共老我白发On the other hand,potassium tri?uoro(organo)borates are promising alternatives to the use of the known organo-boronic acids,exhibiting higher reactivity and exceptional stability.13Germanium reagents have been recently used in cross-coupling reactions,14exhibiting intermediate reactivity between that of organotin15and organosilicon compounds,16avoiding the toxicity of certain organotin reagents and being more reactive than silicon.
In recent years,an increasing interest has been shown in the possibility of anchoring the substrates to a solid support, facilitating their use in automated parallel synthesis in a combinatorial manner.The main advantages of these solid-phase transformations are the avoidance of tedious workup procedures,the quasi high-dilution effect(high yields by employing an excess of reagent),amenability to automatisation and the non-interference of various functionalities in the building blocks on a solid support.17 1.2.Catalytic systems
The form in which the catalyst is present in the reaction media is fundamental to drive the reaction in an effective manner.A wide range of possibilities can be explored, depending on the different combinations of the components of the catalytic system,for example,the catalyst can be present as nanoparticles,ligandless,unsupported, supported,etc.
Transition-metal nanoparticles have attracted a great deal of attention during the last10years as catalytic systems with great potential,due to the large surface area of the particles. It has been suggested that metal colloids are very ef?cient catalysts because of the ratio of atoms remaining at the surface.In fact,these catalysts are microhetereogenous systems bearing nanoparticles.The application of transition-metal nanoparticles to the formation of carbon–carbon bonds is still,however,in its infancy.18
Recent interest in the development of environmentally benign syntheses and in minimising the cost of the precious metal catalysts has led to the development of polymer-bound metal catalysts for the carbon–carbon coupling reaction that maintain high activity and selectivity.The supported complexes can be recovered from the reaction mixtures,they do not contaminate the product solution and they can be recycled and used for the rapid production of compound libraries.Often,however,there is metal leaching during the course of the reaction and they are often not recyclable.As a result,many efforts have been focussed on the development of new ligand-derivatised polymeric supports for the attachment of metals and on the design of new methods to increase both the activity and the selectivity.19In particular,dendrimers as soluble supports
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have recently attracted much attention in homogeneous catalysis,since these well-de?ned macromolecular struc-tures enable the construction of precisely controlled catalyst structures.Moreover,the globular shapes of the higher generations of dendrimers are particularly suited for membrane?ltration.20
Alternatively,the immobilisation of catalysts can be effected on inorganic matrices,having several important potential advantages such as:(a)the remarkable ease of handling and use,(b)reduced product contamination by having the catalyst fully bound to the solid support,(c) relatively safe handling owing to full chemisorption of the possible toxic chemicals,(d)reduced environmental impact upon work-up,(e)good thermal and chemical stabilities,(f) good dispersion of the active catalytic sites,with a signi?cant improvement in the reactivity and(g)improve-ment in the reaction selectivity,due to the constraints of the pores and the characteristics of surface adsorption.21In general,they offer superior chemical,mechanical and thermal stability compared with the use of organic polymeric supports.
1.3.Solvents
Since most of the chemical reactions are performed in the solution phase,the solvent plays a crucial role to implement any transformation,either on a laboratory or industrial scale.22For a given process,the solvent will always condition the work-up,recycling and disposal techniques employed for the appropriate treatment of the reaction mixture and every one of its components.Within the context of green and sustainable chemistry,the endeavour to replace volatile organic solvents in organometallic catalysis for alternative more practical and environmentally friendly solvents must be highlighted.23Interesting approaches include catalysis based on aqueous systems,ionic liquids, supercritical media,or?uorinated phases. Nonetheless,it is known that many reactions proceed ef?ciently in the solid state.In fact,in some cases,solid-state organic reactions occur more ef?ciently and selectively than their solution counterparts,since molecules in a crystal are arranged tightly and regularly.In addition,the solvent-free reactions make syntheses simpler for process and handling,saving energy and preventing solvent waste, hazards and toxicity.24
1.3.1.Supercritical?uids(SCFs).Supercritical?uids are well established as useful solvents for extraction,chroma-tography and a few specialised reactions.25In spite of the fact that they have been used for large-scale industrial production for most of the20th century,only during the last decade have their special properties made them attractive solvents for modern synthetic chemistry.25d,26The proper-ties of SCFs are different from those of ordinary liquids and gases and are tunable simply by changing the pressure and temperature.They form a single-phase mixture with gaseous reactants,sometimes avoiding a rate-limiting mass-transfer step and therefore,enhance the reaction rates. scCO2is readily accessible,with a T c of318C and a P c of 73atm and is abundant,inexpensive,non-?ammable,non-toxic and environmentally benign.Non-polar organic solvents have a high solubility in scCO2and the solubility of polar,ionic,or polymeric compounds can be increased by the addition of a polar additive or an appropriate surfactant. In addition,scCO2facilitates the separation of reactants, catalysts and products,being a substitute for environ-mentally less acceptable solvents.27
Water near its critical point(T c3748C and P c218atm)also offers environmental advantages and possesses properties very different from those of ambient liquid water.The dielectric constant is much lower and the formation of hydrogen bonds is less favoured.As a result,high temperature water behaves like many organic solvents in allowing a high solubility of organic compounds in near-critical water and complete miscibility in supercritical water.28
1.3.
