Toward a Chemical Constructor: A Lego-Like Approach for Formal α‑Alkylation of Cyclic Ketones

A conceptual strategy for a formal α-alkylation of α-methylene ketones was developed. Diverse 1° and 2° alkyl substituents were generated in the α-position of various ketones via synthesis of enaminone (step 1) and treatment with organomagnesium (step 2) with subsequent catalytic hydrogenation (step...

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Veröffentlicht in:Journal of organic chemistry 2024-06, Vol.89 (11), p.8208-8219
Hauptverfasser: Frolov, Andriy I., Chuchvera, Yaroslav O., Ostapchuk, Eugeniy N., Druzhenko, Tetiana V., Volochnyuk, Dmytro M., Ryabukhin, Serhiy V.
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Sprache:eng
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Zusammenfassung:A conceptual strategy for a formal α-alkylation of α-methylene ketones was developed. Diverse 1° and 2° alkyl substituents were generated in the α-position of various ketones via synthesis of enaminone (step 1) and treatment with organomagnesium (step 2) with subsequent catalytic hydrogenation (step 3, 1° alkyl) or organocopper reagents (step 4, 2° alkyl). Tolerance toward ester, Boc-protected amine, and α-fluoro-substituted ketone moieties was demonstrated. The suitability of the method for late-stage natural product modification was shown.
ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/acs.joc.3c02628