Synthesis of New Phase-Transfer Catalysts and Their Application in Asymmetric Alkylation

Despite phase transfer catalysis (PTC) is an important and useful method in organic synthesis, asymmetric synthesis using chiral phase-transfer catalyst has not been well documented and limited number of chiral phase-transfer catalyst have been developed^[1].In 1989,O'Donnell published his pioneering work in the asymmetric synthesis of α-amino acids by enantioselective alkylation of a prochiral protected glycine derivative using chiral phase-transfer catalyst^[2]. Since then, several groups reported their improvements on enantioselectivity and applicability on this useful synthetic reaction^[3,4]. However, almost all of the chiral phase-transfer catalysts reported so far are the derivatives of cinchona^[5]. In this presentation, we wish to describe the design and synthesis of a new type of chiral phase-transfer catalyst based on the camphor and its application in asymmetric alkylation of tert-bntyl glycinate-benzophenone Schiff base.     

Planar Chiral Ligands:Design and Applications in Asymmetric Synthesis

Chiral ligands play an important role in asymmetric synthesis. Among them the ligands having planar chirality attract more interesting of organic chemists because of their unique structure. Recently, some new types of planar chiral ligands, including 1,1'-disubstituted ferrocene 1, bis(ferrocene carboxylic)diaminocyclohexane 2, and benzylic substituted cyclophane 3, are synthesized (Scheme 1)^[1]. These chiral ligands have been successfully used in asymmetric allylic alkylation, Heck reaction, etc. The role of planar chirality in asymmetric induction by using NMR and X-ray are also studied.     

A New Approach in Enantioselective Catalytic with Bis(oxazoline) Ligand-Metal Complexes

In recent years, the research of enantioselective-catalyzed reaction and the catalyst has got great development. Of the various chiral catalysts, great attention was given to the C₂-symmetry chiral bis(oxazoline)ligand-metal complexes for they could be easily synthesized and have shown good enantioselection in various catalytic processes, including cyclopropanation from dihalogenmethane^[1] and diazoacetate^[2].But no report has been found of enantioselective-catalyzed cyclopropanation from sulfonyl-carbanions and alkenes. The test of chiral cyclopropanation from sulfonylcarbanions with nickel bis(oxazolinyl)pyridine catalyst has been made in our lab, and alkylation of aldehydes with diethyl zinc in the presence of nickel or iron bis(oxazolinyl)pyridine was also tested (scheme 1). Some asymmetric effects were observed in these reactions.     

The Chlorination of O-Alkyl S-Alkyl(aryl) Thiophosphoric(-nic) Acid Derivatives with Phosphorus Oxychloride——A New Convenient Method for Synthesis of Chiral S-Alkyl(aryl) Thiophosphoro(-no) Chloridates

In our laboratory, the isomerization/chlorination of a variety of O,O-dialkyl phosphoro(-no)thionates 1 with phosphorus oxychloride have been systematically studied. It was found that when R' equals aryloxy^[1], alkylthio^[2], arylthio^[2], dialkylamino^[3], phenyl^[4], methyl^[5],and nitrogen heterocyclic group^[6] in 1,respectively, this reaction can proceed smoothly and gives the desired products ² and ³. Hence, it provides a general synthitic method for S-alkyl thiophosphoro(-no)chloridates, especially for the asymmetric ones.     

Improved Alkylation Technology with Solid Acid Material as Catalyst

Alkylation of isobutane with C3-C5 olefins has been practiced commercially since the 1940s. Indeed, alkylation which is mainly formed by multibranched paraffins,has a rather low vapor pressure, high octane numbers (RON and MON) and a low sensitive factor. In the past twelve years, about 20 alkylation plants using either HF or H₂SO₄ catalysts have been built in China^[1]. Concerns have been raised about the safety and environmental impact of the handing of the very large quantities of these liquid acids used in alkylation today and a great deal of time and money has been spent in the past 20 years in attempts to develop alkylation catalyst and process that are more environmentally friend than current industrial technology^[2]. To date,no process has been announced that seems to be of commercial interest, but two possible exceptions (Topöse process and UOP Alkylene process) are discussed in this paper. Many difficult technical challenges must be surmount in the next few years for a new solid catalyst alkylation process to be commercialized successfully.     

