Mechanism of silver(I)-catalyzed Mukaiyama aldol reaction: active species in solution in AgPF6-(S)-BINAP versus AgOAc-(S)-BINAP systems

Silver(I)-diphosphine complex is an effective catalyst for Mukaiyama Aldol reaction in polar solvents. AgPF₆-(S)-BINAP cationic chiral complex indicated a good activity and could afford fairly high enantioselectivity in the reaction of aromatic aldehydes and silyl enol ethers. On the other hand, AgOAc-(S)-BINAP system afforded the aldol product of the absolute configuration opposite to that by AgPF₆-(S)-BINAP and very high catalytic activity was shown. The structure and equilibrium state of Ag(I)-BINAP complexes in solution were examined to understand the reaction mechanism. In AgPF₆ system [Ag((S)-BINAP)₂]PF₆ (1a), [Ag((S)-BINAP)]PF₆ (1b), [Ag₂((S)-BINAP)](PF₆)₂ (1c) and AgPF₆ are present in solution. The active species of the aldol reaction in DMF is [Ag((S)-BINAP)]PF₆ (1b), which exists as a minor species in solution. For this cationic Ag(I) catalyst, cyclic transition state containing substrate and silyl enol ether is assumed. In AgOAc-(S)-BINAP system, active species is also monomeric AgOAc((S)-BINAP) (2b) species which exists as a major component in solution and strong interaction was observed with a silyl enol ether. The reaction by AgOAc-(S)-BINAP catalyst is concluded to proceed as follows: nucleophile forms a complex with AgOAc-(S)-BINAP species and is activated. This complex attacks aldehydes to afford aldol adduct via acyclic transition state.     

Synthesis of Pt compounds containing chiral (2S,4S) -pentane-2,4-diyl-bis(5H-dibenzo[b]phosphindole) as ligand and their use in asymmetric hydroformylation of styrene derivatives

Unlike bis(diphenyl)phosphine derivatives in general, (2S,4S)-pentane-2,4-diyl-bis(5H-dibenzo[b]phosphindole), S,S-BDBPP, gives a trans oligomeric compound [PtCl₂(S,S-BDBPP)]_n, 1, in reaction with dichloro-Pt precursors such as PtCl₂(PhCN)₂, PtCl₂(CH₃CN)₂ and PtCl₂(COD) at room temperature. Compound 1, which could be readily isolated, slowly rearranges in solutions at room temperature to the expected cis-monomer PtCl₂(S,S-BDBPP), 3. Heating or the presence of PtCl₂(COD) accelerates the transformation of compound 1 to 3. SnCl₂ adducts of both compounds, trans-[PtCl(SnCl₃)(S,S-BDBPP)]_n, 2, and cis-PtCl(SnCl₃)(S,S-BDBPP), 4, as well as the known cis-PtCl(SnCl₃)(S,S-BDPP), 5, (S,S-BDPP = (2S,4S)-2,4-bis(diphenylphosphino)pentane) have been tested as catalysts in the asymmetric hydroformylation of p-isobutylstyrene. The phenyl analog 5 provides up to 75% e.e. but moderate yields to chiral 2-(4-isobutylphenyl)-2-propanal. Compared to this, the regioselectivity to the branched aldehyde is remarkably increased; however, the enantioselectivity is drastically decreased by the use of both dibenzophosphole derivatives 2 and 4. The similarities in the selectivities provided by 2 and 4 indicate that the trans oligomer 2 transforms to the cis-monomer 4 during the catalytic process. X-ray crystal structure determination of compound 3 shows a half-chair conformation for the chelate ring with a symmetric arrangement of dibenzophosphole groups. Besides a preference for the latter achiral conformation, the planar structure of the dibenzophosphole groups can also be considered as reason for the moderate enantioselectivities provided by 4.     

