Enantioselective synthesis of the excitatory amino acid (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid

An enantioselective synthesis of the alpha,alpha-dialkyl-alpha-amino acid (1S,3R)-ACPD has been achieved using an alkylidene carbene 1,5-CH insertion reaction as a key step. The ketone cyclization precursor was synthesized from Garner's aldehyde in high yield via a Wittig homologation and subsequent catalytic hydrogenation. Treatment of the ketone with 1.2 equiv of lithio(trimethylsilyl)diazomethane in THF resulted in the formation of the corresponding cyclopentene-containing CH-insertion product in 62-69% yield in high enantiomeric excess. Subsequent functional group manipulation allowed the synthesis of the amino acid (1S,3R)-ACPD to be completed.     

An efficient enantioselective synthesis of (2R)-hydroxymethyl glutamic acid and an approach to the (2R)-hydroxymethyl-substituted sphingofungins

We have developed a short enantioselective synthesis of (2R)-hydroxymethyl glutamic acid (HMG) starting from Garner's aldehyde using an alkylidene carbene 1,5-CH insertion as a method to construct the quaternary stereocenter. A variety of conditions were examined for the oxidative cleavage of the key cyclopentene intermediate and we found that RuCl3/NaIO4 led directly to the desired amino bis-acid product. We were also able to show that oxidative cleavage of the cyclopentene 1,5-CH insertion product could be used to produce the amino acid-containing skeleton of the sphingofungin family of natural products.     

Novel reactivity of ruthenium alkylidenes in protic solvents: degenerate alkylidene proton exchange.

A novel organometallic transformation is reported in which the alkylidene protons of water-soluble ruthenium alkylidenes 1 and 2 undergo nondestructive, degenerate exchange with solvent-derived deuterons in perdeuterated protic solvents such as D(2)O and CD(3)OD. Deuterated alkylidene complex (1-D) was isolated from a solution of alkylidene 1 in D(2)O, and the new alkylidene was fully characterized by (1)H, (2)H, (13)C, and (31)P NMR spectroscopy and fast-atom bombardment mass spectroscopy (FAB-MS). The rate of alkylidene proton exchange for this transformation was found to correlate with the bulk dielectric constant of the solvent or solvent mixtures employed. The data support a mechanism for proton exchange involving the dissociation of a chloride ion from the ruthenium metal center. The rate of alkylidene H/D exchange for alkylidene 2 was faster than the rate of exchange for alkylidene 1, demonstrating that relative rates of exchange are influenced by the electron densities at the metal centers of these complexes. Several additional ruthenium alkylidenes were found to undergo analogous alkylidene H/D exchange reactions, including parent alkylidene (Cy(3)P)(2)Cl(2)Ru=CHPh (3) in CD(2)Cl(2)/CD(3)OD mixtures. These data suggest that this novel reactivity may be general for an entire class of ruthenium alkylidenes provided that protic species are available in solution and that the dielectric constant of the reaction medium is sufficiently high to ionize the halide ligands.     

Ligand Substitution of RuII–Alkylidenes to Ru(bpy)32+: Sequential Olefin Metathesis/Photoredox Catalysis

Ruthenium(II) alkylidene complexes such as the Grubbs’ 1st and 2nd generation catalysts undergo a ligand substitution with 2,2′-bipyridine, which readily leads to the common photoredox catalyst Ru(bpy)₃²⁺. The application of this catalyst transformation in sequential olefin metathesis/photoredox catalysis is demonstrated by way of ring-closing metathesis (RCM)/photoredox ATRA reactions.     

