Synthesis on soluble polymers

Reported applications of the technique to combinatorial syntheses include libraries of peptides ([69,71,72]), 4-amino-benzenesulfonamides ([69,71,72]), and peptidomimetics (poly-a-aza-amino acids or azatides, [69,71,73]). The latter synthesis also illustrates one of the advantages of the soluble polymer approach over solid-phase synthesis, namely. 

A recently reported synthesis sequence [152] starts from MeOPEG-bound 4-fluoro-3-nitro-benzoic acid. After the nucleophilic aromatic substitution of the fluorine with piperazine, homopiperazine and 4-aminomethyl-piperidine (only the secondary amino group reacted) the remaining free amino function was acylated or sulfonated. 

In another application, PEG-bound a-aminoaldehydes served as a starting point for the combinatorial synthesis of polyamines [154], Reductive amination with an amine of type 5, followed by alkylation of the formed secondary amine (via reductive amination) and cleavage of the cyclic aminal yielded the starting aldehyde for the next cycle. 

Various PEGs have been examined for their performance in the synthesis of a biaryl library via Suzuki coupling. Considering both the ease of precipitation and the loading PEG 6000 was found to offer optimum conditions [87]. 

Soluble polymers may also serve as carriers for catalysts and other auxiliary reagents. In this form they can be easily separated from the reaction products by simple precipitation of the polymer. Thus, a Sharpless asymmetric dihydroxylation with PEG-bound (DHQD)2PHAL (bis-ether of 1,4-dihydroxyphthalazine and dihydroquinidine) of various olefins gave the corresponding diols in good yields with high enantiomeric excesses [74]. 

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Abstract Current microwave-assisted protocols for reaction on solid-phase and soluble supports are critically reviewed. The compatibility of commercially available polymer supports with the relatively harsh conditions of microwave heating and the possibilities for reaction monitoring are discussed. Instrmnentation available for microwave-assisted solid-phase chemistry is presented. This review also summarizes the recent applications of controlled microwave heating to sohd-phase and SPOT-chemistry, as well as to synthesis on soluble polymers, fluorous phases and functional ionic liquid supports. The presented examples indicate that the combination of microwave dielectric heating with solid- or soluble-polymer supported chemistry techniques provides significant enhancements both at the level of reaction rate and ease of purification compared to conventional procedures. 

Gravert, D. J. Janda, K. D. Organic Synthesis on Soluble Polymer Supports Liquid-Phase Methodologies, Chem. Rev. 1997, 97, 489-509. 

Gravert DJ, Janda KD, Organic synthesis on soluble polymer supports Liquid-phase methodologies, Chem. Rev., 97 489-510, 1997. 

DJ Gravert, KD Janda. Synthesis on soluble polymers new reactions and the construction of small molecules. Curr Opin Chem Biol 1 107-113, 1997. 

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