ELECTROPHILIC ACTIVATION AND FUNCTIONALIZATION of C–H BONDS WITH HIGH VALENT GOLD COMPLEXES – CHAUCACAO

The main limitation to the development of Au(I)/Au(III) catalysis is the accessibility to gold(III) oxidation state under mild conditions. In most cases, a strong external oxidant is required to cycle between Au(I) and Au(III) oxidation states. In this project, we have developed an original approach in which a key gold (III) species was generated under mild conditions by oxidative addition of aryl halides to gold(I) complexes. The reactivity of the ensuing high valent gold electrophilic species towards arenes was investigated in detail to delineate the reactivity/selectivity of these gold(III) species. This project was carried out through a combination of organometallic synthesis, mechanistic studies, and methodologic development.

Thanks to a rational ligand design approach, we have demonstrated for the first time that gold, long considered useless for catalysis, is indeed a very efficient catalyst for the synthesis of added-value organic molecules. We have designed and understood, step by step, all the elementary reactions composing the Au(I)/Au(III) catalytic cycle. Thus we were able to develop new catalytic transformations in organic synthesis, previously impossible with gold. The reported results opened interesting perspectives in the field of gold catalysis.

We have demonstrated that redox gold(I)/gold(III) catalysis is readily accessible through a ligand design approach. The perspectives of this project stand in the field of new gold catalytic approaches, in particular, the development of asymmetric transformations.

Several scientific publications resulted directly or indirectly from this project. In the framework of this project we particularly developed the first gold-catalyzed cross-coupling reaction without external oxidant (Nat. Comm. 2017, Chem. Sci. 2019). We demonstrated the importance of ligand design to modulate the reactivity of gold(III) catalysts for hydroarylation of alkynes (ACIE 2018).

This project aims at exploiting the high electrophilic character of high valent gold(III) species for C–H activation to develop new transition metal catalytic systems based on gold for a major scientific challenge in modern chemical synthesis that is the selective transformation of ubiquitous hydrocarbon compounds into high added value functionalized molecules. Two main strategies will be explored for the development of gold catalyzed C-H functionalization reactions: The first approach concerns the development of direct arylation of arenes and alkanes via Au(I)/Au(III) redox catalytic cycles. In this original approach, the key gold (III) species will be generated in mild conditions by oxidative addition of aryl halides to gold(I) complexes, and the high valent gold electrophilic gold species will be reacted with arenes first, and then with more challenging Csp3–H bonds. The C-H activation step will be investigated in details to delineate the reactivity/selectivity of these gold(III) species. Here, the steric/electronic effect of the ancillary ligand at gold will be an advantage to fine-tune the electrophilic character of gold(III). Thus, mechanistic investigations on this original catalytic pathway involving oxidative addition, C-H auration and reductive elimination will help to define the optimal conditions for viable catalytic formation of C-C bonds. These gold species will be applied to catalytic late stage C-H bond functionalization. The second approach will consists in the use of well-defined gold(III) complexes for the oxidative functionalization of Csp3–H bonds, with the ultimate goal being the functionalization of light alkanes. In this part, we will particularly explore the reactivity of these gold(III) species in the presence of strong oxidant, and notably the possible involvement of unknown gold(V) species in the C-H bond functionalization process. The synthesis of model organogold compounds and precise mechanistic investigations will provide key informations into the feasibility of the process and document the development of gold(III) catalyzed functionalization of alkanes.