Catalytic Asymmetric Construction of Axially and Centrally Chiral Heterobiaryls by Minisci Reaction
Catalytic Asymmetric Construction of Axially and Centrally Chiral Heterobiaryls by Minisci Reaction
复制标题
DOI：
10.1021/jacs.2c01116
复制
发表时间：
2022-04-06
影响因子：
15
通讯作者：
Xiao, Wen-Jing
中科院分区：
文献类型：
--
作者：
Liang, Dong;Chen, Jia-Rong;Xiao, Wen-Jing
轴向手性联芳基和杂联芳基构成阻转异构体的最具代表性的亚类，在天然产物、生物活性化合物、特权手性配体/催化剂和光学纯材料中普遍存在。尽管有许多离子方案用于其构建，但基于自由基的变体代表了另一种非常理想和有趣的策略，但远未得到开发。此外，通过自由基途径有效合成轴向手性杂联芳基分子，特别是具有多个杂原子和其他类型的手性元素的杂联芳基分子仍然非常有限。我们在此公开了通过5-芳基嘧啶和α-氨基酸衍生的氧化还原活性酯的Minisci反应的轴向和中心手性杂联芳基的第一催化不对称、无金属构建。这通过使用4CzIPN作为有机光氧化还原催化剂与手性磷酸催化剂结合来实现。该反应获得了多种感兴趣的5-芳基嘧啶，其特征在于轴向手性杂联芳基和中心手性α-支链胺的结合，具有通常优异的区域-、非对映-和对映选择性（高达82%产率; >19：1 dr; > 99%ee）。这一发现也为通过自由基参与的手性杂环芳烃的阻转选择性功能化来发展前手性杂联芳基化合物的去对称化方法搭建了一个新的平台。
Axially chiral biaryls and heterobiaryls constitute the most represented subclass of atropisomers with prevalence in natural products, bioactive compounds, privileged chiral ligand/catalysts, and optically pure materials. Despite many ionic protocols for their construction, radical-based variants represent another highly desirable and intriguing strategy but are far less developed. Moreover, efficient synthesis of axially chiral heterobiaryl molecules, especially ones having multiple heteroatoms and other types of chiral elements, through radical routes remains extremely limited. We herein disclose the first catalytic asymmetric, metal-free construction of axially and centrally chiral heterobiaryls by Minisci reaction of 5-arylpyrimidines and alpha-amino acid-derived redox-active esters. This is enabled by the use of 4CzIPN as an organic photoredox catalyst in conjunction with a chiral phosphoric acid catalyst. The reaction achieved a variety of interesting 5-arylpyrimidines featuring the union of an axially chiral heterobiaryl and a centrally chiral alpha-branched amine with generally excellent regio-, diastereo-, and enantioselectivity (up to 82% yield; >19:1 dr; >99% ee). This finding also builds up a new platform for the development of desymmetrization methods via radical-involved atroposelective functionalization at heteroarene of prochiral heterobiaryls.