Research On Bioinspired Electron Transfer Reaction Based On Pyruvate Derivatives

Pyruvate derivatives are important intermediates for the oxidative metabolism of biological cells.In addition,because they contain active carbonyl groups,they are widely used as a basic chemical raw material in many fields such as chemistry,pharmacy,food,agriculture,etc.Different from the vigorous development of other carbonyl compounds in the field of free radical oxidation conversion,pyruvate derivatives are prone to give the decarboxylation products by the use of various oxidants,so the oxidation conversion of pyruvate compounds is still a challenge task.Inspired by the electron"hopping"mechanism in the remote electron transfer of long-chain amino acids,by introducing auxiliary groups into the pyruvate derivatives as the"hopping"site for electron transfer,we successfully get the oxidative conversion products of the pyruvate derivatives.(1)With the help of theγ-thioether group and using TEMPO+as the oxidant,we successfully achieved theα-C(sp~3)-H radical oxidative hydroxylamination ofγ-thioetherα-ketoester.Theα-carbonyl radical is generated by the ms-PCET strategy,and the product has good diastereoselectivity.The target product with high enantioselectivity can be prepared from the starting materialsβ,γ-unsaturatedα-ketoester and thiol in a one-pot method.(2)Under the action of the single-electron oxidants DDQ and TEMPO~+,we successfully completed the oxidative dehydrogenation and cyclization ofγ-indoleα-ketoester.The dehydrogenation productβ,γ-unsaturatedα-ketoester can be obtained with high diastereoselectivity,and the product has a moderate oxidation potential,under appropriate conditions,the oxidative rearrangement reaction can be continued to obtain indole-3-ketone structure.The cyclization product pyrano[2,3-b]indole derivative is an important scaffold in biomolecules and drug molecules.When a base is added to the system,the enol intermediate can be oxidized to obtain anα-oxyaminated product.(3)With the help of theγ-indoyl,the photocatalytic strategy was used to successfully achieve the carbonyl protonation reaction ofγ-indoleα-ketoester.Different from the traditional strategy of directly reducing the carbonyl group in the protonation process of the carbonyl group,in this reaction,carbon radicals that are easier to be reduced are generated through the oxidized enol intermediate,which overcomes the limitation of the high reduction potential of the carbonyl group,and the atom economy is as high as 100%.Subsequent studies have shown that this reaction can achieve asymmetric catalysis under the action of cinchona base derivatives.