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Allylation of C-, N-, and O-Nucleophiles via a Mechanochemically-Driven Tsuji-Trost Reaction Suitable for Late-Stage Modification of Bioactive Molecules.

ABSTRACT: We present the first solvent-free, mechanochemical protocol for a palladium-catalyzed Tsuji-Trost allylation. This approach features exceptionally low catalyst loadings (0.5 mol %), short reaction times (<90 min), and a simple setup, eliminating the need for air or moisture precautions, making the process highly efficient and environmentally benign. We introduce solid, nontoxic, and easy-to-handle allyl trimethylammonium salts as valuable alternative to volatile or hazardous reagents. Our approach enables the allylation of various O-, N-, and C-nucleophiles in yields up to 99 % even for structurally complex bioactive compounds, owing to its mild conditions and exceptional functional group tolerance.

SUBMITTER: Templ J

PROVIDER: S-EPMC10952285 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Allylation of C-, N-, and O-Nucleophiles via a Mechanochemically-Driven Tsuji-Trost Reaction Suitable for Late-Stage Modification of Bioactive Molecules.

Templ Johanna J Schnürch Michael M

Angewandte Chemie (International ed. in English) 20231129 1

We present the first solvent-free, mechanochemical protocol for a palladium-catalyzed Tsuji-Trost allylation. This approach features exceptionally low catalyst loadings (0.5 mol %), short reaction times (<90 min), and a simple setup, eliminating the need for air or moisture precautions, making the process highly efficient and environmentally benign. We introduce solid, nontoxic, and easy-to-handle allyl trimethylammonium salts as valuable alternative to volatile or hazardous reagents. Our approa ...[more]

PMID: 37931225

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Allylation of C‐, N‐, and O‐Nucleophiles via a Mechanochemically‐Driven Tsuji–Trost Reaction Suitable for Late‐Stage Modification of Bioactive Molecules

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