State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China.
Molecules. 2023 May 23;28(11):4279. doi: 10.3390/molecules28114279.
The desymmetrization of -pyrazolyl maleimides was realized through an asymmetric Michael addition by using pyrazolones under mild conditions, leading to the formation of a tri--heterocyclic pyrazole-succinimide-pyrazolone assembly in high yields with excellent enantioselectivities (up to 99% yield, up to 99% ee). The use of a quinine-derived thiourea catalyst was essential for achieving stereocontrol of the vicinal quaternary-tertiary stereocenters together with the C-N chiral axis. Salient features of this protocol included a broad substrate scope, atom economy, mild conditions and simple operation. Moreover, a gram-scale experiment and derivatization of the product further illustrated the practicability and potential application value of this methodology.
通过使用吡唑啉酮在温和条件下的不对称迈克尔加成，实现了 -吡唑基马来酰亚胺的去对称化，从而以高产率和优异的对映选择性（高达 99%的产率，高达 99%的对映体过量）形成了三杂环吡唑-琥珀酰亚胺-吡唑啉酮的组装。使用来源于奎宁的硫脲催化剂对于实现与 C-N 手性轴一起的相邻季碳-叔碳立体中心的立体控制是必不可少的。该协议的突出特点包括广泛的底物范围、原子经济性、温和的条件和简单的操作。此外，克级实验和产物的衍生化进一步说明了该方法的实用性和潜在应用价值。