Enantioselective Hydroarylation of Olefins Using Palladium/Chiral Quinoline Oxazolines

Palladium-catalyzed arylation and alkenylation of olefins, known as the Heck reaction, is one of the most efficient catalytic methods for carbon-carbon bond formation in organic synthesis^[1]. During the last decade, asymmetric Heck reactions have attracted great attention, and a number of highly enantioselective chiral ligands have been developed to enhance chiral discrimination in these reactions^[2]. However, asymmetric Heck-type hydroarylations of olefins, addition of aryl halides or triflates to carbon-carbon double bonds, have not been well studied. In 1991, Brunner reported an asymmetric hydroarylation of norbornene and norbornadiene with aryl iodides using chiral bisphosphine ligands, and around 40% ee was achieved^[3]. Later on, Achiwa reached around 70% ee in the asymmetric hydroarylation of norbornene with phenyl triflate by using chiral P-N ligands^[4,5]. Herein, we wish to describe our investigations on chiral quinolinyl-oxazoline ligands that provide the first examples of efficient bisnitrogen ligands in Heck-type hydroarylation and the application of this reaction in the asymmetric synthesis of Epibatidine.     

Synthesis of Chiral 1,3-Bis(oxazolinyl)benzene

In recent years, C₂-symmetric chiral bis (oxazoline) ligand-metal complexes have received a great of attention through their use in various catalytic processes^[1-2]. Since the early 1990s, many impressive enantioselective carbon-carbon bond forming reactions, aziridination reactions, hydrosilylations, oxidations and reductions have been recorded using bis (oxazoline)-metal complexes with wide structural diversity^[3-4]. The latest review is intended to focus on the recent developments of bis(oxazoline) ligand-metal catalyzed asymmetric reactions and their applications in organic synthesis. Herein we intend to report the synthesis of a new type of chiral bis(oxazoline), 1,3-bis(oxazolinyl)benzene. Application of their asymmetric catalysis is under working.     

Chemical Reaction Engineering in Pharmaceutical Industry

In this presentation, examples will be given to illustrate the role played by catalysis and reaction engineering in the development of robust and high yielding chemical processes in the pharmaceutical industry. These examples include heterogeneously-catalyzed Suzuki cross coupling and Heck coupling reaction^[1], asymmetric hydrogenation of a-ketoesters over cinchona-modified Pt/alumina catalysts^[2], kinetic influences on enantioselectivty in asymmetric hydrogenation^[3,4], and applications of in-situ kinetic probes for kinetic and pathway analysis of catalytic reactions^[5].     

Asymmetric Borohydride Reduction of Acetophenone Catalyzed by Chiral Salen-Co(Ⅱ) Complex Using Sodium Borohydride

Development of efficient catalytic asymmetric reactions is the most challenging task in current synthetic chemistry; much effort has been devoted to create the chiral metal complexes of asymmetric catalysis. In the last two decades' many brand-new ligands had been synthesized and their combination with various metal ions has been applied in asymmetric catalysis. However, most ligands have only narrow applications and their use is limited to some reactions. Exceptionally, a few ligands and their metal complexes such as binaphthol, semicollin,and binap show wide applicability. Chiral salen ligand is one of such ligands and their metal complexes are now used as the catalysts for a variety of asymmetric reactions such as epoxidation^[1], aziridination^[2], cyclopropanation^[3], Diels-Alder reaction^[4], asymmetric transfer hydrogenation of aromatic ketones^[5] and kinetic resolution of racemic epoxides^[6] and so on.     

A new approach to all—cis triquinane synthesis and a new route to the C16—hexaquinane system

A new synthesis of all-cis triquinanes is presented. The examples bear a cis substituent on the fifth position of the central ring, and are thus all-cis pentasubstituted cyclopentanes. The stereo-controlled addition of organometallics of 7-ketonorbornenes is considered, as is “reductive solvolysis” of such adducts to the corresponding hydrocarbons. The preparation of trans-3,4-dimethoxycyclopentyl chloride is given, as is that of the corresponding organolithium. The use of quinoxaline derivatives in aldol-type reactions is considered, with examples. A new approach to the C₁₆-hexaquinane system is developed. The ring systems reported include: tricyclo-[8.2.1.0^2,9]tridecane, tricyclo[6.3.0.0^3,7]undecane, tetracyclo-[10.1.0.0^2,9.0^10,13]tridecane, pentacyclo[8.5.1.0^2,6.0^7,16.0^11,15]hexadene and hexacyclo(8.5.1.0^2,6.0^3,14.0^7,16.0^11,15]hexadecane.     

手性二环[3.3.0]辛-3-烯类化合物的合成

研究了5-(1-孟氧基)-3-溴-2(5H)-呋喃酮新手性源(1)与某些碳亲核试剂发生的串联不对称Michael加成/分子内亲核取代反应,反应中生成2个新的手性中心得到一般方法难以合成的光学纳二环[3.3.0]辛-3-烯类化合物.通过[α]、IR、UV、¹HNMR、¹³CNMR、MS、元素分析以及X射线四圆衍射等方法确定了手性二环[3.3.0]辛-3-稀类化合物化学结构和绝对构型.     

