Pu Xiang, Dang Qiu-Di, Yang Lei, Zhang Xia, Niu Dawen
Department of Emergency, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and School of Chemical Engineering, Sichuan University, Chengdu, 610041, China.
Nat Commun. 2022 May 4;13(1):2457. doi: 10.1038/s41467-022-29986-y.
The construction of vicinal, congested stereocenters with high selectivities is of general utility in chemistry. To build two such stereocenters in one step from readily available starting materials is very desirable, but remains challenging. We report here a doubly stereoconvergent, Cu/Mg-catalyzed asymmetric propargylic substitution reaction to convert simple starting materials to products with vicinal tertiary and all-carbon quaternary stereocenters in high yields and excellent diastereo- and enantioselectivities. Both the nucleophiles and the electrophiles employed in this transformation are racemic. This reaction uses earth abundant metal catalysts, operates under ambient conditions, and demonstrates broad substrate scope. The products of this reaction are functional group rich and synthetically versatile. Key to the success of this development is the devise of a Cu/Mg dual catalytic system and the identification of a bulky tridentate pyridinebisimidazoline (PyBim) ligand.
以高选择性构建相邻的、拥挤的立体中心在化学领域具有普遍用途。从容易获得的起始原料一步构建两个这样的立体中心是非常理想的，但仍然具有挑战性。我们在此报告一种双重立体汇聚的、铜/镁催化的不对称炔丙基取代反应，该反应能将简单的起始原料高产率地转化为具有相邻叔碳和全碳季碳立体中心的产物，且具有出色的非对映和对映选择性。此转化中使用的亲核试剂和亲电试剂均为外消旋体。该反应使用储量丰富的金属催化剂，在环境条件下进行，且底物范围广泛。该反应的产物富含官能团且具有多种合成用途。这一进展成功的关键在于设计了一种铜/镁双催化体系以及鉴定出一种庞大的三齿吡啶双咪唑啉（PyBim）配体。
