Multicomponent synthesis of fluorinated organic compounds using novel lewis acid catalysis and related chemistry

UnrestrictedThis dissertation focuses on the development of new methodologies for the synthesis of both fluorinated and non-fluorinated biologically important molecules via the use of green Lewis acid catalysts. It also describes the syntheses of fluorinated cyclic ethers via Mitsunobu conditions. In addition, the stereoselective construction of fluorine bearing chiral carbon centers have also been explored.; In chapter 1, a general overview of Lewis Acids with the emphasis on TMSOTf catalyzed reactions are described. The need for a green Lewis acid catalyst and the significance of fluorine containing molecules are also mentioned.; In chapter 2, the direct reductive amination of aldehydes in the presence of silanes using Ga(OTf)3 as a catalyst has been disclosed. Mild conditions, easy work-up and high purity of products with excellent yields are the major advantages of this method.; In chapter 3, a versatile carbonyl defunctionalization system has been achieved using a water tolerant, recyclable, catalytic Ga(OTf)3/Me2SiHCl system. Both aromatic and aliphatic ketones were effectively reduced to the corresponding methylene products with high functional groups tolerance, under very mild conditions in a relatively short time with good to excellent yield.; In chapter 4, the one-pot three-component Strecker reaction of ketones/fluorinated ketones for the preparation of α-aminonitriles/fluorinated α-aminonitriles has been achieved using trimethylsilyl trifluoromethanesulfonate (TMSOTf) as a metal-free strong Lewis acid catalyst. These reactions are simple and clean, giving the products in high yield and high purity.; In chapter 5, the one-pot synthesis of biologically active fluorinated heterocycles such as benzimidazolines, benzothiazolines, benzoxazolines, dihydrobenzoxazinones, 1,2,3,4-tetrahydroquinazolines, 4H-3,1-benzoxazines and 3,1-benzoxathiin-4-ones using TMSOTf as a metal free catalyst has been disclosed.; In chapter 6, synthesis of trifluoromethylated cyclic ethers has been achieved via the Mitsunobu cyclodehydration of fluorinated diols with high efficacy. The methodology is found to be widely applicable to the synthesis of cyclic ethers with varying ring size (3-7) from fluorinated diols of differing acidities and steric demands. Cyclic ethers with considerable ring strain can be achieved in moderate yields by this protocol. The methodology is suitable for both primary and secondary alcohols as well as benzylic and aliphatic alcohols as electrophiles to afford the corresponding products in moderate to good yields.; In chapter 7, both synthetic and theoretical aspects of the asymmetric organocatalyst mediated conjugate addition of FNSM to nitro-olefins for the construction of fluorinated stereogenic center has been explored