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

Abstract

The aerobic oxidative cross-coupling of tetrahydroisoquinolines (THIQs) with diethylzinc catalyzed by CuCl has been examined by means of electrospray mass spectrometry (ESI-MS). Substrates, intermediates, and the product were readily detected. Particular emphasis has been placed on the role of CuCl . Formation of the intermediate iminium species has been investigated in more detail by ESI-MS, electrochemistry-coupled ESI mass spectrometry (EC-MS), and cyclic voltammetry (CV). Our experiments have consistently revealed strong influences of the N-substituent of the THIQ derivative and its oxidation stability with respect to CuCl . The results may help to expand the synthetic scope of the reaction, while also further establishing EC-MS as a valuable technique for linking mass spectrometry with cyclic voltammetry in mechanistic studies of organic redox reactions.

Novel pH-sensitive catechol dyes synthesised by a three component one-pot reaction

“…Subsequently, a copper-promoted oxidation of the THIQ ring at the benzylic position, leading to an iminium ion, is suggested (intermediate I ). A similar oxidation of the THIQ skeleton has been previously reported in the oxidative coupling of N -aryl-1.2,3,4-tetrahydroisoquinolines with different nucleophiles, using copper-based catalysts and several oxidants ( Boess et al, 2012 ; Willms et al, 2018 ; Boess et al, 2020 ; Bjerg et al, 2022 ). Moreover, commonly, metal-catalysed oxidative coupling reactions with tertiary amines have been also proposed to proceed via iminium ion species ( Murahashi et al, 2003 ; Yoo et al, 2010 ).…”

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis

“…This proposal was evidenced by SV luminescence quenching experiments, wherein quenching was observed only in the presence of all three of the substrate benzaldehyde, DABCO, and oxalic acid; omitting one of these components resulted in no luminescence quenching. Following reductive PCET, the oxidized Ru(III) complex ( E 1/2 Ru(III)/Ru(II)= +1.26 V vs SCE in MeCN) 64 then reacts with the N -arylamine substrate (e.g., for N -Ph tetrahydroisoquinoline, E p/2 ox = +0.43 V vs Fc + /Fc in MeCN) 890 to the corresponding aminium radical cation and regenerates ground-state Ru(II). The aminium radical cation is deprotonated by DABCO, resulting in an α-amino radical, which rapidly combines with the neutral radical generated through reductive PCET in a radical–radical cross-coupling step to furnish the desired product.…”

Investigating the Oxidation Step in the CuCl2-Catalyzed Aerobic Oxidative Coupling Reaction of N-Aryl Tetrahydroisoquinolines

“…In recent years, a number of detailed experimental and theoretical studies have uncovered many aspects of the reaction mechanisms with N -aryl tetrahydroisoquinolines 1 , depending on the catalyst and oxidant used. Well-investigated systems are the combination of CuCl 2 as the catalyst with oxygen, CuBr as the catalyst with tert -butyl hydroperoxide ( t BuOOH), ,, Rh 2 cap 4 with t BuOOH (albeit using N , N -dimethylanilines, not 1 ), a binuclear Cu-catalyst with oxygen, photocatalytic reactions with and without photocatalysts, as well as the use of the oxidant DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) without catalysts …”