Catalytic META C-H ACYLation of arenes

Project Information

METACYL

Grant agreement ID: 894026

DOI

10.3030/894026

Project closed

EC signature date 18 March 2020

Start date 16 November 2020

End date 15 November 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 183 473,28

EU contribution

€ 183 473,28

Coordinated by

UNIVERSITA DEGLI STUDI DI PARMA
Italy

Periodic Reporting for period 1 - METACYL (Catalytic META C-H ACYLation of arenes)

Reporting period: 2020-11-16 to 2022-11-15

Summary of the context and overall objectives of the project

The ability to transform inert C–H bonds into reactive functional groups has become central of the modern synthetic chemistry. This approach can provide simplification of synthetic routes, new disconnections, and new synthetic starting points by avoiding pre-installed reactive handles. In this direction, the site-selective C-H activation and functionalization of aromatic arenes constitutes a challenge of paramount importance in organic synthesis. The use of suitable directing groups together with transition metal-catalysts has enabled the activation of ortho C–H bonds of aromatic rings in multiple versions. Moreover, if ortho- and para-substitution of aromatic arenes have been quite thoroughly explored by the aid of classical organic synthetic reactions, activation of the meta-position in an arene system remain challenging and, at the same time, essential since this allows the direct green synthesis of several natural products, medicinal drugs and agrochemicals. On the other hand, C-H acylation reactions represent an outstanding step- and atom-economical tool for the environmentally friendly construction of synthetically useful molecular scaffolds. In contrast to ortho and para C-H acylation of arenes and heteroarenes, meta C-H acylations are rarely reported. The aim of METACYL is the development of unconventional C-H Acylation methods to access meta-substituted carbonylated compounds in an environmentally benign manner.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Over the past two years we have developed new catalytic methodologies for the synthesis of meta-substituted carbonylated compounds featuring high molecular complexity. Catellani reactions, which promote the simultaneous functionalization of the ortho and the ipso positions of an aryl halide through the use of a transient directing group (norbornene), have been exploited for the synthesis of high value-added organic compounds bearing an acyl group in meta position, that are hardly accessible with alternative methodologies. The use of carbon monoxide and its surrogates has been extensively investigated for the installation of acyl moieties on aromatic rings. Similarly, richly decorated biaryls containing the free carboxylic acid group have been efficiently synthesized and these products represent potential substrates for the synthesis of five, six and seven member oxygen heterocycles. In particular, seven membered lactones, that are intermediates in the preparation of commercial drugs, were synthesized with a two-step procedure. The studies that were performed in the framework of the action allowed the production of two scientific papers published in peer-reviewed journals. Several other publications are in phase of preparation or submitted for peer-review.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Impact in the scientific community and society

The exploitation of the cooperative catalysis (palladium and norbornene) for the synthesis of complex organic architectures and the selective functionalization of remote C-H bonds has been demonstrated. In particular, the selective installation of acyl groups (esters, amides, acids) in less favorable positions, which is a common challenging task, has been here achieved. The results of this project will be highly useful for the development of new advanced organic syntheses and new efficient catalytic systems both in academia and industry to access pharmaceutical intermediates, fine chemicals and organic materials.

Impact for the fellow

The METACYL project demonstrated to be an excellent platform for the consolidation of the ER career. The ER improved his expertise in organic synthesis, catalysis, carbonylation reactions as well as in mentoring, project leading and management. The ER contributed to the preparation of high impact articles stimulating his independence and initiative skills. The provided high-level training programme of METACYL has significantly improved the career prospects of the ER by nurturing and promoting scientific rigor, excellence, problem solving aptitude, interdisciplinary and creativity. The training received during the fellowship and the close mentoring provided by the supervisor has contributed to enhance the ability of the fellow to effectively communicate with colleagues from different backgrounds and settings (e.g. chemical engineering), which will be a great advantage for his subsequent professional development.

General overview