Synthesis of polymer- and silica-supported manganese phosphine complexes and their reaction with oxygen

A series of polymer- and silica-supported manganese phosphine complexes has been prepared and characterized. These complexes react reversibly with molecular oxygen in the solid state to yield 1:1 Mn:O₂ adducts. The reaction may be reversed either by a pressure drop or a temperature rise. All the O₂ adducts are highly colored and binding curves as a function of the partial pressure of oxygen have been constructed. The silica-supported complexes can be prepared from ligand-silanes either by reaction with dehydrated silica and then with anhydrous manganese(II) bromide or vice versa.     

Water soluble platinum(II) and palladium(II) complexes of alkyl sulfonated phosphines

The reactions of the alkylsulfonated phosphines LM=Ph₂P(CH₂)_nSO₃Na/K (n=2, 3, 4) with K₂PtCl₄ and K₂PdCl₄ have been studied in homogeneous aqueous solution as a function of pH. In homogeneous acidic solution the protonated phosphines react to give cis- and trans-PtCl₂(LH)₂. The biphasic reaction between 1,5-cyclooctadiene platinum(II) chloride in dichloromethane and acidified aqueous LNa/K gives a higher proportion of the cis isomer. In neutral solution the initial reaction to give [PtCl(LNa/K)₃]⁺Cl⁻ is followed by slow formation of cis-PtCl₂(LNa/K)₂. K₂PdCl₄ reacts more rapidly to give PdCl₂(LNa/K)₂. In homogeneous alkaline solution rapid oxidation of the phosphine occurs with only small amounts of platinum complex being observable. The biphasic reaction yields phosphine oxide in the aqueous layer and a small amount of the chelate complexes PtL₂ in the organic. Representative complexes have been isolated and characterised and the mechanisms for the reactions discussed. The electrospray mass spectra of solutions of the isolated complexes have been recorded in both positive and negative ionisation modes. The positive ionisation spectra are complicated, but platinum and palladium containing ions derived from loss of chloride, H⁺ and HCl are observed in the negative ionisation spectra.     

Asymmetric aldol reactions catalyzed by efficient and recyclable silica-supported proline-based peptides

A series of silica-supported proline-based peptides were synthesized and applied as catalysts for direct asymmetric intermolecular aldol reactions. Among these, a peptide with two L-proline units was found to be the most efficient one for the asymmetric aldol reactions between acetone and aromatic aldehydes. The reactions generated the corresponding products with satisfactory isolated yields (up to 97%) and enantiomeric excesses (up to 96%) in the presence of this catalyst (5 mol %). Furthermore, the silica-supported organocatalyst could be recovered and recycled by a simple filtration of the reaction solution and used for five consecutive trials without loss of its reactivity.     

trans-o-Hydroxybenzylidenepyruvate hydratase-aldolase as a biocatalyst

The hydratase-aldolase-catalyzed conversion of trans-o-hydroxybenzylidenepyruvate to salicylaldehyde and pyruvate is an intermediate reaction in the conversion of naphthalene to salicylate by bacteria. Here, a variety of aromatic aldehydes and some nonaromatic aldehydes together with pyruvate have been shown to be substrates for aldol condensations catalyzed by this enzyme in extracts of the recombinant strain Escherichia coli JM109(pRE701). Some of the products of these reactions were also compared as substrates in the opposite (hydration-aldol cleavage) reaction.     

Catalyst-free tandem aldol condensation/Michael addition of 1,3-cyclohexanediones with enolizable aldehydes

An efficient tandem aldol condensation/Michael addition process of unactivated aldehydes and 1,3-cyclohexanedione is described. This transformation proceeds without any catalyst at room temperature with high isolated yields. By a fine-tuning of reaction conditions an access to both the aldol condensation/Michael addition products or to the dehydrated cyclized 9-substituted 1,8-dioxo-xanthenes is given.     

