Heterocyclic Group Transfer Reactions with I(III) N-HVI Reagents: Access to N-Alkyl (Heteroaryl)onium Salts via Olefin Aminolactonization

Abstract

<p>Pyridinium and related N-alkyl (heteroaryl)onium salts are versatile synthetic intermediates in organic chemistry, with applications ranging from ring functionalizations to provide diverse piperidine scaffolds to their recent emergence as radical precursors in deaminative cross couplings. Despite their ever-expanding applications, methods for their synthesis have seen little innovation, continuing to rely on a limited set of decades old transforms. Herein, we leverage (bis)cationic nitrogen-ligated I(III) hypervalent iodine reagents, or <i>N</i>-HVIs, as “heterocyclic group transfer reagents” to provide access to a broad scope of (heteroaryl)onium salts via the aminolactonization of alkenoic acids. The reactions proceed in excellent yields, under mild conditions, and are capable of incorporating a broad scope of sterically and electronically diverse aromatic heterocycles. The <i>N</i>-HVI reagents can be generated <i>in situ</i>, the products isolated via simple trituration, and subsequent derivatizations demonstrate the power of this platform for diversity-oriented synthesis of 6-membered nitrogen heterocycles. Mechanistic studies indicate the reaction proceeds via initial olefin activation followed by lactonization and subsequent intermolecular nucleophilic displacement of an (alkyl)(aryl)iodonium salt hypernucleofuge.</p>

I(III)-Mediated Arene C-H Amination using (Hetero)Aryl Nucleophiles

“…[9][10][11][12] In recent years, our laboratory has developed the I(III) N-HVI reagent class (4), which possess datively bound Nheterocyclic ligands (Scheme 1B, inset). [13][14][15][16][17] These reagents are bench stable, can be accessed in a single step from commercial materials, and are compatible with a broad range of heterocyclic ligands. 18 Recent work from our group has demonstrated their utility in "heterocyclic group transfer" (HGT) reactions with olefins as a novel means of accessing complex N-alkyl pyridinium salts.…”

“…18 Recent work from our group has demonstrated their utility in "heterocyclic group transfer" (HGT) reactions with olefins as a novel means of accessing complex N-alkyl pyridinium salts. 17 These salts then serve as a powerful platform for subsequent diversification, either via dearomatizative 19,20 or deaminative 21 functionalizations. In considering the extension of HGT reactions to C(sp 2 )-N bond formation, we recognized that an N-HVI HGT-strategy could serve as a convenient and potentially general approach to I(III)-mediated arene amination (Scheme 1B).…”