Guo Hao, Ao Yu-Fei, Wang De-Xian, Wang Qi-Qiang
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Beilstein J Org Chem. 2022 May 2;18:486-496. doi: 10.3762/bjoc.18.51. eCollection 2022.
A series of tetraamino-bisthiourea chiral macrocycles containing two diarylthiourea and two chiral diamine units were synthesized by a fragment-coupling approach in high yields. Different chiral diamine units, including cyclohexanediamines and diphenylethanediamines were readily incorporated by both homo and hetero [1 + 1] macrocyclic condensation of bisamine and bisisothiocyanate fragments. With the easy synthesis, gram-scale of macrocycle products can be readily obtained. These chiral macrocycles were applied in catalyzing bioinspired decarboxylative Mannich reactions. Only 5 mol % of the optimal macrocycle catalyst efficiently catalyzed the decarboxylative addition of a broad scope of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. The rigid macrocyclic framework and the cooperation between the thiourea and tertiary amine sites were found to be crucial for achieving efficient activation and stereocontrol. As shown in control experiments, catalysis with the acyclic analogues having the same structural motifs were non-selective.
通过片段偶联方法以高产率合成了一系列含有两个二芳基硫脲和两个手性二胺单元的四氨基双硫脲手性大环化合物。不同的手性二胺单元，包括环己二胺和二苯乙二胺，可通过双胺和双异硫氰酸酯片段的均相和杂相[1 + 1]大环缩合轻松引入。由于合成简便，可轻松获得克级规模的大环产物。这些手性大环化合物用于催化仿生脱羧曼尼希反应。仅5 mol％的最佳大环催化剂就能有效地催化各种丙二酸半硫酯与异吲哚酮衍生的酮亚胺的脱羧加成反应，产率优异，对映选择性良好。发现刚性大环骨架以及硫脲和叔胺位点之间的协同作用对于实现有效的活化和立体控制至关重要。如对照实验所示，具有相同结构基序的无环类似物催化反应没有选择性。
