Our thorough study of the oxidative addition of p-substituted iodoarenes to (P,N)AuCl has shown that, whatever the ligand, (P,P), (N,N) or (P,N), oxidative addition proceeds faster with electron–donating substituents, a reactivity trend opposite to that typically found with palladium. We have also demonstrated that gold is fruitful for the oxidative addition of allyl–X bonds, affording Au(III) π-allyl complexes, whose access by oxidative addition had not been described before. The only two Au(III) π-allyl complexes described to date have been prepared by Mg to Au(III) transmetallation. One of them was prepared during this fellowship using a (P,C) ligand. All these new Au(III) complexes were readily prepared and isolated and their structure was analyzed combining spectroscopic and crystallographic studies with detailed DFT calculations.
Furthermore, we have shown that the ensuing Au(III) complexes efficiently engage in C–C and C–N catalytic cross-coupling. Regarding C–C bond formation, we have obtained complete C3-regioselectivity in the arylation of indoles under very mild conditions. Thus, gold is very complementary to other transition metals, in particular palladium, which usually promote C2-arylation. The catalytic reactions tolerate a variety of functional groups at both the indole, N-nucleophile and electrophilic coupling partners. Moreover, we recently found the involvement of Au(III) π-allyl complexes in gold-catalyzed allylation reactions.
The stoichiometric reactivity of the (P,C) Au(III) π-allyl complexes with β-diketo enolates was also studied, showing that Au(III) presents a very specific reactivity with a reversible nucleophilic addition taking place through attack at the central carbon of the allyl group.
Impact for the fellow
The training on the design and handling of highly reactive organometallic species (synthesis, characterization by multi-nuclear NMR, X-ray diffraction), the study of their catalytic properties and the theoretical bonding/mechanistic analysis have widened the knowledge of the fellow in transition metal complexes and its application in catalysis. During this fellowship and combined with her previous high-level expertise in chemical biology, the fellow has gained an excellent background in diverse areas of chemistry (inorganic, organic, biological, organometallic and catalysis), broading her posibilities to develop widely diverse research projects and initiate her independent career.
Furthermore, the fellow has been involved in the tutoring of students and in the preparation of all manuscripts that arised from the project, together with the financial management of the fellowship, acquiring leadership and project management skills.
Impact in the scientific community and society
Direct beneficiaries of the results arised from this project are researchers in the fields of catalysis (Hashmi, Toste, Patil), organometallic chemistry (Nevado, Tilset) and biological chemistry (Spokoyny, Casini) across the globe. For example, (P,N) Au(III) complexes have already been applied for the modification of proteins (Spokoyny, JACS, 2018, 140, 7065) or for the construction of hybrid nanoclusters (Spokoyny, JACS, 2020, 142, 327). Besides the fundamental knowledge arising from the development of well-defined and stable Au(III) complexes, the efficient preparation of highly functionalized compounds by new catalytic reactions is definitely of high interest for a broad public audience and for pharmaceutical purposes.
