Synthesis of 2,3-Diperfluoroalkylated Quinoxalines via Selenium-Catalyzed Reductive C–C Coupling of Vicinal Perfluoroalkyl Formimidoyl Chlorides

Abstract

A direct and efficient approach to access structurally interesting 2,3-diperfluoroalkylated quinoxalines via seleniumcatalyzed reductive C−C construction of vicinal bis(perfluoroalkyl formimidoyl chloride)s has been disclosed. This protocol features the use of easily accessible starting materials, scalability, and a diverse functional group tolerance. Mechanism studies suggested that this reaction may involve an interesting selenium-containing seven-membered-ring intermediate and proceed through an electrocyclization/selenium reductive elimination pathway, which is significantly different from the traditional transition-metal-catalyzed reductive coupling strategies of alkyl halides.Q uinoxalines are fundamental heterocyclic compounds that exist in many biologically active compounds and have wide applications in materials and medicine areas. 1 Quinoxaline derivatives find tremendous applications in materials science as dyes, cavitands, luminescent materials, etc. 2 Moreover, in the pharmaceutical area, quinoxaline medicines possess a variety of biological activities such as antitubercular, antibacterial, anticancer, antitumoral, antiinflammatory, antidepressant, anti-HIV, etc. (Figure 1). 3 Consequently, it is of great value to develop synthetic methods for the preparation of such important structural motifs. The most frequently utilized methodology for the synthesis of quinoxalines is the condensation or cyclization of o-phenylenediamines. In 1887, Hinsberg reported the first example of acid -catalyzed condensation of o-phenylenediamines and 1,2diketones to access quinoxalines. 4 However, this method requires high temperatures, long reaction times, and a strong acid catalyst. Subsequently, abundant analogues of 1,2diketones such as α-hydroxy ketones, α-halogenated ketones, epoxides, and 1,2-diol compounds were developed as synthetic blocks to construct quinoxalines by condensation with ophenylenediamines. 5 The synthesis of quinoxalines is also achieved through the use of transition metal catalysis 6 or hypervalent iodine(III)-or base/oxidant-mediated formal [4 + 2] annulation of alkynes with o-phenylenediamines. 7 In addition, the cyclization reaction between o-phenylenediamines and primary amines 8 and the dual protein cascade reaction using o-phenylenediamines, 1,2-diketones, and TsN 3 9