Asymmetric Reduction of 2‐Chloro‐3‐oxo Esters by Transfer Hydrogenation

Asymmetric reduction of 2‐chloro‐3‐oxo esters was achieved by catalytic transfer hydrogenation using [RuCl₂(p‐cymene)](S,S)‐TsDPEN as the chiral catalyst and HCOOH‐Et₃N as the hydrogen source. Moderate to good yields (up to 85%) and good enantioselectivities (up to 98% ee) were obtained.     

Reaction of Frustrated Lewis Pairs with Ketones and Esters

The frustrated Lewis pair (FLP) Mes₂PCH₂CH₂B(C₆F₅)₂ ( 1 ) reacts with an enolizable conjugated ynone by 1,4‐addition involving enolate tautomerization to give an eight‐membered zwitterionic heterocycle. The conjugated endione PhCO‐CH?CH‐COPh reacts with the intermolecular FLP tBu₃P/B(C₆F₅)₃ by a simple 1,4‐addition to an enone subunit. The same substrate undergoes a more complex reaction with the FLP 1 that involves internal acetal formation to give a heterobicyclic zwitterionic product. FLP 1 reacts with dimethyl maleate by selective overall addition to the C?C double bond to give a six‐membered heterocycle. It adds analogously to the triple bond of an acetylenic ester to give a similarly structured six‐membered heterocycle. The intermolecular FLP P(o‐tolyl)₃/B(C₆F₅)₃ reacts analogously with acetylenic ester by trans‐addition to the carbon–carbon triple bond. An excess of the intermolecular FLP tBu₃P/B(C₆F₅)₃, which contains a more nucleophilic phosphane, reacts differently with acetylenic ester examples, namely by O? C(alkyl) bond cleavage to give the {R‐CO₂[B(C₆F₅)₃]₂^?}[alkyl‐PtBu₃⁺] salts. Simple aryl or alkyl esters react analogously by using the borane‐stabilized carboxylates as good leaving groups. All essential products were characterized by X‐ray diffraction.     

Chiral Borated Esters in Asymmetric Synthesis： 1. The First Asymmetric Reaction Catalyzed by Chiral Spiroborated Esters with an O3BN Framework

The first asymmetric reaction catalyzed by chiral spiroborated esters with an O3BN framework was reported. In the presence of 0.1 equivalent of (R,S)-1 or (S,S)-1, acetophenone was reduced by 0.6 equivalent of borane in THF at 0-5℃ for 2 h to give (R)-1-phenylethanol of up to 76% ee and 73% isolated yield. Influence of reaction conditions on the stereoselectivity of the reduction was investigated and a possible catalytic mechanism of the chiral spiroborated esters toward the reduction was also suggested.     

Stereoretentive N-Arylation of Amino Acid Esters with Cyclohexanones Utilizing a Continuous-Flow System

The N-arylation of chiral amino acid esters with minimal racemization is a challenging transformation because of the sensitivity of the α-stereocenter. A versatile synthetic method was developed to prepare N-arylated amino acid esters using cyclohexanones as aryl sources under continuous-flow conditions. The designed flow system, which consists of a coil reactor and a packed-bed reactor containing a Pd(OH)₂/C catalyst, efficiently afforded the desired N-arylated amino acids without significant racemization, accompanied by only small amounts of easily removable co-products (i. e., H₂O and alkanes). The efficiency and robustness of this method allowed for the continuous synthesis of the desired product in very high yield and enantiopurity with high space-time yield (74.1 g L⁻¹ h⁻¹) and turnover frequency (5.9 h⁻¹) for at least 3 days.     

