Catalytic Asymmetric Michael Addition Of Unprotected3-Substituted Oxindoles To Nitroolefins

Oxindoles bearing a quaternary stereogenic carbon center at the C3position are widely presented in natural products, drugs and pharmaceutically active compounds. The catalytic enantioselective synthesis of quaternary3,3-disbustituted oxindoles is of current research interest. This thesis mainly focuses on the asymmetric Michael addition of N-unprotected3-substituted oxindoles to nitroolefins to enantioselectively construct the C3quaternary stereogenic carbon center, which includes two parts:1. We developed the first example of Michael addition of unprotected3-substituted oxindoles to nitroolefins. It was found that the reaction can be successfully catalyzed by Quinidine using acetone as solvent, at0℃and up to5.0:1.0dr was achieved. Oxindoles bearing aryl groups at C3position are well-tolerated while low reactivity was observed for alkyl groups. The relative configuration of the product was assigned via conversion to known compound. Initial asymmetric investigation revealed that the bifunctional tertiary amine-thiourea catalyst can afford the desired product in up to2.1:1.0dr and85%ee.2. A newly developed cinchonidine-derived phosphoramide catalyst, which is simple and easily available, is identified as a powerful catalyst for the highly enantioselective Michael addition of both unprotected3-aryl and3-alkyloxindoles of high reactivity to nitroolefins to furnish the C3quaternary stereogenic carbon center with moderate to excellent diastereoselectivity and excellent enantioselectivity. The highest diastereoselectivity can be up to21:1.0and enantioselectivity can be up to99%. The enantioenriched products could be readily transformed to other oxindole derivatives.