Copper-catalyzed coupling of oxime acetates with aldehydes: a new strategy for synthesis of pyridines

Copper-catalyzed coupling of oxime acetates with aldehydes offers a new strategy for the synthesis of highly substituted pyridines. This novel method tolerates a wide range of functionality and allows for rapid elaboration of the oxime acetates into a variety of substituted pyridines.     

镍催化环丁酮肟酯与芳基锌试剂的Negishi偶联反应

发展了一种镍催化环丁酮肟酯和芳基锌试剂之间Negishi偶联的方法.镍既作为亚胺自由基的引发剂,也作为芳基锌试剂与烷基自由基偶联反应的催化剂在反应中起作用.本方法可避免使用剧毒的氰化物,且具有很广的底物适应性和官能团兼容性,因此可能是一种具有潜在吸引力的高效合成烷基腈类化合物的新策略.初步的机理研究显示,该反应极可能经历自由基历程.     

Integrated Tandem Electrochemical-chemical-electrochemical Coupling of Biomass and Nitrate to Sustainable Alanine

Alanine is widely employed for synthesizing polymers, pharmaceuticals, and agrochemicals. Electrocatalytic coupling of biomass molecules and waste nitrate is attractive for the nitrate removal and alanine production under ambient conditions. However, the reaction efficiency is relatively low due to the activation of the stable substrates, and the coupling of two reactive intermediates remains challenging. Herein, we realize the integrated tandem electrochemical-chemical-electochemical synthesis of alanine from the biomass-derived pyruvic acid (PA) and waste nitrate (NO₃⁻) catalyzed by PdCu nano-bead-wires (PdCu NBWs). The overall reaction pathway is demonstrated as a multiple-step catalytic cascade process via coupling the reactive intermediates NH₂OH and PA on the catalyst surface. Interestingly, in this integrated tandem electrochemical-chemical-electrochemical catalytic cascade process, Cu facilitates the electrochemical reduction of nitrate to NH₂OH intermediates, which chemically couple with PA to form the pyruvic oxime, and Pd promotes the electrochemical reduction of pyruvic oxime to the desirable alanine. This work provides a green strategy to convert waste NO₃⁻ to wealth and enriches the substrate scope of renewable biomass feedstocks to produce high-value amino acids.     

Highly efficient synthesis of peptide-oligonucleotide conjugates: chemoselective oxime and thiazolidine formation

A convergent strategy for the synthesis of peptide-oligonucleotide conjugates (POC) is presented. Chemoselective ligation of peptide to oligonucleotide was accomplished by oxime and thiazolidine formation. Oxime conjugation was performed by treating an oxyamine-containing peptide with an aldehyde-containing oligonucleotide or vice versa. Ligation by thiazolidine formation was achieved by coupling a peptide, acylated with a cysteine residue, to an oligonucleotide that was derivatised by an aldehyde function. For both approaches, the conjugates were obtained in good yield without the need for a protection strategy and under mild aqueous conditions. Moreover, the oxime ligation proved useful for directly conjugating duplex oligonucleotides. Combined with molecular biology tools, this methodology opens up new prospects for post-functionalisation of high-molecular-weight DNA structures.     

铜(Ⅱ)-羟肟络合物的电子自旋共振谱研究

本文报导芳香族羟肟铜(Ⅱ)络合物的电子自旋共振(ESR)谱的研究。讨论了这类配位体上取代基的电子效应对络合物中铜(Ⅱ)的超精细分裂常数A_(Cu)值的影响,以及A_(Cu)值与这些配位体萃取铜的分配系数的关系。     

A novel in situ deprotection/coupling and iterative divergent/convergent strategy for the synthesis of oligo(1,4-phenyleneethynylene)s

A novel in situ deprotection/coupling and iterative divergent/convergent strategy for the synthesis of oligo(1,4-phenyleneethynylene)s is described.     

An Iterative Acetylene–Epoxide Coupling Strategy for the Total Synthesis of Aspinolide A

The total synthesis of aspinolide A ( 1 ) was successfully achieved by an iterative acetylene? epoxide coupling strategy and a Yamaguchi lactonization as the key steps.     

Quantum chemical study on enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine. Part 1. Structures of catalyst–borane–keto oxime ether adducts

In the present work, quantum chemical computations of the enantioselective reduction of keto oxime ether with borane catalyzed by chiral oxazaborolidine are performed by means of the Hartree–Fock and the density functional methods. The structures of oxazaborolidine, oxazaborolidine–borane adduct, and oxazaborolidine–borane–keto oxime ether adducts are optimized completely at the HF/6‐31g* and B3LYP/6‐31g* levels and their properties studied in detail. The oxazaborolidine catalyst is a twisted chair structure and reacts with borane at the nitrogen site of the catalyst to form the catalyst–borane adduct whose formation reaction is exothermic. The catalyst–borane adduct reacts easily with keto oxime ether to form catalyst–borane–keto oxime ether adducts that have eight stable structures. The coordination of the carbonyl oxygen in keto oxime ether at the boron site of the catalyst is of more advantage to the enantioselective reduction of keto oxime ether than the coordination of the oxime nitrogen in the keto oxime ether at the boron site is. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 81: 291–304, 2001     

