The Activation And Applications Of Fluorinated Enol Silyl Ethers

This thesis focuses on the activation and applications of fluorinated enol silyl ether. Three type of reactions using fluorinated enol silyl ethers have been developed by taking advantage of C-F…H-O interaction, tertiary amine-H bonding bifunctional catalysis, phosphoramide-secondary amine catalysis and cationic Au(I) catalysis. These protocols paves a facile way for the synthesis of value-added fluoroalkyl substituted alcohols, Ca-tetrasubstituted α-amino acid derivatives and all-carbon quaternary oxindoles, which includes following research work:1) An "on water" catalyst-free nucleophilic addition of difluoroenoxysilanes to aldehydes, activated ketones and isatylidene malononitriles is established, providing a highly efficient synthesis of α,α-difluoro-β-hydroxyl ketones and all-carbon quaternary oxindoles. By control experiments and DFT calculations, it is believed that the formation of C-F…H-O interaction between difluoroenoxysilanes and water on the phase boundary, together with the activation of electrophiles through H-bonding interaction, plays a crucial role for highly efficiency of this reaction.2) A highly stereoselective Mukaiyama-Mannich reaction of fluorinated enol silyl ether with cyclic N-sulfonyl ketimines is developed by using hydroquinine derived urea-tertiary amine bifunctional catalyst, affording a variety of fluorinated benzosultam based α-quaternary amino acid derivatives in high yields and enantioselectivities. The thus obtained products could be readily elaborated.A Ph3PAuOTf catalyzed Mukaiyama-Mannich reaction of difluoroenoxysilanes to N-Boc isatin ketimines and cyclic ketimines is realized. This provides a highly efficient approach to access 3-difluoroalkyl substituted 3-aminooxindoles and gem-difluoroalkyl substituted a-amino acid derivatives. This also represents the first application of Au(I) as a a-Lewis acid in Mukaiyama-Mannich reaction. The method has been applied to the total synthesis of difluoromethylated analogue of AG-041R, a gastrin/CCK-B receptor antagonist.3) A novel chiral 1,2-cyclohexanediamine derived bifunctional secondary amine-phosphoramide catalyst is developed and applied to the highly stereoselective Mukaiyama-Michael reaction of fluorinated enol silyl ethers. The method provides a highly enantioselective protocol for the forge of fluoroalkyl substituted all-carbon quaternary stereocenter. Control experiments reveal that phosphoramide as a structure unit of catalyst is superior to amide, sulfonamide and (thio)urea in terms of reactivity and selectivity. Under the same conditions, the corresponding tertiary amine-phosphoramide bifunctional catalysts catalyze the reaction to afford the opposite enantiomer of the products.