新型过渡金属硅基化合物的合成、表征及反应性

在这篇综述中,我们将简要地介绍我们在新一类的金属硅基化合物(RCH₂)₃MSiR′₃(M=Ti, Zr), (RCH₂)₂Ta(=CHR)SiR′₃和(RCH₂)₂W(≡CR)SiR′₃方面的工作,并讨论亚烷基、氨基化合物与硅烷之间的反应。这些研究具有以下的两重意义：(1)探索从分子前体形成金属硅化物的机理。(2)研究新一类金属硅基化合物的合成、结构及它们与硅烷的反应性。我们还通过对烷基和硅基配体在形成亚烷基配合物时不同的反应机理的研究来比较元素碳和硅之间的反应性。在这方面的研究中,我们发现“(RCH₂)₂Ta(=CHR)Cl”为在(RCH₂)₃TaCl₂和Li(THF)₃SiR₃的反应中形成硅基亚烷基化合物(RCH₂)₂Ta(=CHR)SiR₃(R=SiMe₃)的中间体而Ta(CH₂R)₅(R=CMe₃, SiMe₃)则是从(RCH₂)₃TaCl₂生成烷基亚烷基化合物(RCH₂)₃Ta=CHR的中间体。除此之外,金属氨基(M-NR₂)化合物与硅烷之间的反应被证明可以可逆地生成氨基氢化物和氨基硅烷。我们将一并讨论这一结果对于阐明金属硅化物和M-Si-N三元体系物质的形成机理的意义。     

Acetals of lactams and acid amides. 42. Cyclization of dienamino esters,dienamino nitriles,and acylamidines to pyridine derivatives

The reaction of derivatives of alkylidene (cycloalkylidene) cyanoacetic ester, -malo-nodinitrile, and -cyanoacetamide with dimethylformamide diethylacetal with subsequent cyclization of the resulting enamine systems gives derivatives of pyridine, 2-pyridine, and isoquinoline. 2-Amino-3-cyano-4-methylpyridine, which was synthesized by this method, was converted to a pyrido[1,2-a]pyrimidine derivative.See [1] for communication 41.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 799–802, June, 1984.     

DFT calculations of d0 M(NR)(CHtBu)(X)(Y) (M = Mo, W; R = CPh3, 2,6-iPr-C6H3; X and Y = CH2tBu, OtBu, OSi(OtBu)3) olefin metathesis catalysts: structural, spectroscopic and electronic properties

DFT(B3PW91) calculations have been carried out to rationalise the structural, electronic and spectroscopic properties of Mo and W imido M(NR1)(CHR2)(X)(Y) olefin metathesis catalysts by using either simplified or actual ligands of the experimental complexes. The calculated structures, energetics (preference for the syn isomer and alkylidene rotational barrier for the syn/anti interconversion), and spectroscopic properties (NMR J(C-H) coupling constants) are in good agreement with available experimental data. Additionally, the alkylidene nu(C-H) stretching frequencies, not available experimentally, have been calculated. These quasi-tetrahedral complexes have a linear imido group and a C-H alkylidene agostic interaction, which stabilizes the syn isomer. Whether looking at M(NR1)(CHR2)(X)(Y), M = Mo, W, or the isolobal Re complexes, Re(CR1)(CHR2)(X)(Y), a linear correlation is obtained between both the alkylidene nu(C-H) stretching frequencies and J(C-H) coupling constants with the calculated alkylidene C-H bond lengths. These correlations show that the strength of the alpha-C-H agostic interaction increases from alkylidyne Re to imido group 6 complexes and from Mo to W. The NBO and AIM Bader analyses show firstly that the imido and alkylidyne groups are both triply bonded to the metal, but that the triply bonded imido ligand is a weaker electron donor than the alkylidyne, hence the stronger alpha-C-H agostic interaction for group 6 imido complexes. Secondly, one of the pi bonds of the triply bonded ligand is weakened at the transition state of the alkylidene rotation: while no lone pair is formed, the metal-ligand triple bond is polarized. This is more favourable for an imido than for an alkylidyne ligand, hence the lower alkylidene rotational barrier for the former complexes. Conversely, the aryl imido is even less of an electron donor than the alkyl imido group, which in turn strengthens the alpha-C-H agostic interaction and lowers the alkylidene rotational barrier even more.     

