Development of new enantioselective domino reactions catalyzed by Au(I) and Au(III) complexes ; Développement de nouvelles réactions domino énantiosélectives catalysées par des complexes d'Au(I) et Au(III)

Over the last decades, gold catalysis has been recognized as a powerful tool for chemist to access really complex scaffolds from simple unsaturated starting materials. Indeed, thanks to the strong Lewis acid properties, gold catalysts have the capacity to selectively activate π-system (alkynes and allenes) toward the addition of a wild range of nucleophiles such as alkenes, alcohols, amines, carboxylic acids… In another hand, asymmetry have also triggered chemist because enantiomers could express differences in olfactory strengths, olfactive notes or in bioactivities. In this context the development of enantioselective gold-catalyzed transformations drags our interest. The main challenge of this chemistry remains in the linear geometry of gold(I) catalyst which is currently the main oxidation state of gold in homogeneous catalysis. Gold(III) complexes are a promising alternative to improve the enantioselectivity because of their square planar geometry that brings closer the chiral information from the coordination site.In 2009, the groups of Echavarren and Helmchen had published “Prins type” cyclisation reactions from 1,6-enynes in presence of a carbonyl and a achiral gold catalyst. Depending of the scaffold of the 1,6-enynes two different functionalized heterocycles can be obtained, respectively bicyclic or tricyclic molecules with an excellent diastereoselectivity. In collaboration with the Toste's group, we first tested chiral (biphenyl)Au(III)Cl complexes. Even though the yields were good only few inductions of chirality were observed. We have also tested other chiral NHCAu(I)Cl complexes and we were able to increase the enantiomeric excesses to 56% and 52%. For the Helmchen's “Prins type” cyclisation reaction, the scope of the enantioselective version was evaluated and 13 examples had been synthetized with enantiomeric excesses from 14% to 82%. The crystallizations in MeOH gives highly enriched enantiomers used to determine the sense of the enantioselectivity of this transformation via circular dichroism ...