Photooxidative set initiated N-demethylation of N,N'-dimethylanlines: Mimicking the cytochrome P-450 type oxygenations

N-Dealkylation of Amines

“…Different photochemical N -dealkylation methods using various photocatalysts have been developed for the synthesis of various N -dealkylated chemicals [ 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 ]. An early report by Pandey et al [ 160 ] showed that the photolysis of a tertiary N -methyl amine using dicyanonaphtalene 128a as electron acceptor in the presence of sodium hydroxide in methanol led to high yields of N -demethylated products ( 51c , 94c , 129c , and 130c ) ( Figure 18 ).…”

“…Different photochemical N -dealkylation methods using various photocatalysts have been developed for the synthesis of various N -dealkylated chemicals [ 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 ]. An early report by Pandey et al [ 160 ] showed that the photolysis of a tertiary N -methyl amine using dicyanonaphtalene 128a as electron acceptor in the presence of sodium hydroxide in methanol led to high yields of N -demethylated products ( 51c , 94c , 129c , and 130c ) ( Figure 18 ). Santamaria et al [ 161 ] showed that photochemical oxidation of different alkaloids such as 24a , 27a 56a , 131a , and 132a under oxygen atmosphere in the presence of N , N ′-dimethyl-2,7-diazapyrenium difluoroborate 128b as electron acceptor resulted in N -demethylated alkaloids with excellent yields.…”

Copper‐Catalyzed Cascade N‐Dealkylation/N‐Methyl Oxidation of Aromatic Amines by Using TEMPO and Oxygen as Oxidants

“…As an important drug metabolism process in organisms, [7] N ‐dealkylation of tertiary anilines has been extensively researched during past forty years. The N ‐dealkylation transformation are usually accomplished through the following processes: 1) formation/decomposition of carbinolamine or its analogues using cytochromes P‐450, [8] Fe, [9] Cu, [10] Ru, [11] N ‐oxide, [12] nitroxyl radical, [13] dicyanonaphthalene, [14] rose Bengal [15] and iodine‐calcium (Scheme 1c, Path 1); [16] 2) formation/hydrolysis of imine intermediates using Cu, [6g] Fe, [6e] Ir, [17a] m‐chloronitrobenzene, [6j] oxoiminium ions (Scheme 1c, Path 2); [17b] and 3) formation of the N‐oxide intermediates employing peroxide and then decomposed through path 2 and 1 (Scheme 1c, Path 3) [18] . In 2017, the direct transformation from N,N ‐dimethylaniline to N ‐phenylformamide was reported by the Shao's group [19] …”

Minimization of Back‐Electron Transfer Enables the Elusive sp3 C−H Functionalization of Secondary Anilines

“…Taking N , N ‐Me 2 ‐aniline 1 as an example, it is remarkable that while α‐anilinoalkyl radical B generation by SET oxidation followed by deprotonation ( 1 → A → B ) is a standard process in photocatalysis, the translation of the same elementary steps to N ‐Me‐aniline 2 ( 2 → C → D ) is unprecedented (Scheme 1 A). [3] This lack of reactivity can be exemplified considering the photooxidative demethylation of anilines, one of the most studied and applied reaction in the field of photoinduced SET [2c, 4] . This transformation can be triggered by a broad range of photocatalysts but it always stops upon the removal of the first Me‐group ( 1 → 2 ) and 2 never engages in a following demethylation to the free aniline 3 .…”