Nitrogen atoms are important mediators of biomolecular interactions, but installing them at desired positions in a chemical scaffold is not always straightforward. Previous research showed that the Fukuzumi acridinium photoredox catalyst along with a hydrogen atom donor and an appropriate light source could mediate formation of an intramolecular C-N bond at the anti-Markovnikov position, but the generality of this strategy was unknown. Nguyen et al. now substantially expand the scope to include intermolecular reactions between nitrogen-containing compounds and substituted alkenes, focusing on phenethylamines as a medicinally relevant chemical class. The authors first confirmed that the odorless solid diphenyl disulfide could be used in place of the toxic thiophenol as a hydrogen donor. Testing of alkene analogs demonstrated that variations in aryl substituents were well tolerated, with electron-rich rings reacting most quickly. Substrates featuring extensions from the β-position were also converted in good yields, including nonaromatic substrates and one bearing a free alcohol group. Sulfonamide- or Boc-substituted nitrogens were unsuccessful as nucleophiles, though several other heterocycles could be used. The complete anti-Markovnikov selectivity observed in these reactions suggested a mechanism in which the light source excites the acridinium catalyst, causing oxidation of the alkene to form a radical and directing attack of the nitrogen at the less-substituted position. This study provides a compelling use of light to access chemically challenging materials.
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Goodman, C. Light my way. Nat Chem Biol 10, 484 (2014). https://doi.org/10.1038/nchembio.1568
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DOI: https://doi.org/10.1038/nchembio.1568