State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
School of Pharmacy, Fudan University, Shanghai 201203, China.
J Am Chem Soc. 2022 Jan 12;144(1):130-136. doi: 10.1021/jacs.1c12625. Epub 2021 Dec 23.
Acyclic quaternary carbon stereocenters exist widely in natural products and bioactive molecules, but their enantioselective construction remains a prominent challenge. In particular, multicomponent enantioselective couplings of simple precursors to acyclic all-carbon quaternary stereocenters are very rare. We describe herein an N-heterocyclic carbene (NHC)-Ni catalyzed redox-economical three-component reaction of aldehydes, alkynes, and enones that proceeds in a highly chemo-, regio-, and enantioselective manner. A wide variety of valuable acyclic α-quaternary chiral ketones were synthesized in a single step with 100% atom economy. This reaction proceeds through the formation of a transient cyclic enolate followed by an aldol reaction/ring-opening sequence. The strategy is expected to inspire new and efficient approaches to generate other acyclic quaternary stereocenters.
非循环季碳立体中心广泛存在于天然产物和生物活性分子中，但它们的对映选择性构建仍然是一个突出的挑战。特别是，简单前体到非循环全碳季碳立体中心的多组分对映选择性偶联非常罕见。本文描述了一种 N-杂环卡宾 (NHC)-Ni 催化的醛、炔烃和烯酮的氧化还原经济的三组分反应，该反应以高度化学选择性、区域选择性和对映选择性的方式进行。通过一步反应以 100%的原子经济性合成了多种有价值的非循环 α-季碳手性酮。该反应通过形成瞬态环状烯醇化物，然后进行Aldol 反应/开环序列进行。该策略有望激发生成其他非循环季碳立体中心的新的和有效的方法。
