The Chemoselectivity And Aerobic Radical Cascade Reactions Of N-aryltetrahydroisoquinoline Through Visible-light Photoredox Catalysis

Controllable chemoselectivity features the same set of starting substrates to generate distinct complex products through different highly chemoselective processes. This strategy can improve molecular diversity, and thus has been recognized as one of the most promising paradigms in drug discovery. To date, however, rare variantsin visible-light photoredox catalysis have been disclosed. Rueping et al. introduced an example of chemoselective reactions involving N,N-dimethyl anilines with activated alkenes catalyzed by Ir(III) complex; oxygen was employed as a chemical switch to allow an intermolecular addition and an intramolecular radical addition/cyclization, respectively. Cho and co-workers presented an Ir(III) complex-catalyzed chemoselective difluoroalkylation of alkenes, affording difluoroalkylated alkanes and alkenes depending on the employment of different bases. Therefore, the development of photoredox catalytic reactions in a diverse and controllable manner remains highly desirable, and especially, producing more than two types of products represents a formidable task. Undoubtedly, the efficient control of radicals in the process should be a major challenge.Catalytic oxidation of an sp3 C-H bond adjacent to nitrogen of amines is a straightforward pathway to afford N-containing organic compounds. The first instance in photoredox catalysis was presented by Stephenson and co-workers on aza-Henry reactions of N-aryl tetrahydroisoquinolines(THIQs). Since then, a number of corresponding photoredox catalytic methodologies have been established, and most are focusing on the reactions of THIQs. The surveys revealed that THIQs always generate iminium ions by two-electron oxidation of amines when in the presence of molecular oxygen as an oxidant, and Mannich type reactions subsequently occur by the addition of nucleophiles. Alternatively, in the absence of oxygen, ?-amino radicals of THIQs can be trapped by activated alkenes to produce the addition adducts. Nevertheless, the photoredox reaction of THIQs with electrophiles under oxygen through a radical pathway, which would be fascinating for the convenient process and possibly unusual products, has never been reported yet. A huge challenge has been proven that ?-amino radicals of THIQs are very easily to be further oxidized into iminium ions to yield amides.Our group developed a dicyanopyrazine-derived chromophore(DPZ) as a novel photoredox organocatalyst, in a series of reactions the catalyst shows very high catalytic efficiency(between 0.5 mol% to 0.01 mol%) and some special catalytic properties. In this atrical we report a DPZ as photoredox catalysis and N-phenyl-THIQ with N-phenyl itaconimide as model substrate in visible-light photoredox catalysis, successfully got four kinds of valuable N-heterocycles, through modulating reaction media, temperatures and additives. We proposed a radical mechanism of THIQs under oxygen based on literature and our results.