Synthesis, polymer-supported

The present chapter will review the current state-of-the-art regarding the use of polymers as supports for catalysts and related systems. The variety of applications where polymer supports have proved invaluable has expanded enormously in the last decade or so, and to review comprehensively even the limited area of polymer-supported reagents, catalysts and protected groups [1] would be a major undertaking. This chapter will not therefore attempt to do so, but instead will refer to the many excellent books and reviews on this subject, and then describe some more recent works which exemplify the strategically important developments that are currently underway. 

In the case of DNA synthesis controlled-pore-glass (CPG) supports have become the favoured solid phase medium [8] and this raises the question of polymer versus inorganic support . In reality there is no real competition here, although would-be users have the opportunity to examine each option and select the one most suitable for their own needs. In fact, in many respects the two classes of support are complementary and offer different possibilities to potential users. For example, a transition metal complex immobilised on an inorganic support will find itself in quite a different electronic environment than the same complex immobilised on a polymer. Hence the immobilised complexes are in fact likely to be different and therefore to behave differently in catalytic applications. 

Finally, one very useful review source arises from a series of international meetings held biennially since 1982, the so-called Polymer-supported Organic Chemistry (POC) meetings. The proceedings of these have been published regularly and comprise poster abstracts as well as oral presentations [21-26]. POC 92 was subsumed into an lUPAC Symposium, the proceedings of which have also been recorded [27]. 

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Polymer-supported synthesis of natural macrocyclic lactones and other 0-heterocycles 99AG(E)1903. 

These conceptual goals are attained by several combinatorial methods and tools. Characteristic for combinatorial chemistry is the synthesis on solid support or by polymer-supported synthesis, allowing for much higher efficiency in library production. Synthesis can be conducted either in automated parallel synthesis or by split-and-recombine synthesis. Centerpieces of combinatorial methods further include specific analytical methods for combinatorial... 

Solid Phase Synthesis Versns Polymer-Supported Synthesis in Solution... 

Scheme 7.12 Reaction strategies for the polymer-supported synthesis of dialkylaminopropenones.

Table 16 Traceless polymer-supported synthesis of 4,5-disubstituted 3-amino-1,2,4-triazole derivatives (Scheme 5)...

Highly efficient modifications of Mukaiyama s procedure, convenient for combinatorial syntheses, were reported recently, namely the polymer-supported synthesis of isoxazolines via nitrile oxides, starting from primary nitroalkanes, in a one-pot process (75) and by microwave activation of the process (73). 

M. A. Marx, A.-L. Grillot, C. T. Louer, K. A. Beaver, P. A. Bartlett, Synthetic Design for Combinatorial Chemistry. Solution and Polymer-Supported Synthesis of Polycyclic Lactams by Intramolecular Cyclization of Azo-methine Ylides , J. Am. Chem Soc. 1997,119, 6153-6167. 

High selectivity and substrate specificity of glycosyl transferases make them valuable catalysts for special linkages in polymer-supported synthesis. There is, however, still a rather limited set of enzymes available to date, and the need to synthesize a variety of natural and non-natural oligosaccharides prevails. Particularly with regard to combinatorial approaches, chemical solid-phase oligosaccharide synthesis promises to meet the demands most effectively. 

Scheme 9.1 Comparison of one-phase and two-phase polymer-supported synthesis of oligosaccharides. Continued next page.

Scheme 9.2 Comparison of polymer-supported synthesis of oligosaccharides between the attachment of a polymer to a glycosyl donor and a glycosyl acceptor.

Scheme 9.3 Polymer-supported synthesis of oligosaccharides employing a hydrophobic handle attached to the growing chain in the last step of the synthetic sequence. The handle permits separation of the majority of failure sequences accumulated during the synthesis.

Polymer-supported synthesis of S-alkyl and S-aryl dithiocarbamates (Table 4.25)... 

TABLE 4.25 Polymer-supported synthesis of alkyl dithiocarbamates R.NCS.SR1 ... 

Chiral benzamides I and the pyrrolobenzodiazepine-5,11-dio-nes n have proven to be effective substrates for asymmetric organic synthesis. Although the scale of reaction in our studies has rarely exceeded the 50 to 60 g range, there is no reason to believe that considerably larger-scale synthesis will be impractical. Applications of the method to more complex aromatic substrates and to the potentially important domain of polymer supported synthesis are currently under study. We also are developing complementary processes that do not depend on a removable chiral auxiliary but rather utilize stereogenic centers from the chiral pool as integral stereodirectors within the substrate for Birch reduction-alkylation. 

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