Recyclable Tertiary Amine Modified Diarylprolinol Ether as Aminocatalyst for the Sequential Asymmetric Synthesis of Functionalized Cyclohexanes and Chromenes

The one-pot, organocatalytic Hayashi sequential reaction (HSR) of beta-nitroacrylate, aldehyde, toluenethiol, and ethyl 2-(diethoxyphosphoryl)acrylate allowed the synthesis of almost stereoisomerically pure, highly functionalized polysubstituted cyclohexanes with very high diastereo- and enantioselectivity (up to > 99 % ee). The one-pot synthesis consists of the tertiary amine modified diarylprolinol silyl ether-mediated asymmetric Michael reaction, a domino Michael reaction/Horner-Wadsworth-Emmons reaction, and a sulfa-Michael reaction. In addition, we have also demonstrated an improved protocol for the domino oxa-Michael/aldol reaction of salicyladehydes with alpha,beta-unsaturated aldehydes with recyclable tertiary amine-modified diarylprolinol silyl ether 3d as an effective organocatalyst, which results in the formation of chiral chromenes with good enantioselectivities (up to 94 % ee). UV/Vis and CD spectroscopy provide a cross-validation method to elucidate the slight difference between electron-withdrawing 3d and diphenylprolinol silyl ether 3a, which can give indirect evidence for the enhancement of enantioselective induction with 3d in the above transformations.