β-Functionalization of Saturated Aza-Heterocycles Enabled by Organic Photoredox Catalysis

Abstract

The direct β-functionalization of saturated azaheterocycles has remained a synthetic challenge because of the remote and unactivated nature of β-C−H bonds in these motifs. Herein, we demonstrate the β-functionalization of saturated azaheterocycles enabled by a two-step organic photoredox catalysis approach. Initially, a photoredox-catalyzed copper-mediated dehydrogenation of saturated aza-heterocycles produces ene-carbamates. This is followed by an anti-Markovnikov hydrofunctionalization of the ene-carbamates with a range of heteroatom-containing nucleophiles furnishing an array of C−C, C−O, and C−N azaheterocycles at the β-position.

Electro-/photocatalytic alkene-derived radical cation chemistry: recent advances in synthetic applications

“…In 2021, Nicewicz and colleagues described an unparalleled photochemical strategy to achieve the direct β-functionalization of saturated aza-heterocycles through a two-step photocatalytic process (Scheme 18). 36 In this transformation, the first step is the copper-mediated dehydrogenation of saturated aza-heterocycles to generate ene-carbamates, and the second step is the intermolecular anti -Markovnikov hydrofunctionalization of alkenes with nucleophiles in the presence of H-atom donors (PhSH). Importantly, a variety of nucleophiles, including TMSCN, TMSN 3 , CF 3 SO 2 Na, amino acids, TfNH 2 , and ammonium carbamate, were also assessed for use in this transformation, and the relevant β-functionalized products were produced with appreciable yields.…”

Direct Synthesis of Enamides via Electrophilic Activation of Amides

“…However, the most straightforward approach to access enamides is arguably the direct N-dehydrogenation of the corresponding amides. Whereas routes for the direct desaturation to form enecarbamates have recently become well established, pathways leading from carboxamides to enamides remain elusive (Scheme A). Gevorgyan reported a photoinduced palladium-catalyzed dehydrogenation protocol enabled by hydrogen abstraction and starting from prefunctionalized 2-iodobenzamides, while Morandi et al recently published a ruthenium-catalyzed variant of this reaction .…”

Site-Selective Acceptorless Dehydrogenation of Aliphatics Enabled by Organophotoredox/Cobalt Dual Catalysis

“…Dehydrogenation of N -alkyl chains of amides provides a concise route to synthetically valuable enamides . The known methods are elusive and require the use of stoichiometric oxidants. , To our knowledge, acceptorless desaturation of amides to enamides has not been reported yet.…”