Die Totalsynthese des Lycopodium Alkaloids Sieboldin A unter Verwendung von Nickel(0)-katalysierten C-C-Kupplungsreaktionen
Zusammenfassung der Projektergebnisse
In this research project a formal synthesis of sieboldine A was accomplished. The initial goal to develop a total synthetic approach had to be revised after a dead end was reached in the course of the synthesis. The main feature of the synthesis is a nickel-catalyzed alkyne-ketone reductive cyclization used as a key step towards the natural product, effectively forming the hydrindane core and the tertiary alcohol vicinal to the all-carbon quaternary stereocenter. Remarkably, over the whole linear sequence of 19 steps, all but one step have a yield larger then 75%. In addition the majority of the reactions is not only efficient by yield but also by costs using readily available chemicals and reliable reaction conditions (expressed by excellent reproducibility). This is further emphasized by the fact that no chiral reagents were used during the synthesis. Every formed stereocenter was built up substrate controlled with high diastereoselectivity, ultimately emanating from the chiral pool starting material (R)-(+)-pulegone. Adding the remaining 5 steps of the total synthesis, sieboldine A would be completed in 24 steps as longest linear sequence compared to Overman’s 27 steps. In conclusion, the accomplished formal synthesis represents an elegant and overall very efficient approach towards the lycopodium alkaloid sieboldine A.
