Rhodium-catalysed hydroboration employing new Quinazolinap ligands; an investigation into electronic effects

As part of an ongoing effort to improve the efficiency and substrate scope of our Quinazolinap ligand series in the rhodium-catalysed asymmetric hydroboration of vinyl arenes, 2-(p-trifluoromethylphenyl)-Quinazolinap and 2-(p-methoxyphenyl)-Quinazolinap have been synthesised and resolved in good yield. These, along with the previously reported 2-(2-pyridyl)-Quinazolinap and 2-(2-pyrazinyl)-Quinazolinap, form part of an electronic series of Quinazolinap ligands synthesised in order to explore electronic effects in this ligand class. The application of this series of ligands to the rhodium-catalysed asymmetric hydroboration of a range of vinylarenes is described. Good conversions and regioselectivities as well as excellent enantioselectivities up to 97% were obtained. 2-(p-Methoxyphenyl)-Quinazolinap demonstrated consistently high enantioselectivities in the hydroboration of sterically demanding vinylarenes.     

Dithiolene complexes and the nature of molybdopterin

The development of the coordination chemistry of dithiolene ligands is summarised, together with a consideration of the electronic structure of complexes of these ‘non-innocent’ ligands. This information provides a context for a consideration of the role of dithiolenes in natural systems, i.e. as the ligand that binds molybdenum (or tungsten) at the catalytic centre of an extensive series of enzymes. These enzymes catalyse the transfer of an oxygen atom to or from the substrate: e.g. the sulfite oxidases catalyse the conversion of sulfite to sulfate and the nitrate reductases catalyse the conversion of nitrate to nitrite. The nature of the catalytic centres of several of these enzymes has been determined and each involves one or two ‘molybdopterin’ (MPT) cofactors bound to a mononuclear metal centre via their dithiolene group. The biosynthesis of MPT is described and, given its nature, possible roles for this moiety in the function of the oxotransferase enzymes are discussed. The review concludes with a consideration of the coordination chemistry that has been stimulated by the present knowledge of the nature and function of the catalytic centres of these enzymes.     

Simple pyridylmethylamines: efficient and robust N,N-ligands for Suzuki-Miyaura coupling reactions

A series of pyridylmethylamines have been synthesized in one step from commercially available starting material and identified as effective ligands for Pd-catalyzed carbon-carbon bond formation through Suzuki-Miyaura coupling reaction. The N,N-pyridylmethylamine-Pd catalytic systems appeared as an interesting and robust compromise between catalytic efficiency, substrate compatibility, and practical aspects.     

Lutidine‐Based Chiral Pincer Manganese Catalysts for Enantioselective Hydrogenation of Ketones

A series of Mn^I complexes containing lutidine‐based chiral pincer ligands with modular and tunable structures has been developed. The complex shows unprecedentedly high activities (up to 9800 TON; TON=turnover number), broad substrate scope (81 examples), good functional‐group tolerance, and excellent enantioselectivities (85–98 % ee) in the hydrogenation of various ketones. These aspects are rare in earth‐abundant metal catalyzed hydrogenations. The utility of the protocol have been demonstrated in the asymmetric synthesis of a variety of key intermediates for chiral drugs. Preliminary mechanistic investigations indicate that an outer‐sphere mode of substrate–catalyst interactions probably dominates the catalysis.     

Ferrocenyl bis-phosphine ligands bearing sulfinyl,sulfonyl or sulfenyl groups: applications in asymmetric hydrogenation and allylic alkylation reactions

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.     

The Ligand-Exchange Reactions of Rod-Like Au25-nMn (M=Au,Ag, Cu,Pd, Pt) Nanoclusters with Cysteine – A Density Functional Theory Study

The atomic precision of ultrasmall noble-metal nanoclusters (NMNs) is fundamental for elucidating structure-property relationships and probing their practical applications. So far, the atomic structure of NMNs protected by organic ligands has been widely elucidated, whereas the precise atomic structure of NMNs protected by water-soluble ligands (such as peptides and nucleic acid), has been rarely reported. With the concept of “precision to precision”, density functional theory (DFT) calculations were performed to probe the thermodynamic plausibility and inherent determinants for synthesizing atomically precise, water-soluble NMNs via the framework-maintained two-phase ligand-exchange method. A series of rod-like Au_25-nM_n (M=Au, Ag, Cu, Pd, Pt) NMNs with the same framework but varied ligands and metal compositions was chosen as the modeling reactants, and cysteine was used as the modeling water-soluble ligand. It was found that the acidity of the reaction remarkably affects the thermodynamic facility of the ligand exchange reactions. Ligand effects (structural distortion and acidity) dominate the overall thermodynamic facility of the ligand-exchange reaction, while the number and type of doped metal atom(s) has little influence.     

