Zhang Minghao, Huang Zhongxing
State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Hong Kong, China.
Angew Chem Int Ed Engl. 2025 May 26;64(22):e202503149. doi: 10.1002/anie.202503149. Epub 2025 Mar 27.
The use of readily available prochiral or racemic quaternary carbons to access enantioenriched ones offers a promising alternative to conventional synthesis from tertiary or planar substrates. Unlike desymmetrization, which modifies an existing substituent with limited reactivity, a functional group swap can install a new motif, which is structurally distinct and nonderivable from the replaced group. However, achieving enantioconvergence in these quaternary-to-quaternary transformations is challenging, especially for acyclic stereocenters. Here, we report that acyl groups of β-ketonitriles can be stereoselectively replaced by allyl, propargyl, or benzyl moieties using easily accessible alcohols under palladium catalysis. The deacylative functionalization proceeds through a retro-Claisen-type elimination of ketonitrile with alkoxide and the absence of diastereoisomerism in the resulting ketenimine anion assists the subsequent asymmetric addition. Together with the pair of α-substituents, the retained nitrile and the incoming alkyl motif instill significant derivatization potential into the enantioenriched quaternary stereocenters.
使用易于获得的前手性或外消旋季碳来获得对映体富集的季碳，为从叔碳或平面底物进行传统合成提供了一种有前景的替代方法。与去对称化不同，去对称化是用有限反应活性的现有取代基进行修饰，官能团交换可以引入一个新的结构单元，该结构单元在结构上与被取代的基团不同且不可衍生而来。然而，在这些季碳到季碳的转化中实现对映体汇聚具有挑战性，特别是对于无环立体中心。在此，我们报道在钯催化下，使用易于获得的醇类，β-酮腈的酰基可以被烯丙基、炔丙基或苄基部分立体选择性地取代。脱酰基官能化通过酮腈与醇盐的逆克莱森型消除反应进行，并且所得烯酮亚胺阴离子中不存在非对映异构现象有助于随后的不对称加成。与一对α-取代基一起，保留的腈基和引入的烷基结构单元为对映体富集的季立体中心赋予了显著的衍生化潜力。
