Development Of Modified C-2` Cinchonine And Study On Their Catalytic Performance For Asymmetric Reaction Of α-functionalization Of β-ketoester

With the deepening of the study of asymmetric organic catalytic reaction,the organic catalyst of cinchona was successfully applied in a variety of asymmetric catalytic reaction systems.The modification of the structure of cinchona was mainly concentrated in C-6`,C-9 as well as on the ring ring nitrogen atoms.In the past two years,people found that C-2’ modified cinchona also has a good catalytic performance.On the basis of this,a new method for the preparation of C-2’-site modified cinnonine derivatives was developed,and the C-2’ modified cinchonine derivatives were developed for the asymmetric photocatalytic oxidation of β-keto acid.In this paper,brominated intermediate was synthesized by hydrochemistry,oxidation,reduction and bromination and then coupled with aryl boronic acid to synthesize C-2’ modified cinchona.The total yield is 19~33%.A total of 25 C`-2 modified cinchonine derivatives were designed and synthesized with cinchonine as the lead compound.The effects of catalysts in the homogeneous system,non-photocatalytic phase transfer system and photocatalytic phase transfer system were investigated.We found 10 mol% C-2’ 2-naphthylcycloinine-derived quaternary ammonium salt as a catalyst,the oxygen in the air as oxidant,TPP as a photosensitizer,mesitylene as solvent,50% K2HPO4 aqueous solution as base,the oxidation product of(S)-2-hydroxy-1-indanone-2-carboxylate was got with 81% yield and 84% ee at room temperature for 2 h under 3 w LED red light.Subsequently,the substrate was expanded to find that the adamantyl substrate can obtain 51% ee-84% ee product and methyl ester or other small ester substrate can get 47% ee-50% ee hydroxylation products and more than 99% conversion rate.