Highly enantioselective synthesis of terutroban key intermediate via asymmetric hydrogenation

A chiral (R) key intermediate of the biologically active form of terutroban has been prepared by asymmetric hydrogenation. The catalysts are based on very easily accessible ruthenium complexes modified by chiral phosphorous ligands. The use of the chiral catASium^®T ligands family allowed us to realize this transformation efficiently in terms of yield and enantioselectivity (ee up to 92%) with high substrate/catalyst ratios.     

Efficient dynamic kinetic resolution of secondary alcohols with a novel tetrafluorosuccinato ruthenium complex

Dynamic kinetic resolution (DKR) of a series of secondary alcohols has been conducted with a novel dinuclear ruthenium complex, bearing tetrafluorosuccinate and (rac)-BINAP ligands as the racemization catalyst. Novozym 435 has been used as the enzyme, and isopropyl butyrate as the acyl donor. Five substrates underwent DKR successfully: an aliphatic and an aromatic secondary alcohol, an aromatic alcohol with an electron-withdrawing substituent on the phenyl ring, an aromatic alcohol bearing an electron-donating substituent on the ring and a heteroaromatic secondary alcohol. The catalyst performed optimally at 70 °C. Typically the reaction reached complete conversion within 1 day with 0.1 mol % of racemization catalyst relative to the substrate. The addition of the ketone corresponding to the substrate stabilizes the active Ru complex and, therefore, increases the rate of the reaction.     

Synthesis of bivalent ligands of β-carboline-3-carboxylates via a palladium-catalyzed homocoupling process

The first synthesis of bivalent ligands of β-carboline-3-carboxylates has been achieved from β-carboline-3-carboxylate tert-butyl ester (βCCt) via Sonogashira and palladium-catalyzed homocoupling processes. The Boc protected intermediate, an iodo-β-carboline-3-carboxylate, was employed to provide a general entry into a series of bivalent ligands structurally similar to βCCt.     

Conformational analysis of mono- and di-C-substituted derivatives ofcloso-3,3-[η2,3-(2-methylenebicyclo[2.2.1]hepta-2,5-dien-2-yl)]-1-R-2-R1-3,1,2-dicarbollylrhodium (R and R1=h, Me, or PhCH2)-(2-methylenebicyclo[2.2.1]hepta-2,5-dien-2-yl)]-1-R-2-R1-3,1,2-dicarbollylrhodium (R and R1=h, Me, or PhCH2)

A model has been developed that allows one to carry out molecular mechanics calculations of metallacarborane complexes with various ligands with the use of the MM3 program package. Based on X-ray structural data on a number of rhodium complexes in which the rhodium atom is coordinated by the η^2,3-norbornadienyl and η⁵-dicarbollyl ligands, a parameter set was developed for the compounds of the above-mentioned series. The use of this model made it possible to study the effects of various factors on the structures of the molecules ofcloso-3,3-(η^2,3-methylenenorbornadienyl)-1-R-3, 1,2-dicarbollylrhodium (R=Alk or ArAlk).     

Furanoside thioether–phosphinite ligands for Pd-catalyzed asymmetric allylic substitution reactions

A new series of thioether–phosphinite ligands, easily prepared in a few steps from inexpensive d-(+)-xylose, was tested in the Pd-catalyzed allylic substitution of substrates with different steric properties. The results show that the enantiomeric excesses are strongly dependent on the steric properties of the substituent in the thioether moiety. Enantiomeric excesses of up to 93% with high activities were obtained for the substrate rac-1,3-diphenyl-3-acetoxyprop-1-ene 7 with dimethyl malonate as the nucleophile.     

Systematic study on the catalytic synthesis of unsaturated 2-ketocarboxamides: palladium-catalyzed double carbonylation of 1-iodocyclohexene

1-Iodocyclohexene, a benchmark substrate, has been double carbonylated in the presence of palladium-phosphite precatalysts. Triarylphosphites with OR substituents, able to act both as P-monodentate and hemilabile P,O-heterobidentate ligands were used in this reaction. Systematic investigations have revealed that the chemoselectivity towards cyclohexenylglyoxylamides, i.e., the products obtained in aminocarbonylation by the insertion of two carbon monoxide, is strongly influenced by the amine nucleophile, temperature and carbon monoxide pressure. The highest yields of 2-ketocarboxamides were obtained at low temperature (30 °C) and high carbon monoxide pressure (110 bar). However, the structure of the phosphite ligand has practically no effect either on catalytic activity or chemoselectivity. This fact refers to the P-monodentate coordination of the ligands in catalytic intermediates or that palladium nanoparticles are the catalytically active species.     

Highly enantioselective Pd(II)-catalyzed Wacker-type cyclization of 2-allylphenols by use of bisoxazoline ligands with axis-unfixed biphenyl backbone

A series of axis-unfixed bisoxazoline ligands with different steric and electronic properties has been synthesized. Due to the different steric interactions, the ligands afforded only one of the two possible diastereomeric Pd(II)-complexes upon metal coordination. The palladium complex (S,aS)-8c showed excellent catalytic activities and enantioselectivities in Wacker-type cyclization of allylphenols with up to 98% ee.     

