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Remote Construction of N-Heterocycles via 1,4-Palladium Shift-Mediated Double C-H Activation.

ABSTRACT: In the past years, Pd⁰ -catalyzed C(sp³ )-H activation provided efficient and step-economical methods to synthesize carbo- and heterocycles via direct C(sp² )-C(sp³ ) bond formation. We report herein that a 1,4-Pd shift allows access to N-heterocycles which are difficult to build via a direct reaction. It is shown that o-bromo-N-methylanilines undergo a 1,4-Pd shift at the N-methyl group, followed by intramolecular trapping by C(sp² )-H or C(sp³ )-H activation at another nitrogen substituent and remote C-C bond formation to generate biologically relevant isoindolines and β-lactams. The product selectivity is influenced by the employed ligand, with NHCs favoring the product of remote C-C coupling against products arising from direct C-C coupling and N-demethylation.

SUBMITTER: Miyakoshi T

PROVIDER: S-EPMC9303548 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Remote Construction of N-Heterocycles via 1,4-Palladium Shift-Mediated Double C-H Activation.

Miyakoshi Takeru T Niggli Nadja E NE Baudoin Olivier O

Angewandte Chemie (International ed. in English) 20220223 17

In the past years, Pd0 -catalyzed C(sp3 )-H activation provided efficient and step-economical methods to synthesize carbo- and heterocycles via direct C(sp2 )-C(sp3 ) bond formation. We report herein that a 1,4-Pd shift allows access to N-heterocycles which are difficult to build via a direct reaction. It is shown that o-bromo-N-methylanilines undergo a 1,4-Pd shift at the N-methyl group, followed by intramolecular trapping by C(sp2 )-H or C ...[more]

PMID: 35143094

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