Highly regioselective, three-component reactions of diazoacetates with anilines and β,γ-unsaturated α-keto esters: 1,2-addition versus 1,4-addition

摘要

The highly regioselective, three-component reaction of diazoacetates with anilines and β,γ-unsaturated α-keto esters is presented. Ammonium ylides obtained in situ from diazoacetates and anilines can be trapped by β,γ-unsaturated α-keto esters through two distinctly different pathways: 1,2-addition or tandem 1,4-addition/cyclization followed by one-pot dehydration. The course of the reaction is highly dependent on the electronic nature of the diazoacetates. When α-unsubstituted or α-alkyl-substituted diazoacetates are used as the substrates, the three-component reaction proceeds efficiently, in a regiospecific 1,2-addition manner, to afford densely functionalized β-hydroxy α-amino acid derivatives in high yields (71-94%) and good diastereoselectivities. When α-aryl-substituted diazoacetates are used as the substrates, the three-component reaction occurs smoothly to yield polysubstituted 2,3-dihydropyrrole derivatives through tandem 1,4-addition/cyclization followed by one-pot dehydration. The high regioselectivity observed in the three-component reaction can be rationalized on the basis of the hard and soft acids and bases (HSAB) principle.