Synthetic Utilization of α-Aminoalkyl Radicals and Related Species in Visible Light Photoredox Catalysis

Single electron oxidation of amines provides an efficient way to access synthetically useful a-aminoalkyl radicals as reactive intermediates. After the single electron oxidation of amines, fragmentation of the resulting radical cations proceeds to give the alpha-aminoalkyl radicals along with generation of a proton. In the synthetic utilization of the a-aminoalkyl radicals, precise control of single electron transfer is essential, because further oxidation of the alpha-aminoalkyl radicals occurs more easily than the starting amines and the a-aminoalkyl radicals are converted into the corresponding iminium ions. As a result, photoinduced single electron transfer is quite attractive in the synthetic utilization of the alpha-aminoalkyl radicals. Recently, visible light-photoredox catalysis using transition metal-polypyridyl complexes and other dyes as catalysts has attracted considerable attention, where useful molecular transformations can be achieved through the single electron transfer process between the excited catalysts and substrates. In this context, MacMillan et al. (Science2011, 334, 1114, DOI: 10.1126/science.1213920) reported an aromatic substitution reaction of cyanoarenes with amines, where a-aminoalkyl radicals work as key reactive intermediates. Pandey and Reiser et al. ( Org. Lett. 2012, 14, 672, DOI: 10.1021/ol202857t) and our group (Nishibayashi et al. J. Am. Chem. Soc. 2012, 134, 3338, DOI: 10.1021/ja211770y) independently reported reactions of amines with alpha,beta-unsaturated carbonyl compounds, where addition of a-aminoalkyl radicals to alkenes is a key step. After these earliest examples, nowadays, a variety of transformations using the a-aminoalkyl radicals as reactive intermediates have been reported by many groups. The alpha-aminoalkyl radicals are usually produced from amines by single electron oxidation and the subsequent deprotonation of the C-H bond adjacent to the nitrogen atom. In addition, the alpha-aminoalkyl radicals are also produced from a-silylamines and a-amino acids in high efficiency through desilylation or decarboxylation after the single electron oxidation. The generated alpha-aminoalkyl radicals are utilized in a variety of reaction systems. In fact, reactions based on the addition of a-aminoalkyl radicals to alkenes and other unsaturated bonds have been extensively studied. Aromatic and other types of substitution reactions have also been investigated. Some of these transformations are achieved by combination of photoredox catalysts and other catalysts such as Bronsted and Lewis acids, organocatalysts, and transition metal catalysts. It is also noteworthy that the enantioselective reactions have been accomplished by combination of photoredox catalysts and chiral catalysts. The strategy for the generation of alpha-aminoalkyl radicals can be applied to utilize other types of alkyl radicals. In the generation of alpha-aminoalkyl radicals, the bond dissociation of the radical cations occurs at the a-position of amines. In relation to this process, synthetic utilization of other types of alkyl radicals generated by the bond dissociation of the radical cations at a remote position has been also investigated. These alkyl radicals have been applied to molecular transformations in a manner similar to the alpha-aminoalkyl radicals. Recently, organic synthesis using the alpha-aminoalkyl radicals and related alkyl radicals has been studied extensively. In this Account, we describe recent advances in photoredox-catalyzed synthetic utilization of these alkyl radicals.