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

In 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. An organocatalyst with unique properties - 2-(trifluoromethyl)pyrrolidine - activates unsymmetrical diketones by forming an enamine from only one side, while enolization does not constitute a significant competing mechanism. image