(Poly)cationic λ 3 -Iodane Mediated Oxidative Ring Expansion of Secondary Alcohols.

Herein, we report a simplified approach to the synthesis of medium-ring ethers through the electrophilic activation of secondary alcohols with (poly)cationic λ3 -iodanes ( N -HVI). 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 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 reactive pathway, thus providing a predictive power in the application of this approach to complex molecule synthesis.