Visible-Light Photocatalytic Functionalization of Isocyanides for the Synthesis of Secondary Amides and Ketene Aminals.

Rolando Cannalire,Vincenzo Summa,Jussara Amato,Mariateresa Giustiniano,Ettore Novellino,Gian Cesare Tron

doi:10.1021/acs.joc.0c01946

Abstract

A new visible light-induced photocatalytic protocol enabling the formation of secondary amides from electron-poor organic bromides and isocyanides was developed. In addition, the in situ interception of ketenimine intermediates with nitrogen nucleophiles such as amines, hydrazines, and TMSN3 afforded, in a one-pot two-step procedure, valuable scaffolds such as ketene aminals, pyrazolones, and tetrazoles. Mechanistic evidence confirmed a radical pathway where isocyanides acted as radical geminal acceptors generating key imidoyl radical species.

Highlights

The amide bond is one of the most important linkages in biological molecules and is present in 25% of marketed drugs.[1]
The addition of a sacrificial electron donor, such as diazabicyclo[2.2.2]octane (DABCO) (1 equiv), led to a dramatic drop in the yield (Table 1 entry 2), while the use of the same amount of DABCO (1 equiv) along with the 2-fold increase of both bromide 1 and Na2CO3 led to an excellent yield of 97% (Table 1 entry 3)
When the reaction was performed with photoactive organic dyes, such as

Summary

■ INTRODUCTION

The amide bond is one of the most important linkages in biological molecules and is present in 25% of marketed drugs.[1]. Synthetic methods to achieve amide bond formation conventionally rely on coupling of carboxylic acids with amines in the presence of stoichiometric or excess condensing agents,[2] whereas catalytic procedures exploiting boric acid and boronbased reagents as well as transition-metal-catalyzed[3] and N-. During the preparation of this article, Huang et al reported a nickel-catalyzed aminocarbonylation of alkyl iodides with isocyanides, which, was limited to tertiary isocyanides and aliphatic iodines.[14]. Literature-Reported Synthesis of Disubstituted Ketene Aminals and is associated with several drawbacks such as the use of toxic and hazardous reagents (e.g., molecular iodine and sodium hydride) and the need for cooling (0 °C) or refluxing the reaction mixture. Article the obtainment of unsymmetrical trisubstituted products is still considered a challenging task

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES