Peng Siyu, Wang Zhaofeng, Zhang Linxing, Zhang Xinhao, Huang Yong
Key Laboratory of Chemical Genomics, Peking University, Shenzhen Graduate School, 518055, Shenzhen, China.
Nat Commun. 2018 Jan 25;9(1):375. doi: 10.1038/s41467-017-02801-9.
Ynones are a unique class of structural motifs that show remarkable chemical versatility. Chiral ynones, particularly those possessing an α-stereogenic center, are highly attractive templates for structural diversification. So far, only very limited examples have been reported for asymmetric α-functionalization of ynones. Asymmetric double α-functionalization of ynones remains elusive. Here we describe a streamlined strategy for asymmetric α-difunctionalization of ynones. We developed a gold-catalyzed multicomponent condensation reaction from a simple ynone, an amine, and an electrophilic alkynylating reagent to generate a 1,2-dialkynyl enamine, a key stable and isolable intermediate. This intermediate can undergo asymmetric fluorination catalyzed by a chiral phosphoric acid derivative. Chiral ynones with an α-quaternary carbon and containing a fluorine and an alkyne can be synthesized in high yield and high ee. The synthetic utility of this method is demonstrated by the synthesis of enantioenriched tri(hetero)arylmethyl fluorides.
炔酮是一类独特的结构基序，具有显著的化学多样性。手性炔酮，特别是那些具有α-立体中心的炔酮，是结构多样化的极具吸引力的模板。到目前为止，关于炔酮不对称α-官能化的报道非常有限。炔酮的不对称双α-官能化仍然难以实现。在此，我们描述了一种用于炔酮不对称α-双官能化的简化策略。我们开发了一种由简单炔酮、胺和亲电炔基化试剂进行的金催化多组分缩合反应，以生成1,2-二炔基烯胺，这是一种关键的稳定且可分离的中间体。该中间体可以在手性磷酸衍生物催化下进行不对称氟化反应。具有α-季碳且含有氟和炔基的手性炔酮能够以高收率和高对映体过量合成。对映体富集的三（杂）芳基甲基氟化物的合成证明了该方法的合成实用性。