Diastereoselective synthesis of a resolved secondary arsine complex: asymmetric synthesis of (R-(−)589-ethylmethylphenylarsine

The reaction of [R-(R,R)]-(+)₅₈₉-[(η⁵-C₅H₅){1,2-C₆H₄(PMePh)₂}Fe(NCMe)]PF₆ with (±)-AsHMePh in boiling methanol yields crystalline [R-[(R)-(R,R)]-(+)_{589)-[(η⁵-C5H5){1,2-C6H4(PMePh)2}Fe(AsHMePH)}PF₆, optically pure, in ca. 90% yield, in a typical second-order asymmetric transformation. This complex contains the first resolved secondary arsine. Deprotonation of the secondary arsine complex with KOBu^t at −65°C gives the diastereomerically pure tertiary arsenido-iron complex [R-[(R),(R,R)]]-[((η⁵-C₅H₅){1,2-C₆H₄(PMePh)₂}FeAsMePh] · thf, from which optically pure [R-[(S),(R,R)]]-(+)₅₈₉-[(η⁵-C₅H₅){1,2-C₆H₄(PMePh)₂}Fe(AsEtMePh)PF₆ is obtained by reaction with iodoethane. Cyanide displaces (R)-(−)₅₈₉-ethylmethylphenylarsine from the iron complex, thereby effecting the asymmetric synthesis of a tertiary arsine, chiral at arsenic, from (±)-methylphenylarsine and an optically active transition metal auxiliary.     

Optically active transition metal compounds : LXXXI. Crystal structure of (+)546-[C5H5Mo(CO)2LL]PF (LL = 2-benzoylpyridine-(R)-1-phenylethylimine)

Racemic [C₅H₅Mo(CO)₂LL]PF₆, (2) with LL = 2-benzoylpyridine-1-phenylethylimine, undergoes spontaneous resolution upon crystallization from acetone/CH₂Cl₂/ethanol. The absolute configuration of the (+)₅₄₆-isomer was shown to be (R) at the Mo atom and (R) at the asymmetric carbon atom. Comparison of 2 with [C₅H₅Mo(CO)₂LL]PF₆ (1) (LL = 2-carbaldehydepyridine-1-phenylethylimine) reveals distinct changes caused by the differences resulting from the presence of the phenyl group in 2 and the change from the (RR)- to the (RS)-configuration.     

First Total Synthesis of (±)-Ponganone Ⅲ

In recent years, the synthesis and pharmacology of pyranoflavanoids have been extensively investigated due to their wide range of pharmacological properties^[1-3]. Ponganone Ⅲ^[4],a new natural pyranoflavanone isolated from the Pongamia pinnala, was identified as (2S)-3',4'-dimethoxy-6',6"-dimethylpyrano-[2",3":7,8]-flavanone (2) on the basis of spectra data. Its precursor,3,4-dimethoxy-2'-hydroxy-6",6"-dimethylchromeno-[2",3":4',3']-chalcone (1) is also a new natural product^[5] isolated from the roots of Lonchocarpus subglaucescent. Their total synthesis have not been reported. Herein, we wish to report the first total synthesis of compounds 1 and 2 in order to confirm the proposed structure and further more to evaluate its biological activities.     

Microwave-assisted solid-phase synthesis of pseudopeptides containing reduced amide bond

Procedures were developed for reducing the reaction time and improving the yield of reductive alkylation in solid phase pseudopeptide synthesis by utilizing microwave irradiation. We chose dipeptides containing the reduced amide bond ψ[CH₂NH] as a model system and optimized the microwave assisted reductive alkylation reaction in solid phase pseudopeptide synthesis using Fmoc chemistry. Under the optimized condition, the reductive alkylation reaction used for incorporating the reduced amide bond into the dipeptides was completed in only 8.5 min, whereas the normal reductive alkylation reaction required a total of 300 min. The purity and yield of the various dipeptides containing the reduced amide bond synthesized in this way are better than those achieved using the reductive alkylation method without microwave irradiation. We chose α helical peptides, which are known as a difficult sequence to synthesize, and incorporated the reduced amide bond by the microwave-assisted reductive alkylation reaction. We successfully synthesized pseudopeptides containing the reduced amide bond as a major product by using the novel microwave-assisted method, whereas the same products were obtained as a minor product when using the reductive alkylation method without microwave irradiation.     

