"On Water" Catalytic Aldol Reaction between Isatins and Acetophenones: Interfacial Hydrogen Bonding and Enamine Mechanism

Jinsong Han; Jin-Lei Zhang; Wei-Qiang Zhang; Ziwei Gao; Li-Wen Xu; Yajun Jian

doi:10.1021/acs.joc.9b00441

"On Water" Catalytic Aldol Reaction between Isatins and Acetophenones: Interfacial Hydrogen Bonding and Enamine Mechanism

J Org Chem. 2019 Jun 21;84(12):7642-7651. doi: 10.1021/acs.joc.9b00441. Epub 2019 May 31.

Authors

Jinsong Han¹, Jin-Lei Zhang¹, Wei-Qiang Zhang¹, Ziwei Gao¹, Li-Wen Xu^{1

2}, Yajun Jian¹

Affiliations

¹ Key Laboratory of Applied Surface and Colloid Chemistry, MOE, School of Chemistry and Chemical Engineering , Shaanxi Normal University , Xi'an 710062 , P. R. China.
² Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education , Hangzhou Normal University , Hangzhou 310012 , P. R. China.

PMID: 31117556
DOI: 10.1021/acs.joc.9b00441

Abstract

"On water" catalytic aldol reaction catalyzed by polyetheramine (D230) has been developed for easy access to 3-substituted 3-hydroxyindolin-2-ones through the reaction between various substituted isatins and acetophenones/cyclic ketones in high yields under room temperature. Systematic mechanism investigation uncovers the secret for the on water catalytic aldol reaction: comparison of the heterogeneous and homogeneous reaction circumstances with yields of 95 and 20%, respectively, indicates the on-water reaction dominating; interfacial hydrogen bonding between isatin with H₂O is tested based on the downfield shift of the C2 and C3's ¹³C NMR signals when water was added to the CDCl₃ solution of isatin; Lewis base polyetheramine D230 catalyzes the aldol reaction via the enamine mechanism verified by in situ NMR and ESI-MS analysis.