Chiral Bifunctional Phosphoramide‐Amine Controlled Enantiodivergent Conjugate Addition of Difluoroenoxysilanes to Isatylidene Malononitriles †

Comprehensive Summary We report a newly developed ( S , S )‐cyclohexane‐1,2‐diamine‐derived bifunctional phosphoramide‐tertiary amine that proves to be a highly enantioselective catalyst for the Mukaiyama‐Michael addition of difluoroenoxysilanes to isatylidene malononitriles, affording S ‐configured quaternary oxindoles bearing a C3 difluoroalkyl group in up to 98% ee. Notably, it affords the opposite enantiomer as compared to the previously reported analogous phosphoramide‐secondary amine system, which gave the R ‐enantiomer in comparable excellent enantioselectivity (up to 97% ee). This contributes to the first enantiodivergent catalysis enabled by phosphoramide‐based chiral catalysts, as simple variation of the amine part of the bifunctional catalyst from benzyl‐type secondary amine to a N , N ‐dimethyl tertiary amine led to reversal of the enantiofacial control. DFT calculations reveal that the phosphoramide of the catalyst might play a different role in the synthesis of R ‐ and S ‐enantiomers, acting as a Lewis base or an H‐bond donor, respectively. This mechanistic insight, along with the fact that varying phosphoramide of catalysts to other typically used H‐bond donors greatly decreased enantioselectivity, suggests that as a unique mono H‐bond donor featuring two amide substituents, phosphoramide is an interesting functionality for the design and development of new chiral catalysts, despite being currently less explored.