Photoredox‐Catalyzed Tandem Demethylation of N,N‐Dimethyl Anilines Followed by Amidation with α‐Keto or Alkynyl Carboxylic Acids

Abstract

We report herein, a biomimetic approach for highly selective monodemethylation of N,N-dimethyl anilines to generate secondary amines and subsequent coupling with α-ketocarboxylic acids or alkynyl carboxylic acids to form α-ketoamides or alkynamides respectively under visible light photoredox catalyst in a single operation. From the deuterium-labeling experiment, it was probed that demethylation is the slowest step in this tandem process. Whereas, control experiments and spectroscopic studies revealed that photoredox catalyst is also involved in the subsequent amidation step. The reaction proceeds smoothly at room temperature providing moderate to excellent yield of the coupling products. The amides have also been converted to a series of biologically active spiro compounds.

Green and sustainable visible light-mediated formation of amide bonds: an emerging niche in organic chemistry

“…Five years later, Jana and co-workers demonstrated a photoredox-catalyzed amidation of α-ketoacids 26 with N , N -dimethylanilines 23 using [Ru(bpy)](PF 6 ) 2 as a photocatalyst, BrCCl 3 as an oxidant, DABCO as an additive, and MeCN/H 2 O as a solvent under blue LEDs (Scheme 13). 75 Besides, aliphatic amines such as N -methyl morpholine also afforded the product in 39% yield. Based on radical trapping- and Stern–Volmer quenching experiments, the authors proposed that the photoexcited Ru( ii )* is reductively quenched by the generated carboxylate anion 13A to deliver the carboxylate radical 13B .…”

Shining Light on the Light-Bearing Element: A Brief Review of Photomediated C–H Phosphorylation Reactions

“…In 2011, Rueping et al developed the first example of Csp 3 -H activation for C-P bond formation using visible light and a photocatalyst to synthesize -aminophosphonates (Scheme 3). This method relies on the oxidation of tertiary amines, such as tetrahydroisoquinoline derivatives, using an iridium polypyridyl complex, [Ir(ppy) 2 66 and derivatives, which are also typical CDC substrates due to their low oxidation potential. 67 The transformation presented here features the use of an additional cobalt-oxime complex, which acts as a proton reduction catalyst favoring iminium formation.…”

“…This method relies on the oxidation of tertiary amines, such as tetrahydroisoquinoline derivatives, using an iridium polypyridyl complex, [Ir(ppy) 2 (bpy)][PF 6 ], and adding a dialkyl/aryl phosphite under visible-light irradiation (Scheme 4). 65 66 and derivatives, which are also typical CDC substrates due to their low oxidation potential. 67 The transformation presented here features the use of an additional cobalt-oxime complex, which acts as a proton reduction catalyst favoring iminium formation.…”

Visible‐Light Mediated Photooxidative Phosphorylation of Benzylamines: A Novel and Mild Pathway Towards α‐Aminophosphorus Compounds

“…To put things in perspective, the oxidation potential in acetonitrile versus saturated calomel electrode (SCE) for both N,Ndimethylaniline and N-phenyl-1,2,3,4-tetrahydroisoquinoline are E 1/2 = + 0.74 V vs. SCE and E 1/2 = + 0.82 V vs. SCE, respectively. [44,48] More challenging aliphatic substrates such as benzylamine (E 1/2 = + 1.04 V vs. SCE) [49] and dibenzylamine (E 1/2 = + 1.37 V vs. SCE) [50] could potentially be desirable amine targets to phosphorylate. Such substrates have previously been photooxidized to N-benzylidenebenzylamines using of photoexcited oxygen as a sustainable and harmless source of oxidant (Scheme 1,II).…”