Synthesis of Heterocyclic Compounds from 2-Phenyl-l,2,3-Triazole-4-Formylhydrize

Many compounds containing the 1,3,4-oxadiazole and/or1,2,3(or 4)-triazole and thiadiazole ring system are reported to possess antibacterial^[1], antiinflammatory^[2], anticonrulsant^[3],CNS stimulant^[4] and pesticidal^[5] activities and excellent anthelmintic properties^[6,7]. In view of this and the results of the combined different nuclei system in a molecular always enhancing the therapeutic activities,the present work deals with the synthesis of the combined different pharmacologically active nuclei system mentioned above in a molecular through some new method.     

The asymmetric hydrogenation of 2-phenethylacrylic acid as the key step for the enantioselective synthesis of Citralis Nitrile

A catalytic approach to the enantioselective synthesis of Citralis Nitrile^® (3-methyl-5-phenyl-pentanenitrile, a citrus-type odorant) is described. The key step is the transition-metal catalyzed asymmetric hydrogenation of 2-phenethylacrylic acid. Among the different catalysts tested, the most efficient appears to be the one formed by combining in situ [Ru(benzene)Cl₂]₂ with the atropisomeric diphosphine MeOBIPHEP and triethylamine, which allows us to obtain enantiomeric excesses up to 98% under mild conditions. Very good results (ees >80%) have also been obtained using iridium cationic complexes in combination with a phosphinooxazoline ligand.     

[OHO] and [NHO] hydrogen bonds in the 2:1 adduct of pentachlorophenol with 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene [(PCP)2·MTBD]

The results of X-ray diffraction and IR spectroscopic studies for 2:1 pentachlorophenol-7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene [(PCP)₂·MTBD] adduct are reported. The geometry of MTBD cations reflects the equal distribution of the positive charge among three nitrogen atoms. Short asymmetric [OHO]⁻ hydrogen bonds with OO distance of 2.508(2) Å and NH⁺O⁻ hydrogen bonds with NO distance of 2.802(2) Å are formed showing broad IR absorption with two maxima located at 1200 and 2400 cm⁻¹. The second maximum is interpreted as due to the 0→2 transition between split levels in an asymmetric double minimum potential. One of the oxygen atoms forms an additional OH–N⁺ hydrogen bonding with an MTBD cation. The situation is somewhat different in acetonitrile solution whose IR spectrum shows continuous absorption extended over whole the IR region. In acetonitrile, dissociation to free OHO⁻ and ⁺NH ions takes place and the OHO⁻ bridges become dynamically symmetric. The broadening is interpreted in terms of a stochastic distribution of the geometry and the Zundel polarizability theory.     

Synthesis and Spectroscopic Characterization of Transition Metal Complexes of Maleionitriledithiolate and 5-Nitro-Phenanthroline

The dithiolenes and diimines and their metal complexes are an important research field in the organic and coordination chemistry^[1-3]. Transition metal complexes of a dithiolene and a diimine have excellent electronic functions due to the intramolecular charge transfer from a ligand to other ligand (LL'CT)^[3], in which are interested authors^[4,5]. Recently we have been studied in detail the synthesis and properties of the title complexes M(mnt)(5-NO₂-phen), M=Mn^Ⅱ, Fe^Ⅱ, Co^Ⅱ, Ni^Ⅱ, Cu^Ⅱ, Zn^Ⅱ. The structure and properties of the M(mnt)(5-NO₂-phen) were characterized by the elemental analysis, TDA-TG, MASS, IR, UV-Vis, fluorescence and EPR spectra,molar conductivity and magnetic susceptibility. In the present abstract we report only the synthesis and spectroscopic characterization of these complexes.     

Hydrothermal Synthesis,Structure and Properties of a New Phosphomolybdate Based on Novel [Co(H2O)4(HP2Mo5O23)]8- Anions and [H8(H2O)16]8+ Water Cluster Cations

A pure inorganic [P₂Mo₅O₂₃]^6- based cobalt complex [H₈(H₂O)₁₆][Co(H₂O)₄(HP₂Mo₅O₂₃)₂] with a sandglass-like shape was synthesized and characterized by means of single-crystal X-ray diffraction, powder X-ray diffraction(PXRD), infrared spectroscopy(IR), thermogravimetry/differential scanning calorimetry(TG/DSC), ultraviolet-visible spectroscopy(UV-Vis) and cyclic voltammogram(CV). Single-crystal X-ray diffraction analysis reveals that the asymmetric unit of compound 1 consists of a half cobalt ion, one [P₂Mo₅O₂₃]^6- anion, two coordinated water molecules and eight lattice water molecules. It is especially intriguing to note that two [P₂Mo₅O₂₃]^6- clusters are symmetrical about the Co ion, like a sandglass. And a chair-like water cluster with an unprecedented centrosymmetric [H₈(H₂O)₁₆]⁸⁺ can be observed in compound 1. Additionally, the electrochemical and catalytic properties of compound 1 were also investigated.