4-Hydroxy-2-quinolones 171*. Synthesis,isomerism, and antitubercular activity of 1-R-4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid alkylidenehydrazides

Alkylidenehydrazides have been synthesized by the reaction of 1-R-4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid hydrazides with lower dialkyl ketones in order to reveal a structure-antitubercular activity relationship. It was shown by ¹H NMR spectroscopy that hydrazones obtained from the unsymmetrical ketone – methyl ethyl ketone – exist primarily in the E-isomer form. It was found that the presence of two aliphatic substituents in the alkylidene fragment of the compounds investigated leads to a marked lowering of antimicobacterial properties.     

Synthesis of 3,4‐Fused Tricyclic Indoles Using 3‐Alkylidene Indolines as Versatile Precursors

In this personal account, our recent studies of novel synthetic methods of 3,4‐fused tricyclic indole derivatives using 3‐alkylidene indoline derivatives as versatile precursors are discussed. Two types of cascade reactions producing 3,4‐fused tricyclic 3‐alkylidene indolines were developed based on a palladium‐catalyzed intramolecular Heck insertion to an allene‐allylic amination cascade and a platinum‐catalyzed intramolecular Friedel‐Crafts type C?H coupling‐allylic amination cascade. Furthermore, three types of 3,4‐fused tricyclic indoles were accessible from a single 3‐alkylidene indoline precursor via acid‐promoted olefin isomerization or oxidative treatments. The application of the developed methods to the synthesis of natural products bearing a 3,4‐fused tricyclic indole skeleton, (?)‐aurantioclavine, fargesine, and synthetic studies of dragmacidin E are also highlighted.     

An unusual exchange between alkylidyne alkyl and bis(alkylidene) tungsten complexes promoted by phosphine coordination: kinetic, thermodynamic, and theoretical studies

d0 Tungsten alkylidyne alkyl complex (Me3SiCH2)3W(CSiMe3)(PMe3) (4a) was found to undergo a rare, PMe3-promoted exchange with its bis(alkylidene) tautomer (Me3SiCH2)2W(=CHSiMe3)2(PMe3) (4b). Thermodynamic studies of the exchange showed that 4b is favored and gave Keq and the enthalpy and entropy of the equilibrium: DeltaH degrees = -1.8(0.5) kcal/mol and DeltaS degrees = -1.5(1.7) eu. Kinetic studies of the alpha-H migration between 4a and 4b by variable-temperature NMR gave rate constants k1 and k-1 for the reversible reactions and activation enthalpies and entropies: DeltaH1 = 16.2(1.2) kcal/mol and DeltaS1 = -22.3(4.0) eu for the forward reaction (4a --> 4b); DeltaH2 = 18.0(1.3) kcal/mol and DeltaS2 = -20.9(4.3) eu for the reverse reaction (4b --> 4a). Ab initio calculations at the B3LYP level revealed that PMe3 binds with the bis(alkylidene) tautomer relatively more strongly than with the alkylidyne tautomer and thus stabilizes the bis(alkylidene) tautomer.     

Redox-responsive organometallic foldamers from ferrocene amino acid: solid-phase synthesis, secondary structure and mixed-valence properties

Oligoferrocenes Fmoc-Fca(n)-OMe (n=3-5) are assembled in a stepwise precise manner from Fmoc-protected ferrocene amino acid Fmoc-Fca-OH (H-Fca-OH = 1-amino-1'-ferrocene carboxylic acid; Fmoc = 9-fluorenylmethyloxycarbonyl) via amide bonds on solid supports by sequential Fmoc deprotection, acid activation and coupling steps. The resulting well-defined oligomers form ordered zigzag structures in THF solution with characteristic hydrogen bonding patterns. Electrochemical experiments reveal sequential oxidations of the individual ferrocene units in these peptides giving mixed-valent cations. Optical intervalence electron transfer is detected by intervalence transitions in the near-IR.     

