Weiser Michael, Pálvölgyi Ádám Márk, Weil Matthias, Bica-Schröder Katharina
Institute of Applied Synthetic Chemistry, TU Wien, 1060 Vienna, Austria.
Institute of Chemical Technologies and Analytics, TU Wien, 1060 Vienna, Austria.
J Org Chem. 2024 Jun 21;89(12):8906-8914. doi: 10.1021/acs.joc.4c00759. Epub 2024 Jun 10.
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--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.
受酮与简单卤代烃对映选择性直接分子间α-烷基化反应稀缺性的驱动，我们报道了一种光有机催化过程，可高收率和对映选择性地获得2-(2-氧代环己基)丙二酸二乙酯及其衍生物。该反应设计基于高度丰富且源自天然的9-氨基-9-脱氧奎宁生物碱，以将酮活化为瞬态二级烯胺，其与亚胺处于不利的平衡状态。这些缩合物种可通过直接光激发作为强大的光引发剂。这一概念可获得两种对映体。除了引入简单的批次优化程序外，我们还研究了在连续流中实施该反应的可行性和局限性，从而能够以47 μmol/h的生产率和84%的对映选择性获得2-(2-氧代环己基)丙二酸二乙酯。
