The Diels Alder/retro-Diels Alder concept on solid support : a study of the scope, limitations and conceivable applications as a traceless thermocleavable linker

摘要

This thesis deals with the conceivable transfer of the Diels Alder/retro-Diels Alder concept to the solid phase in order to broaden the scope of the methodology to a combinatorial level. In addition, based on this methodology the development of a traceless thermocleavable linking system for Solid-Phase Organic Synthesis (SPOS) is described. As a possible application of this linker system, the solid-phase synthesis of precursors of pharmaceutically interesting CNS-active heterocyclic compounds via N-acyliminium ion chemistry was investigated. Experiments with immobilised cyclopentadiene, anthracene and furan show their scope and limitations in the Diels Alder/retro-Diels Alder concept: All three immobilised dienes undergo Diels Alder additions to give the immobilised cycloadducts. The thermal cycloreversion could only be efficiently accomplished with an immobilised furan cycloadduct. Both for the cyclopentadiene and the anthracene adducts, the temperatures required to accomplish the cycloreversion reaction were too high for practical purposes. Therefore, the immobilised anthracene and cyclopentadiene adducts are not applicable in a thermocleavable traceless linking strategy. The immobilised furan adducts, however, look promising as key intermediates for this purpose, for example in the synthesis of 5-hydroxypyrrolinones. N-acyliminium ion mediated syntheses of nitrogen heterocycles under acidic conditions using immobilised furan adducts, however, is hampered due to the acid lability of the furan adducts.