Sequential 1,4‐/1,2‐Addition of Lithium(trimethylsilyl)diazomethane onto Cyclic Enones to Induce C−C Fragmentation and N−Li Insertion

α,β‐Unsaturated ketones generally undergo addition reactions with nucleophiles with a preference for either 1,2‐ or 1,4‐addition, but rarely both. However, the right combination of reagents allows for consecutive 1,4‐ and 1,2‐additions to occur: Cyclic α,β‐unsaturated ketones undergo double additions with lithium(trimethylsilyl)diazomethane, effectively generating various molecular frameworks with complexity and diversity. Owing to the sequential generation of several intermediates of multifaceted reactivity, including diazoalkane derivatives and alkylidene carbenes, it is possible to induce novel Grob‐type C?C fragmentations, alkylidene carbene mediated Li?N insertions, and dipolar cycloadditions by controlling the reaction parameters.     

Alkylidene derivatives of datiscin

With lower ketones (acetone, methyl ethyl ketone) in weakly acidic solution, flavonoid rhamnosides and rutinosides form alkylidene derivatives at the cisdiol grouping of the rhamnose residue. It has been found that the formation of alkylidene derivatives of flavonoid glycosides is a side reaction that takes place during the chromatographic process on an “acid” polyamide sorbent.     

Oxidation of propylene by palladium chloride in acetic acid

Conclusions The oxidation of propylene by palladium chloride in glacial acetic acid leads to the formation of isopropenyl acetate, cis-n-propenyl acetate, trans-n-propenyl acetate, the corresponding alkylidene diacetate, and small amounts of allyl acetate.Translated from Izvestiya Akademii Nauk SSSR, Khimicheskaya, No. 12, pp. 2204–2206, December, 1965     

C-terminal amino acid residue loss for deprotonated peptide ions containing glutamic acid, aspartic acid, or serine residues at the C-terminus

Deprotonated peptides containing C-terminal glutamic acid, aspartic acid, or serine residues were studied by sustained off-resonance irradiation collision-induced dissociation (SORI-CID) in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer with ion production by electrospray ionization (ESI). Additional studies were performed by post source decay (PSD) in a matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) mass spectrometer. This work included both model peptides synthesized in our laboratory and bioactive peptides with more complex sequences. During SORI-CID and PSD, [M - H]- and [M - 2H]2- underwent an unusual cleavage corresponding to the elimination of the C-terminal residue. Two mechanisms are proposed to occur. They involve nucleophilic attack on the carbonyl carbon of the adjacent residue by either the carboxylate group of the C-terminus or the side chain carboxylate group of C-terminal glutamic acid and aspartic acid residues. To confirm the proposed mechanisms, AAAAAD was labelled by 18O specifically on the side chain of the aspartic acid residue. For peptides that contain multiple C-terminal glutamic acid residues, each of these residues can be sequentially eliminated from the deprotonated ions; a driving force may be the formation of a very stable pyroglutamatic acid neutral. For peptides with multiple aspartic acid residues at the C-terminus, aspartic acid residue loss is not sequential. For peptides with multiple serine residues at the C-terminus, C-terminal residue loss is sequential; however, abundant loss of other neutral molecules also occurs. In addition, the presence of basic residues (arginine or lysine) in the sequence has no effect on C-terminal residue elimination in the negative ion mode.     

Preparation of tungsten alkyl alkylidene alkylidyne complexes and kinetic studies of their formation

An equilibrium mixture of alkyl alkylidyne W(CH2SiMe3)3(CSiMe3)(PMe3) (1a) and its bis(alkylidene) tautomer W(CH2SiMe3)2(=CHSiMe3)2(PMe3) (1b) has been found to undergo an alpha-hydrogen abstraction reaction in the presence of PMe3 to form alkyl alkylidene alkylidyne W(CH2SiMe3)(=CHSiMe3)(CSiMe3)(PMe3)2 (2). In the presence of PMe3, the formation of 2 follows first-order kinetics, and the observed rate constant was found to be independent of the concentration of PMe3. The activation parameters for the formation of 2 are Delta H = 28.3(1.7) kcal/mol and Delta S = 3(5) eu. In the presence of PMe2Ph, an equilibrium mixture of W(CH2SiMe3)3(CSiMe3)(PMe2Ph) (3a) and its bis(alkylidene) tautomer W(CH2SiMe3)2(=CHSiMe3)2(PMe2Ph) (3b) was similarly converted to W(CH2SiMe3)(=CHSiMe3)(CSiMe3)(PMe2Ph)2 (4). The observed rate of this reaction was also independent of the concentration of PMe2Ph. These observations suggest a pathway in which the tautomeric mixtures 1a,b and 3a,b undergo rate-determining, alpha-hydrogen abstraction, followed by phosphine coordination, resulting in the formation of the alkyl alkylidene alkylidyne complexes 2 and 4.     