Applicability of the Mosher MPTA-Ester Methodology to Monosaccharides

Caryophyllose 1 is a novel twelve carbon 4-C-branched monosaccharide and a component of the polysaccharide chains found in the lypopolysaccharide fraction from Pseudormnas caryophylli bacterium.¹ Its absolute stereochemistry was elucidated² by applying the exciton chiral coupling method to two fragments obtained by NaIO₄, oxidation of the polysaccharide chain. The absolute configuration of a chiral secondary alcohol can be defined by Mosher's method.³ It analyzes the signs of the differences between the chemical shifts of the protons vicinal to the chiral Center in the (S)- and (R)-α-methoxy-α-trifluoromethylphenylacetate (MPTA) esters obtained from the compound. However, the Mosher ester methodology failed to give completely reliable results when applied to the bisisopropylidene derivative 2 of caryophyllose. In fact, whereas Δδ_H(δ_R-δ_S) was positive for 3′-H and negative for 5′-H, indicating R configuration for the 4′ chiral centre, it was positive for 1-H but of opposite sign for the two protons at C-3 (negative for 3_eq and positive for 3_ax), failing to indicate the configuration at C-2. This result, however, was in line with Mosher's warning³ about circumspection in applying his correlation to molecules which “contain additional chiral centres, possess heteroatoms, or show unusual conformational restraints”. It also prompted us to an investigation of applicability of Mosher arguments to sugar MPTA esters, in view of our interest in carbohydrate structure elucidation.     

Terpyridine Diphosphine Ruthenium Complexes as Efficient Photocatalysts for the Transfer Hydrogenation of Carbonyl Compounds

The cationic achiral and chiral terpyridine diphosphine ruthenium complexes [RuCl(PP)(tpy)]Cl (PP=dppp ( 1 ), (R,R)-Skewphos ( 2 ) and (S,S)-Skewphos ( 3 )) are easily obtained in 85–88 % yield through a one-pot synthesis from [RuCl₂(PPh₃)₃], the diphosphine and 2,2′:6′,2′′-terpyridine (tpy) in 1-butanol. Treatment of 1 – 3 with NaPF₆ in methanol at RT affords quantitatively the corresponding derivatives [RuCl(PP)(tpy)]PF₆ (PP=dppp ( 1 a ), (R,R)-Skewphos ( 2 a ) and (S,S)-Skewphos ( 3 a )). Reaction of [RuCl₂(PPh₃)₃] with (S,R)-Josiphos or (R)-BINAP in toluene, followed by treatment with tpy in 1-butanol and finally with NaPF₆ in MeOH gives [RuCl(PP)(tpy)]PF₆ (PP=(S,R)-Josiphos ( 4 a ), (R)-BINAP ( 5 a )) isolated in 78 % and 86 % yield, respectively. The chiral derivatives have been isolated as single stereoisomers and 3 a , 4 a have been characterized by single crystal X-ray diffraction studies. The tpy complexes with NaOiPr display high photocatalytic activity in the transfer hydrogenation (TH) of carbonyl compounds using 2-propanol as the only hydrogen donor and visible light at 30 °C, at remarkably high S/C (up to 5000) and TOF values up to 264 h⁻¹. The chiral enantiomers 2 , 2 a and 3 , 3 a induce the asymmetric photocatalytic TH of acetophenone, affording (S)- and (R)-1-phenylethanol with 51 and 52 % ee, respectively, in a MeOH/2-propanol mixture.     

Di‐μ‐chlorido‐bis[chlorido(4′‐p‐tolyl‐2,2′:6′,2′′‐terpyridine‐κ3N,N′,N′′)nickel(II)]: a supramolecular system constructed by C—H...Cl interactions

The title complex, [Ni₂Cl₄(C₂₂H₁₇N₃)₂], was synthesized solvothermally. The molecule is a centrosymmetric dimer with the unique Ni^II centre in a distorted octahedral N₃Cl₃ coordination environment. The chloride bridges are highly asymmetric. In the 4′‐p‐tolyl‐2,2′:6′,2′′‐terpyridine ligand, the p‐tolyl group is perfectly coplanar with the attached pyridine ring, and this differs from the situation found in previously reported compounds; however, there are no π–π interactions between the ligands. The terminal Cl atom forms four intermolecular C—H...Cl hydrogen bonds with one methyl and three methine groups. The methyl group also forms intermolecular C—H...π interactions with a pyridine ring. These nonclassical hydrogen bonds extend the molecule into a three‐dimensional network.     

