Transition metal & photoredox catalysis: The modern approach towards Csp 2–heteroatom bond formation

Abstract

This thesis focuses on transition metal and photoredox catalyzed C-heteroatom (N, S, Se) bond-forming reactions, which are highly significant in delivering important motifs in the pharmaceutical and agrochemical domains. Keywords: • C˗H bond functionalization • Transition metal catalysis • Photoredox catalysis • Latestage functionalization • Olefin metathesis • Stereoselective ❖ Chapter 1: Introduction The formation of C-heteroatom bonds is an emerging area of synthetic organic chemistry, due to its widespread applications across various academic as well as industrial domains. Several strategies like transition metal catalysis, photoredox catalysis, electrocatalysis, and Lewis/ Bronsted acid-catalysis are already well-exposed to forge C-heteroatom bonds. This chapter provides an overview of Cheteroatom bond-forming reactions, highlighting the significance of the protocols, strategic pathways, as well as their advantages and limitations. This clearly illustrates the importance of our work in addressing the research gap in this area. ❖ Chapter 2A: Copper-Catalyzed Regioselective Remote C–H Bond Chalcogenation of Aromatic Amine Derivatives without Using Any Large Template This chapter presents an effective and convenient method for the p-selective chalcogenation of anilide scaffolds through the functionalization of C–H bonds. This strategy leverages one of the most inexpensive and readily available Cu(II) catalysts, as well as easily synthesizable aryl-chalcogen sources, without the need for any complicated directing template, exogenous ligand, acid/base, oxidant, or other additives. The key feature of this methodology lies in impressive regioselectivity along with a wide range of functional group tolerance with good to excellent yield under aerobic conditions. Chapter 2B: Fe(III)-Catalyzed p-Selective C–H Bond Chalcogenation of Phenols This chapter unveils a robust, sustainable, and scalable strategy for the p-selective C–X (X= Se/S) bond formation of phenols using a green solvent, ethanol, and a less toxic, earth-abundant Fe(III) catalyst. Additives, stabilizing ligands, oxidants, or directing templates are not required. The impressive p-selectivity with good yields and broad functional group compatibility under mild aerobic reaction conditions is the key attraction of this methodology. Synthetic potential is revealed by the scalability of the protocol and the synthetic modification of the products towards value-added molecules. Chapter 3A: Merging Photochemical Olefin Metathesis with an Amination Reaction A merger of photochemical olefin metathesis and C‒H amination allows us to access a rare protocol for synthesizing functionalized olefins. Our method enables the stereoselective generation of enamines using a mild and bench-stable oxime ester precursor as the N-linchpin. The key feature is the multitasking catalysis of fac-Ir(ppy)3, which not only enables the energy transfer (EnT) mediated N‒O bond cleavage of an oxime ester to produce an N-centred radical (NCR) and a benzoate radical (•OBz) but also promotes the cycloaddition of two styrene moieties to form a cyclobutane analogue at different stages of the reaction. Further, mechanistic investigations and DFT calculations provide crucial insights on a rare ring-opening metathesis, prompted by the oxidation of the cyclobutane intermediate, followed by nucleophilic attack of an in situ generated benzoate anion (–OBz) and radical-coupling with NCR leading to a highly stable singlet intermediate that undergoes sequential N-protonation and single electron reduction to effectuate elimination and regeneration of •OBz, delivering the Z-selective aminated stilbene. Key features of this newly discovered methodology include reasonable functionality tolerance, satisfactory yield, and exclusive stereoselectivity. Chapter 3B: Ir (III)-Photocatalyzed Stereoselective Synthesis of 2-Azadienes In this chapter, a photocatalyzed, stereoselective C–N bond formation reaction has been developed to synthesize 2-azadiene scaffolds containing trifluoromethyl groups under mild reaction conditions. This current methodology employs the multitasking photocatalysis of fac-Ir(ppy)3 to generate iminyl radicals from bench-stable oxime-ester precursors via an energy transfer (EnT) mechanism. This iminyl radical is installed in the olefinic system as an N-linchpin without any prefunctionalization through a photoredox cycle. The advantages of the reaction consist of the mild aerobic reaction conditions, broad scopes, high yield, and impressive stereoselectivity. Chapter 4: Outlook & Thesis Summary In this chapter, we have summarized the main attractions and achievements of all the experimental works. ❖ Chapter 5: Experimental Details of Chapter 2A, 2B, 3A, 3B In this chapter all the experimental details, mechanistic aspects, details of all the synthesized compounds, and their characterization techniques have been discussed in details.