One-Pot Three-Component Coupling Reaction of α-Amino Aryl Ketones, Indoles, and Perbromomethane Under Mild Conditions.

De Chen,Renhua Qiu,Wei Deng,Yuxuan Liu,Hao Lu,Jiannan Xiang

doi:10.3389/fchem.2022.825772

Abstract

A simple and efficient one-pot three-component cascade reaction of α-amino aryl ketones, indoles, and CBr4 in moderate to good yields has been developed. This new strategy exhibits excellent mild reaction conditions and step-economy, easily accessible reactants, and simultaneous construction of three different new bonds (C=N, C–C, and N-Br) in a single step. It is worth noting that the protocol developed provides a simple and practical tool for the construction of diverse indole-containing heterocyclic frameworks, indicating its potential applications in medicinal and material chemistry.

Highlights

As one of the most important heterocycles, indole is widely present in natural products and medicines due to its remarkable biological activity, such as antibacterial (Van Order and Lindwall., 1942; Bell et al, 1994), anti-obesity (Sashidhara et al, 2012), antimicrobial (Sivaprasad et al, 2006), vaginal spermicide (Paira et al, 2009), and apoptosis in acute myelogenous leukemia (AML) (Contractor et al, 2005)
Transition metal–catalyzed C-H functionalization at the C3 position of indoles has become a field of extensive research, and tremendous progress has been made in this regard (Kumar et al, 2021)
Lithium diisopropylamide (LDA) replaced NaOH as the dehydrogenation medium, and it was found that it did not participate in the reaction (Table 1, entry 15)

Summary

INTRODUCTION

As one of the most important heterocycles, indole is widely present in natural products and medicines due to its remarkable biological activity, such as antibacterial (Van Order and Lindwall., 1942; Bell et al, 1994), anti-obesity (Sashidhara et al, 2012), antimicrobial (Sivaprasad et al, 2006), vaginal spermicide (Paira et al, 2009), and apoptosis in acute myelogenous leukemia (AML) (Contractor et al, 2005). With indoles in 2016 (Zhang et al, 2016; Scheme 1C) These synthetic methods all use transition metals and additional oxidants, so it is necessary to explore more green ways. We report a more effective and green method for the transition metal–free C-H bond functionalization reaction of αamino aryl ketones, indoles, and CBr4 under mild conditions (Scheme 1D). This new methodology of green chemistry has several advantages, such as transition metal–free, cheap, and environmental benign reagents, mild reaction conditions, and step-economy. KOH aReaction condition: All reactions were carried out with 1-phenyl-2-(phenylamino)ethan-1-one (1a) (0.3 mmol), 1H-indole (2a) (0.3 mmol), CBr4 (0.6 mmol), and base (1.2 mmol) in solvent (2 ml) at certain temperature for 12 h. bIsolated yield. cReaction for 6 h. dReaction for 18 h

RESULTS AND DISCUSSION

CONCLUSION

Experimental Section