Mechanistic Studies on Bioinspired Aerobic C–H Oxidation of Amines with an ortho-Quinone Catalyst

Abstract

We report herein our mechanistic studies of the ortho-quinone-catalyzed aerobic oxidation of primary, secondary, and tertiary amines. Two different catalytic pathways were discovered for the reductive half reactions: for primary amines, the reaction was found to proceed via a transamination pathway, while the reactions with secondary amines and tertiary amines proceeded via hydride transfer. We also found that the amine substrates could significantly promote the regeneration of the ortho-quinone catalyst in the oxidative half reaction, in which a proton transfer occurs between the amine substrates and catechol derivatives (the reduced form of the ortho-quinone catalyst).

Asymmetric Hydrogenation of 1-aryl substituted-3,4-Dihydroisoquinolines with Iridium Catalysts Bearing Different Phosphorus-Based Ligands

“…After that, the solvent was reduced in vacuo, and the obtained product was purified by flash chromatography (yield: 50-85%). All the obtained substrates were characterized, and the analytical results matched those reported in the literature [25,[50][51][52][53][54]. The chiral 5,6,7,8-tetrahydroquinoline-8-ol was obtained as previously reported with a yield of 89% for the (R)-enantiomer (99% e.e.)…”

Aerobic catalytic systems inspired by copper amine oxidases

“…The utility of the protocol has been proved in the preparation of pharmaceutical intermediates [36]. In the same vein, Luo and co-workers have reported the high efficiency of their o-quinone 10 (10 mol%) in tertiary amine dehydrogenation reactions [16,37]. Especially, cross-dehydrogenative-coupling reactions of N-aryl tetrahydroisoquinoline derivatives were performed in the presence of various nucleophiles (2 equiv.…”

“…), at 60 °C, under aerobic neat conditions. Functionalization adjacent to the nitrogen atom could be obtained in high yields with nitroalkanes, dialkyl malonates, dialkylphosphonates, indoles and even ketones [37]. Finally, o-quinone 10 was found to be the only bioinspired organocatalyst able to oxidize the three classes of amines.…”

Modification of N-Terminal α-Amine of Proteins via Biomimetic ortho-quinone-mediated Oxidation

“…1B). [11][12][13] These biomimetic quinone-based catalysts show specific chemoselectivity toward the dehydrogenation of primary, secondary, tertiary amines or other reactions. [14][15][16] The applications of quinone oxidation have been largely limited to small molecule transformations despite the significant progress in this area of research.…”

“…To begin our journey, a range of quinone derivates 1-6 were prepared with different functionalities with an aim toward fine-tuning their reactivity to be selective for the α-amine selective rather than the ε-amine of Lys, as well as other functionalities. 7,[11][12] We tested the transamination reaction of model peptide 7 (1 mM) with the sequence of GFHAKGY in an aqueous solution buffered at pH 6.5 using 10 mM (saturated) of each of the quinone (1-6) as the oxidant ( Fig. 2A).…”