Organic halides are important building blocks in synthesis, but their use in (photo)redox chemistry is limited by their low reduction potentials. Halogen-atom transfer remains the most reliable approach to exploit these substrates in radical processes despite its requirement for hazardous reagents and initiators such as tributyltin hydride. In this study, we demonstrate that α-aminoalkyl radicals, easily accessible from simple amines, promote the homolytic activation of carbon-halogen bonds with a reactivity profile mirroring that of classical tin radicals. This strategy conveniently engages alkyl and aryl halides in a wide range of redox transformations to construct sp3-sp3, sp3-sp2, and sp2-sp2 carbon-carbon bonds under mild conditions with high chemoselectivity.

The development of photoredox reactions of aryloxy-amides for the generation of amidyl radicals and their use in hydroamination-cyclization and N-arylation reactions is reported. Owing to the ease of single-electron-transfer reduction of the aryloxy-amides, the organic dye eosin Y was used as the photoredox catalyst, which results in fully transition-metal-free processes. These transformations exhibit a broad scope, are tolerant to several important functionalities, and have been used in the late-stage modification of complex and high-value N-containing molecules.

Shown herein is that polyfunctionalized nitrogen heterocycles can be easily prepared by a visible‐light‐mediated radical cascade process. This divergent strategy features the oxidative generation of iminyl radicals and subsequent cyclization/radical trapping, which allows the effective construction of highly functionalized heterocycles. The reactions proceed efficiently at room temperature, utilize an organic photocatalyst, use simple and readily available materials, and generate, in a single step, valuable building blocks that would be difficult to prepare by other methods.

A photoinduced cascade strategy leading to a variety of differentially functionalised nitriles and ketones has been developed. These reactions rely on the oxidative generation of iminyl radicals from simple oximes. Radical transposition by C(sp3)−(sp3) and C(sp3)−H bond cleavage gives access to distal carbon radicals that undergo SH2 functionalisations. These mild, visible‐light‐mediated procedures can be used for remote fluorination, chlorination, and azidation, and were applied to the modification of bioactive and structurally complex molecules.

The selective functionalization of C(sp3)−H bonds at distal positions to functional groups is a challenging task in synthetic chemistry. Reported here is a photoinduced radical cascade strategy for the divergent functionalization of amides and protected amines. The process is based on the oxidative generation of electrophilic amidyl radicals and their subsequent transposition by 1,5‐H‐atom transfer, resulting in remote fluorination, chlorination and, for the first time, thioetherification, cyanation, and alkynylation. The process is tolerant of most common functional groups and delivers useful building blocks that can be further elaborated. The utility of this strategy is demonstrated through the late‐stage functionalization of amino acids and a dipeptide.

A general and enantioselective synthesis of 2-substituted 2-phenylpyrrolidines and -piperidines, an important class of pharmaceutically relevant compounds that contain a quaternary stereocenter, has been developed. The approach involves lithiation-substitution of enantioenriched N-Boc-2-phenylpyrrolidine or -piperidine (prepared by asymmetric Negishi arylation or catalytic asymmetric reduction, respectively). The combined use of synthetic experiments and in situ IR spectroscopic monitoring allowed optimum lithiation conditions to be identified: n-BuLi in THF at -50 °C for 5-30 min. Monitoring of the lithiation using in situ IR spectroscopy indicated that the rotation of the tert-butoxycarbonyl (Boc) group is slower in a 2-lithiated pyrrolidine than a 2-lithiated piperidine; low yields for the lithiation-substitution of N-Boc-2-phenylpyrrolidine at -78 °C can be ascribed to this slow rotation. For N-Boc-2-phenylpyrrolidine and -piperidine, the barriers to rotation of the Boc group were determined using density functional theory calculations and variable-temperature (1)H NMR spectroscopy. For the pyrrolidine, the half-life (t(1/2)) for rotation of the Boc group was found to be ∼10 h at -78 °C and ∼3.5 min at -50 °C. In contrast, for the piperidine, t(1/2) was determined to be ∼4 s at -78 °C.

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Herein we report the development of a photocatalytic strategy for the divergent preparation of functionalized bicyclo[1.1.1]pentylamines. This approach exploits, for the first time, the ability of nitrogen‐radicals to undergo strain‐release reaction with [1.1.1]propellane. This reactivity is facilitated by the electrophilic nature of these open‐shell intermediates and the presence of strong polar effects in the transition‐state for C−N bond formation/ring‐opening. With the aid of a simple reductive quenching photoredox cycle, we have successfully harnessed this novel radical strain‐release amination as part of a multicomponent cascade compatible with several external trapping agents. Overall, this radical strategy enables the rapid construction of novel amino‐functionalized building blocks with potential application in medicinal chemistry programs as p‐substituted aniline bioisosteres.