Asymmetric hydrogenations of ketones catalyzed by Ru–achiral phosphine-enantiopure diamine complexes

Five novel ruthenium complexes, RuCl₂(MOTPP)₂[(S,S)-DPEN] [MOTPP = tris(4-methoxyphenyl)phosphine] (1), RuCl₂(TFTPP)₂[(S,S)-DPEN] [TFTPP = tris(4-trifluoromethylphenyl)phosphine] (2), RuCl₂(PPh₃)₂[(S,S)-DPEN] (3), RuCl₂(BDPX)[(S,S)-DPEN] [BDPX = 1,2-bis(diphenylphosphinomethyl)benzene] (4), RuCl₂(BISBI)[(S,S)-DPEN][BISBI = 2,2′-bis((diphenylphosphino)methyl)-1,1′-biphenyl]] (5) were synthesized and used for the hydrogenation of aromatic ketones. The complexes showed high catalytic activities, especially that the catalytic activity of complex 5 containing the diphosphine with large bite angle and complex 1 containing triarylphosphine with electron-donating group were higher than the other three complexes. The enantioselectivities of products were almost not influenced by the electron factors of phosphine.     

Indenyl complexes of ruthenium(II) containing optically active diphosphines. X-ray structures of (S,S)-(η-C9H7)-Ru{Ph2PCH(CH3)CH(CH3)PPh2}Cl and of its η-C5H5 analogue

The optically active indenyl complexes ((η⁵-C₉H₇)Ru(L---L)Cl (where L---L is either (S,S)-1,2-dimethyl-1,2-ethanediylbis(diphenylphosphine) (chiraphos) or (R,R)-1,2-cyclopentanediylbis(diphenylphosphine) (cypenphos)) have been synthesized and spectroscopically characterized and compared with the corresponding cyclopentadienyl complexes. Reaction of the new complexes with 2-e-donors give cationic adducts in which the pentahaptocoordination of the indenyl ligand is maintained. The crystal structures of (S,S)-(η⁵-C₉H₇)Ru{Ph₂PCH(CH₃)CH(CH₃)PPh₂}Cl (1) and (S,S)-η⁵-C₅H₅Ru{Ph₂PCH(CH₃)CH(CH₃)PPh₂}Cl (3) have been determined.     

Tris-chelate complexes with chiral ligands: In search of diastereoisomeric selectivity with remote stereogenic centres

The chiral ligands, 4,4′-bis{(1S,2R,4S)-(−)-bornyloxy}-2,2′-bipyridine, (1S,2R,4S)-1, and 4,4′-bis{(1R,2S,4R)-(+)-bornyloxy}-2,2′-bipyridine, (1R,2S,4R)-1, have been prepared and characterized by spectroscopic techniques and, for (1S,2R,4S)-1, by single crystal X-ray diffraction. Despite the use of enantiomerically pure ligands, the formation of the complexes [Fe((1S,2R,4S)-1)₃]²⁺, [Ru((1S,2R,4S)-1)₃]²⁺, [Ru((1S,2R,4S)-1)(bpy)₂]²⁺ and [Ru((1R,2S,4R)-1)(bpy)₂]²⁺ proceeds without preference for either the Δ or Λ-diastereoisomers.     

Preparation of (S)-2-substituted succinates by stereospecific reductions of fumarate and derivatives with resting cells of Clostridium formicoaceticum

Fumarate derivatives have been reduced to (S)-2-methylsuccinate 2a, (S)-2-ethylsuccinate 3a and (S)-2-chlorosuccinate 4a in up to 1 M concentrations with Clostridium formicoaceticum. Formate was the electron donor and viologens or anthraquinone-2,6-disulphonate acted as artificial electron mediators. Reductions with freeze-dried cells in ²H₂O-buffers led to the (2R,3S)-[2,3-2,²H]-dideuterated succinate derivatives. The productivity numbers¹ ranged from 450 to 5000 and the enantiomeric excess of all (S)-2-substituted succinates was 99 %.     

