α-Amino Radicals via Photocatalytic Single-Electron Reduction of Imine Derivatives

Abstract

The construction and manipulation of amine-containing architectures is of importance to academic and industrial development and discovery programs. The photochemical single-electron reduction of imine derivatives to generate α-amino radical intermediates has emerged as a powerful umpolung strategy for opening up underexplored routes to such amine motifs. Furthermore, these radicals have been shown to engage in a wide variety of chemistry, including radical–radical coupling, addition to electrophiles, and reductive amination chemistry. The concept has also begun to see application to iminium ion intermediates and the extension to enantiocontrolled C–C bond formation. This Perspective covers recent efforts in this synthetic strategy to simple and complex amine structures alike.

Photoredox-catalyzed multicomponent Petasis reaction in batch and continuous flow with alkyl boronic acids

“…This result can explain the necessity of a higher loading of the photocatalyst (3.5 mol %) in our optimized conditions. Indeed, the presence of free imine, in constant equilibrium with iminium ion, can be involved in the reductive quenching of the photocatalyst ( Leitch et al., 2020 ). An experiment of radical trapping via TEMPO confirmed the formation of alkyl (R) radical (detected by GC-MS) from BA precursor ( Scheme S1 ).…”

Switchable, Reagent‐Controlled Diastereodivergent Photocatalytic Carbocyclisation of Imine‐Derived α‐Amino Radicals

“…From a mechanistic standpoint, and in order to elucidate the origin of the reagent‐controlled diastereodivergent photocatalytic cyclisation, in‐depth DFT (density functional theory) analysis (see Supporting Information for full computational details) was performed (Scheme 6 ). The α‐amino radical 1 , generated by the well‐established iridium photocatalyst mediated proton‐coupled electron transfer (PCET) of imine 1 b ,[ 1a , 5a , 7 , 8 ] undergoes the first cyclisation through Giese addition to the tethered α,β‐unsaturated ester (Scheme 6 A ). [ 5c , 22 ] Studies on the first cyclisation revealed that the formation of trans intermediate 2‐ trans through the transition structure (TS) TS2 is kinetically favoured in comparison to TS1 that forms 2‐ cis .…”

Synthesis of Chiral Amines by C–C Bond Formation with Photoredox Catalysis

“…This phenomenon is clearly illustrated (Scheme 2) by the formation of -amino radicals from either alkylamines by oxidation (reductive quenching of the photocatalyst) 10 or from imino compounds by reduction (oxidative quenching of the photocatalyst). 11 Alkylamines and imino compounds are readily available and conveniently handled. Furthermore, -amino acids can serve as surrogates for alkylamines in such transformations, as the carboxylate group is a handle for decarboxylation to also furnish -amino radicals.…”