Au(I) as a π-Lewis Base Catalyst: Controlled Synthesis of Sterically Congested Bis(triflyl)enals from α-Allenols

For many years, allenes have been considered very unstable molecules, which has caused a lack of knowledge of their chemical and synthetic applications in the scientific community. However, in the last decades these compounds have experienced great growth in the field of organic synthesis due to their interesting reactivity that allows a great variety of possible transformations. In particular, the allenol moiety is a special type of allene that exhibits a rich and fruitful reactivity.

On the other hand, metal catalysis allows the strict regulation of selectivity in chemical reactions which is crucial in organic synthesis because it enables the preparation of distinct molecules in a controlled manner. In this context, gold catalysis has been used for the cycloisomerization or oxycyclization of α-allenols showing useful levels of chemo-, regio-, and/or stereoselectivity.

We have recently achieved a gold-catalyzed bis[(trifluoromethyl)sulfonyl]ethylation of α-allenols, which allows the preparation of sterically congested bis(triflyl)enals. This sequence differs from the conventional reaction pathway of α-allenols under π-acid catalysis. In our case, Au(I) functions as a π-Lewis base catalyst rather than a π-Lewis acid to activate the allene.

In addittion, it should be also noted that the strongly electron-withdrawing (trifluoromethyl)sulfonyl (triflyl, Tf = SO₂CF₃) group confers a positive effect on the metabolic stability and lipophilicity of potential drugs important to the field of medicinal chemistry.