Catalytic and structural studies of Rh complexes of (−)-(2S,4S)-2,4-bis(diphenylphosphino)pentane. Asymmetric hydrogenation of acetophenonebenzylimine and acetophenone

Rhodium(I) complexes formed by (−)-(2S,4S)-2,4-bis(diphenylphosphino)pentane (BDPP) are efficient catalysts for the hydrogenation of acetophenone and acetophenonebenzylimine. The composition of the solvent mixture and the reaction temperature have a marked influenced on the enantioselectivity. These effects are thought to be related to the enhanced conformational flexibility of six-membered rings when simple substrates without functional groups are coordinated to the rhodium. X-ray crystallographic studies reveal that in [Rh((S,S)-BDPP)NBD]⁺ (1) the ligand is in a chair conformation, and that in [Rh((S,S)-BDPP)COD]⁺ (2) the chelate ring is in a δ-skew conformation. Studies of Rh((S,S)-BDPP)(NBD)Cl (3) in solution indicate a trigonal bipyramidal structure with a chair conformation of the ring in aromatic solvents and a conformationally labile ring in methanol.     

Ferroelectric liquid crystal materials synthesized from 2(S)-[2(S)-methylbutyloxy]propanol

A new chiral alcohol, 2(S)-[2(S)-methylbutyloxy]propanol (3), containing two chiral centres has been synthesized from ethyl lactate and (S)-1-iodo-2-methylbutane. It was used as a chiral building block for the preparation of ferroelectric liquid crystal materials. Several of the new materials exhibit an enantiotropic S*_c phase with a wide temperature range. The results indicate that the molecular structure of 3 is useful for synthesizing ferroelectric liquid crystal materials.     

Synthesis of (2R,3S,4S)-4-aryl-3-hydroxyprolinols

Synthesis of (2R,3S,4S)-4-aryl-3-hydroxyprolinols has been established starting from 2-benzyloxymethylpyrrolidin-2-one framework, which is derived from commercially available trans-(2S,4R)-4-hydroxyproline. The single diastereomer having a trans–cis relative configuration with C₂ and C₃ and C₃ and C₄ is constructed in two one-pot functional group transformations of Grignard addition/dehydration and epoxidation/isomerization as the key steps in moderate yield.     

Molecular structure and electrochemical properties of the Pt complex of 1,1′-bis(methylthio)ferrocene and the Pd complexes of 1,4,7-trithia[7]- and 1,5,9-trithia[9] (1,1′)ferrocenophanes

Molecular structures of (triphenylphosphine) [1,1′-bis-(methylthio)ferrocene-S,S′,Fe]Pt(BF₄)₂ (1), (1,5,9-trithia[9]ferrocenophane-S,S′,S″,Fe)Pd(BF₄)₂ (2), and (acetonitrile)(1,4,7-trithia[7]ferrocenophane-S,S′,S″,Fe)Pd(BF₄)₂ (3) were determined by X-ray analyses. The Pt in 1 and the Pd atom in 2 have a somewhat distorted square-planar geometry including the Fe atom of the ferrocene moiety, while the Pd atom in 3 is coordinated by one equivalent of acetonitrile and takes a distorted tetragonal-pyramidal geometry. The distances of the Fe---M bond (M = Pd, Pt) in 1–3 are 2.851(2), 2.827(2), and 3.0962(8) Å, respectively. Cyclic voltammetry of 1–3 gave no reversible wave, but afforded some information supporting the presence of a dative bond.     

The Total Synthesis of (±)-13-Hydroxyneocembrene

(13S)-hydroxyneocembrene(18), a cembranoid which was isolated in 1988 from soft coral Sarcophyton trocheliophorum¹, has been shown to be an effective inductor of the release of labeled glucose from the lecithincholesterol liposomes and have cytostatic activities². The geometrical structure and absolute configuration of 18 have been defined to be 1S, 2E, 7E, 11E, 13S. Herein, we report the total synthesis of (±)-13hydroxyneocembrene(18).     

cis,cis-Spiro[4.4]nonane-1,6-diol: A new chiral auxiliary for the asymmetric Diels-Alder reaction

