Periodic Reporting for period 1 - MLCat (Multifunctional Ligands for Enhanced Catalysis)
Reporting period: 2022-08-01 to 2025-01-31
Synthetic organic compounds are essential to our society’s way of living and its economic growth. It influences all aspects of our lives, including healthcare, agriculture, well-being, and food industries. Because of limited natural resources, developing novel strategies to efficiently access function-tailored chemical entities with lower ecological and economic impacts represents a fundamental goal of modern organic chemistry. Transition metal catalysis is crucial in achieving this sustainable goal. It offers unique mechanistic opportunities to access compounds that are difficult to obtain by conventional means, lowers the reactions’ activation barriers, and improves their selectivity, rendering the transformations less energy-intensive and more efficient. Despite the incredible achievements in synthetic organic chemistry granted by transition metal catalysis, two pressing challenges must be addressed to meet green chemistry’s objectives. First, one must reduce the reliance on precious transition metals that are expensive and in short supply. In this context, earth-abundant transition metals are a more appealing alternative to the commonly used precious metals in terms of price, availability, carbon footprint, and toxicity. Second, most transition metal-catalyzed transformations require starting materials possessing preferential functional groups (e.g. halides). Installing these functional groups implies additional synthetic steps, making the overall transformation less atom-economical. Thus, new synthetic strategies catalyzed by earth-abundant transition metals that involve commonly occurring functional groups (e.g. C-H bonds, carboxylic acids) are highly sought after.
The overarching goal of the proposal is to develop and study innovative synthetic methodologies involving C-H bond functionalization with catalyst-based transition metals (Co, Cr, Ni) to access new or existing organic compounds from widely available starting materials while ensuring a selectivity control of which bond will be activated. The MLCat will solve the selectivity and reactivity problem associated with the C-H functionalization reactions with transition metals. The materialization of this concept requires the use of multifunctional ligands and a bimetallic catalytic system. The project relies on arenes’ ability to form π-complexes with Cr(0) that drastically activates the aromatic ring, rendering the C-H bonds more acidic towards the C-H activation. Our ultimate goal entails generating a catalytic amount of π-chromium-arene complex that will facilitate the functionalization of C-H of the aromatic ring with the assistance of the second transition metal responsible for the C-FG bond formation.
The overarching goal of the proposal is to develop and study innovative synthetic methodologies involving C-H bond functionalization with catalyst-based transition metals (Co, Cr, Ni) to access new or existing organic compounds from widely available starting materials while ensuring a selectivity control of which bond will be activated. The MLCat will solve the selectivity and reactivity problem associated with the C-H functionalization reactions with transition metals. The materialization of this concept requires the use of multifunctional ligands and a bimetallic catalytic system. The project relies on arenes’ ability to form π-complexes with Cr(0) that drastically activates the aromatic ring, rendering the C-H bonds more acidic towards the C-H activation. Our ultimate goal entails generating a catalytic amount of π-chromium-arene complex that will facilitate the functionalization of C-H of the aromatic ring with the assistance of the second transition metal responsible for the C-FG bond formation.
We identified several sub–aims that will enable us to reach the overarching goal of the MLCat project, which consists of developing efficient aromatic and aliphatic C-H functionalization reactions using a bimetallic catalytic system, such as: (1) Prove, assess, and explore the effect of chromium units on the reactivity of the C-H bonds; (2) Prove, assess, and explore the effect of chromium units on the selectivity of the C-H bonds;(3) Synthesis, characterization, and study of (η6-arene)Cr(CO)2L; (4) Development of a bimetallic catalytic system for the (η6-arene)Cr(CO)2L; (5) Application and diversification of developed bimetallic technologies towards a range of C-C and C-heteroatom bond-forming reactions; (6) Explore the radical reactivity for the aromatic and benzylic C-H bond functionalization via radical addition /rearomatization and hydrogen atom abstraction, respectively. As of now, we have confirmed and gotten conclusive results on the first two sub-aims. We have also been able to move forward with the synthesis and characterization of (η6-arene)Cr(CO)2L. We are actively diversifying the type C-C and C-heteroatom bond-forming reactions. Finally, we want to explore the radical reactivity manifold for the aromatic and benzylic C-H functionalization over the next three years.
We have developed completely novel strategies to control and explore transition metal-catalyzed functionalization involving commonly occurring functional groups compared to the state-of-the-art. The developed approach will enable efficient and straightforward access to functionalized polyaromatic units that represent a privileged structural motif found in natural products, biologically active compounds, and precursors of organic materials with applications in electronics, photonics, and optoelectronics. Also, our approach enables a directing-group-free functionalization of the mono-substituted aromatic rings in high selectivity. These types of transformations are very challenging and highly sought-after in the synthetic organic chemistry community.