Nickel and palladium complexes for C–H functionalizations of heteroarenes: synthesis, scope and Mechanistic aspects

Abstract

The thesis is divided into five different chapters. Chapter-1 deals with the detailed literature survey on the synthesis of palladacycle complexes, and their applications in traditional cross-coupling as well as in direct C–H bond functionalization of arenes and heteroarenes. Mechanistic aspect of the palladium-catalyzed coupling reaction is also reviewed. Similarly, this chapter includes reports on the NNN-pincer nickel complexes, their application in traditional cross coupling and C–H functionalization, and catalytic aspects. The C–H bond functionalization of heteroarenes with simple nickel precursor is also discussed in this chapter.Chapter-2 describes the syntheses of mono- and binuclear palladacycles via regioselective C‒H bond activation, and application in azoles arylation. Palladacycles containing C-anionic four-electron donor (CE) or six-electron donor (ECE) ligand (E = donor group) have many attractive structural features. Generally, the selective synthesis of CE- and ECE-palladacycle requires the introduction of a site selective activating group (-SiMe3) in the ligand backbone.Thus, in this chapter, we focussed on the syntheses of new unsymmetrical “POCN” pincer-type ligands, and their “PC”-chelated binuclear, [κP,κC-PC-PdCl]2 (CE-type) and “POCN”-coordinated mononuclear, (κP,κC,κN-POCN)PdCl (ECE’-type) palladacycle complexes via the regioselective C−H bond activation. More importantly, the steric and electronic influence of base on the regioselective C−H palladation is demonstrated by extensive kinetics analysis. All the palladacycles were well-characterized by various analytical techniques, including X-ray crystal structure determination. The palladacycle complexes were screened and employed as catalysts for direct C−H bond arylation of azoles with aryl iodides. Chapter 3 describes the nickel-catalyzed chemo and regioselective C-2 alkylation of indoles with unactivated primary and secondary alkyl chlorides. We have demonstrated a new methodology, wherein a simple Ni-catalyst system (thf)2NiBr2/bpy was efficiently employed for the C-2 alkylation of indoles at mild condition using unactivated alkyl chlorides as coupling partners. We have successfully demonstrated various substrate scopes for alkylation of indoles using diverse unactivated alkyl chlorides. Different functional groups, like halides, alkenyl, alkynyl, ether, thioether, furanyl, pyrrolyl, indolyl and carbazolyl including acyclic and cyclic alkyls were well tolerated under optimized reaction condition. Mechanistic experiments like kinetics, external additive experiment, radical probe experiment, deuterium labeling experiments were performed to get more insight of the reaction mechanism. EPR and XPS studies were done to analyze the reactive nickel intermediate. A comprehensive mechanistic study highlights that the alkylation proceeds through a single-electron transfer (SET) process with Ni(I)-species being the active catalyst. Overall, the alkylation follows a Ni(I)/Ni(III) pathway involving the rateinfluencing two-step single-electron oxidative addition of alkyl chloride.Chapter 4 describes regioselective nickel-catalyzed C-2 arylation of indoles with unactivated aryl chlorides. A simple nickel catalyst system Ni(OAc)2/dppf was found to be suitable for the arylation of indole and pyrrole derivatives with diverse aryl chlorides at relatively mild conditions. Varieties of functional groups, such as –F, –OMe, –OCF3, ether, thioether, pyrrolyl, indolyl and carbazolyl were tolerated under the reaction conditions. Detailed mechanistic study for this arylation reaction has been performed, including external additive experiments, deuterium labeling experiments and kinetic experiments to get insight of the reaction mechanism. Mechanistic study highlights that the arylation proceeds through a single-electron transfer (SET) process.Chapter 5 discusses about the synthesis of hemilabile (QNNNR2)–H ligand and pincer nickel complexes. The synthesized complexes were characterized by different spectroscopic techniques and the structures were confirmed with the help of X-ray diffraction technique. These complexes were screened and employed for the C–H bond alkylation of indole. Selective substrates scope has been demonstrated using this nickel catalyst. This chapter also deals with the one-pot strategy for the dehydrogenative alkylation of indolines to achieve C-2 alkylated indoles via a monodentate-chelate assistance strategy