Liquid-Phase Organic Synthesis Based On Poly (Ethylene Glycol) Bound A-Phenylseleno Carboxylic Acid Ester Reagents

In this dissertation, the preparation of poly(ethylene glycol) supportedα-phenylseleno carboxylic acid ester reagents and their applications in liquid-phase organic synthesis reaction were investigated.Firstly, Reaction of difunctional PEG 4000 withα-phenylselenopropanoic acid in anhydrous dichloromethane in the presence of DCC/DMAP readily gave rise to PEG-boundα-phenylselenopropionate ester, which was reacted with LDA, followed successively by treatment with aldehyde and 30 % hydrogen peroxide afforded PEG-bound Baylis-Hillman product intermesiate, and subsequent cleavage from the PEG using 0.1 N MeONa in methanol or sodium hydroxide aqueous solution afford Baylis-Hillman product with good yields (80-94 %) and high purities (>92 % by HPLC analysis) of the crude products.Secondly, Treatment of PEG-supported Baylis-Hillman products, which were prepared from PEG-supportedα-phenylselenopropionate with aldehydes, with sodium arylsulfinate in anhydrous MeOH/DMF (V/V, 3/1) mixture solvents at 80 oC afforded the corresponding PEG-supported trisubstituted ethylene——2-arylsulfonyl- methyl-2-alkenoate intermediates. The resulting PEG-bound sulfonylated products were cleaved from the PEG efficiently using 0.1 N MeONa in methanol affording methyl (2Z)-2-arylsulfonylmethyl-2-alkenoates stereoselectively in good yields (75-91 %) and high purities (91-95 % by HPLC analysis).Finally, PEG-supportedα-phenylselenoacetate and PEG-supportedα-phenylselenophenylacetate esters were prepared from PEG 4000 withα-phenylselenoacetic acid andα-phenylselenophenylacetic acid in similar methods as above, respectively. Treatment of these PEG-supportedα-phenylselenocarboxylic acid esters with LDA, followed successively by treatment with epoxide and 30 % hydrogen peroxide afforded PEG-boundγ-hydroxy-α,β-unsaturatecarboxylic acid ester intermesiates, and subsequent cleavage from the PEG using p-toluenesulfonic acid monohydrate in toluene at refluxing temperature afford substituted (5- and 3,5-di) α,β-butenolides with good yields (80-94 %). The described technology and sequence has potential application in combinatorial synthesis of butenolide-containing natural product libraries for chemical biological screening and the drug discovery process.