Divergent and consecutive skeletal editing of saturated primary amines.

Given the prevalence of nitrogen heterocycles in pharmaceuticals, divergent skeletal editing techniques that enable rapid access to a diverse library of azacycles from a single substrate are highly desirable. Herein, we report a skeletal editing approach that converts abundant saturated primary amines into N-heterocycles, with exceptional functional-group compatibility, broad skeletal diversity, superior regioselectivity, and diastereospecificity (both >20:1). By harnessing the reactivity of hypervalent iodines, an imino ether intermediate is generated through mild iodane-mediated oxidation, facile N-internalization, and methoxy anion addition. This pivotal intermediate serves as a versatile platform capable of interception by a wide spectrum of nucleophiles, thereby enabling the generation of structurally diverse nitrogen heterocycles (>15 classes). Furthermore, this strategy enables challenging site-controlled carbon-to-nitrogen transmutation and ring contraction of natural products through a one-pot, consecutive skeletal editing sequence. Editor's summary: Cyclic fragments incorporating nitrogen are ubiquitous components of pharmaceuticals. Recently, chemists have introduced a variety of editing techniques to modify these frameworks one atom at a time, mostly focusing on unsaturated rings. Two groups now report complementary methods to diversify saturated cyclic amines (see the Perspective by Wu). Li et al. used mild oxidation to pull an exocyclic nitrogen into a carbon ring. Zhang et al. replaced carbonyl groups embedded in rings with nitrogen, taking advantage of a companion reaction that can readily migrate the carbonyl around the framework beforehand. —Jake S. Yeston [ABSTRACT FROM AUTHOR]