Cleavage reactions, polymer synthesis

It is well known that even small changes in the structures of the transition metal complexes and of the organic counterparts have a substantial effect upon the double bond cleavage reactions. That is why it worth searching for well defined transition-metal carbene- or oxo-complexes (or of their precursors) capable of providing new routes to synthesis of common and new polymers with interesting structures and properties. 

Because of this uncertainly, we try, first, to control the course of the synthesis as completely as possible during its processing. Second, we try to determine the quality of the synthetic end product on polymer by the aid of Edman degradation with quantitative exploitation of the phenylthiohydantoines obtained [161,164]. In this way contaminations of the product by false sequences can be detected in relative amounts of as small as 0.1% of the main chain. Generally we experienced purer peptides synthesized than liberated from polymer by any detachment reaction. This can be demonstrated qualitatively by the aid of thin layer chromatograms of the crude peptide products released from the support after the cleavage reaction and by end-group determinations before and after peptide detachment. 

In 1963, R. B. Merrifield reported an unconventional method of peptide synthesis for which the name solid-phase peptide synthesis was coined. This method differed from general organic synthetic methods in that one of the reactants was reversibly and covalently bound to an insoluble, solid polymer support which was then reacted with the reagent to give a resin-bound product. After filtering the latter from the reaction mixture and after repetition of as many steps as necessary to achieve the synthesis, the product was obtained by a suitable cleavage reaction (Merrifield, 1963 Marshall and Merrifield, 1965). It may be recalled that, in... 

In contrast to peptide synthesis, the application of insoluble supports on the basis of polystyrene has never found broad ajqilication [40,59,131,132]. One of the main reasons for that is probably the steric hindrance by the structure of crosslinked polymers during condensation and cleavage reactions. Also, non-crosslinked, soluble carriers based on polystyrene are not especially appropriate because the solubility of loaded supports decreases with increasing numbers of condensation reactions. However, hydrophilic supports, such as poly(vinyl alcohol), have been used successfully for the synthesis of oligonucleotides. 

Braslau and coworkers [83] synthesized cyclic PSTY through the combination of nitroxide-mediated radical polymerization (NMRP) and CuAAC click reaction. The synthesis procedure was relatively complex compared with other strategies. 1 - [4-(Chloromethyl)phenyl] ethyl alkoxyamine was used to mediate the styrene polymerization, followed by successive azidation and oxidative cleavage with ammonium cerium(IY) nitrite in the presence of propargyl alcohol. The azide and alkyne groups were then introduced to each end of the polymer. Finally, the cyclization reaction was carried out in toluene with CuBr and PMDETA as catalyst at 100°C (Scheme 35). The cyclization results showed about 64% click product, as derived from Gaussian curve fitting. 

Cyclative cleavage of polymer-bound substrates is also a known procedure for amide resins. Recently, Dodd et al. released 5-aminopyrazoles 176 from resins linked to /i-ketoamides (Scheme 27) [181]. As a side reaction, they found the formation of 5-pyrazolones 175 which are formed via cyclative cleavage from the resins prior to product isolation. The whole synthesis has been performed on 4-formyl-3-(methoxyphenoxy)methylpolystyrene (FMP) resin with immobilized amines that react with /8-ketoamides to give 172. 

A further application of the benzotriazole linker is the synthesis of fi-diketones 382. Polymer-supported benzotriazoles 371 were transformed into the corresponding azolides which were cleaved with various ketone hhio eno-lates to build diketones 382 [261]. Other cleavage reactions with nucleophiles should be possible as benzotriazole auxiliaries are often used as advantageous N, C-, S- and 0-acylating reagents [262]. A well-known application is the solid phase synthesis of unsymmetric ureas (R = NR2) with secondary amines as cleaving nucleophiles [258]. 

The intramolecular Heck reaction of polymer bound aryl halides such as 84 affords indole analogs 85 after cleavage of the final product from the resin with TFA <96TL4189>, Other notable uses of the Heck cyclization include a synthesis of an antimigraine agent <96TL4289>, and thia-tryptophans <96T14975>. 

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