The use of a mono-pivalate mono-acrylate bis-ester of (+)-1S,5S,6S-spiro[4.4]nonane-1,6-diol in an asymmetric Diels-Alder reaction with cyclopentadiene (2 equiv. BCl₃, −85°C, CH₂Cl₂) provided the expected endo bicyclo adduct in >97% de. Iodolactonization of the bicyclo adduct provided the (+)-lactone (5) with a 1S,4S,6S,8R,9S configuration (97% ee). The de's obtained from using various types and amounts of Lewis acids, and both chiral and racemic bis-esters in the Diels-Alder reaction with cyclopentadiene are also reported.     

(S)-(+)-1-Methyl-2-(6,7,-dimethoxy-2,3-naphthalimido)ethyl trifluoromethanesulfonate as a fluorescence chiral derivatizing reagent for carboxylic acid enantiomers in high-performance liquid chromatography

A new triflate-type fluorescence chiral derivatizing reagent, (S)-(+)-1-methyl-2-(6,7-dimethoxy-2,3-naphthalimido)ethyl trifluoromethanesulfonate, [S-(+)-MDNE-OTf], has been developed for the determination of the enantiomers of carboxylic acids. By introducing the two methoxy groups on the naphthalimido ring moiety, the red shift in the fluorescence spectrum and a high resolution in reversed-mode separation of the diastereomers of chiral carboxylic acids have been achieved. The detection limits (S/N=3) with ultraviolet and fluorescence detection are 8 fmol (λ_max=283 nm) and 4 fmol (λ_ex=283 nm, λ_em=467 nm), respectively.     

Enantioselective organic syntheses using chiral transition metal complexes V. (2S,3S)-Bis(dibenzophospholyl)butane, a rigid (S,S)-CHIRAPHOS analog

The P–Ph cleavage of phenyldibenzophosphole (1) with lithium in THF gives lithium dibenzophospholide (2). Reaction of 2 with ethyleneglycol ditosylate produces the known chelate ligand 1,2-bis(dibenzophospholyl)ethane (3) in good yield. Similarly, 2 and (2R,3R)-butanediol ditosylate give the new chiral chelate ligand (2S,3S)-bis(dibenzophospholyl)butane (4). Ligand exchange of [CpRu(PPh₃)₂Cl] with 3 or 4 yields the halfsandwich complexes [CpRu(C₁₂H₈PC₂H₄PC₁₂H₈)Cl] (5) and [CpRu((S,S)-C₁₂H₈PCHMeCHMePC₁₂H₈)Cl] (6). Complex 6 was characterized crystallographically (monoclinic, space group P2₁ (no. 4), a=820.6(4), b=1501.0(3), c=1172.8(6) pm, β=108.87(2)°, V=1.367(1)×10⁹ pm³, Z=2). The most conspicuous feature of the structure of 6 is the perfect coplanarity of the two dibenzophosphole moieties imposed by their steric interaction with the Cp ligand. Complex 6 and the thiophene complex [CpRu((S,S)-C₁₂H₈PCHMeCHMePC₁₂H₈)(SC₄H₄)]BF₄ (7) derived therefrom are remarkably unreactive with regard to ligand substitutions. A possible explanation is the lack of intramolecular

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–C stabilization en route to the transition state of ligand substitution. The enantiomeric purity of 6 and 7 could nevertheless be demonstrated by conversion to diastereomerically pure [CpRu((S,S)-C₁₂H₈PCHMeCHMePC₁₂H₈)((S)-CNCHMePh)]BF₄ (8).     