An Easy Access to Oxime Ethers by Pd‐Catalyzed C—O Cross‐Coupling of Activated Aryl Bromides with Ketoximes and Chalcone Oximes

An efficient Pd‐catalyzed method for C—O cross‐coupling of ketoximes and chalcone oximes with activated aryl bromides and bromo‐chalcones has been developed. All oxime ethers were obtained in good to excellent yields by [(π‐allyl)PdCl]₂/tBuXPhos ( L7 ) catalyst system. TrixiePhos ( L11 ) was also found to be effective for the oxime coupling. This method offers an easy and smooth coupling of chalcone oximes with activated aryl bromides and bromo‐chalcones, which has not been previously explored.     

Combining two-directional synthesis and tandem reactions. Part 4: A concise approach to the spirocyclic core of halichlorine and the pinnaic acids

A synthesis of the spirocyclic core structure of halichlorine, an inhibitor of the induced expression of VCAM-1 and the pinnaic acids, inhibitors of PLA₂, is presented. A two-directional strategy is employed, in conjunction with a tandem oxime formation/Michael addition/cycloaddition to form the key azaspirocyclic skeleton in a very direct manner.     

New strategy for the synthesis of 3',5'-bifunctionalized oligonucleotide conjugates through sequential formation of chemoselective oxime bonds

A convenient strategy for the synthesis of bifunctionalized oligonucleotide conjugates bearing two different reporters at the 3' and 5' ends of the oligonucleotide is presented. The method involves the preparation of oligonucleotides bearing an aldehyde and/or aminooxy functionality at each end, followed by reaction to form oxime bonds with appropriately functionalized reporters. The conjugation reactions are carried out under mild aqueous conditions with good reaction yield.     

Enantioselective synthesis of (−)-pinellic acid

An enantioselective convergent approach toward the total synthesis of pinellic acid 1 from 1,9-nonanediol is described. The synthetic strategy features iterative Sharpless asymmetric dihydroxylation, Sonogashira coupling and Birch reduction.     

Image recording material based on the polymeric photobase generator containing oxime‐urethane groups

A polymeric photobase generator containing oxime‐urethane groups was prepared from copolymerization of MMA with N‐[4‐(benzophenoneoximino‐carbonylamino)phenyl]maleimide, a maleimide monomer containing oxime‐urethane group, and its properties as an image recording material were studied. The irradiation of this copolymer with UV light dissociates the urethane linkage to result in the formation of aromatic amino groups, which can be developed by the diazo‐coupling reaction. Various colors could be developed depending on the phenolic coupling reagents as the developer.     

Heck‐Type Reactions of Imine Derivatives: A DFT Study

The mechanism of a recently discovered intramolecular Heck‐type coupling of oximes with aryl halides (Angew. Chem. Int. Ed. 2007 , 46, 6325) was systematically studied by using density functional methods enhanced with a polarized continuum solvation model. The overall catalytic cycle of the reaction was found to consist of four steps: oxidative addition, migratory insertion, β‐H elimination, and catalyst regeneration, whereas an alternative base‐promoted C? H activation pathway was determined to be less favorable. Migratory insertion was found to be the rate determining step in the catalytic cycle. The apparent activation barrier of migratory insertion of the (E)‐oxime was +20.5 kcal mol^?1, whereas the barrier of (Z)‐oxime was as high as +32.7 kcal mol^?1. However, (Z)‐oxime could isomerize to form the more active (E)‐oxime with the assistance of K₂CO₃, so that both the (E)‐ and (Z)‐oxime substrates could be transformed to the desired product. Our calculations also indicated that the Z product was predominant in the equilibrium of the isomerization of the imine double bond, which constituted the reason for the good Z‐selectivity observed for the reaction. Furthermore, we examined the difference between the intermolecular Heck‐type reactions of imines and of olefins. It was found that in the intermolecular Heck‐type coupling of imines, the apparent activation barrier of migratory insertion was as high as +35 kcal mol^?1, which should be the main obstacle of the reaction. The analysis also revealed the main problem for the intermolecular Heck‐type reactions of imines, which was that the breaking of a C?N π bond was much more difficult than the breaking of a C?C π bond. After systematic examination of a series of substituted imines, (Z)‐N‐amino imine and N‐acetyl imine were found to have relatively low barriers of migratory insertion, so that they might be possible substrates for intermolecular Heck‐type coupling.     

