酸触媒高速ナザロフ反応の開発とその立体制御

抄録

We have developed a highly efficient acid-catalyzed Nazarov reaction of β-alkoxy divinylketones providing 5-oxycyclopent-2-enones, as a single regioisomer. This Nazarov cyclization, involving 1,3-shift of the β-alkoxy group, was accomplished within a few minutes catalyzed by TfOH, Tf₂O (0.1-0.001 mol%) or Sc(OTf)₃ (10 mol%), in which the β-alkoxy group accelerates the catalytic reaction and controls the regioselectivity by the stabilization of the intermediates and the spontaneous elimination followed by trapping.
In order to advance this reaction, we have developed the asymmetric transformation, and found that Sc(OTf)₃-pybox/Ph complex is an efficient catalyst. In the presence of iPrOH as a solvent, stereoselectivity was improved up to 91% ee. It is noteworthy that this reaction constructs a quaternary asymmetric center by nucleophilic addition to the α-position of the resulting ketone.