手性膦氮配体的合成及其钯配合物催化的不对称烯丙基烷基化反应

以价廉的天然产物辛可宁和奎宁为原料,在温和的条件下方便地合成了两个手性膦氮配体.考察了它们与过渡金属钯配合物在不对称烯丙基烷基化反应中的催化活性和不对称诱导作用.在1,3-二苯基-2-烯丙基-1-醇的乙酸酯与丙二酸二甲酯的反应中,两个配体均表现出中等的手性诱导活性(最高为73.5%e.e.).     

Contrast performance in catalytic ability—new cinchona phase transfer catalysts for asymmetric synthesis of α-amino acids

Two new cinchona phase transfer catalysts are prepared from dihydrocinchonidine using 13-picenylmethyl bromide and 1-pyrenylmethyl bromide, respectively. A total contrast in catalytic efficiency is observed during the asymmetric alkylation of glycinate esters; with one catalyst, the reaction is either incomplete or the enantioselectivity is very poor (15% ee) while the other catalyst afforded high selectivity up to 94% ee.     

Cinchona alkaloid phase-transfer catalysts revisited: influence of substituted aryl groups on the enantioselectivity of glycine ester enolate alkylation

We report herein, the influence of substituted aryl groups in quaternary ammonium salts derived from cinchona alkaloids on enantioselectivity of the alkylation of glycine ester enolates.     

Organocatalyzed Asymmetric Friedel‐Crafts Reactions: An Update

The Friedel‐Crafts alkylation (F‐CA) reaction is a special kind of carbon?carbon bond formations, which is frequently being used for the formation of such bond in some aromatic rings in organic synthesis. Its asymmetric variant gives enantiorich products. Commonly, an in situ organocatalyzed asymmetric Friedel‐Crafts alkylation (AF‐CA) proceeds via generation of an enamine as an intermediate. The organocatalyzed‐AF‐CA was discovered and established in the mid‐1980s and reviewed comprehensively in 2010. In this report, we are trying to update the applications of novel organocatalysts in the AF‐CA as a versatile synthetic strategy, which is frequently used in the effective asymmetric synthesis of complex molecules, pharmaceutically important compounds and most importantly in the total synthesis of biologically active natural products.     

Chiral stationary phases based on cinchona alkaloids for the HPLC resolution of racemates

Summary The employment of three chiral stationary phases (CSPs) obtained by derivatizing γ-mercaptopropyl-silanized silica gel with quinine, quinidine and N-methyl-quinium iodide, for the separation of organic racemates, is presented. They are quite useful in the resolution of alkylarylcarbinols, binaphthyl derivatives, amides and other substances of pharmaceutical interest.     

聚偏二氯乙烯负载金鸡纳碱催化剂的合成及其对不对称Michael反应的催化性能

将天然的金鸡纳碱——辛可宁与聚偏二氯乙烯进行接枝反应,制备了聚偏二氯乙烯负载辛可宁的催化剂.将制备的催化剂用于催化不对称Michael反应,并探索了溶剂、催化剂用量、温度、底物等不同条件对其催化性能的影响.结果表明,该催化剂在甲苯中有很高的催化活性和较好的立体选择性,Michael反应中部分产率达到80%以上,e.e值达到72%,且该催化剂具有一定的重复使用性能.     

金鸡纳生物碱的金属络合物用于苯乙酮的不对称催化还原

金鸡纳生物碱的金属络合物用于苯乙酮的不对称催化还原刘湘（无锡轻工大学化工系无锡２１４０３６）李纪国张正（南京大学化学系南京２１００９３）关键词金鸡纳生物碱手性络合物不对称还原苯乙酮分类号Ｏ６４３．３２近１０多年来，前手性酮的不对称还原反应作为制备光学...     

Synthesis of new axially dissymmetric ligand with large perfluoroalkyl groups

A new axially dissymmetric ligand with large perfluoroalkyl groups, 2,2′-bis(1-hydroxy-1H-perfluorooctyl)biphenyl (1c), which could not be obtained by the coupling reaction of the aryl bromide using copper powder, was synthesized successfully by the coupling reaction using Ni(COD)₂. This ligand showed much higher asymmetric induction in the reaction of diethylzinc with benzaldehyde than the trifluoromethyl (1a) or pentafluoroethyl (1b) analogues.     