O-Glycosidation reactions promoted by in situ generated silver N-heterocyclic carbenes in ionic liquids

We herein report O-glycosidation reactions promoted via silver N-heterocyclic carbene complexes formed in situ in ionic liquids. Seven different room temperature ionic liquids were screened for the glycosidation reaction of 4-nitrophenol with tetra-O-acetyl-α-d-galactopyranosyl bromide. Good to excellent yields were obtained using Ag–NHC complexes derived from imidazolium halide salts to promote the glycosidation reaction, whereas yields considered moderate to low were obtained without use of the silver carbene complex. Anion metathesis of the ionic liquids with inexpensive alkylammonium halides also resulted in silver N-heterocyclic carbene formation and subsequent O-glycosidation in the presence of silver carbonate. Effective utility of this methodology has been demonstrated with biologically relevant acceptors (including flavones and steroids) where O-β-glycoside products were obtained selectively in moderate to good yields. We have also demonstrated that the Ag–NHC complex is a superior promoter to traditionally used silver carbonate for the glycosidation of polyphenolic acceptors. The ionic liquids used in the study could be recycled three times without apparent loss in activity.     

trans-o-Hydroxybenzylidenepyruvate Hydratase-Aldolase as a Biocatalyst

The hydratase-aldolase-catalyzed conversion of trans-o-hydroxybenzylidenepyruvate to salicylaldehyde and pyruvate is an intermediate reaction in the conversion of naphthalene to salicylate by bacteria. Here, a variety of aromatic aldehydes and some nonaromatic aldehydes together with pyruvate have been shown to be substrates for aldol condensations catalyzed by this enzyme in extracts of the recombinant strain Escherichia coli JM109(pRE701). Some of the products of these reactions were also compared as substrates in the opposite (hydration-aldol cleavage) reaction.     

Green Asymmetric Synthesis: β‐Amino Alcohol‐Catalyzed Direct Asymmetric Aldol Reactions in Aqueous Micelles

The ability of chiral β‐amino alcohols to catalyze the direct asymmetric aldol reaction was evaluated for the first time in aqueous micellar media. A family of cheap and easily accessible β‐amino alcohols, obtained in one step from naturally occurring amino acids, was shown to successfully catalyze the asymmetric aldol reaction between a series of ketones and aromatic aldehydes. These aldol reactions furnished the corresponding β‐hydroxy ketones with up to 93% isolated yield and 89% ee. (S)‐2‐phenylglycinol and Triton X‐100 proved to be the best organocatalyst and surfactant, respectively. Chirality 25:119–125, 2013. © 2012 Wiley Periodicals, Inc.     

Theoretical insight into the influences of alpha-substituents in aliphatic aldehydes on the enantioselectivities of aldol reactions

Density functional theory has been applied to study the influences of alpha-substituents in aliphatic aldehydes on the enantioselectivities of the (S)-proline-catalyzed direct aldol reactions. Reaction scenarios of three kinds of aliphatic aldehydes were investigated. Four transition states associated with the stereocontrolling step of each reaction have been obtained. They are corresponding to the syn and anti arrangements of enamine intermediates and the si and re attacks to the carbonyl group of an aldehyde. The solvent effect of DMSO was investigated using self-consistent reaction field method based on the polarizable continuum model. The computed energies of transition states explain the origin of the catalysis and enantioselectivities for these (S)-proline-catalyzed aldol reactions and reveal the influences of alpha-substituents in aliphatic aldehydes on the enantioselectivities of these reactions.     

Trypsin-catalyzed direct asymmetric aldol reaction

Unnatural catalytic activity of trypsin from porcine pancreas for direct asymmetric aldol reaction was discovered. The reactions between aromatic aldehydes and various ketones gave products in moderate yields and enantioselectivities in the presence of a small amount of water. The influences of solvent, water content, temperature, mole ratio of substrates, and enzyme concentration were investigated. The mechanism of trypsin-catalyzed aldol reaction was discussed. This enzymatic promiscuity widens the application of trypsin to new chemical transformations.     

Protonation of cyclopropene complexes of platinum(0) and the reduction of cyclopropene by nitrogenases

The reactions of a series of platinum(0) cyclopropene complexes with HCl have been studied, and it is shown that the products include both ring-intact (cyclopropane-type) and ring-opened (propene-type) materials. All products are believed to be formed by hydrocarbon insertions into transient platinum-hydrogen bonds formed by addition of HCl to platinum. Mechanistic interpretation is complicated by group migrations, and double-bond shifts. Oxidative addition of a σ-cyclopropys to platinum plays a part in ring-opening reactions, whereas the cyclopropanesare believed to be produced by further hydrocarbon insertions into transient platinum-hydrogen bonds. The relevance of these models to the mechanism of reduction of cyclopropene by nitrogenases is discussed.     

