Synthesis Of α-trifluoromethyl Tertiary Alcohols Based On Benzothiazole Trifluoromethyl Ketone Hydrates

α-Trifluoromethyl tertiary alcohols are an important kind of organofluorinated compounds,which are widely used in pharmaceuticals,dyes,and materials.In view of its importance,many methods on the synthesis ofα-trifluoromethyl tertiary alcohols have been reported.Most methods are based on the 1,2-addition reaction between nucleophile and trifluoromethyl ketone catalyzed by metals and organocatalysts.However,there are still some problems,such as limited substrate scope,long reaction time,and high loading of catalysts.These shortcomings may limit their wide applications in industrial production.This thesis summarizes the synthesis ofα-trifluoromethyl tertiary alcohols in recent years.On the basis of previous studies,we have developed four methods to synthesizeα-trifluoromethyl tertiary alcohols using benzothiazole trifluoromethyl ketone hydrates as the starting materials.This thesis is divided into five chapters.In chapter 1,the methods of synthesizingα-trifluoromethyl tertiary alcohols are summarized from three aspects in recent years.It mainly includes the 1,2-addition reaction between nucleophile and trifluoromethyl ketones,the reaction between carbonyl compounds and trifluoromethylation nucleophile reagents,and the ring-opening reaction of trifluoroethylene oxides.In chapter 2,a highly efficient Br?nsted acid-catalyzed asymmetric Friedel-Crafts alkylation of indoles with benzothiazole-bearing trifluoromethyl ketone hydrates as electrophiles has been developed.The mild organocatalytic reaction proceeded well with low catalyst loading to afford a range of enantioenrichedα-trifluoromethyl tertiary alcohols containing both benzothiazole and indole rings with excellent yields and enantioselectivity.In chapter 3,an efficient organocatalytic enantioselective cross-aldol reaction of aryl ketones to heteroaromatic trifluoromethyl ketone hydrates has been demonstrated.The cross-aldol reactions proceeded well under mild conditions by using Takemoto-type thiourea catalysts,furnishing a variety ofα-trifluoromethyl tertiary alcohols with good to high yields and enantioselectivities.This protocol features broad substrate scope,good functional groups tolerance,and easy gram-scale preparation,and provides access to the synthesis of chiralα-trifluoromethyl tertiary alcohols in a highly efficient manner.In chapter 4,an efficient catalyst-free C(sp~3)-H bond functionalization of methyl azaarenes with heteroaromatic trifluoromethyl ketone hydrates in water has been developed for the synthesis ofα-trifluoromethyl tertiary alcohols bearing N-heteroaromatics.This method not only features excellent efficiency,broad substrate scope,catalyst-free conditions,and easy gram-scale preparation,but also represents a new and rare example of trifluoromethylate molecules synthesis in water.In chapter 5,an efficient visible light-induced cascade reduction decarboxylation/esterification of benzothiazole trifluoromethyl ketone hydrates withα-keto acids has been demonstrated and a series ofα-trifluoromethyl contained compounds were synthesized with good yields.The method features no photocatalyst,broad substrate scope,good functional group tolerance,and easy gram-scale preparation.Control experiments show that light is critical for this reaction.