Mechanistic studies of the palladium-catalyzed S,O-ligand promoted C-H olefination of aromatic compounds

Pd-catalyzed C-H functionalization reactions of non-directed substrates have recently emerged as an attractive alternative to the use of directing groups. Key to the success of these transformations has been the discovery of new ligands capable of increasing both the reactivity of the inert C-H bond and the selectivity of the process. Among them, a new type of S,O-ligand has been shown to be highly efficient in promoting a variety of Pd-catalyzed C-H olefination reactions of non-directed arenes. Despite the success of this type of S,O-ligand, its role in the C-H functionalization processes is unknown. Herein, we describe a detailed mechanistic study focused on elucidating the role of the S,O-ligand in the Pd-catalyzed C-H olefination of non-directed arenes. For this purpose, several mechanistic tools, including isolation and characterization of reactive intermediates, NMR and kinetic studies, isotope effects and DFT calculations have been employed. The data from these experiments suggest that the C-H activation is the rate-determining step in both cases with and without the S,O-ligand. Furthermore, the results indicate that the S,O-ligand triggers the formation of more reactive Pd cationic species, which explains the observed acceleration of the reaction. Together, these studies shed light on the role of the S,O-ligand in promoting Pd-catalyzed C-H functionalization reactions.</p

Synthesis of α-Substituted Diphenylphosphinocarboxylic Acids and Their Palladium Complexes

© Georg Thieme Verlag Stuttgart · New York-Synlett 2017. A general and efficient synthesis of α-substituted phosphinoacetic acids using simple esters and diphenylchlorophosphine-borane as readily available starting materials is here described. The formation and structure of the corresponding palladium complex derived from 2-ethyl diphenylphosphinoacetic acid is also reported

Bidentate ligand promoted palladium-catalyzed C–H olefination of aromatic compounds

Metal-catalyzed C–H functionalization is an attractive strategy to introduce complexity in organic molecules since no pre-functionalization of the starting materials is required. However, the low reactivity of C‒H bonds and the poor selectivity observed in molecules that contain diverse C–H bonds are the main obstacles in the development of efficient C‒H bond transformations. To unlock the full potential of metal-catalyzed C–H functionalization, the discovery of new ligands capable of increasing the reactivity and selectivity of these processes is of central importance. Herein, we described the design, synthesis and evaluation of a new class of bidentate ligands, based on both heteroatom and carboxylic acid functionalities, for C–H functionalization reactions. In Chapter 2, the development of a new and general methodology for the synthesis of α-substituted phosphinoacetic acids (P,O-ligands) is reported. In Chapters 3–5, the synthesis of new class of ligands in metal catalysis, namely thioethercarboxylic acids (S,O-ligands), is described. The application of these ligands in palladium-catalyzed C–H olefination of simple arenes, including anilines, is presented. The new methodologies proceed efficiently with a broad range of substrates and olefins providing the olefinated product in good yields. We have shown that these methodologies are operationally simple, scalable, and can be used in late-stage functionalization of complex molecules. The S,O-ligand is responsible for the dramatic improvements in substrate scope and the high selectivity observed in these transformations. In Chapter 6, mechanistic studies to understand the role of the S,O-ligand in these reactions are presented

Selective C-H Olefination of Indolines (C5) and Tetrahydroquinolines (C6) by Pd/S,O-Ligand Catalysis

Herein, we report a highly selective C-H olefination of directing-group-free indolines (C5) and tetrahydroquinolines (C6) by Pd/S,O-ligand catalysis. In the presence of the S,O-ligand, a wide range of challenging indolines, tetrahydroquinolines, and olefins was efficiently olefinated under mild reaction conditions. The synthetic potential of this methodology was demonstrated by the efficient olefination of several indoline-based natural products