quantitatively and diastereoselectively into (S,S)-2,4-pentanediol with 98% ee.
Project description:A para-terphenyl diphosphine was employed to support a dipalladium(I) moiety. Unlike previously reported dipalladium(I) species, the present system provides a single molecular hemisphere for binding of ligands across two metal centers, enabling the characterization and comparison of the binding of a wide variety of saturated and unsaturated organic molecules. The dipalladium(I) terphenyl diphosphine toluene-capped complex was synthesized from a dipalladium(I) hexaacetonitrile precursor in the presence of toluene. The palladium centers display interactions with the ?-systems of the central ring of the terphenyl unit and that of the toluene. Exchange of toluene for anisole, 1,3-butadiene, 1,3-cyclohexadiene, thiophenes, pyrroles, or furans resulted in well-defined ?-bound complexes which were studied by crystallography, nuclear magnetic resonance (NMR) spectroscopy, and density functional theory. Structural characterization shows that the interactions of the dipalladium unit with the central arene of the diphosphine does not vary significantly in this series allowing for a systematic comparison of the binding of the incoming ligands to the dipalladium moiety. Several of the complexes exhibit rare ?-?(2):?(2) or ?-?(2):?(1)(O or S) bridging motifs. Hydrogenation of the thiophene and benzothiophene adducts was demonstrated to proceed at room temperature. The relative binding strength of the neutral ligands was determined by competition experiments monitored by NMR spectroscopy. The relative equilibrium constants for ligand substitution span over 13 orders of magnitude. This represents the most comprehensive analysis to date of the relative binding of heterocycles and unsaturated ligands to bimetallic sites. Binding interactions were computationally studied with electrostatic potentials and molecular orbital analysis. Anionic ligands were also demonstrated to form ?-bound complexes.
Project description:[reaction: see text] The 1-fluoro-1-haloalkenes undergo Pd-catalyzed Negishi cross-couplings with primary alkylzinc bromides to give multisubstituted fluoroalkenes. The alkylation was trans-selective giving pure Z-fluoroalkenes in most cases. The highest yields were obtained with Pd2(dba)3 and PdCl2(dppb) catalysts but the best stereochemical outcome was obtained with less reactive Pd(PPh3)4. The tertiary alkylzincs also produced desired fluoroalkenes in high yields. Coupling of beta,beta-dichlorostyrene with organozinc reagent resulted in the formation of monocoupled product.
Project description:X-ray crystal structures of two [(diphosphine)Au2 Cl2 ] complexes (in which diphosphine=P-Phos and xylyl-P-Phos; P-Phos=[2,2',6,6'-Tetramethoxy-4,4'-bis(diphenylphosphino)-3,3'-bipyridine]) were determined and compared to the reported structures of similar atropisomeric gold complexes. Correlations between the Au???Au distances and torsional angles for the biaryl series of ligands (MeOBIPHEP, SEGPhos, and P-Phos; BIPHEP=2,2'-bis(diphenylphosphino)-1,1'-biphenyl, SEGPhos=[(4,4'-bi-1,3-benzodioxole)-5,5'-diyl]bis[diphenylphosphine]) can be made; these measurements appear to be very dependent upon the phosphorous substituent. Conversely, the same effect was not observed for ligands based on the binaphthyl (BINAP) series. The catalytic activity of these complexes was subsequently assessed in the enantioselective cycloisomerisation of 1,6-enynes and revealed an over-riding electronic effect: more-electron-rich phosphines promote greater enantioselectivity. The possibility of silver acting as a (co-)catalyst was ruled out in these reactions.
Project description:Metal-catalyzed cross-coupling reactions are extensively employed in both academia and industry for the synthesis of biaryl derivatives for applications to both medicine and material science. Application of these methods to prepare tetra-ortho-substituted biaryls leads to chiral atropisomeric products that introduces the opportunity to use catalyst-control to develop asymmetric cross-coupling procedures to access these important compounds. Asymmetric Pd-catalyzed Suzuki-Miyaura and Negishi cross-coupling reactions to form tetra-ortho-substituted biaryls were studied employing a collection of P-chiral dihydrobenzooxaphosphole (BOP) and dihydrobenzoazaphosphole (BAP) ligands. Enantioselectivities of up to 95:5 and 85:15 er were identified for the Suzuki-Miyaura and Negishi cross-coupling reactions, respectively. Unique ligands for the Suzuki-Miyaura reaction vs the Negishi reaction were identified. A computational study on these Suzuki-Miyaura and Negishi cross-coupling reactions enabled an understanding in the differences between the enantiodiscriminating events between these two cross-coupling reactions. These results support that enantioselectivity in the Negishi reaction results from the reductive elimination step, whereas all steps in the Suzuki-Miyaura catalytic cycle contribute to the overall enantioselection with transmetalation and reductive elimination providing the most contribution to the observed selectivities.
Project description:Ligands that can adapt their coordination mode to the electronic properties of a metal center are of interest to support catalysis or small molecule activation processes. In this context, the ability of imine moieties to bind in either an ?1(N)-fashion via ?-donation of the lone pair or, less commonly, in an ?2(C,N)-fashion via ?-coordination is potentially attractive for the design of new metal-ligand cooperative systems. Herein, the coordination chemistry of chelating ligands with a diphosphine imine framework (PCNP) to nickel is investigated. The imine moiety binds in an ?1(N)-fashion in a Ni(II)Cl2 complex. The uncommon ?2(C,N)-interaction is obtained in Ni(0) complexes in the presence of a PPh3 coligand. Increasing the bulk on the phosphine side-arms in the Ni(0) complexes, by substituting phenyl for o-tolyl groups, leads to a distinct binding mode in which only one of the phosphorus atoms is coordinated. In the absence of a coligand, a mixture of two different dimeric Ni(0) complexes is formed. In one of them, the imine adopts an uncommon ?1(N)?2(C,N) bridging mode of the ligand to nickel, while the second one may involve reactivity on the ligand by the formation of a new C-C bond by oxidative coupling. The latter is supported by the isolation and structural characterization of a crystalline bis-CO derivative featuring a C-C bond formed by oxidative coupling of two imine moieties.
Project description:The first method for the stereoconvergent cross-coupling of racemic ?-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched ?-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of ?-alkyl-?-aryl nitriles that bear secondary ?-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon-carbon bond formation at a remarkably low temperature (-78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide.