Synthesis of Enesulfonamides and Benzoxazolidines through Transition-metal Catalyzed C-N Bond Formation

Abstract

Owing to the ubiquity of carbon-nitrogen bond in numerous functional materials, natural products and pharmaceutical agents, the construction of such bonds has been emerged as a frontier area in organic synthesis. In recent years, the transition metal mediated C-C and C- heteroatom bond formation reaction have opened a new avenue with regard to efficiency and versatility. Though, extensive progress in this field has been made, still the formation C-C and C- heteroatom bond, particularly at the unactivated C(sp2) centers is challenging. Notably, the majority of transition-metal-mediated coupling reactions rely on the use of nucleophilic substrates that are prefunctionalized with organometallic traceless activation groups (e.g., boronic acids, stannanes, zinc reagent, and grignard reagent). However, an ever-increasing impetus to improve the versatility, cost, and operational simplicity of transition-metal-based methods has led to the development of elegant protocols that employ organic, native functionality as activation handles for complex fragment coupling reactions. The Fujiwara- Moritani reaction, reported in 1967, is apparently the first representative Pd-catalyzed coupling reaction for C−H alkenylation of arenes. Since then, adequate progress has been made for the transition metal catalyzed C-C and C-heteroatom bond formation reactions by using various unfunctionalized olefines. In turn, the N-alkenylation of amines and amides leading to biologically potent enamines and enamides, respectively, has been investigated extensively. In contrast, skimpy efforts have been made for the N-alkenylation of sulfonamides, although the resulting enesulfonamides are not only privileged as pharmaceutical compounds, but also serve as highly versatile synthetic intermediates, especially in the formation of heterocycles such as saturated oxazolidines, imidazolidines, piperidines, alkaloids and in asymmetric synthesis to access a wide variety of functional benzenesulfonamides. Additionally, the reported methods on enesulfonamide synthesis mainly embark the synthesis of E-enesulfonamides. There are only two methods including the use of Ir- and Rh-catalyst have been developed to access the Z- enesulfonamides from the azides and triazoles respectively. As such, the synthesis thermodynamically unfavorable Z–enesulfonamide is challenging.
In this context, our recent efforts toward the transition metal catalyzed C-N bond formation leading to the stereoselective synthesis of Z-enesulfonamides have been described in this thesis. Furthermore, a novel protocol for the synthesis of benzoxazolidines via enesulfonamide intermediate was also described. The current thesis entitled “Synthesis of Enesulfonamides and Benzoxazolidines through Transition-metal Catalyzed C-N Bond Formation” has been divided into five chapters. A summary of the chapters are as follows:
Chapter 1. Synthesis and Reactions of Enesulfonamides: A Brief Overview

In this chapter we have described the various methods of enamide and enesulfonamide synthesis. Scope and limitations of the earlier works along with the objective of the present work on enesulfonamide and benzoxazolidine synthesis through C-N bond formation have been presented.

Chapter 2. Stereoselective Synthesis of Enesulfonamides via Pd-catalyzed Oxidative Sulfamidation of Terminal Alkenes
This chapter describes the development of a novel catalytic protocol for the synthesis of Z- enesulfonamides by the oxidative sulfamidation of olefins in the presence of ambient air. This protocol is also found to be suitable for the cross coupling of sterically hindered secondary sulfonamides with electron deficient olefins leading to E-enesulfonamides in good yield.

Chapter 3. Palladium-Catalyzed Oxamidation of Alkenes: A New Approach to Benzoxazolidines
This chapter reveals the palladium catalyzed protocol for the synthesis of benzoxazolidine by the reaction of sulfamidophenol and electron deficint terminal alkene. This oxamidation process is simple and does not require any ligand, base or inert atmosphere for the overall transformation.

Chapter 4. Synthesis of benzoxazolidines via Ni-catalyzed Deacylative Oxosulfonamidation of Vinyl acetate
In this chapter Ni-catalyzed a simple and efficient method for the synthesis of benzoxazolidines from the reaction of sulfonamidoalcohol and electron rich alkenes was reported. Subsequently in-situ halofunctionalization was also performed in the presence of Ni-catalyst and a halogen source.

Chapter 5. Conclusion and Future scopes

In the last chapter, the overall conclusions and future scopes of the present work have been described.