Gold Catalysis: From Fundamentals to the Synthesis of Bullvalenes and Naturally Occurring Sesquiterpenes

The present thesis comprises the development of novel gold(I)-catalyzed transformations for the construction of complex polycyclic frameworks and their application to methodology and total synthesis of natural products. Organometallic investigations in gold(I) systems and mechanistic studies through DFT calculations have also been performed.

The first total synthesis of the natural product repraesentin F has been accomplished by implementation of a highly diastereoselective gold(I)-catalyzed cyclization cascade as the key step. This unprecedented cycloisomerization/ring expansion/Prins-type tandem transformation of the appropriate cyclopropyl enyne substrate enabled a single-step access to the atypical tricyclic carbon skeleton of the natural product with the required syn/anti/syn ring fusion. The synthetic preparation of repraesentin F allowed reassignment of its relative configuration and determination of its absolute configuration.

An efficient methodology for the synthesis of 1-substitued barbaralones from 7-ethynyl-1,3,5-cycloheptatriene substrates via a gold(I)-catalyzed oxidative cyclization has been developed. It constitutes one of the shortest, mildest and most efficient synthesis of barbaralones to date. This methodology simplified the preparation of related fluxional molecules such as bullvalones and bullvalenes, key structures in the understanding of valence tautomerization, and enabled access to complex cage-type compounds.

Organometallic, mechanistic and computational studies have been performed in order to clarify the role of σ-monogold and σ,π-digold alkyne complexes in gold(I)-catalyzed reactions of enynes. The investigations showed that gold(I) acetylides and σ,π-digold(I) alkyne complexes derived from 1,6-enynes fail to cyclize under temperature demanding conditions, being the latest poor catalysts in these transformations. These results, supported by DFT calculations, confirmed that the aforementioned species are not catalytic intermediates; rather, these complexes are “dead ends” in catalytic reactions of enynes.