New approaches to enantioselective fluorination: Cinchona alkaloids combinations and chiral ligands/metal complexes

The selective construction of carbon-fluorine bonds is of great interest to medicinal chemists because the replacement of a hydrogen or an oxygen atom with a fluorine atom in biologically active molecules can confer the molecules with improved physicochemical properties and biological activities. Since the first discovery of enantioselective fluorination using N-fluorocamphorsultam, our synthetic interest had been focused on the development of chiral N-fluorosulfonamide derivatives capable of enantioselective fluorination. However, these initial efforts revealed several limitations in both chemical yields and enantioselectivities of the fluorinated products. We present here the background of our personal story of the enantioselective fluorination reaction and some successful applications of the methods to the design and synthesis of biologically active products. Two novel approaches using cinchona alkaloid/Selectfluor^® combinations and chiral ligands/metal complexes have been pursued, respectively. In addition, the recent advances in this area by other groups are also described briefly.     

Organocatalytic asymmetric synthesis of quinine and quinidine

Quinine and quinidine were synthesized by a highly enantio- and stereoselective approach starting from a proline-catalyzed asymmetric cycloaldolization of benzyl bis(2-formylethyl)carbamate which gave a 70:30 mixture of (3R,4R)-N-Cbz-3-hydroxymethyl-4-hydroxypiperidine (96% ee) and its 4S-epimer (92% ee) in 94% yield after in situ NaBH₄ reduction.     

A convenient microwave-assisted synthesis of cinchona alkaloid-derived ligands

An efficient synthesis of cinchona alkaloid-derived ligands based on solvent-free microwave-assisted reaction was described. The coupling of 1,4-dichlorophthalazine or 3,6-dichloropyridazine with quinine, cinchonine or cinchonidine provide bis-or monocinchona alkaloid-derived ligands in moderate to good yields （52-89%） within 15 min under optimum microwave conditions.     

Resin-OsO4-金鸡纳生物碱:一种在(E)-二苯乙烯不对称双羟化反应中可循环使用的高效催化剂

用改进的方法把季铵盐共价结合在Merrifield树脂上作为离子交换剂与K2O5O4作用制成Resin—OsO4催化剂，在NaH存在下，以DMF作溶剂，在70℃下奎宁或奎尼丁与1，4-二氯二氮杂萘反应高产率地生成(QN)2PHAL或(QD)2PHAL，Resin—OsO4通过简单过滤可定量回收，回收的催化剂重复使用五次，其活性不变，Resin—OsO4-(QN)2PHAL或(QD)2PHAL催化体系在(E)-二苯乙烯的不对称双羟化反应中的化学产率为84～91％，立体选择性为96-99％ee。     

Improved organocatalytic electrophilic α-cyanation of β-keto amides with 1-cyanato-4-nitrobenzene

By using a readily accessible, new and safe cyano-transfer reagent, 1-cyanato-4-nitrobenzene, the enantioselectivity of the direct electrophilic α-cyanation of 1-indanone-derived β-keto amides was greatly improved as a result of an enhanced double-hydrogen bonding. Thus, in the presence of cinchonine as the bifunctional organocatalyst, a series of α-cyano β-keto amides were produced in excellent yields (73–97%) and good to high enantioselectivities (75–91% ee) under mild reaction conditions.     

Advanced dress-up chiral columns: New removable chiral stationary phases for enantioseparation of chiral carboxylic acids

This paper describes the preparation of new dress-up columns featuring reproducibly removable and replaceable chiral stationary phases. After synthesizing perfluroalkylated quinine and quinidine derivatives as chiral stationary phase compounds (F-CSPs), we adsorbed them reversibly onto a fluorous LC column through pumping of their solutions. Using this dress-up chiral column and fluorophobic elution of aqueous ammonium formate/MeOH mixtures, we could enantioseparate four racemic N-acetyl amino acids, dichlorprop, and sixteen fluorescent 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)-derivatized amino acids. Dressing and undressing of the coated F-CSPs could be controlled by varying the fluorophilicity and fluorophobicity of the eluent. The relative standard deviations of the retention times, the retention factors, the number of theoretical plates, the enantioseparation factors, and the resolutions of each of four preparations of such dress-up columns were all less than or equal to 5.26% (from 20 repeated analyses); the reproducibilities from four different preparations were all less than or equal to 10.6%. These columns also facilitated highly sensitive and selective analyses of AQC-amino acids when detected using LC–MS/MS.     