Synthesis and Characterization of Poly(chiral methylpropargyl ester)s Carrying Azobenzene Moieties

Novel chiral methylpropargyl esters bearing azobenzene groups, namely, 4‐[4′‐(benzyloxy)phenylazophenyl]‐ carbonyl‐(S)‐1‐methylpropargyl ester ( e ), 4‐[4′‐(n‐butyloxy)phenylazophenyl]carbonyl‐(S)‐1‐methylpropargyl ester ( f ), 4‐[4′‐(n‐hexyloxy)phenylazophenyl]carbonyl‐(S)‐1‐methylpropargyl ester ( g ), and 4‐[4′‐(n‐octyloxy)phenylazo‐ phenyl]carbonyl‐(S)‐1‐methylpropargyl ester ( h ) were synthesized and polymerized with Rh⁺(nbd)[η⁶‐C₆H₅B^?‐ (C₆H₅)₃] (nbd=norbornadiene) catalyst to give the corresponding polymers with moderate molecular weights (M_n=8.4×10³–15.7×10³) in good yields (76%? –?91%). The structures of polymers were illustrated by IR and NMR spectroscopies. Polymers were soluble in comment organic solvents including toluene, CHCl₃ CH₂Cl₂, THF, and DMSO, while insoluble in diethyl ether, n‐hexane and methanol. Large optical rotations of polymer solutions demonstrated that all the polymers take a helical structure with a predominantly one‐handed screw sense in organic solvents.     

Linear polymers of some vinyl monomers containing a terminal acetylenic group

The synthesis and polymerization of representative acrylic-type esters containing a terminal acetylene group, CH₂?C(R)COO(CHR′)_m? C?CH, where R and R′ are H and CH₃ and m = 1 or 2, by anionic initiation to linear polymers are described. In contrast, crosslinked polymers were formed when radical and cationic initiators were used. Crosslinked polymers were also obtained with organolithium compounds but not with sodium naphthalene and sodium benzalaniline; this observation is discussed and compared to the behavior of the acetylenic acrylic esters which do not contain a terminal acetylenic hydrogen. The unpolymerized acetylenic bonds in the resulting linear polymers were shown to be present by infrared spectroscopic methods and by the following post-reactions of these bonds: (1) the heat- and radical-initiated crosslinking of the polymers through the acetylenic bonds; (2) the post-bromination of the acetylenic bonds; and (3) the reaction of decaborane with the acetylenic bonds. The anionic copolymerization of acrylonitrile and styrene with these acetylenic monomers were performed and compared to the copolymerizations with 1-acryloxy-2-butyne and 1-methacryloxy-2-butyne. Dibromination of the linear polymers affords self-extinguishing polymers, while decaboronation yields soluble polymers which do not soften up to 300°C. The linear polymers may be classified as “self-reactive” polymers which yield thermosetting polymers.     

Synthesis and resolution of β2,2-HBin,the first enantiomerically stable β-amino acid with chirality only due to axial dissymmetry

The first gem-disubstituted β^2,2-amino acid possessing only axial chirality, was synthesized by bis-alkylation of methyl or ethyl cyanoacetate with both racemic and enantiomerically pure (R)-2,2′-bis-(bromomethyl)-1,1′-binaphthyl, followed by NaBH₄/CoCl₂ reduction of the cyano group, treatment of the resulting amino esters with Boc₂O and finally saponification of the ester function, to afford the C- and/or N-protected derivatives of 2′,1′:1,2;1′′,2′′:3,4-dinaphthcyclohepta-1,3-diene-6-aminomethyl-6-carboxylic acid: (RS)- and (R)-X-β^2,2-HBin-OR (X=Boc; H) (R=Me, Et or H). For the medium-scale resolution of β^2,2-HBin, the racemic amino esters (RS)-H-β^2,2-HBin-OR (R=Me, Et) were treated with benzoic anhydride and the resulting derivatives (RS)-Bz-β^2,2-HBin-OR were saponified. The obtained (RS)-Bz-β^2,2-HBin-OH was coupled with l-phenylalanine cyclohexylamide by the EDC/HOBt method to afford the dipeptide diastereoisomers Bz-(R)-Bin-l-Phe-NH-C₆H₁₁ and Bz-(S)-Bin-l-Phe-NH-C₆H₁₁, which were separated by chromatography. Complete hydrolysis under acidic conditions, followed by esterification of the resulting free amino acid enantiomers, N-protection and saponification, led to the enantiomerically pure derivatives (R)- and (S)-X-β^2,2-HBin-OR (X=Boc; H) (R=Me, H).     

