Selective Heteroaryl N-Oxidation of Amine-Containing Molecules

Dyer, Robert M. B.; Hahn, Philip L.; Hilinski, Michael K.

doi:10.1021/acs.orglett.8b00558

Cited by 17 publications

(11 citation statements)

References 30 publications

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“…Moreover, because these catalysts exhibit high chemoselectivity in the presence of electron-rich heterocycles, we thought they might have the mechanistic generality to serve as selective pyridine N -oxidation catalysts, as projected in Figure d. Several other designs of catalytic residues for enantioselective pyridine N -oxidation were also considered based on the previous literature …”

Section: Resultsmentioning

confidence: 99%

Catalytic Enantioselective Pyridine N-Oxidation

et al. 2019

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The catalytic, enantioselective N-oxidation of substituted pyridines is described. The approach is predicated on a biomolecule-inspired catalytic cycle wherein high levels of asymmetric induction are provided by aspartic-acid-containing peptides as the aspartyl side chain shuttles between free acid and peracid forms. Desymmetrizations of bis(pyridine) substrates bearing a remote pro-stereogenic center substituted with a group capable of hydrogen bonding to the catalyst are demonstrated. Our approach presents a new entry into chiral pyridine frameworks in a heterocycle-rich molecular environment. Representative functionalizations of the enantioenriched pyridine N-oxides further document the utility of this approach. Demonstration of the asymmetric N-oxidation in two venerable drug-like scaffolds, Loratadine and Varenicline, show the likely generality of the method for highly variable and distinct chiral environments, while also revealing that the approach is applicable to both pyridines and 1,4-pyrazines.

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Section: Resultsmentioning

confidence: 99%

Catalytic Enantioselective Pyridine N-Oxidation

et al. 2019

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“…The N ‐oxides were selectively formed in the presence of more reactive secondary and tertiary amines using an in situ protonation strategy and an iminium salt organocatalyst 8 (Scheme 3). [17] Hilinski's team initially investigated the reaction using traditional peracid oxidants under acidic conditions, but only the undesired tertiary amine oxide was formed. The group then employed trifluoromethyl iminium salt 8 , which they previously developed for use in catalytic oxaziridinium‐mediated oxidation.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

et al. 2020

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While remarkable progress has recently been made for the direct C−H‐functionalization of azines, its application is still limited by a lack of accessible functional groups (primarily carbon‐based) and poor regioselectivity. In contrast, C2‐functionalized pyridines and quinolines can be easily synthesized by treating readily available N‐oxides with various reagents under appropriate activation conditions. This review seeks to comprehensively document the available synthetic methods for introducing functional groups at the C2 position of pyridines and quinolines. In this work, we highlight recent developments in the C2‐functionalization of pyridine and quinoline N‐oxides and address both the mechanisms and regioselectivity of the reactions. We also describe the pathways and reactive species involved in these processes and highlight a number of medically relevant nitrogen heteroaromatics.

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“…The appropriate N ‐oxides of pyridines, pyrazines, pyrimidines and quinolines are precursors for a huge variety of C2‐functionalized bioactive compounds used in medicine today (Wang et al ., 2016). No less important are N ‐oxides themselves as N → O moiety is present in various pharmaceuticals, chemical catalysts, agriculture agents and pyrotechnic compounds, and they are promising units in future studies as well (Dyer et al ., 2018). Quinoxaline 1,4‐di‐ N ‐oxide derivatives show a broad range of biological properties, including anti‐tubercular, antimicrobial, antitumoral, antitrypanosomal and antiinflammatory activities, thus possess potential applications in human and veterinary medicines (Srinivasarao et al ., 2020).…”

Section: Introductionmentioning

confidence: 99%

An efficient and regioselective biocatalytic synthesis of aromatic N‐oxides by using a soluble di‐iron monooxygenase PmlABCDEF produced in the Pseudomonas species

Petkevičius

Vaitekūnas

Gasparavičiūtė

et al. 2021

Microbial Biotechnology

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Here, we present an improved whole-cell biocatalysis system for the synthesis of heteroaromatic N-oxides based on the production of a soluble di-iron monooxygenase PmlABCDEF in Pseudomonas sp. MIL9 and Pseudomonas putida KT2440. The presented biocatalysis system performs under environmentally benign conditions, features a straightforward and inexpensive procedure and possesses a high substrate conversion and product yield. The capacity of gram-scale production was reached in the simple shake-flask cultivation. The template substrates (pyridine, pyrazine, 2aminopyrimidine) have been converted into pyridine-1-oxide, pyrazine-1-oxide and 2-aminopyrimidine-1oxide in product titres of 18.0, 19.1 and 18.3 g l -1 , respectively. To our knowledge, this is the highest reported productivity of aromatic N-oxides using biocatalysis methods. Moreover, comparing to the chemical method of aromatic N-oxides synthesis based on meta-chloroperoxybenzoic acid, the developed approach is applicable for a regioselective oxidation that is an additional advantageous option in the preparation of the anticipated N-oxides.

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Selective Heteroaryl N-Oxidation of Amine-Containing Molecules

Cited by 17 publications

References 30 publications

Catalytic Enantioselective Pyridine N-Oxidation

Catalytic Enantioselective Pyridine N-Oxidation

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

An efficient and regioselective biocatalytic synthesis of aromatic N‐oxides by using a soluble di‐iron monooxygenase PmlABCDEF produced in the Pseudomonas species

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