Reforging Mitsunobu reaction via sulfoxides-catalyzed C(sp<sup>3</sup>)-O bond activation of alkanols.

Li, Qigang; Zhang, Wannan; Liu, Jiaxin; Yang, Jun · Nat Commun · 2026

basic_science · Level V

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Abstract

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(sp<sup>3</sup>)-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 H<sub>2</sub>O 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.