Metal complexes of biologically important ligands: Synthesis of amino acidato complexes of Pd containing a C,N-cyclometallated group as an ancillary ligand

New amino acidato complexes of Pd^II of stoichiometry [Pd(C---N)(Aa)] (C---N=C,N-cyclometallated ligand, Aa = N,O-amino acidato ligand) have been obtained by reaction of [Pd(C---N)(acac)] (C---N=N,N-dimethylbenzylamine-C²,N (dmba) (1) or N,N-dimethyl(S--phenylethyl)amine-C²,N (S-dmphea) (2)) with glycine, chiral amino acids (alanine, phenylalanine and valine), and amino acid derivatives (N-acetylglycine and N-acetyl-,β-dehydroalanine) in MeOH. The compounds are characterized by IR, ¹H and ¹³C NMR. The geometry of these complexes has been unambiguously determined by NOE difference experiments and NOESY measurements.     

Preparation of both enantiomers of malic and citramalic acid and other hydroxysuccinic acid derivatives by stereospecific hydrations of cis or trans 2-butene-1,4-dioic acids with resting cells of Clostridium formicoaceticum

(R)-Malic, (S)-malic, (R)citramalic, (S)-citramalic, (2R,3S)-2-hydroxy-3-methyl-succinic and (2R,3S)-2,3-dimethyl-2-hydroxysuccinic acid were prepared on scales up to 25 mmol by stereospecific addition of water to different 2-butene-1,4-dioic acid derivatives catalyzed by resting cells of Clostridium formicoaceticum (Scheme 1). The (3R)-monodeuterio (R)- and (S)-malic acid as well as (R)- and (S)-citramalic acid were prepared using freeze-dried cells in ²H₂O-buffer. The stereochemical purity of the products was in most cases ≥ 99%.     

2,4-二硫代尿嘧啶的紫外吸收光谱和共振拉曼光谱

硫代嘧啶碱基是光动力疗法潜在的重要光敏剂,其最低单重激发态的光物理研究已有广泛报道。然而,其较高激发态的跃迁性质和反应动力学研究较为稀少。因此,本文采用共振拉曼光谱和密度泛函理论计算方法研究2,4-二硫代尿嘧啶的紫外光谱和几个较高单重激发态的短时结构动力学。首先,基于共振拉曼光谱强度与电子吸收带振子强度f的关系,将紫外光谱去卷积成四个吸收带,分别为358 nm(f=0.0336)中等强度吸收带(A带),338 nm(f=0.1491)、301 nm(f=0.1795)和278 nm(f=0.3532)强而宽的吸收带(B、C和D带)。这一结果既吻合密度泛函理论计算结果,又符合共振拉曼光谱强度模式对紫外光谱带的预期。据此,去卷积得到的四个吸收带被分别指认为S0→S2跃迁、S0→S6跃迁、S0→S7跃迁和S_0→S_8跃迁。同时,分别对B,C和D带共振拉曼光谱进行了详细的指认,获得了短时动力学信息。结果表明,S_8态短时动力学的显著特征是在Franck-Condon区域或附近发生了S8(ππ~*)/S(nπ~*)势能面交叉引发的、伴随超快结构扭转的非绝热过程。S7和S6态短时动力学的主要特征是反应坐标的多维性,它们分别沿C_5C_6/C_2S_8/C_4S_(10)/N_2C_3+C_4N_3H_9/N_1C_2N_3/C_2N_1C_6/C_6N_1H_7/C_5C_6H_(12)和C_5C_6/N_3C_2/C_4S_(10)/C_2S_8+C_6N_1H_7/C_5C_6H_(12)/C_5C_6N_1/C_5C_6H_(12)/C_2N_1C_6/N_1C_2N_3/C_4N_3H_9/N_1C_2N_3等内坐标演化。     

X-ray study of the hetero ring flexibility in trans-5,6- trimethylene- and tetramethylene-5,6-dihydro 2-phenyl-[4H]-1,3-thiazines

