Photoredox/Nickel Dual Catalysis-Enabled Aryl Formylation with 2,2-Dimethoxy-N,N-dimethylethan-1-amine as CO Source

Abstract

Herein, a dual photoredox/nickel catalyzed formylation of aryl bromide with commercially available 2,2-dimethoxy-N,N-dimethylethan-1-amine as an effective CO source has been successfully achieved, delivering a series of aromatic aldehydes in moderate to good yields. Compared with the traditional reductive carbonylation process, this newly designed synthetic protocol provides a straightforward toolbox to access aromatic aldehydes, obviating the use of carbon monoxide and stoichiometric reductants. Finally, the utility of this direct formylation reaction was demonstrated in the pharmaceutical analogue synthesis.

Visible Light-Induced, Nickel-Catalyzed Late-Stage 4-Alkylation of Hantzsch Esters with Alkyl Bromide

“…Based on the experimental results and previous reports, − a plausible reaction mechanism is proposed as shown in Scheme . Initially, (dtbbpy)­Ni II CO 3 I was reduced by photoexcited HE* to deliver the real catalyst species (dtbbpy)­Ni I X II .…”

“…Notably, Hantzsch ester was frequently employed to facilitate the single electron transfer (SET) or ligand–metal charge transfer (LMCT) progress to generate reactive Ni I species . Thereafter, single-electron reduction of alkyl halide by low-valent nickel species triggered the subsequent transformations to accomplish a range of alkylation transformations . Inspired by these advances and our previous work on photoredox/nickel catalysis, we questioned whether the alkyl radicals generated by photoredox/nickel catalysis could trigger an alkylation of DHPs through an aromatization-dearomatization pathway to produce a variety of 4-alkyl-substituted DHPs, wherein the HE serves as the reductant and reaction substrate simultaneously.…”