Solvent-Dependent Oxidative Ring Opening of Cyclopropylamides Mediated by Halogen Bonding

A solvent-dependent approach to the oxidative ring opening of cyclopropylamides with NIS under mild reaction conditions has been developed. In the presence of hexane as the solvent, 3-iodo <i>N,O</i>-acetal was obtained in good yields, whereas employment of CCl₄ as the solvent favors the formation of 1,3-oxazines. This divergent method avoids the use of an external base, an acid, and a metal and exhibits excellent functional-group tolerance. Primary mechanistic studies revealed that halogen bonding facilitates the nucleophilic attack of 3-iodo <i>N,O</i>-acetal to 1,3-oxazine.