Reforging Mitsunobu reaction via sulfoxides-catalyzed C(sp3)-O bond activation of alkanols

The stereospecific conversion of alkanols plays a pivotal role in synthetic chemistry and drug discovery. Among the substantial advances, the Mitsunobu reaction has long stood out as a powerful platform for C(sp3)-O bond activation to achieve the transformation of alkanols. Due to the inherent environmental drawbacks of phosphorus chemistry, an alternative element is pressingly demanded. Herein, we develop well-designed sulfoxide catalysts for an alternative catalytic Mitsunobu-type reaction with broad substrate scope, generating H2O as the sole by-product. Kinetic studies, mechanistic investigations, and density functional theory (DFT) calculations provide comprehensive mechanistic insights and uncover key structure-reactivity relationships. This approach establishes a sustainable and atom-economical pathway for the Mitsunobu-type reaction, and expands the conceptual scope of sulfur catalysis. Due to the inherent environmental drawbacks of phosphorus chemistry, an alternative to the Mitsunobu reaction is pressingly demanded. Herein, the authors develop well-designed sulfoxide catalysts for an alternative catalytic Mitsunobu-type reaction with broad substrate scope, generating H2O as the sole by-product.