RNF 19-73-10100
"Development of effective catalysts based on Nickel and palladium complexes with N-heterocyclic carbenes (NHC) in carbon-heteroate bond formation reactions for the synthesis of practically important molecules»
The project is aimed at solving the problem of deactivation of metal-complex catalysts and creating highly active, selective and stable catalytic systems for carbon-heteroate bond formation reactions (C-X, X = S, O, N, etc.) used in the production of pharmaceuticals and agrochemicals.

Carbon-sulfur, carbon-oxygen, and carbon-nitrogen bond formation reactions catalyzed by transition metal complexes are widely used in both laboratory and industrial organic synthesis. However, an important problem of metal-catalyzed C-X bond formation reactions is the rapid deactivation of metal-complex catalysts. This problem is caused by the ability of many heteroatom-containing reagents and products to form strong bonds with metals, leading to the substitution of ligands and the destruction of catalytically active metal complexes. For example, a typical reason for deactivation of palladium and Nickel complexes in thiolation reactions is the substitution of auxiliary ligands with thiols and the formation of inactive polymer metal sulfides containing metal-sulfur-metal bridge bonds. Due to the problem of rapid deactivation in many practically important processes based on C-X bond formation reactions, it is necessary to use increased loads of metal-complex catalysts and develop special methods for cleaning products from metal impurities.

One of the main approaches to solving the problem of deactivation is the use of highly stable metal-complex catalysts with increased stability of the metal-auxiliary ligand bond. Such catalysts include transition metal complexes with N-heterocyclic carbenes (M/NHC), which are becoming increasingly common in the catalysis of carbon-heteroate bond formation reactions. M/NHC complexes are characterized by high binding strength of metals to NHC ligands and wide possibilities for varying the ligand environment. However, despite the high strength of the metal-NHC bond, when many C-X bond formation reactions are catalyzed, M/NHC complexes lose their catalytic activity quite quickly. The ways of deactivation of complexes and the main factors that ensure the activity and stability of M/NHC complexes in the catalysis of carbon-heteroate bond formation reactions are still poorly understood.

In this project, for the first time, a systematic study of the transformations of Pd/NHC and Ni/NHC complexes during the catalysis of typical carbon-heteroate bond formation reactions (C-S, C-O, C-N) will be performed. It is expected to obtain breakthrough data on transformations of metal complexes in the process of catalysis, which will reveal the main factors that determine the activity and stability of catalytic systems, and understand the reasons for deactivation. Considerable attention will be paid to the little-studied reactions of reducing elimination of NHC ligands by type X-NHC combination (X = S, O, N) and their effect on catalysis. To create highly active and stable M/NHC catalysts, new approaches to modifying the structure of NHC ligands based on the introduction of special ionizing and chelating groups that affect the electronic state and spatial environment of the metal will be investigated. New approaches will be tested based on the introduction of specific soligands and reagents into reaction mixtures that affect the activation and stabilization, or regeneration of metal complexes. As a result, it is planned to develop new highly active and stable catalytic systems based on M/NHC complexes and effective processes for the synthesis of practically important sulfur -, oxygen-and nitrogen-containing compounds, including drugs and agrochemicals used in practice.

Expected result:

New fundamental knowledge will be obtained about the transformations of m/NHC complexes (M = Pd, Ni) in the process of catalysis of typical reactions of carbon-heteroate bond formation (heteroate — N, O, S, etc.) — hydrothyolation of unsaturated compounds, aryl - and alkylthyolation, hydroxylation, alkoxylation, phenoxylation and amination of aromatic and heteroaromatic compounds. The nature of the active centers, the mechanisms of catalysis and deactivation, as well as the main factors determining the activity and stability of M/NHC complexes during the catalysis process will be determined. New methods of stabilization of M/NHC complexes based on modification of the structure of NHC ligands by introducing specific ionizing and chelating groups have been developed, which will ensure high activity and stability of catalytic systems in typical C-X bond formation reactions (X = N, O, S, etc.); new highly active and stable catalytic systems based on M/NHC complexes and effective methods for the synthesis of a number of drugs and agrochemicals have been created.
The expected results will contribute to the development of homogeneous metal complex catalysis and General methodology for the synthesis of organic substances based on metal-catalyzed reactions forming bonds of carbon with oxygen hetero-atom.