Novel Iminium Ion Equivalents Prepared through C−H Oxidation for the Stereocontrolled Synthesis of Functionalized Propargylic Amine Derivatives

Abstract

Access to stereochemically complex, polyfunctionalized amine derivatives is made possible using novel oxathiazinane N,O-acetal starting materials. These heterocycles are prepared through intramolecular sulfamate ester C−H insertion with a Rh²⁺-carboxylate catalyst and PhI(OAc)₂ as the terminal oxidant. Such compounds function as unique iminium ion equivalents to which nucleophilic alkynylzinc reagents add smoothly in the presence of BF₃·OEt₂. The coupled products are isolated in high yield (63−92%) and with good levels of diastereoinduction (6 → 20:1). The alkyne-substituted oxathiazinanes serve as versatile building blocks and may be further manipulated through nucleophilic ring-opening reactions of the sulfamate core. The efficient construction of 1,7,8-trihydroxyindolizidine in six steps and in 34% overall yield highlights the power of these combined methods for synthesis.