Mangan(III)acetat vermittelte sowie Palladium- und Gold-katalysierte Cyclisierungsreaktionen von Malonaten zur Synthese der Oxazolomycine
Zusammenfassung der Projektergebnisse
In this project a palladium catalysed tandem reaction for the cyclisation/coupling of butynyl amino malonates and various halides has been developed. The reaction offers a mild and efficient way for the synthesis of highly functionalised pyrrolidines (and piperidines) with a tri- or tetrasubstituted double bond. The further functionalisation of the products towards the core structure of the oxazolomycins has been attempted and a revised synthetic scheme based on the results obtained so far has been proposed. The investigation was shifted to the manganese promoted cyclisation which afforded exo-methylene compounds which serve as valuable starting materials for the proposed natural product synthesis. We also discovered that a simple acetic acid catalysed cyclisation is possible in the case of terminal butynoic amido malonates which we are able to use in our revised route, which simplifies the overall synthesis even further. The dihydroxylation of the exo-methylene pyrrolidines, the first step towards the oxazolomycin core was optimised and the desired product could be obtained in good yield. A new route was proposed which should deliver the desired compound in a few efficient steps. In addition to the palladium catalysed reaction which is limited to base stable starting materials and the manganese promoted reaction which can only be used with amido malonates the zinc chloride catalysed Conia-ene reaction was investigated. This mild and inexpensive reaction offers a complementary approach compared to the other reactions. E-substituted exo-methylene pyrrolidines and pyrrolidinones can be obtained with internal alkynes, in contrast to the other two reactions where the substituent is Z-oriented towards the malonate diester. Three promising and complementary (in terms of stereo- and chemoselectivity) cyclisation reactions were developed in the course of this project.
