Transition Metal-Catalyzed C-C and C-Heteroatom Bond Formation Through Radical Process

Abstract

During the past few decades, radical reactions have been exploited extensively to generate carbon-carbon and carbon-heteroatom bonds in synthesizing valuable natural products and organic compounds. Free-radical reactions have advantages over ionic reactions in terms of wider functional group tolerance, ease in performing group and atom replacement, the potential to build complex structures from simple building blocks, and most notably, the mild reaction condition. Radicals are single electron species and are highly reactive; hence undergoes a variety of chemical reaction such as addition, substitution, cyclization, fragmentation, and hydrogen atom transfer reaction. Since the addition reaction of radicals to multiple bonds is generally a kinetically controlled process, the steric effect and radical stability are less significant in product formation, especially in radical addition and cyclization reactions. In recent years, TM-catalyzed radical cross-coupling reactions have created a revolution in organic chemistry by assembling simpler coupling partners into more complex organic compounds in a sustainable, economical, and efficient manner. The current thesis entitled “Transition Metal-Catalyzed C-C and C-Heteroatom Bond Formation through Radical Process” mainly describe a study on the development of some newer catalytic protocols for C-C and C-heteroatom bond formation reactions with the aid of transition-metal catalyst via a radical pathway. In particular, we have developed new radical cross-coupling protocols for the synthesis of N-sulfonyl ketimines, symmetrical and unsymmetrical biarylsulfones, symmetrical biaryls and vinyl arenes. Iron-catalyzed oxidation of diols to α-hydroxy ketone through a radical process, and subsequent reaction with hydrazones to afford 1,3- and 1,3,5-substituted pyrazoles in the presence of iron-catalyst was also explained. The current thesis contains 5 chapters which are summarised as follows: Chapter 1: A short review on transition metal-catalyzed radical cross-coupling reaction This chapter briefly overviews the TM-catalyzed radical cross-coupling reaction for C-C and C-heteroatom bond formation. Additionally, nitrogen heteroatom containing directing group mediated C-H acylation of different arenes has been described. In addition, a critical overview and objective of the present work are also presented.
Chapter 2: Palladium-catalyzed ortho-benzoylation of sulfonamides through C–H activation: Expedient synthesis of cyclic N-sulfonyl ketimines In this chapter, Pd-catalyzed ortho-carbonylation of sulfonylarene by non-hazardous carbaldehydes as a carbonyl precursor has been discussed. Sulfonamide group served as the directing group for C-H activation under ligand-free conditions. The scope of the strategy has been extended towards the one-pot two-step synthesis of cyclic N-sulfonyl ketimines under mild-reaction conditions. Chapter 3. N-Methoxyarenesulfonamide as a sulfonyl equivalent for palladium-catalyzed sulfonylation of arenes through C-H activation This chapter deals with the synthesis of diaryl sulfones from the unbiased arenes through palladium-catalyzed C−H activation. N-methoxy arenesulfonamide was exploited as a potential sulfonyl donor by the cleavage of the S−N bond through a radical pathway. The present methodology has several advantages: a simple, readily available catalytic system; the use of a stable sulfonyl donor; a relatively moderate excess of arene coupling partner for an undirected C−H activation process, along with the tolerances of aryl bromides and iodides, which in turn permits further cross-coupling reactions to afford cross-coupled sulfones. Chapter 4: Pd-catalyzed desulfitative arylation of olefins by N-methoxysulfonamide This chapter describes a Pd-catalyzed protocol desulfitative Heck-type reaction of N-methoxy aryl sulfonamides with alkenes. Expectedly, the reaction proceeds through the CuCl2- promoted generation of nitrogen radical and subsequent desulfonylation to afford the aryl radical for the Pd-catalyzed coupling reaction. N-methyl sulfonamide was further exploited for the synthesis of symmetrical biaryls under a similar reaction condition. Chapter 5. Facile Synthesis of Pyrazoles by Iron-catalyzed Regioselective Cyclization of Hydrazones and 1,2-diols under Ligand-free Conditions This chapter describes a facile synthesis of pyrazoles by the cyclization of hydrazones and 1,2-diols. In the presence of ferric nitrate, the reaction occurs under neat conditions and makes use of the potassium persulfate to oxidize the diol to α-hydroxy carbaldehyde for the reaction with hydrazones to produce 1,3- and 1,3,5-substituted pyrazoles selectively. The overall regioselective transformation occurs in one pot under ligand-free, mild conditions even in the presence of air. Chapter 5. Conclusion and Future Scope In the last chapter, the overall summary and future scopes of the present work have been described.