Shaanxi Institute of Flexible Electronics, Northwestern Polytechnical University, Xi'an, 710072, China.
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
Nat Commun. 2019 Jul 11;10(1):3061. doi: 10.1038/s41467-019-10940-4.
The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.
轴向手性在对映选择性合成中的重要性已经被广泛认识了几十年。然而，以对映纯形式获得某些结构，如被称为诺宾的联芳基氨基苯酚，仍然是一个挑战。在药物输送中，近年来，在系统筛选中加入轴向手性分子也引起了极大的兴趣，这需要创新和实用的合成具有不同结构的轴向手性实体。在此，我们提出了一种操作简单的用商业可得的手性胺催化剂进行磺酰胺的 N-烷基化反应，以提供两类重要的轴向手性化合物：结构多样的诺宾类似物以及具有优异对映纯度的轴向手性 N-芳基磺酰胺。结构相关的手性磺酰胺在药物分子中显示出巨大的潜力，但它们的对映选择性合成以前从未完成过。我们方法的实际催化程序也为它们在对映选择性合成中的广泛应用提供了良好的前景。
