The Research Of Organocatalytic Selective Reduction And Cascade Reaction Of ?,?-unsaturated Ketones

?,?-unsaturated ketone is a kind of important pharmaceutical intermediate and its selective reduction product is also applied extensively.In recent years,?,?-unsaturated ketone was selective reduced by small organic molecules and transition metal catalysts.However,these methods have some limitations: expensive catalysts,unfriendly to the environment,difficultly product separation and so on.Therefore,it is meaningful to find a suitable catalyst system to selective catalytic reduction of ?,?-unsaturated ketone.Trichlorosilane is a very cheap chemical reagent,and it is a common source of hydrogen of asymmetric reduction.Under the activation of Lewis base,it has very high reduction activity.In this article,the DMF was first used to active trichlorosilane for high selectivity and efficiency reduction of carbon-carbon double bond in ?,?-unsaturated ketone.The optimum reaction conditions of the reduction of ?,?-unsaturated ketone were explored.The conditions are:substrate(1 eq),trichlorosilane(2 eq)as a source of hydrogen,DMF(5 eq)as the Lewis base catalyst,methylene chloride(1 mL)as the reaction solvent,the reaction temperature was 0 ?,the reaction time was 12 hours.22 ?,?-unsaturated ketone were designed and synthesized.The substrate scope was investigated under the optimum reaction conditions and the yield was up to 99%.At the same time,the ?,?-unsaturated ketone reduction/Aldol cascade reaction was first studied with DMF as catalyst.The reaction condition was optimized.The best reaction condition was: substrate(1 eq),trichlorosilane(2 eq)as a source of hydrogen,DMF(5 eq)as the Lewis base catalyst,benzaldehyde(2 eq),toluene(1 mL)as the reaction solvent,the reaction temperature was 0 ?,the reaction time was 20 hours(two-step cascade reaction,the first step reaction time was 12 hours,the second was 8 hours).The substrate scope was investigated under the optimum reaction conditions and the yield was up to 89%.Finally,11 chiral Lewis base catalysts were designed and synthesized.Together with 23 catalysts in our laboratory,the asymmetric selective reduction of prochiral ?,?-unsaturated ketone was explored with trichlorosilane as the hydrogen soruce.The results showed that the pyridine dihydrooxazole compounds were the potential chiral catalysts.Meanwhile,the chiral catalysts C12 to C26 were used to catalyze the ?,?-unsaturated ketone reduction/Aldol cascade reaction.The results showed that the efficiency of these catalysts is not good,the enantioselectivity is moderate(up to 65% ee)and the diastereoselectivity of some catalysts is excellent(up to 100% d.r.value).The research results laid a foundation for further study.