氨基酸合成方法研究(Ⅸ)——固液相转移催化下1,4-二乙酰基-2,5-哌嗪二酮与醛的缩合反应

研究了在固液相转移催化条件下,1,4-二乙酰基-2,5-哌嗪二酮(2)与醛(3a-n)的缩合反应。合成了14种(Z)-1-乙酰基-3-亚芳基(亚烷基)-2,5-哌嗪二酮(4a-n),并讨论了产物的构型。     

Automatic sequential injection analysis electronic tongue with integrated reference electrode for the determination of ascorbic acid, uric acid and paracetamol

A new approach towards a voltammetric electronic tongue has been developed. Automation of the system was achieved by the use of a sequential injection analysis (SIA) system. Design and construction of a small detection device containing 3 working electrodes was carried out. Platinum, gold and epoxy-graphite discs were used for this purpose. An Ag/AgCl reference electrode was integrated into the measuring cell in order to minimise electrical noise. Three oxidisable compounds of clinical interest i.e., ascorbic acid, uric acid and paracetamol, could be quantified by the system. Employing the voltammograms as departure information, artificial neural networks (ANN) have been used as chemometric tool for the modelling of the system.     

Synthesis and crystal structure of some 3,5-pyrazolidinediones

Syntheses of various derivatives of 3,5-pyrazolidenedione are reported. This includes 4-arylidene (alkylidene or aralkylidene)-3,5-pyrazolidinediones, which on epoxidation gave unreported oxiranes. The syntheses of these derivatives were based on either the Knoevenagel reaction of carbonyl derivatives with 3,4-pyrazolidinedione or cyclization of arylidene (alkylidene) malonic acid hydrazide with glacial acetic acid. 4-Arylazo-3,5-pyrazolidinedione derivatives were also prepared by coupling of aryldiazonium salts with 3,5-pyrazolidinedione or cyclization of arylazomalonic acid hydrazide. Reduction of 4-benzylidene derivatives gave the corresponding benzyl derivatives. The structure of the new products was confirmed by elemental and spectral analyses and X-ray crystallography.     

(Imido)vanadium(V)‐alkyl,Alkylidene Complexes Exhibiting Unique Reactivities towards Olefins,Phenols, and Benzene via 1,2‐C‐H Bond Activation

Recent examples for synthesis and reaction chemistry with (imido)vanadium(V)‐alkyl, ‐alkylidene complexes have been briefly summarized. (Arylimido)vanadium(V) dichloride complexes especially containing aryloxo ligands exhibited notable activities for ethylene polymerization, and the reacition pathways for the polymerization/dimerization using (imido)vanadium(V) dichloride complexes containing (2‐anilidomethyl)pyridine ligands can be tuned by modification of the steric bulk in the imido substituents; the adamantylimido analogues exhibited exceptionally high both activity and selectivity in the dimerization. These vanadium(V)‐alkyl complexes showed unique reactivity toward phenols; the reaction proceeds via coordination of phenols to the vanadium. The vanadium(V)‐alkylidene complexes were generated by α‐hydrogen elimination from the dialkyl analogues in the presence of PMe₃ etc.; the subsequent 1,2‐C‐H bond activation of benzene with (arylimido)vanadium(V)‐alkylidene containing 1,3‐(2′,6′‐diiso‐propylphenyl)imidazolin‐2‐iminato (Im^DIPPN) ligand took place cleanly.