Cobalt‐Catalyzed Enantioselective Hydroamination of Arylalkenes with Secondary Amines

Abstract

Catalytic asymmetric hydroamination of alkenes with Lewis basic amines is of great interest but remains a challenge in synthetic chemistry. Here, we developed a Co-catalyzed asymmetric hydroamination of arylalkenes directly using commercially accessible secondary amines. This process enables the efficient access to valuable α-chiral tertiary amines in good to excellent yields and enantioselectivities. Mechanistic studies suggest that the reaction includes a CoHmediated hydrogen atom transfer (MHAT) with arylalkenes, followed by a pivotal catalyst controlled S N 2-like pathway between in situ generated electrophilic cationic alkylcobalt(IV) species and free amines. This radicalpolar crossover strategy not only provides a straightforward and alternative approach for the synthesis of enantioenriched α-tertiary amines, but also underpins the substantial opportunities in developing asymmetric radical functionalization of alkenes with various free nucleophiles in oxidative MHAT catalysis.

Electrocatalytic Access to Azetidines via Intramolecular Allylic Hydroamination: Scrutinizing Key Oxidation Steps through Electrochemical Kinetic Analysis

“…For comparative purpose, a set of experiments was conducted under a series of conventionally employed chemical oxidants ( 11–21 ) and solvent systems without electrochemical input (see SI Figure S3 and pages S15–S17). The activated alkene precursor 9 that is prone to competitive hydrogenation was tested under previously employed catalytic systems in the alkene hydrofunctionalizations. ,,− Notably, reactions conducted under chemical oxidants predominantly yielded hydrogenated products (reduction by HAT) highlighting the crucial role of electricity in our reaction.…”

Constructing Four-Membered Heterocycles by Cycloisomerization

“…This catalytic process is realized by the combination of a cobalt catalyst, an oxidant, and a silyl hydride that generates key cobalt hydride and a highly reactive carbocationic intermediate [cationic alkylcobalt­(IV) complexes] from alkenes via carbon radicals under near-neutral conditions. Following our report on cobalt-catalyzed MHAT/RPC reactions, this catalytic system has been extensively utilized in cycloisomerizations, deprotective cyclizations, intermolecular additions, rearrangements, asymmetric variants, and polymerizations . Notably, our group, , Pronin, and Zhu have reported various cycloisomerizations to furnish numerous cyclic ethers and cyclic amines except for the synthetically challenging four-membered heterocycles.…”

Cobalt‐Catalyzed Wagner–Meerwein Rearrangements with Concomitant Nucleophilic Hydrofluorination

“…These organocobalt species are formed via hydrogen atom transfer from a metal hydride to an alkene and an oxidative radical–polar crossover event. Initial studies have focused on the intra‐ and intermolecular displacement of the cobalt complex with various nucleophilic functional groups [20–31] . The ability of alkylcobalt(IV) intermediates to acts as carbocation surrogates has been demonstrated by catalyst‐controlled product‐selective reactions of tertiary allylic alcohol substrates [32] .…”