DOI: 10.1021/acs.orglett.6c04236 ISSN: 1523-7060
Frustrated Ion-Pair-Catalyzed Biocompatible Synthesis of Acyclic N , S -Acetals
Lei Wang, Liling Jia, Mengyu Kuang, Zhaoqi Xu, Teck-Peng Loh, Peng Chen, Zhenhua JiaAbstract
Addition of thiols to acyclic imines under aqueous conditions remains challenging because the C═N bond is susceptible to hydrolysis. Herein, we describe a biocompatible strategy of imine–thiol addition, catalyzed by frustrated ion pair [Ph3C]+[B(C6F5)4]−, to afford diverse acyclic N,S-acetals through direct C–S bond formation. The reaction proceeded efficiently in water and tolerated a broad range of imines and thiols. Moreover, this metal-free protocol enabled selective conjugation of cysteine residues on a protein with acyclic imines, providing a direct method for site-selective protein modification.