Research On Asymmetric Hydrogen Atom Transfer Reactions

Hydrogen atom transfer(HAT)reaction is one of the most important elementary reactions in radical chemistry.The ubiquitous tertiary chiral stereocenters in organic compounds can be constructed via enantioselective hydrogen atom transfer reaction reduction of carbon-centered radicals.However,given the generally high activity of radical attack reactions,which leads poor stereochemical communications between radical intermediate,fairly small steric hindered transferring H-atom and catalyst in the early stereodetermining transition state.Accordingly,research on asymmetric hydrogen atom transfer reaction is considered to be a very important but challenging theme.To date,enantioselective hydrogen atom transfer remains rare.Coordination control with chiral Lewis acid has been has been applied to asymmetric hydrogen atom transfer reactions.The limitation of this reaction is that chiral Lewis acids therein are often employed stoichiometrically to ensure effective enantioselectivity.That results from irrelative radical generation and chirality control system.In this study,we implemented the first example of catalytic Lewis acid co-ordination-induced enantioselective hydrogen atom transfer via a transition-metal redox catalysis strategy.In this strategy,the reductive transition catalyst impel a single electron transfer(SET)to generate a carbon radical.and the oxidative transition catalyst provides a chiral environment via coordinating with radical intermediates.As thus,the oxidation state-varied catalysis renders the radical initiation and chirality control cooperatively interrelated.thus enabling the catalytic asymmetric HAT reaction.Specifically,we synthesized important chiral-α-tertiary stereocenter β-hydroxyester structural unit from racemic glycidyl esters in an enantioconvergent manner via a salen-Ti catalyzed asymmetric hydrogen transfer reaction.The structure is of high synthetically value due to its widespread existence in macrolide and polyether antibiotics.This paper consists of three thesis:Part I:review of symmetric hydrogen atom transfer ractionWe briefly introduce the recent progress of asymmetric hydrogen atom transfer reaction,including chiral hydrogen atom transfer reagent catalysis,polarity inversion catalysis,enzyme catalysis,Lewis acid coordination control and chiral hydrogen bond coordination control.Part Ⅱ:reaction optimization and substrate scope for titanium-catalyzed asymmetric hydrogen atom transfer.We optimized the reaction conditions with methyl-substituted glycidyl esters as template substrates and determined the optimal reaction conditions.With ideal conditions in hand,we found that a wide variety of glycidic esters can be accommodated,and obtained satisfactory separation yields and enantioselectivities.Part Ⅲ:study on the mechanism of titanium-catalyzed asymmetric HAT reaction.Spin trapping experiment approved of the carbon radical generation event;Isotope labeling experiment specifyed that tin-hydrogen is the only source of hydrogen atoms;High conversion and enantioselectivity are maintained under different equivalent catalysts,indicating that the catalytic system is very powerful,and no other background reactions that affect the selectivity;Discriminative energy distinction between SET and HAT processes ensures the efficiency and selectivity of the reaction;The study of different substituted substrates illustrated that the ester group of substrate is crucial.Firstly,it facilitates the homolytic opening of epoxide triggered by salen-TiⅢ,secondly,it enables the enantiocontrol through coordinating with salen-TiⅣ.