| a-alkyl-p-keto ester is a class of important pharmaceutical intermediate.Lots of natural products and biologically active heterocyclic compounds can be prepared from it.There are three ways to synthesizeα-alkyl-β-keto cstcrs in the literature.One is Heck or Heck-type reaction of Baylis-Hillman adducts.The second is the Roskamp reaction.The third is substitution of halohydrocarbons.However,the existing synthetic methods have some limitations,such as unavailable materials,expesive catalysts,prerequisite organic solvent and so on.Therefore,it is important to explore an inexpensive,simple,efficient and green way to synthesizeα-alkyl-β-ketone esters.In the paper,thioureas were used as catalysts to prepare a-alkyl-β-ketone esters in water for the first time.The optimal conditions are:thiourea C15(20 mol%)as catalyst,water as the reaction solvent,dihydropyridine ester(1.2 eq)as a source of hydrogen,the reaction temperature was 100 ℃,the reaction time was 24 h.Under the optimal conditions,we researched the universality of substrates and synthesized a series of a-alkyl-β-ketone esters compounds.The yield is up to 99%.At the same time,we discussed the chirality of a-alkyl-β-ketone esters and found that the obtained products have a certain enantioselectivity.Although the enantioselectivity excess is not stable for the racemization of the compound,this is the first time to get enantioselective a-alkyl-β-ketone esters compounds under metal-free conditions in the water.On the other hand,we synthesized a number of very important pharmaceutical intermediates through derivation of α-alkyl-β-ketone esters compounds. |
