Functionalization of enamides via visible-light photoredox catalysis
Creators: name: Dickson, Jalen L.
Publisher: name: University of Iowa
Year: 2023
Subjects: Amines
Enamides
Hydroarylation
Photoredox
public abstract

description: The direct use of light in chemical transformations by Nature has long since influenced scientists to harness this elegant strategy in small molecule transformations. The unique photochemistry of metal complexes has been studied for decades to find candidates that have long-lived excited states. These long-lived excited states that are generated have the ability to go through unique intermolecular quenching pathways such as single-electron transfer (SET) and energy transfer (EnT). Generation of these excited states by visible light using small organic molecules to quench the excited state via single-electron chemistry has been shown to be highly advantageous over stoichiometric radical initiators. In recent years, the use of these visible-light photoredox catalysts in organic synthesis has gained widespread recognition and application to a plethora of different synthetic strategies.
description: Enamides as starting materials for the synthesis of amines ha been prevalent for decades and have been shown to have a range of reactivity where they can act as a nucleophile or an electrophile. The majority of their transformations are based on two electron chemistry, whereas their use in single-electron chemistry is less abundant. Recently, strategies involving the use of the single-electron nature of visible-light photoredox catalysis has been shown to be a highly efficient in the transformation of enamides to complex structures.
description: With our group’s background in chiral amine synthesis and radical chemistry of enamides we sought to apply visible-light photoredox catalysis in novel strategies for the synthesis of chiral amines. Successful nonreductive radical additions to enamides and tandem radical addition and intramolecular Friedel–Crafts alkylation has been demonstrated in our group, but through the use of stoichiometric radical initiators. We hypothesized that visible-light photoredox catalysis could be utilized as an efficient strategy to overcome the difficulties that were faced in our previous work involving tandem radical addition and Friedel–Crafts alkylation. While we were not successful in achieving photoredox catalyzed radical addition and intramolecular Friedel– Crafts transformations, we were able to achieve successful tandem radical addition, radical–polar crossover, and trapping of iminium by water.
description: Along the way we also discovered a highly efficient, atom-economical strategy for the direct synthesis of benzylic amines from petroleum feedstocks by developing a photoredox hydroarylation of enamides. This methodology was successful in coupling a variety of enamides with electron rich (hetero)arenes with no prefunctionalization necessary. To demonstrate the synthetic utility of this transformation we applied this photoredox hydroarylation methodology to the gram-scale synthesis of the benzylic amine moiety of cinacalcet, a pharmaceutical used to treat hyperparathyroidism. Future studies will be aimed toward the detailed study of the mechanism of this photoredox hydroarylation of enamides.