Transition Metal-Promoted Synthesis of Remotely Functionalized 2-Aryl Benzoxazoles from 2-Amidophenol through C-H Functionalization

Abstract

2- Substituted benzoxazoles are an important class of heterocycles found in several biologically relevant compounds, natural products, and designed pharmaceutical molecules. They also serve as valuable functional compounds in many organic syntheses and show a remarkable chromophoric effect. In addition to the classical methods, innovative transitionmetal-catalyzed methods have been developed to synthesize variously functionalized benzoxazoles with the aid of diverse directing groups through oxidative sp2 C-H bond activation. The ligating ability of the nitrogen atom in the benzoxazole ring has been exploited significantly for the ortho- C-H bond activation. In contrast, synthesizing the benzoxazole framework with C-H functionalization at the fused-benzene ring is less literature precedent. As such, synthesizing functionalized benzoxazole at the fused benzene ring site is challenging. The current thesis entitled “Transition Metal-Promoted Synthesis of Remotely Functionalized 2-Aryl Benzoxazoles from 2-Amidophenol through C-H Functionalization” mainly addresses our initiatives to access C4-H, C5-H and C7-H functionalized 2-aryl benzoxazoles directly with the aid of transition-metal catalyst under ligand-free conditions. The present thesis has been divided into five chapters. Chapter 1. A Short Review on Transition Metal-catalyzed Synthesis of Functionalized 2- Aryl Benzoxazoles This chapter describes the transition metal-catalyzed different methods for synthesizing functionalized 2-aryl benzoxazoles via C-H activation. In addition, a critical overview and objective of the present work were also presented. Chapter 2. Synthesis of 4-Alkenyl Benzoxazoles via Pd-catalyzed ortho C-H Functionalization of 2-Amidophenols In this chapter, one-pot direct synthesis of remotely C-H alkenylated 2-aryl benzoxazoles from the reaction of amidophenol and electronically deficient olefin in the presence of Pd-catalyst was reported. Control experiments confirm that the Pd-catalyzed anilide-directed regioselective C−H activation/alkenylation occurs at the first step by leading to ortho-alkenylated amidophenol, which subsequently underwent tandem intramolecular annulation to afford C4-alkenylated 2-aryl benzoxazole derivatives. xi Chapter 3. Access to C4-Arylated Benzoxazoles from 2-Amidophenol through C-H Activation In this chapter, a Pd-catalyzed aerobic approach to access C4-aryl benzoxazoles from the tandem C-H ortho-arylation and acid-mediated annulation of 2-amidophenol has been presented. The competing directing potential of the –NHCOR group over the –OH group was exploited for selective arylation adjacent to the amide group. One-pot hydrolysis of the resulting C4-arylated benzoxazole was also accomplished to access structurally challenging 3- aryl aminophenols for further applications. Chapter 4. Iron(III) Chloride Mediated Para-Selective C-H Functionalization: Access to C5-Chloro and C5, C7 Dichloro/Dianisyl Substituted 2-Aryl Benzoxazoles This chapter reveals the iron(III) chloride-mediated para-selective C-H chlorination and subsequent annulation of 2- amidophenol to synthesize C5- and C5, C7-chlorinated benzoxazoles. Further, the oxidative cross-dehydrogenative coupling of amidophenol with anisole by ferric chloride was presented to achieve the remotely anisylated benzoxazoles. Chapter 5. Conclusion and Future Scope In the last chapter, the present work's overall summary and future scopes have been described.