(Poly)cationic λ3‐Iodane‐Mediated Oxidative Ring Expansion of Secondary Alcohols

Herein, a simplified approach to the synthesis of medium‐ring ethers through the electrophilic activation of secondary alcohols with (poly)cationic λ3‐iodanes (N‐HVIs) is reported. Excellent levels of selectivity are achieved for C–O bond migration over established α‐elimination pathways, enabled by the unique reactivity of a novel 2‐OMe‐pyridine‐ligated N‐HVI. The resulting hexafluoroisopropanol (HFIP) acetals are readily derivatized with a range of nucleophiles, providing a versatile functional handle for subsequent manipulations. The utility of this methodology for late‐stage natural product derivatization was also demonstrated, providing a new tool for diversity‐oriented synthesis and complexity‐to‐diversity (CTD) efforts. Preliminary mechanistic investigations reveal a strong effect of alcohol conformation on the reactive pathway, thus providing a predictive power in the application of this approach to complex molecule synthesis. The unique reactivity of poly(cationic) λ3‐iodanes (N‐HVIs) enables a simplified approach to cyclic ethers through the oxidative ring expansion of secondary alcohols. The method can be applied to the synthesis of 5‐, 6‐, and 7‐membered rings as well as the late‐stage derivatization of natural product scaffolds. The obtained hexafluoroisopropanol (HFIP) acetals are readily functionalized, providing a versatile approach to the synthesis of valuable cyclic ether scaffolds.