Photoinduced Nickel-Catalyzed Selective N-Demethylation of Trialkylamines Using C(sp²)–Bromides as HAT Reagents

Abstract

N-Demethylation of trialkylamines is a useful transformation, but typically requires harsh reaction conditions and stepwise procedures, as well as judicious protection of labile functional groups. Herein we report a mild, catalytic approach for the demethylation of trialkylamines by utilizing photoinduced nickel catalysis wherein C(sp2)–bromides serve as hydrogen-atom transfer (HAT) reagents. This method achieves direct demethylation of trialkylamines with wide functional group compatibility, making it highly suitable for late-stage derivatization of complex molecules. Mechanistic investigations provide evidence that C(sp2) radicals generated via photoinduced Ni–C(sp2) bond homolysis are involved in hydrogen atom abstraction from trialkylamines. Utilizing steric control of the C(sp2)–bromides, our HAT approach achieves demethylation with excellent site selectivity in the presence of benzyl-substituted amines, which is complementary to the selectivity of classical approaches that afford debenzylation product instead.

Photoexcited NiII–Aryl Complex-Mediated Giese Reaction of Aryl Bromides

“…Recently, the nickel-mediated photocatalysis has been demonstrated to be an efficient approach to address the challenging and previously inaccessible cross-coupling reactions . However, there is a scarcity of studies on the catalytic reactivities of photoexcited nickel complexes . In 2018, Doyle and co-workers found that photoexcitation of Ni II –aryl halide complexes resulted in the generation of long-lived excited 3 d–d state, suggesting that Ni could be utilized as an alternative metal photocatalyst (Scheme ).…”

Mild and Functional Group-Tolerant Aerobic N-Dealkylation of Tertiary Amines Promoted by Photoredox Catalysis

“…The N -demethylation of tertiary amines has been established by several methods, including photochemical transformations − as well as Cu, Ru, Pd, and Fe ,, catalysis (Scheme A,B). However, most of these studies are performed primarily with simple substrates.…”

Catalytic Conversion of Caffeine into Molecules of Valuable Interest Via N‐Demethylation Reaction

“…[19][20][21][22] Disadvantages include the use of expensive and toxic reagents, the number of reaction steps under severe conditions, and hazardous by-products. Some recent reports use metal-catalyzed, [23] photocatalyst-free, [24] anodic oxidation [25] highlighting difficulties and revealing the search for new practical discoveries of Ndemethylation methods.…”