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Deaminative chlorination of aminoheterocycles.

ABSTRACT: Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH₂ groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp²)‒NH₂ can be converted into C(sp²)‒Cl bonds. The method is characterized by its wide functional group tolerance and substrate scope, allowing the modification of >20 different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH₂ into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents.

SUBMITTER: Ghiazza C

PROVIDER: S-EPMC8755540 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Deaminative chlorination of aminoheterocycles.

Ghiazza Clément C Faber Teresa T Gómez-Palomino Alejandro A Cornella Josep J

Nature chemistry 20211216 1

Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)‒NH2 can be converted into C(sp<s ...[more]

PMID: 34916597

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