School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
J Org Chem. 2020 Aug 7;85(15):10152-10166. doi: 10.1021/acs.joc.0c01528. Epub 2020 Jul 27.
A catalytic asymmetric synthesis of 3,3'-bisindoles bearing single axial chirality has been established via chiral phosphoric acid (CPA)-catalyzed enantioselective addition reaction of 3,3'-bisindoles with ninhydrin-derived 3-indolylmethanols. The selection of ninhydrin-derived 3-indolylmethanols as suitable electrophiles is based on the consideration that the symmetric and bulky moiety of ninhydrin would increase the steric congestion around the axis to generate stable axial chirality and avoid the generation of central chirality. By this approach, a series of 3,3'-bisindoles bearing single axial chirality were synthesized via the dynamic kinetic resolution (DKR) process in generally acceptable yields and considerable enantioselectivities. In addition, an in-depth investigation on the property (stability and rotation barrier) of the synthesized axially chiral 3,3'-bisindoles was carried out, thus providing useful information on this class of axially chiral frameworks. This approach makes use of the strategy of dynamic kinetic resolution of 3,3'-bisindoles, therefore expanding the generality and applicability of this strategy for catalytic asymmetric synthesis of 3,3'-bisindoles bearing single axial chirality.
通过手性磷酸（CPA）催化的 3,3'-双吲哚与邻苯二酮衍生的 3-吲哚甲醇的对映选择性加成反应，建立了具有单轴手性的 3,3'-双吲哚的催化不对称合成。选择邻苯二酮衍生的 3-吲哚甲醇作为合适的亲电试剂是基于这样的考虑，即邻苯二酮的对称和庞大的部分会增加轴周围的空间位阻，从而产生稳定的轴手性，并避免产生中心手性。通过这种方法，通过动态动力学拆分（DKR）过程，以一般可接受的产率和相当高的对映选择性合成了一系列具有单轴手性的 3,3'-双吲哚。此外，还对合成的轴手性 3,3'-双吲哚的性质（稳定性和旋转势垒）进行了深入研究，从而为这类轴手性框架提供了有用的信息。该方法利用了 3,3'-双吲哚的动态动力学拆分策略，从而扩展了该策略在手性催化不对称合成具有单轴手性的 3,3'-双吲哚中的通用性和适用性。
