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Pyridylic anions are soft nucleophiles in the palladium-catalyzed C(sp³)-H allylation of 4-alkylpyridines.

ABSTRACT: We report a mild palladium-catalyzed method for the selective allylation of 4-alkylpyridines in which highly basic pyridylic anions behave as soft nucleophiles. This method exploits alkylidene dihydropyridines, which are semi-stable intermediates readily formed using a 'soft-enolization' approach, in a new mechanistic manifold for decarboxylative allylation. Notably, the catalytic generation of pyridylic anions results in a substantially broader functional group tolerance compared to other pyridine allylation methods. Experimental and theoretical mechanistic studies strongly suggest that pyridylic anions are indeed the active nucleophiles in these reactions, and that they participate in an outer-sphere reductive elimination step. This finding establishes a new pK _a boundary of 35 for soft nucleophiles in transition metal-catalyzed allylations.

SUBMITTER: Wasfy N

PROVIDER: S-EPMC8179045 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Pyridylic anions are soft nucleophiles in the palladium-catalyzed C(sp3)-H allylation of 4-alkylpyridines.

Wasfy Nour N Rasheed Faizan F Robidas Raphaël R Hunter Isabelle I Shi Jiaqi J Doan Brian B Legault Claude Y CY Fishlock Dan D Orellana Arturo A

Chemical science 20201210 4

We report a mild palladium-catalyzed method for the selective allylation of 4-alkylpyridines in which highly basic pyridylic anions behave as soft nucleophiles. This method exploits alkylidene dihydropyridines, which are semi-stable intermediates readily formed using a 'soft-enolization' approach, in a new mechanistic manifold for decarboxylative allylation. Notably, the catalytic generation of pyridylic anions results in a substantially broader functional group tolerance compared to other pyrid ...[more]

PMID: 34163914

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