REGIOSELECTIVE SYNTHESIS OF B-HYDROXY SULFIDES, SPIROOXINDOLES AND BENZYLIDENE SUCCINIMIDE-TETHERED PROPANONES SCAFFOLDS

Abstract

The thesis entitled “Regioselective synthesis of  -hydroxy sulfides, spirooxindoles and benzylidene succinimide-tethered propanones scaffolds” is divided into three chapters, viz. (i) Introduction, (ii) Objectives, Results and Discussion, and (iii) Experimental. Chapter 1: Introduction Regioselective synthesis has always been the point initial concern as this affects the outcome of nearly all kind of reactions involving carbon–carbon and carbon–heteroatom bond formation formation. Consequently, it is attracting much attention since last few decades. Various methods have been developed for the synthesis of CC and C bonds. However, some protocols involve transition metals, expensive reagents or additives and therefore this area is still under exploration to develop environment friendly strategies for the construction of important scaffolds having biologically significant moieties like oxindoles, spirooxindoles and biaryls. There have been many synthetic protocols such as radical addition, cycloaddition, Michael addition and domino reactions to construct CC and CX bonds. A few of such strategies have been employed successfully to access useful scaffolds such as  -hydroxy sulfides, benzylidene succinimide-tethered propanones, spirooxindoles which are having significance similarities to bio-active scaffolds. Chapter 2: Objectives, Results and Discussion This chapter deals with the objectives, results and discussion which are divided into four sections. 2.1. Synthesis of substituted  -hydroxy sulfides we have developed a metal-free, green and environmentally friendly, highly regioselective method for the synthesis of  -hydroxy sulfides in good to excellent yields from styrenes and thiophenols using an inexpensive, nontoxic and eco-friendly iodine/DMSO system. The reaction involves single step CS and CO bonds construction. The results obtained from iodine-mediated synthesis of various sulfur containing compounds are presented here. iv Figure 18: Iodine-catalyzed synthesis of  -hydroxy sulfides. 2.2. Synthesis of highly substituted spirooxindolic-cyclopentanes via [3 + 2] cycloaddition reactions We have successfully demonstrated a DBU-catalyzed regioselective synthesis of a series of spirooxindoles via a [3 + 2] cycloaddition strategy using mild reaction conditions. The current rapid protocol offers valuable fully substituted cyclopentanes with five contiguous stereocenters in good yields with excellent diastereoselectivity in regioselective manner from easily accessible starting materials. Moreover, this methodology is simple and does not require purification steps such as recrystallization and column chromatography. Figure 19: DBU-catalyzed highly diastereoselective synthesis of substituted spirooxindoles. 2.3. Synthesis of benzylidene succinimide-tethered propanones via Michael addition reactions We have illustrated a novel approach to access benzylidene succinimide-tethered propanones via an efficient, metal-free, base mediated protocol. The present work involves a simple Michael addition strategy of 3-benzylidene succinimides as a readily available v nucleophile source for chalcones through C–C bond formation. All the products were obtained in good yields with excellent regeo- and diastereoselectivity and the products can be obtained just by simple filtration followed by simple washing with ethanol. Figure 20: DBU-calalyzed highly diastereoselective synthesis of benzylidene succinimidetethered propanones. 2.4. Synthesis of highly conjugated xanthene-tethered unsymmetrical biarylic spirooxindoles via domino reactions We investigated Brønsted acid assisted domino ring opening cyclization between donoracceptor cyclopropanes and  -naphthols. The protocol involves the construction of three CC and one CO bonds during the course of reaction in one-pot manner to furnish the highly conjugated biaryl-xanthene-spirooxindoles hybrid with one quaternary carbon atom regioselectively. vi Figure 21: Triflic acid mediated synthesis of xanthene-tethered biarylic spirooxindoles. Chapter 3: Experimental The third chapter provides experimental procedures in detail along with physical and spectroscopic data such as MP, yield, 1H and 13C NMR and mass spectral data.