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Updated: Jun 24, 2025

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Continuous Enantioselective α-Alkylation of Ketones via Direct Photoexcitation
Michael Weiser1, Ádám Márk Pálvölgyi1, Matthias Weil2
1Institute of Applied Synthetic Chemistry, TU Wien, 1060 Vienna, Austria.
Abstract:
Motivated by the scarcity of enantioselective direct intermolecular α-alkylation reactions of ketones with simple alkyl halides, we report a photo-organocatalytic process to access diethyl 2-(2-oxocyclohexyl)malonate and derivatives in good yield and enantioselectivity. The reaction design is based on highly abundant and nature-derived 9-amino-9-deoxy-epi-cinchona alkaloids to activate ketones as transient secondary enamines, which exist unfavorably in equilibrium with imines. These condensed species can serve as powerful photoinitiators via direct photoexcitation. This concept provides access to both enantiomeric antipodes. In addition to introducing an uncomplicated batch-optimized procedure, we investigated the feasibility and limitations of implementing the reaction in continuous flow, thus enabling to obtain diethyl 2-(2-oxocyclohexyl)malonate with a productivity of 47 μmol/h and 84% enantioselectivity.
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