氟两相催化反应的进展

对氟两相催化反应作一介绍。氟两相体系是一种新的相分离和固定化技术,全氟溶剂与大多数有机溶剂不互溶,而在催化剂分子中引入适当数量、大小和形状的氟尾能使之优先溶于全氟溶剂,在氟两相体系中进行催化反应就使催化剂的回收再用产物的纯化都变得极为方便。     

Fluorous mixture synthesis of two libraries with hydantoin-, and benzodiazepinedione-fused heterocyclic scaffolds

Diversity-oriented synthesis (DOS) and fluorous mixture synthesis (FMS) are two aspects of combinatorial chemistry. DOS generates library scaffolds with skeletal, substitution, and stereochemistry variations, whereas FMS is a highly efficient tool for library production. The combination of these two aspects in solution-phase synthesis of two novel heterocyclic compound libraries is presented in this paper. Mixtures of different fluorous amino acids undergo [3 + 2] cycloadditions followed by postcondensation reactions. The mixtures are then demixed by fluorous HPLC. Fluorous tags are removed by cyclization to afford hydantoin- and benzodiazepinedione-fused heterocyclic compounds as individual, pure, and structurally defined molecules. The application of MS-directed HPLC purification and parallel four-channel LC/MS analysis further increases the efficiency of FMS.     

Fluorous dimethyl sulfide: a convenient,odorless, recyclable borane carrier

Borane gas and 2-(perfluorooctyl)ethyl methyl sulfide form a solid comprised of an approximately 1:1 mixture (fluorous BMS) of sulfide and the corresponding sulfide-borane. Fluorous BMS permits hydroboration of alkenes in a dichloromethane/perfluorinated hydrocarbon mixture with subsequent recycling of the fluorous sulfide by fluorous extraction. The use of fluorous BMS in the asymmetric reduction of ketones catalyzed by a chiral oxaborolidine catalyst, and in the reduction of other functional groups, is also reported. [reaction: see text]     

Highly efficient asymmetric aldol reaction in brine using a fluorous sulfonamide organocatalyst

A fluorous organocatalyst promotes direct asymmetric aldol reactions of aromatic aldehydes with ketones in brine to afford the corresponding anti-aldol products in high yield with up to 96% ee. Fluorous organocatalyst can be readily recovered by solid phase extraction using fluorous silica gel and reused without purification.     

Synthesis of monosaccharide units using fluorous method

The efficient synthesis of monosaccharide units, glycosyl acceptor, and donor, by using the fluorous tag method was achieved. Fluorous tag 5 was stable in each reaction condition to the preparation of various monosaccharide units. Each fluorous synthetic intermediate could be obtained in a straightforward manner by a simple fluorous-organic solvent partition.     

An alternative and facile purification procedure of amidation and esterification reactions using a medium fluorous Mukaiyama reagent

A convenient methodology for the separation of a fluorous by-product using fluorous chemistry is described. A Mukaiyama coupling reagent bearing a medium fluorous tag, between 40% and 60% fluorine by weight, can be effectively separated from non-fluorous components by increasing the water content of the crude reaction mixture and subsequent filtration. Additional fluorous solid phase extraction is not necessary.     

Direct asymmetric aldol reactions in brine with recyclable fluorous β-aminosulfonamide organocatalysts

Fluorous organocatalyst 3 promotes direct asymmetric aldol reactions of ketones with aldehydes in brine, leading to the synthesis of the corresponding anti-aldol products in high yields with up to 96% ee. Fluorous organocatalyst 3 is easily recovered by solid-phase extraction using fluorous silica gel and can be reused up to five times without purification.     

Fluorous glycol derivatives: novel carbonyl protective groups

Fluorous glycol derivatives 5 were prepared and evaluated as reagents for the protection of carbonyl groups for use in fluorous synthesis. The acetals formed from fluorous diol 5b (Rf=n-C₈F₁₇) with carbonyl compounds can be separated and purified by simple fluorous-organic extraction.     

Highly enantioselective aldol reactions catalyzed by a recyclable fluorous (S) pyrrolidine sulfonamide on water

Fluorous (S) pyrrolidine sulfonamide serves as an efficient promoter for highly enantioselective aldol reactions of ketones and aldehydes with aromatic aldehydes on water. A notable feature of the organocatalyst is that it can be recovered from the reaction mixtures by simple fluorous solid-phase extraction and subsequently reused (up to seven cycles) without a significant loss of catalytic activity and stereoselectivity.     