Improvement of chiral stationary phases based on cinchona alkaloids bonded to crown ethers by chiral modification

To improve the chiral recognition capability of a cinchona alkaloid crown ether chiral stationary phase, the crown ether moiety was modified by the chiral group of (1S, 2S)‐2‐aminocyclohexyl phenylcarbamate. Both quinine and quinidine‐based stationary phases were evaluated by chiral acids, chiral primary amines and amino acids. The quinine/quinidine and crown ether provided ion‐exchange sites and complex interaction site for carboxyl group and primary amine group in amino acids, respectively, which were necessary for the chiral discrimination of amino acid enantiomers. The introduction of the chiral group greatly improved the chiral recognition for chiral primary amines. The structure of crown ether moiety was proved to play a dominant role in the chiral recognitions for chiral primary amines and amino acids.     

聚合物负载金鸡纳碱类手性相转移催化剂制备手性α-氨基酸研究进展

近年来,基于聚合物载体易分离、可重用等优点,聚合物负载催化剂得到了迅速的发展。本文就聚合物负载金鸡纳碱类催化剂在制备手性α-氨基酸上的应用进行了讨论,并对本领域未来的发展作一展望。     

Catalytic enantioselective conjugate additions with α,β-unsaturated sulfones

We describe the development of a highly efficient catalytic asymmetric conjugate addition to α,β-unsaturated sulfones. Utilizing practical bifunctional organic catalysts and involving air- and moisture-tolerant conditions, conjugate additions of a wide range of Michael donors to α,β-unsaturated sulfones proceeded in excellent enantioselectivity/diastereoselectivity and high yield. This efficient and operationally simple new catalytic asymmetric reaction should provide a versatile approach for the asymmetric synthesis of chiral sulfones bearing all-carbon quaternary stereocenters.     

Magnetic nanoparticles supported cinchona alkaloids for asymmetric Michael addition reaction of 1,3-dicarbonyls and maleimides

New magnetically recoverable cinchona alkaloid organocatalysts have been successfully developed for the asymmetric Michael addition reaction of 1,3-dicarbonyls and maleimides.     

Novel cinchona alkaloid O9-hydrazide derivatives as chiral anion-exchange-type selectors: Synthesis and chromatographic evaluation

Summary Six new quinine (QN) O₉-hydrazide derivatives with different substituents have been synthesized and immobilized on porous silica gel for HPLC. The chiral resolving power of these anion-exchange-type chiral stationary phases (CSPs) has been investigated and compared with that of four carbamate QN derivatives with analogous substitution. The unsubstituted QN-hydrazide derivative was usually the best chiral selector of the hydrazide series. Among the substituted hydrazide derivatives the introduction of a tritylcarbonyl or atert-butylcarbonyl group at the β position of the hydrazide function improved chiral recognition by the resulting CSPs. Although carbamate functionality seemed to favour the resolution of the enantiomers of many of the racemic compounds tested, the hydrazide series resulted in better separations of the enantiomers of the DNP derivatives of amino acids and of certain acidic drugs of therapeutic interest, such as the profens. The selectivity factors of these types of compounds on these QN-hydrazide derivatives are the best yet obtained on QN-derived chiral selectors.     

Novel Pirkle-type quinine 3,5-dinitrophenylcarbamate chiral stationary phase implementing click chemistry

A new Pirkle-anion exchange hybrid-type chiral stationary phase (CSP-1) has been synthesized by immobilizing 10,11-didehydroquinine 3,5-dinitrophenylcarbamate onto 3-azidopropyl silica gel using click chemistry (1,3-dipolar Huisgen cycloaddition). This chiral selector and CSP contain a strong π-accepting 3,5-dinitrophenyl residue besides the π-basic quinoline group and an ionizable tertiary amino group. In concert with ion pairing it offers π-donor-π-acceptor interactions resulting in an enhancement of the selectivity toward specific π-donating analytes such as aryloxypropionic acids and profens. A representative set of these analytes has been investigated under various chromatographic conditions (polar-organic, reversed- and normal-phase) leading to base-line enantioseparations with selectivity (α) values up to 1.8. Control experiments with related quinine tert-butylcarbamate phase grafted onto the surface either by thioether (Chiralpak QN-AX) or 1,2,3-triazole linker revealed the impact of the additional aromatic moiety in the chiral selector motif.