Catalytic Enantioselective Multicomponent Reactions of Sulfoxonium Ylides Enabled by a Formal Rearrangement—A Versatile Entry to Enantioenriched α‐Sulfanyl Carbonyl Compounds
Abstract
ABSTRACT Sulfur ylides have emerged as versatile carbenoids for catalytic enantioselective X–H insertion reactions (X = C, N, O, and S), while offering a better safety profile compared to traditional diazo‐based metal carbene precursors. However, the realization of valuable multicomponent reactions (MCRs) with sulfur ylides has been so far out of reach. Here, we report the enantioselective MCR of sulfoxonium ylides, aldehydes, and thiols catalyzed by a chiral phosphoric acid. Departing from carbenoid reactivity, the reaction pathway entails two sequential but nonoverlapping catalytic cycles, where the assembly of the components is followed by a delayed stereodetermining rearrangement across the central C─C bond of the molecule. The organocatalytic MCR delivers β‐hydroxy‐α‐sulfanyl carbonyl products as single anti‐diastereoisomers and generally in high yields and enantioselectivities. These products cannot be readily accessed by other catalytic means and are synthetic linchpins to a variety of α‐sulfanyl carbonyl compounds via stereospecific substitutions of their hydroxy group.
Article Details
Authors (11)
Nicolò Santarelli
Department of Chemistry
Pietro Pecchini
Department of Industrial Chemistry “Toso Montanari” Center For Chemical Catalysis – C3 and INSTM RU Bologna Alma Mater Studiorum – University of Bologna Bologna Italy
Nunzio Matera
University of Bologna, Department of Industrial Chemistry Toso Montanari, via Piero Gobetti 85, 40129 Bologna, Italy
Andrea Pellegrini
Department of Industrial Chemistry “Toso Montanari”, University of Bologna, Via P. Gobetti 85, 40129 Bologna, Italy
Riccardo Fabbri
Department of Industrial Chemistry “Toso Montanari” Center For Chemical Catalysis – C3 and INSTM RU Bologna Alma Mater Studiorum – University of Bologna Bologna Italy
Irati Celada Cubero
Department of Industrial Chemistry “Toso Montanari” Center For Chemical Catalysis – C3 and INSTM RU Bologna Alma Mater Studiorum – University of Bologna Bologna Italy
Leire Navarro Rubio
Department of Industrial Chemistry “Toso Montanari” Center For Chemical Catalysis – C3 and INSTM RU Bologna Alma Mater Studiorum – University of Bologna Bologna Italy
Cristina Di Pietro
Department of Industrial Chemistry “Toso Montanari” Center For Chemical Catalysis – C3 and INSTM RU Bologna Alma Mater Studiorum – University of Bologna Bologna Italy
Andrea Mazzanti
University of Bologna, Department of Industrial Chemistry Toso Montanari, via Piero Gobetti 85, 40129 Bologna, Italy
Mariafrancesca Fochi
Department of Industrial Chemistry “Toso Montanari” Center For Chemical Catalysis – C3 and INSTM RU Bologna Alma Mater Studiorum – University of Bologna Bologna Italy
Luca Bernardi
Department of Industrial Chemistry “Toso Montanari” Center For Chemical Catalysis – C3 and INSTM RU Bologna Alma Mater Studiorum – University of Bologna Bologna Italy