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. Die Rhodium(III)‐katalysierte C‐H‐Aktivierung und Cyclopropylierung von O‐Sulfonylphenolen gelingt mit hohen Enantio‐, Diastereo‐ und Regioselektivitäten sowie Cyclopropenylalkoholen als Cyclopropylierungsreagenzien. Mechanistische Studien zeigen, dass die Reaktion über ein RhV‐Nitrenoid‐Intermediat verläuft, das an einem konzertierten, Proton‐Hydrid‐Transfer vom Noroyi‐Typ teilnimmt.