香港大学Zhongxing Huang研究团队宣布他们开发了一种统一的、去对称化的合成手性叔碳卤代烷的方法。2022年1月25日，国际知名学术期刊《美国化学会杂志》发表了这一成果。

课题组人员报道了一类双核锌催化剂与脯氨醇或哌啶甲醇衍生的四齿配体，可以对许多容易获得的卤代丙二酸酯还原性去对称化，生成α-卤代-β-羟基酯。这些多功能化的叔烷基氟化物、氯化物和溴化物被证明是氟代药物类似物和多卤代单萜的有用中间体。另外，对手性氯代和溴代产品的简易分子内环氧化还能够迅速获得含有叔醇基团的天然产物。

据了解，对映体富集的叔烷基卤化物普遍存在于生物活性分子中，也可以作为获得复杂结构的灵活的合成中间体。这些基团传统的获取途径通常取决于立体选择性碳-卤素或碳-碳键形成反应，而与之相比，以卤代碳和前手性四取代碳为原料的去对称方法在很大程度上还未被开发。

附：英文原文

Title: A Unified and Desymmetric Approach to Chiral Tertiary Alkyl Halides

Author: Yin Zheng, Suihan Zhang, Kam-Hung Low, Weiwei Zi, Zhongxing Huang

Issue&Volume: January 25, 2022

Abstract: Enantioenriched tertiary alkyl halides are prevalent in bioactive molecules and can serve as versatile synthetic intermediates to construct complex structures. While conventional access to these motifs often hinges on stereoselective carbon–halogen or carbon–carbon bond formation reactions, desymmetric approaches using halogenated and prochiral tetrasubstituted carbons are largely elusive in comparison. Here, we report that a suite of dinuclear zinc catalysts with a prolinol- or pipecolinol-derived tetradentate ligand can reductively desymmetrize a large collection of easily available halomalonic esters to α-halo-β-hydroxyesters. These polyfunctionalized tertiary alkyl fluorides, chlorides, and bromides proved to be useful intermediates toward fluorinated drug analogs and polyhalogenated monoterpenes. The facile intramolecular epoxidation of the chiral chloride and bromide products has also enabled expeditious access to natural products containing tertiary alcohol motifs.

DOI: 10.1021/jacs.1c12404

Source: https://pubs.acs.org/doi/10.1021/jacs.1c12404