2.Ionic liquids(ILs).Ionic liquids can be generally de?ned as liquid electrolytes composed entirely of ions.By applying the melting point criterion,they can be considered as salts with a melting point below the boiling point of water.They are,however,better described as liquid compounds that display ionic-covalent structures.Most ILs have an organic cation and an inorganic polyatomic anion.The most commonly used cations in room temperature ionic liquids are alkylammonium,alkylphos-phonium,29N,N0-dialkylimidazolium and N-alkylpyri-dinium cations and the most commonly utilised alkyl chains are methyl,ethyl,butyl,hexyl,octyl and decyl. Although the pyridinium-and imidazolium-based chloro-aluminate ionic liquids share the disadvantage of being reactive with water,the more recent tetra?uoroborate, hexa?uorophosphate,nitrate,sulfate and acetate salts are stable towards hydrolysis.Their physical and chemical properties can be?nely tuned for a range of applications by varying the cations or anions.30
This fascinating group of chemicals exhibits a great potential to improve development in organic chemistry, due to their particular properties:a very wide liquid range, relatively wide electrochemically stable window,good electrical conductivity,high ionic mobility with strong ion–ion interactions,negligible vapour pressure,non-?ammability,excellent chemical and thermal stability and ability to act as catalysts.Reactions in ILs have different thermodynamic and kinetic behaviour,which often lead to improved process performance.Moreover,ILs allow an enhanced stability of organometallic reagents and bio-catalysts and an easy recovery,as well as possible recycling of homogeneous catalysts.
The potential for recyclability,ability to dissolve a variety of materials and the non-volatile nature of the ILs are some of their unique attributes responsible for their popularity. Although originally studied in electrochemistry,ILs are currently being explored as environmentally benign solvent substitutes in a variety of applications such as chemical synthesis,liquid–liquid separations,extractions,dissolution processes,catalysis,biocatalysis and polymerisation.31 More recently,they have also found application in asymmetric synthesis,32as well as in the synthesis of nanoparticles and other inorganic nanostructures.33
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It has recently been shown that there is a possibility of performing chemical reactions in ILs in conjunction with microwave irradiation,34as well as with separation routes utilising binary ionic liquid–scCO2systems.35
In spite of the fact that ILs are generally considered as environmentally friendly substitutes for volatile organic solvents,the environmental fate and any potential toxicity issues for most ionic liquids are not known,particularly with respect to alkylimidazolium systems.36In fact,so far,only a few toxicological and ecotoxicological data are available for this group of chemicals.More information seems to be needed in order to assess ILs with regard to sustainability and the principles of green chemistry.37On the other hand, although ILs are easy to obtain,their conventional preparation involves an excess of solvents and alkyl halides and,therefore, new efforts have emerged in a direction to minimize,at least,the amount of solvents in the reaction medium.38 1.3.3.Fluorous media.Fluorous chemistry can be considered as a complementary type of liquid-phase synthetic and separation methodology involving the use of ?uorine-containing reagents and solvents.39Fluorous solvents offer a unique perspective on a chemical reaction that allows one or more stages to be carried out without the need for volatile or noxious organic solvents,making the process simpler and more energy ef?cient and reducing the separation steps.Per?uoroalkanes,per?uorodialkyl ethers and per?uorotrialkylamines are the most common ?uorous solvents used,which are practically non-toxic. These solvents can be used in conjunction with a?uorous reaction component(reagent,catalyst,pre-catalyst,ligand, product,scavenger,protecting group,etc.),to which a ?uorous tag has been deliberately attached in order to make it soluble in?uorous solvents.It must be taken into account that the attachment of?uorous ponytails can signi?cantly change the reactivity of the?uorous reaction component, the insertion of two or three methylene groups before the ?uorous ponytail being necessary,in many cases,to decrease their strong electron-withdrawing effects.