N,N-expeditious dialkylation of cyclen (1,4,7,10-tetraazacyclododecane). An astonishing reactivity of cyclen tricarbonyl molybdenum and chromium complexes

After reaction with alkyl iodides and subsequent oxidative removal of the M(CO)₃ triprotection, molybdenum and chromium fac-LM(CO)₃ complexes of cyclen (L) unexpectedly lead to N¹,N⁷-dialkylated cyclen derivatives.     

Structure-based mutagenesis approaches toward expanding the substrate specificity of D-2-deoxyribose-5-phosphate aldolase

2-Deoxyribose-5-phosphate aldolase (DERA, EC 4.1.2.4) catalyzes the reversible aldol reaction between acetaldehyde and D-glyceraldehyde-3-phosphate to generate D-2-deoxyribose-5-phosphate. It is unique among the aldolases as it catalyzes the reversible asymmetric aldol addition reaction of two aldehydes. In order to expand the substrate scope and stereoselectivity of DERA, structure-based substrate design as well as site-specific mutation has been investigated. Using the 1.05 A crystal structure of DERA in complex with its natural substrate as a guide, five site-directed mutants were designed in order to improve its activity with the unnatural nonphosphorylated substrate, D-2-deoxyribose. Of these, the S238D variant exhibited a 2.5-fold improvement over the wild-type enzyme in the retroaldol reaction of 2-deoxyribose. Interestingly, this S238D mutant enzyme was shown to accept 3-azidopropinaldehyde as a substrate in a sequential asymmetric aldol reaction to form a deoxy-azidoethyl pyranose, which is a precursor to the corresponding lactone and the cholesterol-lowering agent Lipitor. This azidoaldehyde is not a substrate for the wild-type enzyme. Another structure-based design of new nonphosphorylated substrates was focused on the aldol reaction with inversion in enantioselectivity using the wild type or the S238D variant as the catalyst and 2-methyl-substituted aldehydes as substrates. An example was demonstrated in the asymmetric synthesis of a deoxypyranose as a new effective synthon for the total synthesis of epothilones. In addition, to facilitate the discovery of new enzymatic reactions, the engineered E. coli strain SELECT (Deltaace, adhC, DE3) was developed to be used in the future for selection of DERA variants with novel nonphosphorylated acceptor specificity.     

Synthesis of peptide aldehydes via enzymatic acylation of amino aldehyde derivatives

Two ways for semi-enzymatic preparation of the peptide aldehydes are proposed: (1) enzymatic acylation of amino alcohols with acyl peptide esters and subsequent chemical oxidation of the resulting peptide alcohols with DMSO/acetic anhydride mixture or (2) enzymatic acylation of the preliminarily obtained by a chemical route amino aldehyde semicarbazones. Subtilisin 72, serine proteinase with a broad specificity, distributed over macroporous silica, was used as a catalyst in both cases. Due to the practical absence of water in the reaction mixtures the yields of the products in both enzymatic reactions were nearly quantitative. The second way seems to be more attractive because all chemical stages were carried out with amino acid derivatives, far less valuable compounds than peptide ones. A series of peptide aldehydes of general formula Z-Ala-Ala-Xaa-al (where Xaa-al=leucinal, phenylalaninal, alaninal, valinal) was obtained. The inhibition parameters for these compounds, in the hydrolysis reactions of corresponding chromogenic substrates for subtilisin and -chymotrypsin, were determined.     

Reactions of the haloalcohols HO(CH2)nCl (n = 2, 3) with platinum(II) - alkynyl and -alkyne complexes. X-ray crystal structure of trans-[Pt(Me) {C(OCH2CH2Cl) (CH2Ph)} (PPh3)2] [BF4]

