Biocatalytic and Chemo-Enzymatic Synthesis of Quinolines and 2-Quinolones by Monoamine Oxidase (MAO-N) and Horseradish Peroxidase (HRP) Biocatalysts

Abstract

The oxidative aromatization of aliphatic N-heterocycles is a fundamental organic transformation for the preparation of a diverse array of heteroaromatic compounds. Despite many attempts to improve the efficiency and practicality of this transformation, most synthetic methodologies still require toxic and expensive reagents as well as harsh conditions. Herein, we describe two enzymatic strategies for the oxidation of 1,2,3,4tetrahydroquinolines (THQs) and N-cyclopropyl-N-alkylanilines into quinolines and 2-quinolones, respectively. Whole cells and purified monoamine oxidase (MAO-N) enzymes were used to effectively catalyze the biotransformation of THQs into the corresponding aromatic quinoline derivatives, while N-cyclopropyl-N-alkylanilines were converted into 2-quinolone compounds through a horseradish peroxidase (HRP)-catalyzed annulation/aromatization reaction followed by Fe-mediated oxidation.

HFIP Mediated Synthesis of C4‐Aryl‐2‐quinolones through Serial Oxidation

“…In the preliminary investigation, diphenylamine ( 1a ) and propargylic chloride 2a were selected as the model substrates. Stoichiometric amounts of oxidants (K 3 Fe(CN) 6 or KsOsO 2 (OH) 4 ) were employed for the first oxidation step (from disproportionated mixture to quinolinium ion), and renowned condition (K 3 Fe(CN) 6 , K 2 CO 3 , H 2 O) [16] was applied for the second oxidation step (oxidation of quinolinium to quinolone). During the first oxidation step, formation of the quinolinium ion was confirmed by 1 H‐NMR spectroscopy of the crude mixture.…”

Blue‐LED Synthesis of Pummerer's Ketones by Peroxidase‐Lignin‐Catalyzed Oxidative Coupling of Substituted Phenols

“…All reaction products were dried under high vacuum (10 À 3 mbar) before the spectroscopic and spectrometric analyses. 1 H NMR and 13 C NMR were recorded on a Bruker Avance DRX400 (400 MHz/100 MHz) spectrometer. Chemical shifts are reported in parts per million (δ scale) and are internally referenced to CDCl 3 .…”

“…In the last years, Horseradish Peroxidase (HRP) received a great attention as an effective and selective catalyst in synthetic transformations. [1][2][3] The enzyme is activated by heterolytic cleavage of H 2 O 2 with the concomitant formation of the ferryl intermediate, which is in turn converted to the resting state by oxygen atom transfer to substrate. [4][5][6] When H 2 O 2 accumulates in the reaction medium, HRP is inhibited due to undesired overoxidation of the iron atom in the prosthetic group.…”

Photoinduced, Palladium-Catalyzed Enantioselective 1,2-Alkylsulfonylation of 1,3-Dienes

“…We were encouraged by recent reports demonstrating the efficacy of photoinduced palladium catalysis in the difunctionalization of 1,3-dienes, although enantioselective versions of these transformations remained extremely scarce. As our continuous research interests in the catalytic chemistry, we questioned whether it would be possible to achieve metallaphotoredox asymmetric difunctionalization of 1,3-dienes through fine-tuning of the reaction partner and chiral ligand. Herein, we report photoinduced palladium-catalyzed enantioselective three-component 1,2-alkylsulfonylation of 1,3-dienes with alkyl bromides and sulfinates, which can furnish a structurally diverse chiral allylic sulfonylated scaffold with high regioselectivity and enantioselectivity (Scheme c).…”