Organocatalytic Activation of Unsymmetrical 2,3‐Diketones Towards Catalytic Asymmetric Domino Michael–Henry Reaction

Abstract

AbstractIn this study, we explored a method to distinguish between both enolizable regions of unsymmetrical 2,3‐diketones in organocatalytic domino reactions involving nitroalkenes. The selective formation of an enamine from only one side of the molecule was made possible by the use of optically pure 2‐(trifluoromethyl)pyrrolidine. This catalyst, remarkably enhancing the reaction, owes its efficacy to a unique interplay between basicity and nucleophilicity. These features caused the enolization of the substrate at the second possible site to be omitted. The approach resulted in excellent regio‐ diastereo‐ and enantioselectivity (91–99 % ee) across various nitroalkenes, leading to the synthesis of novel cyclopentanone derivatives with three contiguous stereogenic center.