The [3+2] Annulation of CF3-Ketimines by Re Catalysis: Access to CF3-Containing Amino Heterocycles and Polyamides.

Saisai Zhang,Heng-Ying Xiong,Guangwu Zhang,Zhenbang Chang,Xun-Yong Liu,Xinxin Qiao

doi:10.1016/j.isci.2020.101705

Abstract

SummaryTransition metal catalyzed [3 + 2] annulation of imines with double bonds via directed C-H activation offers a direct access to amino cyclic motifs. However, owing to weak coordination and steric hindrance, trifluoromethylated ketimines have been an unaddressed challenge for TM-catalyzed annulations. Here, a rhenium-catalyzed [3 + 2] annulation of trifluoromethylated ketimines with isocyanates via C(sp2)-H activation has been disclosed. This approach provides an efficient platform for rapid access to a privileged library of CF3-containing iminoisoindolinones and polyamides by utilizing challenging CF3-ketimines as the annulation component. The capability of gram scale synthesis, the post-functionalization of the cyclization adduct, the derivation of complex natural molecules and the facile synthesis of polyamides highlight a diversity of synthetic potential of the current methodology.

Highlights

We envisaged that, if the insertion of unsaturated bond into the C-H bond of CF3-ketimines could be accomplished by certain transition metal catalysis, it would allow for the subsequent nucleophilic cyclization (Scheme 1B: route a)
The proposed challenging [3 + 2] strategy would be more straightforward compared with the post-functionalization of a cyclic imine precursor with CF3-nucleophiles to deliver CF3-containing amino cycles (Scheme 1B: route b), and the latter approach may suffer from tedious synthetic steps of cyclic imine precursor and site selectivity issue during nucleophilic trifluoromethylation if other unsaturated bond presented in the imine structure
The imino group being intact during the annulations process in the absence of leaving group highlights the ability for trifluoromethylated amine synthesis of the catalytic protocol

Summary

Introduction

Besides serving as versatile and important organic intermediates for the synthesis of molecules with amine functionality (Layer, 1963; Bloch, 1998; Kobayashi and Ishitani, 1999; Martin, 2009; Blicke, 2011), imines are eminent for the directing role in transition metal-catalyzed C-H functionalizations (Zhang et al, 2014a, 2014b; Chen et al, 2015; Sambiagio et al, 2018; Li and Shi, 2012; Rouquet and Chatani, 2013; Jiao et al, 2016; Gensch et al, 2016; Leitch and Frost, 2017; He et al, 2017; Yang et al, 2017; Hummel et al, 2017; Park et al, 2017; Dong et al, 2017; Gandeepan, et al, 2019). Considering the fact that the electron-withdrawing character of CF3 group might enhance the reactivity of ketimines (Wang et al, 2006), the nucleophilic cyclization step would be likely assisted by CF3 group. To this end, we envisaged that, if the insertion of unsaturated bond into the C-H bond of CF3-ketimines could be accomplished by certain transition metal catalysis, it would allow for the subsequent nucleophilic cyclization (Scheme 1B: route a). The proposed challenging [3 + 2] strategy would be more straightforward compared with the post-functionalization of a cyclic imine precursor with CF3-nucleophiles to deliver CF3-containing amino cycles (Scheme 1B: route b), and the latter approach may suffer from tedious synthetic steps of cyclic imine precursor and site selectivity issue during nucleophilic trifluoromethylation if other unsaturated bond presented in the imine structure

Methods

Results

Conclusion