The chloro complexes trans-[Pt(Me)(Cl)(PPh₃)₂], after treatment with AgBF₄, react with 1-alkynes HC---C---R in the presence of NEt₃ to afford the corresponding acetylide derivatives trans-[Pt(Me) (C---C---R) (PPh₃)₂] (R = p-tolyl (1), Ph (2), C(CH₃)₃ (3)). These complexes, with the exception of the t-butylacetylide complex, react with the chloroalcohols HO(CH₂)_nCl (n = 2, 3) in the presence of 1 equiv. of HBF₄ to afford the alkyl(chloroalkoxy)carbene complexes trans-[Pt(Me) {C[O(CH₂)_nCl](CH₂R) } (PPh₃)₂][BF₄] (R = p-tolyl, N = 2 (4), N = 3 (5); R=Ph, N = 2 (6)). A similar reaction of the bis(acetylide) complex trans-[Pt(C---C---Ph)₂(PMe₂Ph)₂] with 2 equiv. HBF₄ and 3-chloro-1-propanol affords trans-[Pt(C---CPh) {C(OCH₂CH₂CH₂Cl)(CH₂Ph) } (PMe₂Ph)₂][BF₄] (7). T alkyl(chloroalkoxy)-carbene complex trans-[Pt(Me) {C(OCH₂CH₂Cl)(CH₂Ph) } (PPh₃)₂][BF₄] (8) is formed by reaction of trans-[Pt(Me)(Cl)(PPh₃)₂], after treatment with AgBF₄ in HOCH₂CH₂Cl, with phenylacetylene in the presence of 1 equiv. of n-BuLi. The reaction of the dimer [Pt(Cl)(μ-Cl)(PMe₂Ph)]₂ with p-tolylacetylene and 3-chloro-1-propanol yields cis-[PtCl₂{C(OCH₂CH₂CH₂Cl)(CH₂C₆H₄-p-Me}(PMe₂Ph)] (9). The X-ray molecular structure of (8) has been determined. It crystallizes in the orthorhombic system, space group Pna2₁, with a = 11.785(2), B = 29.418(4), C = 15.409(3) Å, V = 4889(1) ų and Z = 4. The carbene ligand is perpendicular to the Pt(II) coordination plane; the PtC(carbene) bond distance is 2.01(1) Å and the short C(carbene)-O bond distance of 1.30(1) Å suggests extensive electronic delocalization within the Pt---C(carbene)---O moietry.     

Reactions of benzocyclobutene chromium complexes with carbon, nitrogen and oxygen nucleophiles: nucleophilic addition and unexpected proximal ring opening reactions

Tricarbonyl(η⁶-1-oxobenzocyclobutene)chromium(0) (1) can be transformed to tricarbonyl(η⁶-1-endo-hydroxybenzocyclobutene) chromium(0) derivatives with substituents R (R=CH₃, CH=CH₂, (CH₂)₄CH=CH₂, (CH₂)₄OSi(Me)₂tBu) at Cl on the exo face of the complex. The relative configuration is proven by an X-ray crystal structure analysis of the trimethylsilyl ether 8 (C₁₆H₁₈CrO₄Si: a=8.693(1), b=9.490(1), c=11.063(1) Å, =97.51(1), β=110.32(1), γ=95.38(1)°, triclinic, space group P (No.2), R=0.037, R_w=0.052 for 4609 observed reflections. Attempts directed at an intramolecular cycloaddition of the ortho-quinodimethane complex derived from 17 by anion promoted ring opening unexpectedly resulted in the formation of 12 as the product of an opening of the proximal bond of the anellated ring located between the hydroxy group and the coordinated aromatic ring in 16. The fact that the intermolecular cycloaddition reaction for 16 is possible in the presence of a dienophile is taken as evidence for an equilibrium between the alcoholate 17 and the two ring opened products 16 and 18. The proximal ring opening of 6 is not observed when the free organic ligand 21 is used as the educt. Ketone complexes 1 and 25 undergo proximal ring opening reaction when treated with alcoholate or primary amines.     

Various Polar Tripeptides as Asymmetric Organocatalyst in Direct Aldol Reactions in Aqueous Media

A series of tripeptide organocatalysts containing a secondary amine group and two amino acids with polar side chain units were developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4‐nitrobenzaldehyde and cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts in aldol reactions to attain high yields of enantio‐ and diastereoselective isomers were investigated. In a comparison, glutamic acid and histidine produced higher % ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric aldol addition reaction in aqueous media. Chirality 25:726–734, 2013. © 2013 Wiley Periodicals, Inc     

