Department of Chemistry, South University of Science and Technology of China, Shenzhen 518055, China.
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.
Nat Commun. 2017 May 19;8:15489. doi: 10.1038/ncomms15489.
The axially chiral arylquinazolinone acts as a privileged structural scaffold, which is present in a large number of natural products and biologically active compounds as well as in chiral ligands. However, a direct catalytic enantioselective approach to access optically pure arylquinazolinones has been underexplored. Here we show a general and efficient approach to access enantiomerically pure arylquinazolinones in one-pot fashion catalysed by chiral phosphoric acids. A variety of axially chiral arylquinazolinones were obtained in high yields with good to excellent enantioselectivities under mild condition. Furthermore, we disclosed a method for atroposelective synthesis of alkyl-substituted arylquinazolinones involving Brønsted acid-catalysed carbon-carbon bond cleavage strategy. Finally, the asymmetric total synthesis of eupolyphagin bearing a cyclic arylquinazolinone skeleton was accomplished with an overall yield of 32% in six steps by utilizing the aforementioned methodology.
轴手性芳基喹唑酮作为一种重要的结构骨架，存在于大量天然产物和生物活性化合物以及手性配体中。然而，直接催化对映选择性方法来获得光学纯芳基喹唑啉酮的研究还很少。在这里，我们展示了一种通过手性磷酸催化一锅法高效获得对映体纯芳基喹唑啉酮的通用方法。在温和条件下，多种轴手性芳基喹唑啉酮以高产率和良好到优秀的对映选择性得到。此外，我们还公开了一种涉及 Brønsted 酸催化碳-碳键断裂策略的轴向手性烷基取代芳基喹唑啉酮的对映选择性合成方法。最后，利用上述方法，以 32%的总收率通过六步反应完成了具有环状芳基喹唑啉酮骨架的 eupolyphagin 的不对称全合成。
