Copper-Catalyzed Annulation-Cyanotrifluoromethylation of 1,6-Enynes Toward 1-Indanones via a Radical Process.

Tian-Shu Zhang,Shu-Jiang Tu,Bo Jiang,Guigen Li,Wen-Juan Hao,Pei-Jun Cai

doi:10.3389/fchem.2020.00234

Abstract

A new Cu(II)-catalyzed annulation–cyanotrifluoromethylation of 1,6-enynes with Togni's reagent and trimethylsilyl cyanide (TMSCN) has been established, enabling the direct construction of trifluoromethylated 1-indanones with an all-carbon quaternary center in good yields. This reaction was performed by using low-cost Cu(OTf)2 as the catalyst and Togni's reagent as both the radical initiator and a CF3 source, providing an efficient protocol for building up an 1-indanone framework with wide functional group compatibility. The reaction mechanism was proposed through a radical triggered addition/5-exo-dig cyclization/oxidation/nucleophilic cascade.

Highlights

Trifluoromethylation of organic molecular skeletons has attracted considerable attention in pharmaceutical chemistry, agrochemicals, and functional materials, owing to the fact that incorporation of the trifluoromethyl group into organic molecules can modulate their abilities including lipophilicity, bioavailability, and metabolic stability (Umemoto, 1996; Müller et al, 2007; Hagmann, 2008; Studer, 2012; Yang et al, 2015)
Graphical Abstract | A new Cu(II)-catalyzed annulation-cyanotrifluoromethylation of 1,6-enynes with Togni’s reagent and trimethylsilyl cyanide (TMSCN) has been established, enabling the direct construction of trifluoromethylated 1-indanones with an all-carbon quaternary center in good yields. This reaction was performed by using low-cost Cu(OTf)2 as the catalyst and Togni’s reagent as both the radical initiator and a CF3 source, providing an efficieA new Cu(II)-catalyzed annulation-cyanotrifluoromethylation of 1,6-enynes with Togni’s reagent and TMSCN has been established, enabling the direct construction of trifluoromethylated 1-indanones with an all-carbon quaternary center in good yields
This reaction was performed by using low-cost Cu(OTf)2 as the catalyst and Togni’s reagent as both the radical initiator and a CF3 source, providing an efficient protocol for building up 1-indanone framework with wide functional group compatibility

Summary

INTRODUCTION

Trifluoromethylation of organic molecular skeletons has attracted considerable attention in pharmaceutical chemistry, agrochemicals, and functional materials, owing to the fact that incorporation of the trifluoromethyl group into organic molecules can modulate their abilities including lipophilicity, bioavailability, and metabolic stability (Umemoto, 1996; Müller et al, 2007; Hagmann, 2008; Studer, 2012; Yang et al, 2015). This reaction was performed by using low-cost Cu(OTf) as the catalyst and Togni’s reagent as both the radical initiator and a CF3 source, providing an efficieA new Cu(II)-catalyzed annulation-cyanotrifluoromethylation of 1,6-enynes with Togni’s reagent and TMSCN has been established, enabling the direct construction of trifluoromethylated 1-indanones with an all-carbon quaternary center in good yields This reaction was performed by using low-cost Cu(OTf) as the catalyst and Togni’s reagent as both the radical initiator and a CF3 source, providing an efficient protocol for building up 1-indanone framework with wide functional group compatibility. An extensive literature survey revealed that the radical-triggered annulation– cyanotrifluoromethylation of 1,6-enynes toward 1-indanones remains unreported to date For this reason, the coppercatalyzed annulation–cyanotrifluoromethylation of 1,6-enynes 1 with Togni’s reagent 2a and trimethylsilyl cyanide (TMSCN) was carried out by 1,10-phenanthroline (phen) as the ligand, enabling a radical-induced three-component cascade to access trifluoromethylated 1-indanones 3 with generally good yields (Scheme 1, path b). 18d [a]Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), Cu(OTf) (10 mol%), L1 (20 mol%), K3PO4 (0.4 mmol), acetonitrile (2.0 ml), TMSCN (0.4 mmol), Ar conditions at 50◦C for 3 h. [b]Isolated yield based on substrates 1. [c]Umemoto’s reagent 2b was used. [d]Mole ratio of 1a, 2a, and TMSCN in 1:3:2

RESULTS AND DISCUSSION

CONCLUSION

MATERIALS AND METHODS