Supported reagents reuse

Onium salts can also be used to support reagents that would transform a substrate. After reaction the IL phase can be recovered and the reagent regenerated for being reused in another cycle. For example, carboxylic acids have been supported on onium halides. Simply synthesized by quatemarisation of methylimidazole followed by acid hydrolysis, this compound can react with epoxides to afford halo-hydrines in 76-95% yields [58], Additionally, an OS supported version of TEMPO has been used in oxidation of alcohol into ketone [59] (Fig. 21). 

The benefits brought by the supported reagent chemistry are considerable efficiency, low cost, possibility of reusing the supports, implementation of nontoxic and cheap materials, ease of set-up and work-up, minimization of pollution, possibility to work in solvent-free conditions. 

Procter and coworkers" have described a Sm(II)-mediated (106), asymmetric capture and release approach (Scheme 7.22) to y-butyrolactones (107) that involves intermolecular radical additions to a,[3-unsaturated esters (105) attached to resin through an ephedrine chiral linker (108). Resin capture-release is a hybrid technique that combines elements of traditional solid-phase synthesis and the use of supported reagents. Fukuzawa s Sm(II)-mediated, asymmetric method to y-butyrolactones was chosen to demonstrate the feasibility of such a process. y-Butyrolactones (107) were obtained by capture of a reactive intermediate from solution through an asymmetric transformation starting from a,p-unsaturated esters (105) immobilized on an ephedrine chiral resin. Lactone products were obtained in moderate yields with selectivities up to 96% ee. Nevertheless, the ephedrine resin can be efficiently reused for many cycles although in some cases lower yields were obtained on reuse of the chiral resin. 

Recently, IL-supported reagents for S5mthetic applications have been reported [58,59]. During the transformations of IL-grafted reagents, they can be regenerated and reused by simple phase separation. 

The use of water-soluble reagents and catalysts allows reactions to be performed in aqueous buffered solutions. PEG-supported triarylphos-phine has been used in a Wittig reaction under mildly basic aqueous conditions (Eq. 8.115). The PEG-supported phosphine oxide byproduct can be easily recovered and reduced by alane to regenerate the starting reagent for reuse.312 The aqueous Wittig reaction has also been used in... 

For the preparation of large compound libraries, the cost of reagents and resins is a further issue that must be considered. Some supports, e.g. resin-bound phenols or N-hydroxybenzotriazole, which enable the preparation of resin-bound, reactive esters (Section 3.3.3), can be reused many times without the need to dismantle the reactor, and are therefore much more cost-efficient than supports that can only be used once [136,137], Reactions such as the acylation of amines with resin-bound acylating agents have the additional advantage that only one equivalent of amine is needed, which again leads to a substantial reduction of costs. 

A further example used the supported amino alcohols 45,46 and 47 (Scheme 4.76), where the reagents were pumped up from the bottom of the polymer using a pair of long needles connected to peristaltic pumps. The product was collected from the top using another pump and quenched in a solution of dilute hydrochloric acid. For the first run with catalyst 46, the yields and ee were excellent (94% yield in 97% ee), but when 46 was recovered and reused, the yield dropped to 75% and the ee to 50%. This was ascribed to degradation of both the chiral and backbone sites of the polymer by diethyl zinc, again demonstrating that not only do the solid supports need to be mechanically sound but both the backbone support and active site must be also chemically resistant to the reaction conditions [171]. 

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