Ruthenium-catalyzed P(?)-directed Ortho-functionalizations Of Tertiary Phosphine

Tertiary phosphines(PR₃)belong to a critically important cornerstone where they are widely used in transition-metal catalysis and functionalizing organic materials for their unique optical properties.Moreover,their steric and electronic properties can be altered by varying the R groups.For instance,Buchwald-biaryl monophosphines with a large steric hindrance have been widely used as supporting ligands in metal-catalyzed C-C,C-O,C-N and C-X bond construction processes.Consequently,efficient and diverse synthesis and modifications of PR₃ has been arguably the most important contributor to the advancement of metal-catalysis field.In recent decade,transition-metal catalyzed C-H bond activation strategy has provided a powerful tool for synthesis of PR₃,which has enabled more efficient chemical synthesis by avoiding the traditional requirement of preinstalled functional handles.In this dissertation,we focused on the ruthenium-catalyzed ortho-C-H bond functionalizations and further derivatizations of tertiary phosphine based on the P-directed strategy.Its main innovations:1.Innovation of catalytic system:P(?)-directed C-H bond activation was extended from transition-metal such as Rh,Ir and Pd-catalyzed systems to cheaper Ru catalytic system,which improved the reaction economy and enriched the catalytic systems.2.Innovation of mechanism research method:Taking control experiments as the core,assisted by ESI-MS technology,combined with basic theoretical knowledge of coordination catalysis,the reasonable analysis of catalytic intermediates was carried out to describe the whole catalytic process as real as possible.The main contents are as follows:1.Ruthenium-catalyzed P(?)-directed gram-scale ortho-C-H arylation of tertiary phosphineThe ruthenium-catalyzed ortho-C-H arylation of PR₃ assisted by monoprotected amino acid ligands is accessed for the first time.By increasing the reaction concentration of the system could not only improve the yields,but also successfully achieve the gram-scale synthesis.This reaction bears a good substrate scope and is suitable for substrates with different electronic and steric substituents.In addition,the reaction system was monitored through controlled experiments by ESI-MS and the plausible reaction route was proposed.2.Ruthenium-catalyzed P(?)-directed ortho-C–H hydroarylation of tertiary phosphineThe ortho-hydroarylation of PR₃ was carried out by using acrylic acid derivatives as the coupling reagents.In addition to a broad scope of substrates,novel skeleton monophosphine ligands can be further obtained by hydrolysis and amidation of the alkylated product.Notably,the six-membered cycloruthenated intermediate was successfully prepared for the first time,which provided strong evidence for the analysis of the reaction mechanism based on the control experiments.3.Ruthenium-catalyzed P(?)-directed ortho-C–H alkylation of tertiary phosphineThe ortho-alkylation of PR₃ was carried out by using acetate derivatives as the alkylating reagents,which provided a direct and more efficient access for the synthesis of Buchwald-type phosphine ligands with primary and secondary flexible alkyl chains through the inert C-O bond cleavage.4.Ruthenium-catalyzed P(?)-directed ortho-C–H oxidative homo-coupling of tertiary phosphineThe oxidative C–H bonds homo-coupling of PR₃ catalyzed by transition metal catalysis was achieved for the first time,and its structure was confirmed by X-ray crystallographic analyse,which successfully realized the direct synthesis of bisphosphine compounds.Additionally,further explorations about this catalytic system are ongoing in our laboratory.