Visible light induced alkene aminopyridylation using N-aminopyridinium salts as bifunctional reagents

Abstract

The development of intermolecular alkene aminopyridylation has great potential for quickly increasing molecular complexity with two valuable groups. Here we report a strategy for the photocatalytic aminopyridylation of alkenes using a variety of N-aminopyridinium salts as both aminating and pyridylating reagents. Using Eosin Y as a photocatalyst, amino and pyridyl groups are simultaneously incorporated into alkenes, affording synthetically useful aminoethyl pyridine derivatives under mild reaction conditions. Remarkably, the C4-regioselectivity in radical trapping with N-aminopyridinium salt can be controlled by electrostatic interaction between the pyridinium nitrogen and sulfonyl group of β-amino radical. This transformation is characterized by a broad substrate scope, good functional group compatibility, and the utility of this transformation was further demonstrated by late-stage functionalization of complex biorelevant molecules. Combining experiments and DFT calculations on the mechanism of the reaction is investigated to propose a complete mechanism and regioselectivity.

Intermolecular radical carboamination of alkenes

“…N-Aminopyridinium salts 58, that were previously used as amidyl radical precursors for radical arene C-H amidation, were successfully applied as bifunctional reagents to the 1,2-aminopyridylation of electron-rich alkenes (Scheme 15). 65 This radical alkene carboamination protocol features high atom economy and proceeds under mild conditions with the use of an organic dye as a photo-sensitizer to initiate the process. Various electron-rich alkenes including vinyl ethers and enamides were found to be eligible acceptors for this carboamination and diverse functional groups at the pyridine ring are tolerated.…”

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

“…The reduction potential of such species was around −0.75 V vs Ag/Ag + , depending on the substitution pattern. This scaffold was employed recently by the Hong group to achieve an intermolecular alkene 1,2-aminopyridylation to give the difunctionalized products 32.3 (Scheme 32) [148]. Eosin Y (OD13) was an efficient dye for the SET reduction of the N-aminopyridinium salts, which act as bifunctional reagents as the released pyridine later added to the olefin 32.1.…”

“…Illustrative example for the photocatalytic reductive generation of amidyl radicals from N-aminopyridinium salts: the intermolecular alkene 1,2-aminopyridylation reported by Hong and co-workers [148].…”

Three‐Component Aminoarylation of Electron‐Rich Alkenes by Merging Photoredox with Nickel Catalysis

“…For 4‐bromoanisole, an additional ligand screening was performed, but aminoarylation could not be achieved (see SI). However, aminoarylation products were obtained in moderate to good yields by using bromopyridines, providing an alternative pathway for alkene aminopyridination going beyond restrictions of three‐component Minisci reactions ( 4 m – 4 t , 55–88 %) [16] . In addition, halogenated pyrimidine, quinolone and benzothiazole heterocycles engaged in the reaction and 4 u – 4 w were isolated in moderate yields (47–53 %).…”