Traceless synthesis using polymer-bound

Traceless Synthesis Using Polymer-Bound Triphenylphosphine... 

An illustrative example of an alternative strategy (cf Fig. 11c) involving the use of a novel traceless linker is found in the multistep synthesis of 6-epi-dysidiolide (363) and several dysidiolide-derived phosphatase inhibitors by Waldmann and coworkers [153], outlined in Scheme 70. During the synthesis, the growing skeleton of 363 remained attached to a robust dienic linker. After completion of intermediate 362, the terminal olefin in 363 was liberated from the solid support by the final metathesis process with concomitant formation of a polymer-bound cyclopentene 364. Notably, during the synthesis it turned out that polymer-bound intermediate 365a, in contrast to soluble benzoate 365b, produced diene 367 only in low yield. After introduction of an additional linker (cf intermediate 366), diene 367 was released in distinctly improved yield by RCM. 

Finally, another related study achieved the synthesis of hydantoins by using acryloyl chloride to prepare a suitable polymer support under reflux conditions in a dedicated microwave instrument [88]. The soluble polymer support was dissolved in dichloromethane and treated with chloroacetyl chloride for 10 min under the action of microwave irradiation. Subsequent nucleophilic substitution using a variety of primary amines was carried out in N,N-dimethylformamide as solvent. The resulting PEG-bound amines were reacted with aryl or alkyl isothiocyanates in dichloromethane to furnish the polymer-bound urea derivatives after microwave irradiation for 5 min (Scheme 16.58). Finally, traceless release of the desired compounds by cyclative cleavage was achieved under mild basic conditions with micro-wave irradiation for 5 min. The 1,3-disubstituted hydantoins were obtained in varying yields but high purity. 

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