Resin-capture-release

This novel resin-bound CHD derivative was then utilized in the preparation of an amide library under microwave irradiation. Reaction of the starting resin-bound CHD with an acyl or aroyl chloride yields an enol ester, which, upon treatment with amines, leads to the corresponding amide, thus regenerating the CHD. This demonstrates the feasibility of using the CHD resin as a capture and release reagent for the synthesis of amides. The resin capture/release methodology [126] aids in the removal of impurities and facilitates product purification. 

Scheme 7.105 Generation of an amide library utilizing resin capture-release methodology.

Scheme 2. The indole core structure is present in natural products and drugs, like for example Indomethacine and can therefore be considered as a privileged structure. A resin-capture-release strategy to synthesize an indole based compound library has been developed by Waldmann and co-workers.

A solid phase library synthesis method based on the Fischer indole synthesis was developed (Scheme A resin-capture-release method... 

Merging Solid-Phase and Solution-Phase Synthesis The Resin-Capture-Release" Hybrid Technique... 

In an earlier example of the resin-capture-release methodology trifluoracetylation of amines was achieved using polymer-bound benzyl thiol 8. Trifluoroacetic anhydride was employed in the capturing process while addition of amines to the intermediate polymer-bound thiolester released the desired trifluoroacetamide from the resin [21]. 

Another example of the resin-capture-release technique which should see widespread applications in the future is the selenium-mediated functionalization of organic compounds. Polymer-supported selenium-derived reagents [34] are very versatile because a rich chemistry around the carbon-selenium bond has been established in solution and the difficulties arising from the odor and the toxicity of low-molecular weight selenium compounds can be avoided. Thus, reagent 26 (X = Cl) was first prepared by Michels, Kato and Heitz [35] and was employed in reactions with carbonyl compounds. This treatment yielded polymer-bound a-seleno intermediates, which were set free back into solution as enones from hydrogen peroxide induced elimination. Recently, new selenium-based functionalized polymers 26 (X = Br)-28 were developed, which have been utilized in syntheses according to Scheme 11 (refer also to Scheme 3) [36],... 

An extended application of the resin-capture-release technique is depicted in Scheme 13. With the help of reagent 31, a functionalized pyridine was captured as an acyl pyridinium cation 32 on a solid support which was followed by Grignard addition and hydrolysis under acidic conditions to afford polymer-supported N-acylated dehydropyridinones 33 [39]. Advantageously, any unreacted acylium complex collapses to the parent resin upon workup. These heterocycles, which ideally can serve as scaffolds, are then released under basic conditions. 

In summary, the resin-capture-release hybrid methodology will become one important instrument in this orchestra of techniques. 

Kirschning A, Monenshein H, Wittenberg R, The resin capture-release hybrid technique A merger between solid and solution-phase synthesis, Chem. Eur. J., 4445-4450, 2000. 

S. Hanashima, S. Manabe, and Y. Ito, Divergent synthesis of sialylated glycan chains Combined use of polymer support, resin capture-release, and chemoenzymatic strategies, Angew Chem. Int. Ed., 44 (2005) 4218 1228. 

Application of the resin capture-release methodology to macrocyclization via an... 

In the strategy described in Fig. 16b, the linear precursor is not built on the polymer, but the final cyclization reaction using the Suzuki-Miyaura coupling takes place on a polymer. The aryl boronic acid is captured on a Dowex ammonium hydroxide resin, leading to the polymer ionically bonded borate, which is subsequently treated in the appropriate conditions to give the final macrocyle. This methodology is called resin capture-release.. ... 

Miyaura coupling an example of resin capture-release. 

Lobregat, V. Alcaraz, G. Bienayme, H. Vaultier. M. Application of the resin-capture-release methodology to macrocyclisation via intramolecular Suzuki-Miyaura coupling. J. Chem. Soc. Chem. Commun. 2001. 817-818. 

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. 

The Suzuki reaction has been appHed to the synthesis of a biarylcyclopep-tide through a resin-capture-release methodology [123]. This involved the capture of aryl boronic acids, containing a remote aryl hahde, on ammonium hydroxide-form Dowex ion exchange resin, followed by a releasing... 

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