Iron‐Catalyzed Radical Asymmetric Aminoazidation and Diazidation of Styrenes

Abstract

Asymmetric aminoazidation and diazidation of alkenes are straightforward strategies to build value‐added chiral nitrogen‐containing compounds from feedstock chemicals. They provide direct access to chiral organoazides and complement enantioselective diamination. Despite the advances in non‐asymmetric reactions, asymmetric aminoazidation or diazidation based on acyclic systems has not been previously reported. Here we describe the iron‐catalyzed intermolecular asymmetric aminoazidation and diazidation of styrenes. The method is practically useful and requires relatively low loading of catalyst and chiral ligand. With mild reaction conditions, the reaction can be completed on a 20 mmol scale. Studies of the mechanism suggest that the reaction proceeds via a radical pathway and involves stereocontrol of an acyclic free radical which probably takes place through a group transfer mechanism.

Iron-catalyzed domino coupling reactions of π-systems

“…Efforts to expand the scope of aminoazidation reactions were met with success in 2021, when a report from the Bao group described a method for accessing chiral organo azides [ 158 ]. Using a chiral BOX ligand, the authors demonstrated a large scope with excellent yields (up to 98%) and enantioselectivity (up to 96% ee).…”

“…Unlike Morandi’s report ( Scheme 44 ) [ 157 ], the authors only included styrene derivatives in the scope of potential alkenes. Adaptation of the reaction conditions also allowed for the synthesis of enantioenriched diazido products [ 158 ].…”

Iron-Catalyzed Asymmetric Decarboxylative Azidation

“…This is mainly because of the fact that (1) transition-metal-catalyzed radical azidations are supposed to undergo an outer-sphere group transfer mechanism in a very fast manner; (2) the N(3) atom of a linear azido group is remote from the catalytic chiral center . Very recently, our group has developed iron-catalyzed asymmetric radical azidation reactions, in which the tridentate HAIXI BOX ligand that has an extended aromatic plane is essential (Scheme a). When commonly used stronger interactions such as hydrogen bond, ionic bond, or dative bond are absent, such planar ligand is supposed to provide weak interaction, such as π-interaction and van der Waals interaction to drag the carbon-centered radical close to the chiral center.…”

“…The benzylic perester 1a can be easily synthesized from commercially available 2-cyclopentyl-2-phenylacetic acid in a one-step reaction with a high yield. Based on our recent radical asymmetric azidations, an iron metal was chosen as the metal catalyst, and a variety of tridentate ligands that have an extended aromatic plane was evaluated, because it is supposed that such planar ligands feature better interaction with carbon-centered radical than others. Therefore, in the presence of Fe­(OTf) 2 and ligand L1 (HAIXI BOX) that has an extended aromatic plane, the desired chiral azide 3a can be obtained in 90% yield and with 79:21 enantiomeric ratio (er).…”

“…On the basis of the radical nature of peresters and recent studies from our group and others, − mechanistic studies were performed. The result of full inhibition of the formation of the desired product by TEMPO and BHT support the belief that this reaction involved radicals.…”