Abstract
Natural products form the majority of small molecule drugs, and thus are good targets for syntheses aiming to construct them and their related analogues. Some of these analogues exhibit some form of interesting biological activity, but in order to access them, reliable synthetic methods need to be established.
This research aimed to utilise the Tsuji-Trost reaction in order to access the structures of psiguadial A and ferulin C more easily. It involved first constructing a suitable substrate to undergo the Tsuji-Trost reaction, which acts on allylic groups, with the aim of creating natural product scaffolds for psiguadial A and ferulin C.
Unfortunately, instability issues with the 7-membered oxepane ring system led to decomposition of the scaffold relating to psiguadial A. This ring system was constructed by the Tsuji-Trost reaction, successfully forging the 7-membered ring. Alkylation attempts all led to either re-isolation of the starting material used, or to decomposition of the substrate.
Some success was found in the pursuit of a ferulin C scaffold, forming a later-stage chromone intermediate successfully. However, subsequent cyclisation attempts to secure the 6,6,5 ring system found in ferulin C led to competitive Rubottom oxidation, preventing the formation of the intended product. We hope that in the future that utilisation of different substrates and methods may lead to the scaffold of ferulin C.
Also investigated was an intriguing Tsuji-Trost type reaction involving a desulfonylation event that was discovered earlier in the Hawkins group. The attempts in this research did not lead to another desulfonylation reaction, however, it did expand the knowledge of how the reaction most likely works under Tsuji-Trost reaction conditions.
A tandem Tsuji-Trost/Heck reaction was also attempted using a substrate specifically designed to undergo the Heck reaction in one pot after the Tsuji-Trost reaction takes place. However, stability issues led to decomposition of the substrate before the Heck reaction could take place.