Polymer-assisted solution phase synthesis reactivation

Thus, isolation of oxoammonium salts on insoluble, cross-linked polymer supports was investigated along with their implementation in polymer-assisted solution-phase synthesis.23 These isolated oxoammonium salts could be employed in a water-free system to generate highly reactive oxidation agents without the overoxidation problems normally seen in the presence of water. 

A small library of 4,5-dihydro-l,4-benzoxazepin-3(2/f)-ones was prepared by polymer assisted solution phase synthesis based on saheyhe aldehydes, a-bromoaeetie acid esters and primary amines <05MI643>. As noted previously, pyrimido[4,5-fe][l,4]-benzoxazepines (and diazepines, and thiazepines) can be accessed via a neat variation of the Pictet-Spengler cyclisation. The compounds are of interest as inhibitors of particular receptor tyrosine kinases <05JOC9629>. Liu et al. have also reported a synthesis of 5,6-dihydro-pyrimido[4,5-Z)][l,4]benzoxazepines 173, 174 based on a cyclocondensation of the imines 172 <05TL7523>. The advantage of the approach was the incorporation of poorly reactive pyrimidyl amines 170,171. 

One of the major innovations in combinatorial and medicinal chemistry in recent years aiming at efficient diversity-oriented synthesis has been the implementation of polymer reagents in polymer-assisted solution phase (PASP) synthesis. This contribution will present—following an introduction to the field—a concept of advanced polymer reagents based on reactive intermediates and active reactants that should extend the scope PASP synthesis significantly. Experimental procedures describing preparation and use of the novel polymer reagents are included. 

Under certain condition, however, reactions are still preferably conducted in solution. This is the case e.g., for heterogeneous reactions and for conversions, which deliver complex product mixtures. In the latter case, further conversion of this mixture on the solid support is not desirable. In these instances, the combination of solution chemistry with polymer-assisted conversions can be an advantageous solution. Polymer-assisted synthesis in solution employs the polymer matrix either as a scavenger or for polymeric reagents. In both cases the virtues of solution phase and solid supported chemistry are ideally combined allowing for the preparation of pure products by filtration of the reactive resin. If several reactive polymers are used sequentially, multi-step syntheses can be conducted in a polymer-supported manner in solution as well. As a further advantage, many reactive polymers can be recycled for multiple use. 

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