Asymmetric Catalytic Reactions Of α-Fluorinated Trifluoromethyl Gem-Diols By Bifunctional Thiourea Catalyst

This dissertation focuses mainly on two aspects: synthesis a series of trifluoromethyl β-dicarbonyl compounds, elcctrophilic fluorination of trifluoromethyl β-dicarbonyl compounds to synthesize a series of trilluoromethyl α-fluorinated gem-diol compounds. Mainly studies on the asymmetric reaction of trilluoromethyl P-dicarbonyl and α-fluorinated trifluoromethyl gem-diol compounds. Then extending the fluorinated building blocks and studying the mechanism of releasing trifluoroacetate group.The first part describes the synthesis of fluorinated building blocks: used the ethyl trilluoroacetate and aryl/alkyl/heteroaryl acetophenons to synthesize a series of trilluoromethyl β-dicarbonyl building blocks, then synthesize series of α-fluorinated trilluoromethyl gem-diol compounds by the available fluorinating reagent Selectlluo under mild reaction conditions.The second part introduces the asymmetric constructions of chiral fluorinated tertiary center via organocatalytie reactions using trilluoromethyl β-dicarbonyl and α-fluorinated trilluoromelhyl gem-diol compounds:1) In this part has been developed an efficient and highly enantioselective catalytic Michael addition reaction using chiral thiourea tertiary amine derivatives as the catalyst, which stresses on the release of trifluoroacetate as a strategy for cleavage of C-C bond. The resulting decarboxylated y-nitro-α-fluorocarbonyl products with two contiguous centers were obtained in91%yields with good diastereoselcclivities (up to20:1dr) and excellent enantioseleelivics (up to98%ee).2) In this part has been developed a new and efficient direct aldol reaction of gem-diols to isatins catalyzed by cinchona alkaloid hi functional thiourea catalyst. The key step ol’ this protocol lies on the release of trilluoroacetate for cleavage of C-C bond by making use of gem-diols as a synthetic equivalent of fluorinaled aryl/alkyl methyl ketone enolates. The resulting deearboxylated chiral lluorinated3-hydroxy-3-phenacyloxindole products were obtained almost quantitatively (up to99%) with excellent diastereoseleetivities (99:1dr) and enantioselectivies (83%-98%ee).3) In this part, the uses the strategy of selective cleavage of carbon-carbon bonds through the mild release of trifluoroacetate group to build lluorinated building blocks and developed a new and efficient direct Mannieh reaction of α-fluorinated trifluoromethyl gem-diol compounds to tert-butyl aryl/alkyl/heteroaryl-(phenylsulfonyl)methylcarbamate catalyzed by cinchona alkaloid bifunctional thiourea catalyst. The resulting decarboxylated fluorinated chiral amino products were obtained almost moderate yield (up to72%), diastereoselectivities (up to5:1dr) and enantioselectivies (up to89%ee).