Fluorous reverse-phase silica gel-supported Lewis acids as recyclable catalysts in water

Fluorous reverse-phase silica gel (FRPSG)-supported Lewis acids which have fluorous ligands acted as effective catalysts of Baeyer-Villiger and Diels-Alder reactions in water. Direct esterification of carboxylic acid with alcohol in organic media was also catalyzed. The FRPSG-supported Lewis acids could be recycled by simple filtration after the reaction.     

Cobalt(II) octanoate and cobalt(II) perfluorooctanoate catalyzed atom transfer radical polymerization of styrene in toluene and fluorous media—A versatile route to catalyst recycling and oligomer formation

Cobalt(II) perfluorooctanoate‐catalyzed atom transfer radical polymerization (ATRP) and reverse ATRP were developed to prepare oligostyrenes (M_n < 2500) with low polydispersities M_w/M_n < 1.5. Fluorous biphase catalysis was applied for effective recycling of catalyst and fluorous solvent. The homogeneous polymerization reaction was performed at 90 °C in toluene/cyclohexane/perfluorodecalin mixture (1:1:1) and fluorine‐free solvents. Temperature‐induced phase separation of this fluorous solvent mixture occurred at room temperature and proved to be the key for the very effective separation of the cobalt(II) perfluorooctanoate from the oligostyrene and fluorine‐free solvents. Both the fluorine‐tagged cobalt catalysts and the fluorous media were recycled and reused up to three times without encountering catalyst activity losses. The roles of cobalt catalysts, fluorous media, and monomer/initiator ratio were examined with respect to the polymerization kinetics. Fluorine‐containing and fluorine‐free cobalt(II) octanoate catalyzed controlled styrene oligomerization according to the ATRP mechanism. The molar mass control range was limited in fluorous biphase catalysis most likely because of precipitation of high molar mass polystyrenes in the fluorous reaction medium. To the best of our knowledge, this is the first time temperature‐induced phase separation of fluorous and fluorine‐free solvents has been successfully applied to polymerization processing. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3804–3813, 2005     

Fluorous phase transfer catalysts: From onium salts to crown ethers

Fluorous quaternary ammonium and phosphonium salts, as well as fluorous macrocyclic ligands, such as crown and aza-crown ethers, have been gradually emerging as viable alternatives to classical phase transfer catalysts. The major results thus far obtained in this burgeoning field will be the focus of this review.     

Esterification of sterically hindered acids and alcohols in fluorous media

Sterically hindered esterification reactions are best performed in specific fluorous media in the presence of catalytic amounts of diphenylammonium triflate. Fluorous media, in addition to their positive effect on yields, have inherent favorable properties respecting environment and permitting simple work-up. Highly congested reagents, however, react only marginally.     

Synthesis and reactions of fluorous carbobenzyloxy (FCbz) derivatives of alpha-amino acids

Fluorous carbobenzyloxy ((F)Cbz) reagents RfCH(2)CH(2)C(6)H(4)CH(2)OC(O)OSu (where Su is succinimidoyl and Rf is C(6)F(13) and C(8)F(17)) have been used to make (F)Cbz derivatives of 18 of the 20 natural amino acids. The potential utility of this new family of reagents in both standard fluorous synthesis with spe separation and fluorous quasiracemic synthesis is illustrated with representative reactions of the (F)Cbz-Phe derivatives.     

Simultaneous preparation of four truncated analogues of discodermolide by fluorous mixture synthesis

[structure: see text] Four truncated analogues of the natural product discodermolide were synthesized in a single synthetic sequence. Precursors bearing four different groups at C22, each with a unique fluorous p-methoxybenzyl substituent on the C17 hydroxy group, were mixed and taken through an nine-step sequence. Demixing by fluorous chromatography followed by deprotection and purification provided the individual analogues in 3-7% overall yields and with a savings of 24 synthetic steps. Fluorous mixture synthesis is recommended as a new technique to make multiple natural product analogues in a single multistep synthesis.     

