贵州大学刘雄利团队报道了手性Phenol- 2NO配体与非手性有机碱在Zn(II)催化吲哚不对称烷基化反应中的协同作用。相关研究成果发表在2024年3月1日出版的国际学术期刊《中国化学》。

优先C2对称刚性苯酚型配体在不对称催化中更具吸引力，但具有挑战性。

该文中，研究人员设计并合成了一类具有刚性特征的手性三齿Phenol-2NO配体，该配体结合了苯酚骨架和基于吡咯并咪唑酮的N-氧化物部分的优点，由易于获得的L-脯氨酸酰胺以操作简单的两步进行，总产率高达44%。更重要的是，使用非手性喹啉衍生物作为添加剂，新开发的Phenol-2NO配体可以在去质子化活化后作为阴离子配体与Zn（II）配位，形成吲哚与2，3-二氧代吡咯烷的不对称Michael型Friedel-Crafts烷基化反应的高度对映选择性催化剂。

在温和的条件下，对各种底物都能获得优异的产率（高达90%）和高的对映选择性（高达99%ee）。实验和DFT计算揭示了反应机理和对映选择性的起源。这也代表了非手性有机碱作为不对称催化添加剂首次活化苯酚型配体/金属络合物。

附：英文原文

Title: Chiral Phenol-2NO Ligand Cooperation with Achiral Organic Base in the Zn(II)-Catalyzed Asymmetric Alkylation Reaction of Indoles

Author: Ke-Lan Xu, Yu-Heng Wang, Xi-Rui Wang, Pan Hu, Bo-Wen Pan, Wen-Jing Zhang, Zi-Yue Chen, Ying Zhou, Xiong-Li Liu

Issue&Volume: 2024-03-01

Abstract: The privileged C2-symmetric rigid phenol-type ligand is more attractive but challenging in asymmetric catalysis. Herein, we designed and synthesized a class of rigid-featured chiral tridentate Phenol-2NO ligands, that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone-based N-oxide moiety, from readily available L-prolinamides in operationally simple two steps and up to 44% overall yield. More importantly, using an achiral quinoline derivative as an additive, the newly developed Phenol-2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II) to form a highly enantioselective catalyst for the asymmetric Michael-type Friedel-Crafts alkylation reaction of indoles with 2,3-dioxopyrrolidines. Excellent yields (up to 90%) and high enantioselectivities (up to 99% ee) are obtained for a wide range of substrates under mild conditions. Experiments and DFT calculations revealed the reaction mechanism and the origins of the enantioselectivity. This also represented the first activation of phenol-type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis.

DOI: 10.1002/cjoc.202400094

Source: https://onlinelibrary.wiley.com/doi/full/10.1002/cjoc.202400094