Hydroformylation of alkenes and alkynes using a heterobinuclear Rh---W catalyst

Hydroformylation reactions of a series of alkenes and alkynes have been carried out using the heteronuclear Rh---W catalyst, (CO)₄ hH(CO)(PPh₃) (1). The results of these reactions have been compared with corresponding reactions using [Rh(OAc)₂]₂ as catalyst. Catalysis of a reaction of styrene using 1 gave a very high yield of the branched chain aldehyde containing only a trace of the straight chain isomer. Reactions of the phosphinoalkene, Ph₂P(CH₂)₃CH=CH₂ (7) and the corresponding alkyne, Ph₂P(CH₂)₃CCH (11) gave similar products using either catalyst system with the alkryne reaction being significantly slower. Reaction of the alkenyl dithiane, H---CH₂CH=CH₂ (2), using the Rh---W catalyst (1) gave a higher ratio of linear to branched aldehydes (47 linear:53 branched) than the corresponding reaction using [Rh(OAc)₂]₂ (25 linear:75 branched). Reactions of vinyl acetate using 1 as catalyst gave a significant amount of linear aldehyde in contrast to reactions using [Rh(OAc)₂]₂ but reactions of allyl acetate gave similar products for both catalyst systems.     

Hydride complexes of platinum(II) containing unsymmetrical di(phosphine) ligands: synthesis, characterization and evidence for pairwise addition of hydrogen based on parahydrogen induced polarization

Unsymmetrical di(phosphine) ligands (dpp)₂Rop (1a, b = bis(diphenylphosphino)-2-alkyl-3-oxapropane (alkyl = methyl and ethyl)) and (dpp)₂oCy (1c = trans-2-diphenylphosphinocyclohexyl diphenylphosphinite) and their Pt(II) dichloride complexes, PtCl₂((dpp)₂mop) (2a), PtCl₂((dpp)₂eop) (2b) and PtCl₂((dpp)₂oCy) (2c), have been synthesized and characterized by NMR spectroscopy. The crystal structures of 2b and 2c show that the geometry about the platinum centers is square planar. In 2b, the metal and di(phosphine) ligand chelate ring are in a chair conformation, whereas in 2c, the chelate ring conformation is a skewed boat. Initial reaction of sodium borohydride with 2a, b, c yields the monohydride monochloride complexes PtHCl((dpp)₂mop) (5a), PtHCl((dpp)₂eop) (5b) and PtHCl((dpp)₂oCy) (5c). At longer reaction times, fluxional dimeric species are obtained, [PtH((dpp)₂mop)]₂ (4a), [PtH((dpp)₂eop)]₂ (4b) and [PtH((dpp)₂oCy)]₂ (4c),and in the case of 4c two different isomers exist. The dihydride complexes PtH₂((dpp)₂mop) (3a), PtH₂((dpp)₂eop) (3b) and PtH₂((dpp)₂oCy) (3c), are prepared by further reaction of NaBH₄ and 2. Hydrogen cycling is facile in the dihydride complexes 3a, b, c, and oxidative addition of H₂ proceeds in a pairwise manner as determined by the observation of parahydrogen induced polarization (PHIP) in the ¹H NMR spectra. The reductive elimination of H₂ is also shown to be concerted by reaction of dihydride complexes with D₂. Crystal data: 2b (C₃₀H₃₂Cl₆OP₂Pt), monoclinic, space group P2₁/c (No. 14), a = 13.7040(1), b = 11.3430(7), c = 21.3880(9) Å, β = 97.923(9)°, V = 3292.9(2) ų and Z = 4; 2c (C₃₀H₃₀Cl₂OP₂Pt), monoclinic, space group P2₁ (No. 4), a = 11.7360(2), b = 8.4311(2), c = 14.2789(2) Å, β = 101.290(1)°, V = 1385.52(4) ų and Z = 2.     

Enantiomerically Pure Bithiophene Diphosphine Oxides as Catalysts for Direct Double Aldol Reactions

The direct aldol reaction between aryl methyl ketones with aromatic aldehydes in the presence of tetrachlorosilane and a catalytic amount of a chiral bithiophene diphosphine oxide was studied; the product of double aldol addition was isolated as diacetate in good diastereoselectivity (up to 95:5) and enantioselectivities up to 91%. The reaction with heteroaromatic aldehydes was also investigated leading to the corresponding 1,3 diols, in some cases with excellent stereoselectivities. Chirality 25:643–647:, 2013. © 2013 Wiley Periodicals, Inc.