氟固相萃取辅助的生物分子质谱分析新方法

氟固相萃取(Fluorous solid-phase extraction,FSPE)是一种基于全氟化合物之间氟-氟相互作用的固相萃取技术,通过在目标分子上进行氟标签衍生,利用高氟化固相吸附剂实现特异性的分离纯化.这一技术在有机合成、催化,以及化学和生物分离分析等诸多领域应用广泛.近年来,由于氟固相萃取和生物质谱技术之间良好的兼容性,两者联用结合的分析方法受到了研究者的广泛关注.本文在简要介绍氟固相萃取技术原理的基础之上,重点综述了其在生物质谱分析领域中的应用,并对其发展前景进行了展望.     

Fluorous Tagged Peptides for Intracellular Delivery and Biomedical Imaging

Fluorous tagged peptides have shown promising features for biomedical applications such as drug delivery and multimodal imaging. The bioconjugation of fluoroalkyl ligands onto cargo peptides greatly enhances their proteolytic stability and membrane penetration via a proposed “fluorine effect”. The tagged peptides also efficiently deliver other biomolecules such as DNA and siRNA into cells via a co-assembly strategy. The fluoroalkyl chains on peptides with antifouling properties enable efficient gene delivery in the presence of serum proteins. Besides intracellular biomolecule delivery, the amphiphilic peptides can be used to stabilized perfluorocarbon-filled microbubbles for ultrasound imaging. The fluorine nucleus on fluoroalkyls provides intrinsic probes for background-free magnetic resonance imaging. Labeling of fluorous tags with radionuclide ¹⁸F also allows tracing the biodistribution of peptides via positron emission tomography imaging. This mini-review will discuss properties and mechanism of the fluorous tagged peptides in these applications.     

Cover Picture: Journal of the Chinese Chemical Society 5/2011

Perflurooctanesulfonates (fluorous sulfonates) have been developed as triflates and nonaflates alternatives for Pd‐catalyzed coupling reactions to form C‐C, C‐N, C‐S, C‐H, and C‐CN bonds. They also serve as a phase‐tag for fluorous solid‐phase extraction (F‐SPE) to facilitate the product purification. The utility of fluorous sulfonate linkers in the synthesis of biologically interested library scaffolds is summarized in this short review article. This article entitled “Convertible Fluorous Sulfonate Linker for the Synthesis of Diverse Library Scaffolds“ was contributed by Prof. Wei Zhang who was invited as a Visiting Lecturer of the Chemistry Research Promotion Center, Taiwan, R.O.C. (November 23 ～ November 29, 2010). For full text, please see pp. 575～582 in this issue.     

Syntheses and phase-transfer properties of dendritic nanocarriers that contain perfluorinated shell structures

Perfect dendrimers that contain perfluorinated shells have recently attracted attention because they have been shown to encapsulate polar molecules in supercritical CO(2) and catalytically active metal nanoparticles in perfluorinated solvents. Moreover, they can then be easily separated after reaction from the biphasic organic/fluorous system. In this paper several dendritic architectures that contain perfluorinated shells were derived by covalent modification of glycerol dendrimers ([G0.5]-[G3.5]), hyperbranched polyglycerol, and polyethyleneimine. These core-shell architectures show interesting physicochemical properties. For example, they are soluble in fluorinated solvents, they are able to transport different guest molecules, and they display thermomorphic behavior. The transport capacity of these molecular nanocarriers increases significantly when amino groups are present in the core. Certain functionalized polyethyleneimines that contain perfluorinated shells show high transport capacities (up to 3 dye molecules per nanocarrier) in perfluorinated solvents. Moreover, these perfluoro-functionalized dendritic polyethyleneimines can act as templates that stabilize nanoparticles; for example, encapsulation and subsequent chemical reduction of Ag(I) ions. Silver nanoparticles with a narrow size distribution (3.9+/-1 nm) have been prepared and characterized by transmission electron microscopy. Furthermore, it has been demonstrated that the encapsulated guest molecules remain accessible to small molecules after transport into the fluorous phase. Therefore, dendritic nanocarriers that contain perfluorinated shells are currently being investigated as polar environments in nonpolar reaction media such as fluorous phases and supercritical CO(2), in particular, for application in homogenous catalysis.