Flip‐type disorder in 3‐substituted 2,2′:5′,2′′‐terthiophenes

In the crystal structures of four thiophene derivatives, (E)‐3′‐[2‐(anthracen‐9‐yl)ethenyl]‐2,2′:5′,2′′‐terthiophene, C₂₈H₁₈S₃, (E)‐3′‐[2‐(1‐pyrenyl)ethenyl]‐2,2′:5′,2′′‐terthiophene, C₃₀H₁₈S₃, (E)‐3′‐[2‐(3,4‐dimethoxyphenyl)ethenyl]‐2,2′:5′,2′′‐terthiophene, C₂₂H₁₈O₂S₃, and (E,E)‐1,4‐bis[2‐(2,2′:5′,2′′‐terthiophen‐3′‐yl)ethenyl]‐2,5‐dimethoxybenzene, C₃₆H₂₆O₂S₆, at least one of the terminal thiophene rings is disordered and the disorder is of the flip type. The terthiophene fragments are far from being coplanar, contrary to terthiophene itself. The central C—C=C—C fragments are almost planar but the bond lengths suggest slight delocalization within this fragment. The crystal packing is determined by van der Waals interactions and some weak, relatively short, C—H...S and C—H...π directional contacts.     

Chiral Borate Esters in Asymmetric Synthesis. Part 2

Asymmetric catalytic activity of the chiral spiroborate esters 1 – 9 with a O₃BN framework (see Fig. 1) toward borane reduction of prochiral ketones was examined. In the presence of 0.1 equiv. of a chiral spiroborate ester, prochiral ketones were reduced by 0.6 equiv. of borane in THF to give (R)‐secondary alcohols in up to 92% ee and 98% isolated yields (Scheme 1). The stereoselectivity of the reductions depends on the constituents of the chiral spiroborate ester (Table 2) and the structure of the prochiral ketones (Table 1). The configuration of the products is independent of the chirality of the diol‐derived parts of the catalysts. A mechanism for the catalytic behavior of the chiral spiroborate esters (R,S)‐ 2 and (S,S)‐ 2 during the reduction is also suggested.     

Efficient singlet oxygen generation by luminescent 2-(2′-thienyl)pyridyl cyclometalated platinum(II) complexes and their calixarene derivatives

Luminescent cyclometalated platinum(II) complexes, namely [Pt(Thpy)(PPh₃)X]ⁿ⁺ (HThpy = 2-(2′-thienyl)pyridine; X = Cl⁻ ( 1 ), n = 0; X = CH₃CN ( 2 ), pyridine ( 3 ), n = 1) and [Pt(Thpy)(HThpy)Y] ^{n +} (Y = Cl⁻ ( 4 ), n = 0; Y = pyridine ( 5 ), n = 1), exhibit structured emission with peak maximum at ∼556 and 598 nm in degassed acetonitrile and with emission quantum yield and lifetime of up to 0.38 and 26 μs, respectively. These complexes are efficient photosensitizers of singlet oxygen with yields up to >90%. Complex 5 exhibited photocytotoxicity towards cancer cells and fluorescence microscopic images of cells incubated with 5 reveal substantial uptake at the nucleus and mitochondria.     

Enantioselective Amination of β-Keto Esters Catalyzed by Chiral Calcium Phosphates

A catalytic enantioselective amination of β-keto esters using (S)-BINOL chiral calcium phosphate has been developed. The reaction produces chiral α-amino-β-keto ester derivatives in most cases with moderate to excellent enantioselectivities (up to 99 %) and good yields (up to 99 %). This mild synthetic method highlights a low catalyst loading and high catalytic efficiency. When the substrate backbone was changed to 1-tetralone-derived β-keto esters, unexpectedly high yields of selective redox products were obtained. The practicality of the reaction was realized by a scale-up without any significant loss in the enantioselectivity and yield. Chiral calcium phosphate was successfully recovered and reused for four runs, indicating its stability and high catalytic activity.     

l‐Methioninium chloride and l‐seleno­methioninium chloride at 103 K

The crystal structures of the title compounds, (S)‐1‐carboxy‐3‐(methyl­sulfanyl)­propanaminium chloride, C₅H₁₂NO₂S⁺·Cl⁻, and (S)‐1‐carboxy‐3‐(methyl­selanyl)­propanaminium chloride, C₅H₁₂NO₂Se⁺·Cl⁻, are isomorphous. The proton­ated l ‐methionine and l ‐seleno­methionine mol­ecules have almost identical conformations and create very similar contacts with the Cl⁻ anions in the crystal structures of both compounds. The amino acid cations and the Cl⁻ anions are linked viaN—H⋯Cl⁻ and O—H⋯Cl⁻ hydrogen bonds.     

