Aerobic Oxidative Homo- and Cross-Coupling of Amines Catalyzed by Phenazine Radical Cations

Abstract

Phenazine radical cations (PhRCs) were used for the first time as efficient metal-free catalysts for the oxidative homo- and cross-coupling of a variety of different amines. A series of functional PhRCs were prepared, characterized with X-ray diffraction, and their radical character was investigated with DFT calculations. They were tested as catalysts under neat conditions with low oxygen pressure to prepare homo- and cross-coupled aliphatic and aromatic imines in high yields. Although all synthesized phenazines were catalytically active, the highest reaction rates and the best selectivity were achieved using the 5,10-dihydro-5,10-dimethylphenazine radical cation. By means of fluorescence, UV–vis and EPR spectroscopy, a mechanism of the oxidative amine coupling, catalyzed by PhRCs, is proposed.

Phenazine Radical Cations as Efficient Homogeneous and Heterogeneous Catalysts for the Cross‐Dehydrogenative Aza‐Henry Reaction

“…[69] The presence of unpaired electrons at the material's surface was assessed by electron paramagnetic resonance (EPR), just as it was previously investigated for its molecular counterparts. [63] A very strong signal was observed at 3524 Gs (g value of 2.003), which is in the typical range for an organic radical ( Figure 3). [70,71] Importantly, this strong signal was observed both in the solid sample and in suspension in methyl tertbutyl ether (MTBE) and was not affected by bubbling of oxygen in the sample (Figure 3).…”

“…The ability of phenazine radical cations to furnish iminium ions from amines through single-electron transfer (SET) under aerobic conditions has been previously observed and confirmed in our previous investigations. [63] Thus, we figured, it should be possible to trap different carbon nucleophiles with these reactive intermediates under the proper conditions (Scheme 4), just as it has been thoroughly exploited in cross-dehydrogenative couplings (CDC), [72] a powerful and elegant methodology for furnishing CÀ C bonds from two different CÀ H groups. [73][74][75] Hence, we selected the cross-dehydrogenative aza-Henry (nitro-Mannich) reaction between hydroisoquinolines and nitromethane as model system to test our hypothesis.…”

“…In our previous work, the ionization energies of these molecules were determined with DFT calculations. [63] For instance, the lower ionization barrier for radical formation of 1f (129.8 kcal mol À 1 ) compared to 1b (139.9 kcal mol À 1 ) suggests a more stable radical state and therefore, lower reactivity under catalytic conditions. To our delight, the newly synthesized covalently linked porous polymer 2 displayed a good catalytic activity under these conditions (80 %, Table 1, entry 7).…”

“…[62] We explored further the exploitation of stable radical cations as oxidation catalysts with the development of a series of 5,10-disubstitued phenazines (Scheme 1,B) which showed remarkable activities for the oxidative homo and cross coupling of amines. [63] Interestingly, even though the strong redox properties of phenazines and the stability of their open-shell derivatives are relatively well-known, there are very few additional reports on their use as redox catalysts. Notable examples are the reports from the Miyake group on their use as catalysts for photoinduced atom transfer radical polymerization, [64,65] and the use the nonfunctionalized 5,10-dihydrophenazine (in stoichiometric amounts) as oxidant and proton-transfer reagent for aldehyde esterification.…”

“…Notable examples are the reports from the Miyake group on their use as catalysts for photoinduced atom transfer radical polymerization, [64,65] and the use the nonfunctionalized 5,10-dihydrophenazine (in stoichiometric amounts) as oxidant and proton-transfer reagent for aldehyde esterification. [53] Inspired by our previous works on the preparation of hybrid porous polymers based on polyhedral oligomeric silsesquioxane (POSS), [42] and the aforementioned pyrazine and phenazine radical-cation oxidation catalysts, [63] we designed and synthesized a novel type of covalently linked porous polymers exhibiting tetrakis(phenyl) silane moieties as structural elements cross-linked by phenazine groups (Scheme 1,C).…”