Soluble Synthesis Using Poly (Ethylene Glycol) As Support

Recently, the synthetic techniques of small molecule libraries using soluble polymer as support were applied successfully to combinatorial chemistry and parallel synthesis. The synthetic approaches have the advantages of homogeneous solution organic synthesis (high reactivity, lack of diffusion phenomena and ease of analysis) and those of solid phase methods (use of excess reagents and easy isolation and purification of products), so the liquid-phase organic synthesis (LPOS) is more and more imported. A series of diisoxazolines were synthesized using poly (ethylene glycol)(PEG) as support in this paper. A series of isoxazolines were also synthesized by treating the PEG-supported Baylis-Hillman reaction products with in situ generated nitrile oxides through 1,3-dipolar cycloaddition. The liquid-phase synthetic methodology of 1,3,4-oxadiazoles using poly (ethylene glycol) as support were designed and some intermediate products were obtained. All reactions were highly efficient by simple operation, which suited with the demands of combinatorial chemistry and parallel synthesis of small molecule libraries. Firstly, PEG-supported acrylate or PEG-supported methyl acrylate reacted with in situ generated nitrile oxides through 1,3-dipolar cycloaddition, followed by cleavage from the resin by CH₃ONa / CH₃OH, to give diisoxazolines. The yields were in the range of (90⁹2%). Secondly, PEG-supported acrylate reacted with benzaldehyde to give PEG-supported α,β-unsaturated ester through Baylis-Hillman reaction. The PEG-supported α,β-unsaturated ester reacted with in situ generated nitrile oxides through 1,3-dipolar cycloaddition, followed by cleavage from the resin by CH₃ONa / CH₃OH, to give isoxazolines. Thirdly, we designed a practice and efficient liquid-phase synthetic methodology of 1, 3,4-oxadiazoles using α,α'-Dichloro-p-xylene as a link and achieved some intermediate products.