Applications of Supported Reagents

THE DEVELOPMENT AND APPLICATION OF SUPPORTED REAGENTS FOR MULTI-STEP ORGANIC SYNTHESIS... 

The Development and Application of Supported Reagents for Multi-step Organic Synthesis... 

Recent developments in the design and application of supported reagent catalysts offer considerable potential for clean synthesis. Synergistic effects between the support material and the reagent can lead to unexpectedly high activity. Thus "clayzic" is a potent solid acid catalyst for certain Friedel-Crafts reactions despite the low activity of the individual components. This and other similar clay and silica-based solid acid catalysts have been shown to have many useful applications in liquid phase reactions and some of them have been commercialised as environmentally friendly replacements for conventional acidic reagents. ... 

A more recent example from our group, where the application of supported reagents was crucial to the success of a synthesis, occurred en route to spongistatin 1... 

In this chapter we have described the multistep application of supported reagents, scavengers, and catch-and-release techniques to the construction of various natural products and natural product-like libraries of compounds. These methods of immobilization can aid considerably the rapid optimization of complex chemical transformations. They avoid or minimize the need for more time-intensive skill-based workup procedures, such as chromatography, distillation, and crystallization, and are therefore valuable new tools to add to the repertoire of the synthesis chemist. 

Supported reagents have been used in synthesis since 1946, but their application in natural product synthesis has been very limited. Indeed, where they had been used, it was only to effect a spedlic transformation where conventional systems had previously failed. Our group, however, has sought to develop the application of immobilized systems to complex synthetic challenges in a multistep mode. The first serious application of supported reagents for natural product synthesis was published in 1999. ° Here, concise routes to two amarylUdaceae alkaloids, oxomaritidine (1) and epimaritidine (2), in just five and six steps, respectively, were reported (Scheme 6.1). 

SCHEME 6.1 The first orchestrated and successive application of supported reagents in the synthesis of the amaryllidaceae alkaloids oxomaritidine and epimaritidine. Copyright 2006 Taylor Francis Group, LLC... 

Jamieson C, Congreave MS, Emiabata-Smith DF, Ley SV, Scicinski J (2002) application of ReactArray robotics and design of experiments techniques in optimisation of supported reagent chemistry. J Org Proc Res Dev 6 823-825... 

Support-bound transition metal complexes have mainly been prepared as insoluble catalysts. Table 4.1 lists representative examples of such polymer-bound complexes. Polystyrene-bound molybdenum carbonyl complexes have been prepared for the study of ligand substitution reactions and oxidative eliminations [51], Moreover, well-defined molybdenum, rhodium, and iridium phosphine complexes have been prepared on copolymers of PEG and silica [52]. Several reviews have covered the preparation and application of support-bound reagents, including transition metal complexes [53-59]. Examples of the preparation and uses of organomercury and organo-zinc compounds are discussed in Section 4.1. 

The use of supported reagents has always been recognized as a powerful tool in classical organic chemistry for a large number of applications, and excellent reviews covered this topic in the past [103-105]. Recently, this technique has been applied to solution-phase combinatorial chemistry, where it looks really promising in terms of simpler work-up procedures, elimination of excess reagents, and isolation of pure reaction products. 

Resins can also be used to hold and deliver reagents or catalysts to facilitate selective reaction chemistry. A review of the application of supported catalysts to organic synthesis has been recently published [21] and references many additional review articles covering polymer-based synthesis. 

Various types of PSRs are described in the following sections. However, rather than classify these reagents by the type of support or by functionality, a classification based on the method of preparation is used here, with the focus on the most commonly employed techniques. Furthermore, rather than providing an exhaustive list of all PSRs described in the literature, the aim of this chapter is to provide an understanding of the principles of preparation and application of such reagents, with a special focus on important reactions and on the combination of several PSRs in one synthetic sequence or, where possible, in one pot. The latter is a rather novel and highly interesting aspect of combinatorial chemistry applications. 

A somewhat different approach to a polymer-supported radical source was described by Giacomelli and coworkers, who used an N-hydroxythiazole 2(3)-thione anchored to a Wang resin [95]. The reagent was prepared in solution and equipped with a pendant COOH group to facilitate attachment to the resin. The applicability of the reagent in radical-mediated reactions was then investigated via a Hunsdiecker reaction (Scheme 6.24). Treatment of the reagent with an acyl... 

In summary, development of functional polymers that can act as efficient organocatalysts is at the origin of the application of modified polymers as reagents and catalysts in chemistry. To date, the most successful accomplishments have been carried out in the area of basic and acid catalysts. Not surprisingly, this area includes some of the most important industrial applications for supported reagents and catalysts. In general, the development of non-chiral polymer-supported organocatalysts is a field of research that involves both industrial and academic research. In many cases, it has been possible to demonstrate how the use of the... 

There are numerous applications for supported reagent catalysts in organic synthesis.3 4,6,7,15,21,22,43 These will be illustrated in sections on the important areas of partial oxidations, acid-catalysed reactions and base-catalysed reactions with other areas illustrated in a final miscellaneous section. 

The use of supported reagents has always been recognized as a powerful tool in classical organic chemistry for a large number of applications, and excellent re-... 

During the last two years the interest in separation techniques based on reactive polymers had a renaissance and many applications of supported quenching reagents in solution phase parallel syntheses were described. Ion exchange resins - as well as polymers with covalently attached... 

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