Synthesis and conformational analysis of novel N(OCH3)-linked disaccharide analogues

N(OMe)-linked disaccharide analogues, isosteric to the corresponding natural disaccharides, have been synthesized by chemoselective assembly of unprotected natural monosaccharides with methyl 6-deoxy-6-methoxyamino-alpha-D-glucopyranoside in an aqueous environment. The coupling reactions were found to be chemo- and stereoselective affording beta-(1-->6) disaccharide mimics when using Glc and GlcNAc; in the case of Gal, the beta-anomer was prevalent (beta:alpha=7:1). An iterative method for the synthesis of linear N(OMe) oligosaccharide analogues was demonstrated, based on the use of an unprotected monosaccharide building block in which an oxime functionality at C-6 is converted during the synthesis into the corresponding methoxyamino group. The conformational analysis of these compounds was carried out by using NMR spectroscopy, ab initio, molecular mechanics, and molecular dynamics methods. Optimized geometries and energies of fourteen conformers for each compound have been calculated at the B3LYP/6-31G* level. Predicted conformational equilibria were compared with the results based on NMR experiments and good agreement was found. It appears that N(OMe)-linked disaccharide analogues exhibit a slightly different conformational behavior to their parent natural disaccharides.     

Investigating the arenyl-diene double [3 + 2] photocycloaddition reaction

The double [3 + 2] photocycloaddition reaction involving arenyl-dienes has been used to assemble seven separate [5.5.5.5] fenestrane structures that include ether and aza variants. The primary photolysis step was a meta photocycloaddition reaction, while a secondary photocycloaddition step formed the fenestrane structure. Investigations involving the insertion of an additional methylene group into the basic arenyl-diene skeleton failed to afford the desired [5.5.5.6] fenestrane structure. The presence of an oxime moiety in the aromatic photosubstrate allowed the primary photolysis step to take place; however, an attempted secondary photocycloaddition reaction involving the oxime did not provide the intended polyheterocyclic fenestrane. An alternative strategy to form various "criss-cross" double meta photocycloadducts was investigated and led to the discovery of a Paterno-Büchi cycloaddition reaction between acetone and an angular meta photocycloadduct. Other novel thermally and photochemically mediated skeletal rearrangement reactions were also recorded.     

Redox-switchable surface for controlling peptide structure

A general surface chemistry strategy is described for the development of a new switchable material. The method modulates a surface-immobilized-molecules structure by using two orthogonal "click" reactions based on Huisgen cycloaddition and oxime chemistry, where the oxime linkage is redox active and switchable. We demonstrate this strategy by developing a noninvasive, biocompatible, in situ surface chemistry that is able to modulate the affinity of a cell-adhesive peptide to cell integrin receptors to study dynamic cell adhesion and cell migration in real time and as a new hide-and-reveal strategy for application in new types of smart biofouling biomaterials.     

Catalytic enantioselective dehydrogenative Si–O coupling of oxime ether-functionalized alcohols

Asymmetric silylation of alcohols is an unusual but effective approach to their kinetic resolution, and the Cu–H-catalyzed dehydrogenative Si–O coupling is particularly noteworthy as dihydrogen is formed as the sole by-product. Our laboratory had previously reported on diastereoselective (with silicon-stereogenic silanes) and enantioselective (with achiral silanes) Si–O couplings of azine donor-functionalized alcohols. The limitation, that is, the requirement of a nitrogen donor atom, prompted us to seek equally useful donor groups. Oxime ethers were identified as a suitable alternative, and we describe herein the preparation of a series of oxime ether-functionalized alcohols. To assess different substitution patterns in their kinetic resolution, these were tested in the reagent-controlled Si–O coupling using a silicon-stereogenic silane. The optimal substituents at the oxime carbon atom (dr=85:15 in the diastereoselective coupling) were then chosen for the related catalyst-controlled Si–O coupling but selectivity factors were only moderate.     

Synthesis of Chiral Tertiary Boronic Esters by Oxime‐Directed Catalytic Asymmetric Hydroboration

Chiral boronic esters are useful intermediates in asymmetric synthesis. We have previously shown that carbonyl‐directed catalytic asymmetric hydroboration (CAHB) is an efficient approach to the synthesis of functionalized primary and secondary chiral boronic esters. We now report that the oxime‐directed CAHB of alkyl‐substituted methylidene and trisubstituted alkene substrates by pinacolborane (pinBH) affords oxime‐containing chiral tertiary boronic esters with yields up to 87 % and enantiomeric ratios up to 96:4 e.r. The utility of the method is demonstrated by the formation of chiral diols and O‐substituted hydroxylamines, the generation of quaternary carbon stereocenters through carbon–carbon coupling reactions, and the preparation of chiral 3,4,4‐trisubstituted isoxazolines.     

Solvatochromic analysis of some N-nitroso oxime derivatives--Taft and Catalan approach

Some novel N-nitroso oxime derivatives were synthesized and characterized by (1)H, (13)C, (1)H-(1)H and (1)H-(13)C COSY NMR spectra. The spectra of all these N-nitroso oximes reveal the presence of two isomers labelled as E (-NOH group is anti to N-N=O moiety) and Z (-NOH group is syn to N-N=O moiety) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values it was found that both E (major) and Z (minor) isomers of N-nitroso oximes exist as an equilibrium mixture of CA and boat conformation (B(1)) and this was also supported by DFT calculation. The photophysical properties of these oxime derivatives were studied and the observed lower fluorescence quantum yield may be due to an increase in the non-radiative deactivation rate constant. This is attributed due to the presence of non-chair conformation of N-nitroso oxime derivatives.