Increasing interests of difluorinated amino acids(DFAAs)have been raised in recent years due to their widespread bio-organic and medical applications.However,to date,only few investigations focused on their asymmetric...Increasing interests of difluorinated amino acids(DFAAs)have been raised in recent years due to their widespread bio-organic and medical applications.However,to date,only few investigations focused on their asymmetric synthesis.Exploring difluoromethyl reagent to tailor a novel pathway and developing efficient catalytic system are highly desirable for constructing structurally diverse chiral DFAAs.Herein,a copper-catalyzed asymmetric difluorobenzylation of aldimine esters is described.By usingα,α-difluorinated benzyltriflones as difluoromethyl reagents,this protocol allows the asymmetric synthesis ofα-quaternary DFAAs with wide scope,good yields and excellent enantioselectivities(90%-98%ee).Control experiments and DESI-MS analysis demonstrate the reaction probably proceeds via a key difluorocarbocation intermediate.Moreover,polyfluoroarenes are found efficient candidates to polyfluoroaryl amino acids via C-F activation.Gram-scale experiment,late-stage functionalization,synthesis of difluorinated dipeptides and bioactive molecular analogues revealed the utility of the protocol,thereby largely enriching the structural diversity of FAAs and providing more potential opportunities in drug discovery.展开更多
In the presence of Dawson-type polyoxotungstate, α 2-[(n-C 4H 9) 4] (11-n)P 2W 17O 61(M n+·Br)[abbreviated as P 2W 17M·Br, M=Co(Ⅱ), Mn(Ⅲ), Cu(Ⅱ)] and saturated [(n-C 4H 9) 4N] 6P 2W 18O 62(abbreviated as...In the presence of Dawson-type polyoxotungstate, α 2-[(n-C 4H 9) 4] (11-n)P 2W 17O 61(M n+·Br)[abbreviated as P 2W 17M·Br, M=Co(Ⅱ), Mn(Ⅲ), Cu(Ⅱ)] and saturated [(n-C 4H 9) 4N] 6P 2W 18O 62(abbreviated as P 2W 18), cycloaddition reaction of carbon dioxide to propylene oxide were studied under moderate reaction conditions without any additional organic solvents. The experimental results indicated that the synthesis of propylene carbonate was completed in 98% yield and 100% selectivity by using {P 2W 17Co·Br} as the catalyst, while the P 2W 18 complex showed the lowest catalytic activity with less than 1% yield of propylene carbonate. The dependency of the catalytic activity on transition metal of mono-substituted polyoxometalate, P 2W 17M·Br, as well as the nucleophilicity of the bromide ion was concluded from the process analysis.展开更多
基金supported financially by the Youth Innovation Promotion Association CAS(No.2022375)National Nature Science Foundation of China(No.22171258)+1 种基金the Biological Resources Programme,Chinese Academy of Sciences(No.KFJ-BRP-008)the Sichuan Science and Technology Program(No.2022ZYD0038)。
文摘Increasing interests of difluorinated amino acids(DFAAs)have been raised in recent years due to their widespread bio-organic and medical applications.However,to date,only few investigations focused on their asymmetric synthesis.Exploring difluoromethyl reagent to tailor a novel pathway and developing efficient catalytic system are highly desirable for constructing structurally diverse chiral DFAAs.Herein,a copper-catalyzed asymmetric difluorobenzylation of aldimine esters is described.By usingα,α-difluorinated benzyltriflones as difluoromethyl reagents,this protocol allows the asymmetric synthesis ofα-quaternary DFAAs with wide scope,good yields and excellent enantioselectivities(90%-98%ee).Control experiments and DESI-MS analysis demonstrate the reaction probably proceeds via a key difluorocarbocation intermediate.Moreover,polyfluoroarenes are found efficient candidates to polyfluoroaryl amino acids via C-F activation.Gram-scale experiment,late-stage functionalization,synthesis of difluorinated dipeptides and bioactive molecular analogues revealed the utility of the protocol,thereby largely enriching the structural diversity of FAAs and providing more potential opportunities in drug discovery.
文摘In the presence of Dawson-type polyoxotungstate, α 2-[(n-C 4H 9) 4] (11-n)P 2W 17O 61(M n+·Br)[abbreviated as P 2W 17M·Br, M=Co(Ⅱ), Mn(Ⅲ), Cu(Ⅱ)] and saturated [(n-C 4H 9) 4N] 6P 2W 18O 62(abbreviated as P 2W 18), cycloaddition reaction of carbon dioxide to propylene oxide were studied under moderate reaction conditions without any additional organic solvents. The experimental results indicated that the synthesis of propylene carbonate was completed in 98% yield and 100% selectivity by using {P 2W 17Co·Br} as the catalyst, while the P 2W 18 complex showed the lowest catalytic activity with less than 1% yield of propylene carbonate. The dependency of the catalytic activity on transition metal of mono-substituted polyoxometalate, P 2W 17M·Br, as well as the nucleophilicity of the bromide ion was concluded from the process analysis.
