Development of novel methodologies in Aryne chemistry and their application in the total synthesis of bioactive natural products

Abstract

The present thesis demonstrates a creative exploration of aryne as versatile building blocks to construct new C–C and C–heteroatom bonds for the synthesis of various scaffolds and complex natural products. Chapter 1 describes a brief history of aryne, different methods available for their generation and various types of aryne reactions. Representative examples of insertion, pericyclic, annulation and multicomponent reactions of aryne are described in detail. Chapter 2 deals with our studies on C–C, C–P and C–N bond forming reactions of aryne, which is divided into three sections. Section 1 covers the transition-metal-free C–arylation of malonamide esters. We have achieved a selective mono- or di-arylation and quaternary centre generation using arynes. Section 2 demonstrates a novel process for C–P bond construction to afford aryl phosphonates, -phosphinates and phosphine oxides for the first time using transition-metal-free protocol. Section 3 describes an unusual nucleophilic nitration protocol using aryne chemistry, and the concept has been further extended for the synthesis of ortho-difuntionalized nitro-aromatics via a multicomponent reaction. Chapter 3 describes our studies on the total synthesis of bioactive natural products using aryne in two sections. Section 1 deals with the synthesis of the spiroannulated benzofuran-3-one scaffold of Leptosphaerins C and congeners via insertion reaction of aryne, whereas section 2 covers the study towards the total synthesis of Lycorane family of natural products via cycloaddition reaction of aryne.