The Photocatalyzed Aza-Henry Reaction of N-Aryltetrahydroisoquinolines: Comprehensive Mechanism, H^•- versus H⁺-Abstraction, and Background Reactions

Abstract

The cross-dehydrogenative coupling (CDC) reaction of N-aryltetrahydroisoquinolines (THIQ) is one of the most exploited photocatalytic transformation and a test reaction for an exceptional variety of catalysts. However, its mechanism remained unclear concerning involved intermediates, reactive pathways of the amine radical cation and the influence of oxygen and the light source. Therefore, nuclear magnetic resonance (NMR), electron spin resonance (ESR) and synthetic methods were combined to provide a comprehensive picture of the reaction mechanism using Ru(bpy)3Cl2 as a photocatalyst under aerobic and anaerobic conditions. The reaction profiles and involved intermediates were monitored and analyzed by NMR spectroscopy. Several intermediates contributing to product formation were identified, the iminium ion, the hydroperoxide and dimer of THIQ, and a new ring opened intermediate, cleaved at the benzylic C-N bond. Mechanistic evidence is given that under anaerobic conditions preferentially the α-amino radical is formed by deprotonation, in contrast to the formation of iminium ions via H(•)-abstraction in the presence of oxygen. Further, the light-induced background reaction in the absence of the catalyst was studied in detail, revealing that the product formation rate is correlated to the intensity and wavelength of the light source and that oxygen is essential for an efficient conversion. The reaction rate and efficiency is comparable to previously reported photocatalytic systems, performed under aerobic conditions in combination with intense blue light sources. Thus, the multitude of reaction parameters investigated reveals the preference for hydrogen atom or proton abstraction in photoreactions and allows to assess the influence of experimental conditions on the mechanistic pathways.

N‐Aryl Groups Are Ubiquitous in Cross‐Dehydrogenative Couplings Because They Stabilize Reactive Intermediates

“…The sequence above that was experimentally observed and computationally modelled is in agreement with some mechanisms proposed for other CDC reactions (e.g., an iron‐catalyzed, tert ‐butyl peroxy radical‐, O 2 ‐, or DDQ‐ mediated CDC) but distinct from mechanisms proposed for others (e.g., metal‐, or t BuOO . / t BuO .…”

Photo‐Chromium: Sensitizer for Visible‐Light‐Induced Oxidative C−H Bond Functionalization—Electron or Energy Transfer?

“…The excited‐state redox potential of rose bengal is significantly higher than that of [Cr(ddpd) 2 ] 3+ (Table ; E (*S/S .− )=0.61 V vs. ferrocene). This enables a parallel but less selective PET pathway for rose bengal as sensitizer via amine radical cations and superoxide. These radicals could be responsible for the formation of side products.…”

Investigations of the Copper‐Catalyzed Oxidative Cross‐Coupling of Tetrahydroisoquinolines with Diethylzinc by a Combination of Mass Spectrometric and Electrochemical Methods

“…The key mechanistic feature of the aerobic cross‐coupling is the formation of an iminium intermediate from the amine substrate by single‐electron‐transfer (SET) and proton‐transfer steps (Scheme ) . Under anaerobic conditions, a radical pathway for the coupling step has been assumed …”