Studies On The Deacetylation And Desilylation Reactions Catalyzed By Hf（OTf）₄

The reaction catalyzed by metal Lewis acid is an important field of organic synthesis.Metal Lewis acids of aluminum,zinc,stannum,aurum,rhodium,and indium etc.,have been widely used in organic synthesis,such as coupling,addition,polymerization,and disproportion reactions,and removal of protecting groups and reactions.The Group IV B transition metal:zirconium（Zr）has a higher charge-to-size value,and Zr（IV）salts have been widely used in many reactions such as addition,reduction,deprotection,cyclization,and rearrangement reactions due to its strong Lewis acidity.In addition,literature reports and our precedent studies showed that Hafnium（Hf）,another Group IV B transition metal,exhibited similar or even better catalytic activity than Zr in several organic reactions such as Kabachnik and esterification reactions.However,the research on Hf（IV）-catalyzed reactions compared to those on Zr（IV）-catalyzed reactions,is still limited.Investigation on the applications of Hf（IV）catalysts is of great importance to both theoretical and practical studies.Based on precedent literature reports and our studies on Zr（IV）and Hf（IV）-catalyzed reactions,the current thesis focuses on the deacetylation and desilylation reactions catalyzed by hafnium triflate（Hf（OTf）₄）.Novel and high efficient protocols have been established for both reactions.The detailed research work are described as follows:（1）Selective anomeric deacetylation of peracetylated saccharides:First,1,2,3,4-tetraacetyl-L-rhamnose was used as a model compound to screen the activity of a series of metal Lewis acids,especially the Group IV B transition metal Lewis acids.Experimental results showed that the catalytic activity of Hf（OTf）₄ was much better than other catalysts,including those reported in literature.Then,the reaction temperature and amount of catalyst were optimized and the solvent effect was studied.In addition,ultrasound was also employed as an aid for this reaction.The results showed that ultrasonic irradiation did not affected the yield and selectivity,but accelerated the reaction rate significantly.Total 11 peracetylated mono-,di-,and trisaccharides were treated with Hf（OTf）₄ in acetonitrile under sonication to afford anomeric deacetylated saccharide products with excellent yields ranging from 82%to95%,establishing a new and efficient method for selective 1-O-deacetylation of peracetylated saccharides.In addition,by varying the water content of solvent,the hydrolysis mechanism of the deacetylation reaction catalyzed by Hf（OTf）₄ was confirmed.Subsequently,we utilized NMR technique to monitor the interactions between peracetylated5-deoxyribose and Hf（IV）.The changes in¹H and¹³C NMR spectra showed that the complexation of peracetylated 5-deoxyribose and Hf（IV）gradually changed from multiple forms to a dominant form at the anomeric acetate,when the amount of Hf（IV）was gradually increased.The NMR data provided spectral evidence for the coordination of metal Lewis acid and anomeric acetyl group for the first time,paving the road for the elucidation of the mechanism of the selectivity of reaction.（2）Highly efficient cleavage of silyl ether protecting groups:Currently,the most commonly used reagents for removal of silyl ether protecting groups are fluorides or proton acids.Meanwhile,the application of metal Lewis acids for this purpose is still very limited.Recently,several studies have reported that certain metal Lewis acids can efficiently catalyze the desilylation under mild conditions.Therefore,the second study of my thesis explored the application of Hf（OTf）₄ in desilylation.Initially,tert-butyldimethylsilyl（TBS）-protected benzyl alcohol was employed as a model compound,and the catalytic activity of a series of Group IVB metal Lewis acids was screened.Hf（OTf）₄ exhibited exceptional catalytic activity for the removal of TBS.Afterwards,the amount of catalyst was optimized and solvent effect was investigated.The experimental results demonstrated the efficacy of Hf（OTf）₄ in desilylation reactions.On the basis of this approach,the desilylation of primary,secondary,and tertiary alcohol,and phenol-based TBS ethers were conducted.The result comparison showed that the amounts of catalysts for different types of TBS deprotection were of remarkable difference.Subsequently,the Hf（IV）method was extended to a series of TBS-protected substrates and achieved not only high efficiency but excellent regioselectivity and chemical selectivity.In addition,we also synthesized a series of substrates with both silyl ethers and other protecting groups.The results showed that the Hf（OTf）₄-catalyzed deprotection of silyl ethers did not affect most commonly protecting groups except DMT.Therefore,this method has the potential to be widely applied in synthetic chemistry.Finally,this method was successfully extended to the regioselective removal of 5′-TBS in more complex substrates,nucleosides.