Competitive Hydrogen Atom Transfer to Oxyl- and Peroxyl Radicals in the Cu-Catalyzed Oxidative Coupling of N-Aryl Tetrahydroisoquinolines Using tert-Butyl Hydroperoxide

Abstract

The question of whether hydrogen atom transfer (HAT) or electron transfer (ET) is the key step in the activation of N-aryl tetrahydroisoquinolines in oxidative coupling reactions using CuBr as catalyst and tert-butyl hydroperoxide (tBuOOH) has been investigated. Strong indications for a HAT mechanism were derived by using different para-substituted N-aryl tetrahydroisoquinolines, showing that electronic effects play a minor role in the reaction. Hammett plots of the Cu-catalyzed reaction, a direct time-resolved kinetic study with in situ generated cumyloxyl radicals, as well as density functional calculations gave essentially the same results. We conclude from these results and from kinetic isotope effect experiments that HAT is mostly mediated by tert-butoxyl radicals and only to a lesser extent by tert-butylperoxyl radicals, in contrast to common assumptions. However, reaction conditions affect the competition between these two pathways, which can significantly change the magnitude of kinetic isotope effects

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

“…/ t BuO . ‐ mediated production of C‐based radicals through initial hydrogen atom transfer) which may nevertheless also benefit from the stabilisation of partially‐formed radicals in the relevant transition states. 11h This highlights an important point: reactions grouped together in the literature under the term “cross‐dehydrogenative couplings” most likely exhibit a range of related reaction mechanisms…”

First-Row-Transition Ion Metals(II)-EDTA Functionalized Magnetic Nanoparticles as Catalysts for Solvent-Free Microwave-Induced Oxidation of Alcohols

“…Either t-BuOO· or t-BuO can perform H-abstraction from the alcohol substrate. However, in a t-BuOOH rich medium it is more likely that t-BuO· transforms into t-BuOO, upon H-abstraction from the peroxide [47,48]. Hence, t-BuOO radical should be the main responsible one for the free-radical H-abstraction from the substrate.…”

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 …”