J. Org. Chem. 2024, 89 (11), 8208-8219
DOI: 10.1021/acs.joc.3c02628
Frolov A.; Chuchvera Y.; Ostapchuk E.; Druzhenko T.; Volochnyuk D.; Ryabukhin S.
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.