Development of new synthetic methods for organic synthesis

Abstract

The thesis entitled “Development of New Synthetic Methods for Organic Synthesis” is divided into five chapters. In the first four chapters, oxidations of olefins have been studied using KMnO as an oxidant and CuSO·5HO as the solid support under heterogeneous conditions, in the presence of catalytic amounts of water and tertbutyl alcohol, to achieve different types of interesting transformations. Formation of an omega phase (also known as third phase or thin layer) has been invoked to explain the role of water and tertbutyl alcohol in these oxidations. The fifth chapter deals with transformations using a combination of benzyltriethylammonium borohydride and chlorotrimethylsilane.

Chapter 1 This chapter is subdivided into Part A and Part B. Part A This part describes a synthetic methodology developed using KMnO-CuSO·5HO under omegaphase catalysis to achieve the synthesis of ketols / diketones directly from cyclic olefins. In the case of citronellyl acetate 1, an appreciable amount of epoxide 2a was formed in addition to ketol 2b (Scheme 1).

Part B The conditions for epoxide formation observed earlier were optimized. It was found that lipophilic substrates tend to form epoxides under the reaction conditions, and the maximum amount of epoxide is obtained when KMnO-CuSO·5HO is used as the oxidant under omegaphase catalysis with dichloromethane as the solvent. Epoxide formation can be reduced or eliminated when montmorillonite K10 is used as the solid support instead of CuSO·5HO under identical conditions. This methodology can be applied to the oxidation of oleic acid derivatives to the corresponding diketones (e.g., 3 4b; Scheme 2).

Chapter 2 This chapter describes studies on the reaction of unsaturated steroids with heterogeneous permanganate under omegaphase catalysis. Interestingly, in all steroids studied, the 5,6epoxide is formed with very high stereoselectivity (> 92%) and in excellent yields (90-95%) (Scheme 3).

Chapter 3 Although numerous methodologies exist for cyclopentenone annulation, few provide 5,5dimethylcyclopentenone directly from carbonyl precursors. This chapter describes the development of such a methodology using substituentdirected oxidative cyclisation. Similarly, allylic spirolactone 5, earlier prepared by a circuitous route, has been synthesized easily and in good yield using this method. A concise synthesis of steroidal spirolactone 6 has also been achieved (Scheme 4).

Chapter 4 The substituentdirected oxidative cyclisation strategy was extended to the synthesis of mediumsized cyclic ketolactones using KMnO-CuSO·5HO or KMnO-montmorillonite K10 under omegaphase catalysis (Scheme 5).

Chapter 5 This chapter discusses the direct conversion of olefins to alcohols using a combination of benzyltriethylammonium borohydride and chlorotrimethylsilane (1:1). The reagent system is suitable for the reduction of carbonyl compounds and carboxylic acids to the corresponding alcohols (Scheme 6). Attempts were also made to delineate the mechanism of this unusual hydration of olefins to alcohols. The role of silicon and incorporation of atmospheric oxygen have been suggested as responsible for the transformation.