Catalytic Enantioselective Pyridine N-Oxidation

17 September 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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 are demonstrated, presenting 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.

Keywords

Desymmetrization
Enantioselective
Heterocycle
Peptide
N-oxidation

Supplementary materials

Title
Description
Actions
Title
N-Oxide-SI-ChemRxiv
Description
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