Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio‐ and diastereoselective construction of cyclopropanes through C−H activation of arenes and coupling with readily available cyclopropenes is highly appealing but remains a challenge. A dual directing‐group‐assisted C−H activation strategy was used to realize mild and redox‐neutral RhIII‐catalyzed C−H activation and cyclopropylation of N‐phenoxylsulfonamides in a highly enantioselective, diastereoselective, and regioselective fashion with cyclopropenyl secondary alcohols as a cyclopropylating reagent. Synthetic applications are demonstrated to highlight the potential of the developed method. Integrated experimental and computational mechanistic studies revealed that the reaction proceeds via a RhV nitrenoid intermediate, and Noyori‐type outer sphere concerted proton‐hydride transfer from the secondary alcohol to the Rh=N bond produces the observed trans selectivity. Chiral RhIII‐catalyzed C−H activation and cyclopropylation of O‐sulfonyl phenols has been realized in a highly enantioselective, diastereoselective, and regioselective manner with cyclopropenyl secondary alcohols as the cyclopropylating reagent. Experimental and computational mechanistic studies suggest that the reaction proceeds via a RhV nitrenoid intermediate that participates in Noroyi‐type outer‐sphere concerted proton‐hydride transfer.