Alcohol

Catalysis

Enantioselective synthesis

Rhodium

Molecule

Stereochemistry

Combinatorial chemistry

Hydrogen

Organic chemistry

Reagent

Cyclopropane

Regioselectivity

Hydride

Chemistry

Selectivity

Ring (chemistry)

Angewandte Chemie International Edition

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.

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