Synthesis,Characterization, Covalent Binding,and Degree of Unwinding of Platinum(II) Bipyridine Complexes

The complexes [Pt(3′′‐clpbpy)Cl₂] ( 1 ) [3′′‐clpbpy = 4‐(3′′‐chlorophenyl)‐6‐phenyl‐2, 2′‐bipyridine], [Pt(4′′‐clpbpy)Cl₂] ( 2 ) [4′′‐clpbpy = 4‐(4′′‐chlorophenyl)‐6‐phenyl‐2, 2′‐bipyridine], [Pt(3′′‐brpbpy)Cl₂] ( 3 ) [3′′‐brpbpy = 4‐(3′′‐bromophenyl)‐6‐phenyl‐2, 2′‐bipyridine], and [Pt(4′′‐brpbpy)Cl₂] ( 4 ) [4′′‐brpbpy = 4‐(4′′‐bromophenyl)‐6‐phenyl‐2, 2′‐bipyridine] were synthesized and characterized. The binding of the complexes with herring sperm DNA (HS DNA) was investigated by absorption titration and viscosity measurements. It was found that the complexes have ability of interaction with DNA by covalent mode. The intrinsic binding constant K_b of the complexes with HS DNA is 8.76 × 10⁴ ( 1 ), 9.89 ×10⁴ ( 2 ), 1.52 × 10⁵ ( 3 ), and 2.31 × 10⁵ ( 4 ) M^–1. The slight depression in relative specific viscosity was observed, which also attributes to covalent binding of complexes with DNA bases. Gel electrophoresis assay demonstrated the ability of the complexes to unwind negatively supercoiled pUC19 plasmid by 14° ( 1 ), 13° ( 2 ), 13° ( 3 ), and 11° ( 4 ). The in vitro cytotoxic property of the synthesized metal complexes was also carried out against brine shrimp bioassay.     

Catalytic Enantioselective Hydrosilylation of Aromatic Ketones Using Rhodium Complexes of TADDOL-Derived Cyclic Phosphonites and Phosphites

Cyclic phosphonites and phosphites 2–4 are readily available from Cl₂PR and (R,R)- or (S,S)-α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols (= TADDOLs 1 , which, in turn, are only two steps away from tartrate); the X-ray crystal structure of one representative, the phenyl phosphonite 2b , was determined. Five previously described and six new ones of the chiral P derivatives were tested as ligands for Rh^I- and Pd^O-catalyzed reactions such as hydrocarbonylations, hydroborations, and hydrosilylations of C?C bonds; while the resulting catalysts were highly active and regioselective, they did not lead to useful enantiomer enrichment in the products (Scheme 1). In contrast, hydrosilylation of phenyl and 2-naphthyl methyl or ethyl ketone by Ph₂SiH₂ (1.2 equiv.) gave, after desilylation, the corresponding secondary alcohols of (R)-configuration with up to 87% ee in the presence of 0.1 equiv. of the penta(2-naphthyl)-substituted phosphonite 3d and 0.02 mol-equiv. of Rh (Table 1).     

Homogeneous Catalysis with Dicationic PdII Complexes: Aldol reaction of methyl isocyanoacetate with benzaldehyde

A series of dicationic Pd^II-acetonitrile complexes containing bi- and tridentate nitrogen and bidentate phosphine ligands (some of which are chiral) has been prepared as their BF₄ salts. The molecular structures for two of these, [Pd(CH₃CN)₂(bipy)] (BF₄)₂ ( 4 ) and [Pd(CH₃CN)((pybox)(i-Pr))] (BF₄)₂((S,S)-pybox(i-Pr) = 2,6-bis[(S)-4′-isopropyloxazolin-2′-yl]pyridine, 5 ) have been determined by X-ray diffraction. All of these complexes are shown to be effective homogeneous catalysts for the aldol-type condensation of the isonitrile, methyl isocyanoacetate, with benzaldehyde. Two isonitrile complexes, [Pd(2,2′-bipyridyl)(CNCH₂COOCH₃)₂] (BF₄)₂ and [Pd((S,S)-pybox(i-Pr))(CNCH₂COOCH₃)] (BF₄)₂, have also been prepared.     

