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Updated: Jun 26, 2025

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Toward a Chemical Constructor: A Lego-Like Approach for Formal α-Alkylation of Cyclic Ketones
Andriy I Frolov1,2, Yaroslav O Chuchvera1, Eugeniy N Ostapchuk1,2
1Enamine Limited, 78 Winston Churchill Street, 02094 Kyiv, Ukraine.
Abstract:
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.
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