The organocatalytic desymmetrization of meso-ferrocene anhydride

A new and unique organocatalytic process for the desymmetrization of meso ferrocene anhydride has been developed. After optimization with a series of quinine, quinidine and squaramide ligands, the method was effective with a 60% isolated yield and 98% ee.     

Enantioselectivity switch controlled by N,N′-di- or N,N,N′,N′-tetra-substituted chiral thiophosphorodiamide ligands,structural relatives of thioureas,in catalytic additions of diethylzinc to aldehydes

We have developed a series of new chiral thiophosphorodiamide ligands derived from (1R,2R)-(+)-1,2-diphenylethylenediamine, which are the structural relatives of thioureas. An investigation into their catalytic properties in asymmetric additions of diethylzinc to aldehydes has shown that N,N,N′,N′-tetra-substituted chiral thiophosphorodiamides can give (R)-secondary alcohols with up to 98% yield and 98% ee, while N,N′-di-substituted chiral thiophosphorodiamides give (S)-secondary alcohols with up to 99% yield and 97% ee values. The enantioselectivity switch is highly efficient with a broad substrate scope. We have also proposed hypothetical reaction pathways, which result in an enantioselectivity switch.     

Concepts for ligand design in asymmetric catalysis: a study of chiral amino thiol ligands

A series of new chiral sulfur–nitrogen chelate ligands, derived from amino acids, has been synthesised rationally. Fruitless experiments into catalytic asymmetric conjugate additions and desymmetrisation of meso-epoxides led us to analyse our ligands in the catalytic asymmetric addition of diethylzinc to aromatic aldehydes. These latter experiments were successful with chiral benzylic alcohols being obtained in up to 82% enantiomeric excess.     

Synthesis and electrochemistry of cis-dioxomolybdenum(VI) complexes with tridentate Schiff base ligands containing O,N and S donor atoms

The synthesis and characterization of a number of cis-dioxomolybdenum(VI) coordination complexes involving tridentate (ONS) ligands is described. The Schiff base ligands were obtained by condensation of 5-substituted salicylaldehydes with o-aminobenzenethiol or 2-aminoethanethiol. The chemical properties of these molybdenum complexes are compared with those having tridentate ligands with the ONO donor atom set. Cyclic voltammetry was used to obtain cathodic reduction potentials (E_pc) for the irreversible reduction of the Mo(VI) complexes. Although the reductions are irreversible, trends are observed in E_pc both within each series and when different series are compared. Cathodic reduction potentials for the four series examined span the range from ?1.53 to ?1.05 V versus NHE. There are three ligand features whose effect systematically alters the Mo(VI) cathodic reduction potentials. These include (1) the X-substituent on the salicylaldehyde portion of each ligand; (2) the degree of ligand delocalization; and (3) the substitution of a sulphur donor atom for an oxygen donor atom. Each of these effects is considered separately with regard to the Mo(VI) cathodic reduction potentials and then their cumulative effect is described.     

Preparation of quarternary ammonium salt-tagged ferrocenylphosphine-imine ligands and their application to palladium-catalyzed asymmetric allylic substitution

A series of novel quarternary ammonium salt-modified chiral ferrocenylphosphine-imine ligands have been synthesized and the molecular structure of BIT5 has been determined by single-crystal X-ray diffraction. The applicability of these ligands in asymmetric C1–C and C1–N bond formation was demonstrated. High enantioselectivity was obtained in the Pd-catalyzed asymmetric substitution of 1,3-diphenyl-2-propenyl acetate, with dimethyl malonate (up to 94.6% ee) and benzylamine (up to 92.6% ee).     

α-Aminoamides as ligands in Goldberg amidations

α-Aminoamides are shown to be useful as ligands in Goldberg amidations. A number of α-aminoamides are examined and the importance of substitution on the α-aminoamides is explored. Acetamide is focused on as the nucleophilic coupling partner due to its low cost, stability and convenience as a protecting group. The initial substrate scope for these catalysts is explored and includes electronically activated and deactivated aryl bromides, however o-substituted aryl bromides are problematic.     

Stereoselectivity in the adduct formation between chiral Eu(III) β-diketone complexes and sulphoxides,sulphones and phosphate esters

The adduct formation which takes place when Eu(III) chelates of triflouroacetyl-d-camphor and heptaflourobutyryl-d-camphor bind substrates has been studied. Enhancement of Eu(III) luminescence as a function of substrate concentration has been used to obtain information on the nature of the chelate/substrate adducts, and the stereochemistry of the complexes was studied by means of circularly polarized luminescence (CPL) spectroscopy. While no optical activity can be measured for, the free chelates, formation of the adduct complexes usually led to the observation of very strong chirality even though the substrates were themselves achiral. It was concluded that adduct formation causes the bulky camphorato ligands to interact and adopt a configuration of lowest energy. This process perturbs the diastereomer ratios and yields a partial resolution of these very labile complexes.