Substituent and Solvent Effects on the Electrochemical Properties and Intervalence Transfer in Asymmetric Mixed‐Valent Complexes Consisting of Cyclometalated Ruthenium and Ferrocene

Four heterodimetallic complexes [Ru(Fcdpb)(L)](PF₆) (Fcdpb=2‐deprotonated form of 1,3‐di(2‐pyridyl)‐5‐ferrocenylbenzene; L=2,6‐bis‐(N‐methylbenzimidazolyl)‐pyridine (Mebip), 2,2′:6′,2′′‐terpyridine (tpy), 4‐nitro‐2,2′:6′,2′′‐terpyridine (NO₂tpy), and trimethyl‐4,4′,4′′‐tricarboxylate‐2,2′:6′,2′′‐terpyridine (Me₃tctpy)) have been prepared. The electrochemical and spectroelectrochemical properties of these complexes have been examined in CH₂Cl₂, CH₃NO₂, CH₃CN, and acetone. These complexes display two consecutive redox couples owing to the stepwise oxidation of the ferrocene (Fc) and ruthenium units, respectively. The potential difference, ΔE_1/2 (E_1/2(Ru^II/III)?E_1/2(Fc^0/+)), decreased slightly with increasing solvent donocity. The mixed‐valent states of these complexes have been generated by electrolysis and the resulting intervalence charge‐transfer (IVCT) bands have been analyzed by Hush theory. Good linear relationships exist between the energy of the IVCT band, E_op, and ΔE_1/2 of four mixed‐valent complexes in a given solvent.     

Acid‐, Water‐ and High‐Temperature‐Stable Ruthenium Complexes for the Total Catalytic Deoxygenation of Glycerol to Propane

The ruthenium aqua complexes [Ru(H₂O)₂(bipy)₂](OTf)₂, [cis‐Ru(6,6′‐Cl₂‐bipy)₂(OH₂)₂](OTf)₂, [Ru(H₂O)₂(phen)₂](OTf)₂, [Ru(H₂O)₃(2,2′:6′,2′′‐terpy)](OTf)₂ and [Ru(H₂O)₃(Phterpy)](OTf)₂ (bipy=2,2′‐bipyridine; OTf^?=triflate; phen=phenanthroline; terpy= terpyridine; Phterpy=4′‐phenyl‐2,2′:6′,2′′‐terpyridine) are water‐ and acid‐stable catalysts for the hydrogenation of aldehydes and ketones in sulfolane solution. In the presence of HOS(O)₂CF₃ (triflic acid) as a dehydration co‐catalyst they directly convert 1,2‐hexanediol to n‐hexanol and hexane. The terpyridine complexes are stable and active as catalysts at temperatures ≥250 °C and in either aqueous sulfolane solution or pure water convert glycerol into n‐propanol and ultimately propane as the final reaction product in up to quantitative yield. For the terpy complexes the active catalyst is postulated to be a carbonyl species [(4′‐R‐2,2′:6′,2′′‐terpy)Ru(CO)(H₂O)₂](OTf)₂ (R=H, Ph) formed by the decarbonylation of aldehydes (hexanal for 1,2‐hexanediol and 3‐hydroxypropanal for glycerol) generated in the reaction mixture through acid‐catalyzed dehydration. The structure of the dimeric complex [{(4′‐phenyl‐2,2′:6′,2′′‐terpy)Ru(CO)}₂(μ‐OCH₃)₂](OTf)₂ has been determined by single crystal X‐ray crystallography (Space group P (a=8.2532(17); b=12.858(3); c=14.363(3) Å; α=64.38(3); β=77.26(3); γ = 87.12(3)°, R=4.36 %).