The structures to two 1,3-thiazine derivatives differing only in the number of CH₂ groups in their trans fused hydrocarbon ring (_n = 3 for I and n = 4 for II) have been established by X-ray crystallography from diffractometer data. Crystals of I (trans-5,6- trimethylene-5,6-dihydro-2-phenyl-[4H] - 1,3-thiazine) are triclinic, space group P with a = 7.661(1), b = 8.282(1), c = 9.566(2) Å, = 91.75(1), β = 100.72(1), γ = 105.45(1)° Z = 2, D_c = 1.260 g cm^-3. Crystals of II (trans-5,6-tetramethylene-5,6-dihydro-2-phenyl [4H]-1,3-thiazine) are monoclinic, space group P2₁/c with a = 7.914(2), b = 19.362(13), c = 8.440(1) Å, β = 109.16(2)°C Z = 4, D_c = 1.258 g cm^-3. The structures determined by Patterson (I) and direct (II) methods were refined to R = 0.050 for 1330 reflections of I and R = 0.082 for 1012 reflections of II. The proper treatment of the positional disorder of the carbon atoms (C(5) and C(6)) forming the trans ring junction in I discovered two discrete conformations with a ratio of 1:2. The opposite chirality of atoms C(51) and C(52), and C(61) and C(62), indicates a simultaneous configurational disorder with a pattern of total disorder: A A . The puckering parameters of the hetero rings in the same enantiomers of molecules IA, IB and II indicate a connection between the conformers: ⁵E(II)→⁵H₆(IB)→E₆IA) via pseudorotation. Their relationship is discussed and compared with the conformational freedom of the analogous 1,3-oxazine derivatives.     

A comparison of ferroelectric liquid crystals containing diastereomeric propionic acids derived from natural ethyl lactate

Two diastereomeric carboxylic acids, 2(S)-[2(R)-methylhexyloxy]propionic acid and 2(S)[2(S)-methylhexyloxy]propionic acid, were prepared from ethyl (S)-lactate and (R)-1-iodo2-methylhexane or (S)-1-iodo-2-methylhexane in the presence of Ag₂O. From these acids two liquid crystals, 2 and 3 , whose configurations are (S , R ) and (S, S) were synthesized and their liquid crystal properties investigated. Although both LCs have the same phase sequence Cr-SmC*-N*-I as well as a wide SmC* phase range, the influence of the relative stereochemistry on their physical properties is clear. The liquid crystal with (S, S)-configuration possesses better properties: lower SmC* phase transition temperature, wider SmC* phase range and higher P_s value. The P_s value difference between the ferroelectric LCs 2 and 3 (97 and 131nCcm^-2, respectively, at T_c - T = 10°C) is unexpectedly large. The consideration, alone, of a zigzag conformation at the chiral molecular part of 2 and 3 is insufficient to explain such a difference.     

Syntheses of heparin - like pentamers containing “opened” uronic acid moieties

The syntheses of four analogues of pentasaccharide Ia, which corresponds to the minimal AT III binding region of heparin, are presented and the biological activities of these analogues will be discussed. Three of these analogues (i.e. compounds II, III and IV) contain an R-glyceric acid oxymethylene residue (i.e. B in fig.3) instead of -L-iduronic acid and in the other analogue (i.e. compound V) the β-D-glucuronic acid unit has been replaced by an s-glyceric acid oxymethylene residue (i.e. A in fig3). The R and S-glyceric acid oxymethylene residues represent an “opened” iduronic acid unit and an “opened” glucuronic acid unit, respectively, containing the essential carboxylate function in the appropriate configuration. The crucial step in the syntheses of these “opened” uronic acid pentamer analogues, was the preparation of the required glyceric acid oxymethylene residues 8a, 8b and 8c.

Analogues II and III, containing an “opened” iduronic acid moiety, display a significant AT III mediated Xa activity. Compound III contains two extra sulphate groups at unit 2. Removal of the contributing O-sulphate groups at position 3 and 6 of unit 6 of compound II (i.e. compound IV) results in a seven-fold drop in Xa activity. Replacement of the β-D-glucuronic acid unit by an S-glyceric acid oxymethylene residue (i.e. compound V) leads to almost a complete loss of Xa activity, notwithstanding the fact that all the essential and contributing charged groups are present in the molecule.