Research On Nitrogen-Centered Radical Reactions Via Visible-light Photoredox Catalysis

Organic nitrogen-containing compounds are widely ubiquitous in natural compounds and synthetic molecules, such as functional materials, pharmaceuticals and organic dyes. In some biologically active molecules, nitrogen functional groups usually act as the key pharmacophores, which exhibit the pharmacological activity. Therefore, the development of synthesis of nitrogen-containing compounds, especially construction of C-N bond has attracted increasing attention from synthetic and medicinal chemists.Free radical reactions represent a powerful class of chemical transformations and have attracted considerable attention from the synthetic community because of their high efficiency and unique reactivity. Compared with the popularity of carbon-centred radicals, however, the synthetic utilities of N-centred radical species remain largely unexplored due to their higher reactivity and the lack of convenient methods for their generation. Traditionally, it is usually necessary to employ radical initiators, such as di-tert-butylperoxide (DTBP), (nBu3Sn)2/hv, Et3B/O2, tertbutylhydroperoxide (TBHP)/I2, or UV-irradiation for the generation of nitrogen-centered radicals. Recently, metal-coordinated nitrogen-centered radicals have attracted much attention and some significant progress has been made. Compared with the traditional methods, metal-coordinated nitrogen-centered radicals are more stable than the free ones and show distinct reactivities, some of them could even be isolated. Over recent years, visible light photocatalysis, using visible light as a renewable energy source, has been established as a powerful and mild technique to facilitate activation of organic reactions. Photoredox reactions often occur under extremely mild conditions, with low catalyst loading and without the presence of highly reactive radical initiators. Visible light promoted nitrogen-centered radicals to construct C-N bond has attracted considerable attention from the synthetic community.The main contents in this thesis are summarized asfollows:1. Direct C(sp2)-H amidation of heteroarenes. By using hydroxylamine derivatives as nitrogen-centered precursor and Ir(ppy)3 as photocatalyst, we achieved the direct C(sp2)·H amidation of heteroarenes, including indoles, pyrroles, furans, and benzofurans, which react at the 2-position. This approach provides a novel and alternative method leading to heteroarylamines. Meanwhile, the mild reaction condition, as well as good functional group tolerance, are prominent features of this transformation.2. Remote C(sp3)-H amidation and chlorination. We achieved the remote C(sp3)-H chlorination under visible light irradiation by using N-chlorosulfonamides as nitrogen-centered precursor and Ir(ppy)2(dtbbpy)PF6 as photocatalyst, followed by intramolecular 1,5-hydrogen atom transfer (HAT). If upon additional solid NaOH, we could obtained the amidation product. Furthermore, we realized the late stage modification of two natural product derivatives, (-)-cismyrtanylamine and (+)-dehydroabietylamine.3. Difunctionalization of olefins, including chloramination, and diamidation. Using N-chlorosulfonamides as nitrogen-centered precursor and Ir(ppy)2(dtbbpy)PF6 as photocatalyst, visible-light-promoted chloramination of olefins was achieved. This transformation was suitable for atyrenes and aliphatic olefins which have a good functional group tolerance. Additionally, we realized solvent-controlled diamidation of styrenes using CH3CN as the reaction solvent while hydroxylamine derivatives was used as nitrogen-centered precursor and Ir(ppy)3 was used as photocatalyst.