Solid-supported reagents oxidation

Caldarelli et al. (240) have recently reported a five-step synthesis of substituted p)Trole libraries L22 and L23 using solid-supported reagents and scavengers. The synthesis involved oxidation of benzyl alcohols Mi to aldehydes (step a, Fig. 8.46), Henry reaction of aldehydes 8.91 with nitroalkanes M2 (step b), and acylation and elimination of nitroalcohols 8.93 (steps c and d) to give the nitrostyrenes 8.94, which were subjected to 1,3-dipolar cycloaddition with an isocyanoacetate (step e) to give the pyrroles 8.95. N-alkylation of these pyrroles with alkyl halides (step f) and final library-from-a-library hydrolysis/decarboxylation of L22 gave a library of trisub-stituted pyrroles L23 (step g. Fig. 8.46). 

Takemoto, T., Yasuda, K., Ley, S. V. Solid-supported reagents for the oxidation of aldehydes to carboxylic acids. Syn/eff 2001, 1555-1556. Fabian, I. The reactions of transition metal ions with chlorine(lll). Coord. Chem. Rev. 2001, 216-217, 449-472. 

Over the past two decades, the use of solid-supported reagents, catalysts, and scavengers has revolutionized the way in which the modem synthetic chemist performs transformations such as oxidations, reductions, and coupling reactions [42-44]. Their growing application can be attributed to the ease of product... 

The first report of the use of solid-supported reagents in the Wittig reaction dates back to 1971 and disclosed the use of polymeric diphenylphosphine 70. This reagent could be transformed into ylide 71 and reacted with benzaldehyde 15 to afford alkene 72. Work-up was made easier since the phosphine oxide by-product was now immobilized on the support as 73. 

The utility of such reagents in the oxidation processes is compromised due to their inherent toxicity, cumbersome preparation, potential danger in handling of metal complexes, difficulties encountered in product isolation and waste disposal problems. Immobilization of metallic reagents on solid supports has circumvented some of these drawbacks and provided an attractive alternative in organic synthesis because of the selectivity and associated ease of manipulation. Further, the localization of metals on the mineral oxide surfaces reduces the possibility of their leaching into the environment. 

There are only few examples for oxidation reactions on solid supports, because most linkers or polymeric supports are sensitive towards some reagents suitable for classical transformations. Classical oxidation reagents are not soluble in most solvents used in the solid-phase organic synthesis step (but e.g. Scheme 3.10). 

In contrast there are many examples for reduction processes on polymeric supports, because it is an especially useful transformation for aromatic nitro compounds in solid-phase chemistry. The reaction can be divided into two general classes polymer-bound substrates and polymer-bound oxidant- and reductant-reagents. 

Various solid-supported perruthenate reagents have been designed for the oxidation of alcohols.Solid-supported NMO has also been used. A number of perruthenate systems employing O2 as the terminal oxidant have also been reported. The use of ionic liquids based upon substituted imidazolium cations as alternative solvent media for the selective oxidation of alcohols to aldehydes and ketones has also been investigated. ... 

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