化学
对映选择合成
乙酰化物
锂(药物)
催化作用
反应性(心理学)
组合化学
亲脂性
有机化学
基质(水族馆)
合理设计
立体化学
纳米技术
医学
海洋学
替代医学
材料科学
病理
地质学
内分泌学
作者
Kenji Yamashita,Yuji Tabata,Katsuya Yamakawa,Takuya Mochizuki,Kai Matsui,Manabu Hatano,Kazuaki Ishihara
摘要
Alkynyl addition to carbonyl compounds is a valuable synthetic method for the preparation of versatile chiral alcohols that are widely found in pharmaceuticals and natural products. Although a variety of enantioselective variations have been reported, alkynyl addition to simple ketones remains an unmet challenge due to their low reactivity and difficult enantiofacial discrimination. Here, we report a method for the catalytic enantioselective addition of lithium acetylide to a variety of ketones using macrocyclic lithium binaphtholates as catalysts. These reactions generally suffer from facile aggregation of lithium species, which leads to less active and selective catalysts. The macrocyclic structure designed in this study prevents such aggregation, affording a monomeric and highly active catalyst that can furnish enantioenriched tertiary alcohols from a variety of ketones within 5-30 min. Moreover, the confined cavity and lipophilicity of the macrocycle confer substrate specificity on the system, demonstrating a multiselectivity similar to that of enzymatic reactions. Thus, these findings offer new insights into the rational design of small-molecule artificial enzymes that exhibit high levels of reactivity and multiselectivity.
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