Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct α-CH₂-Oxygenation of Free Amines

Abstract

Direct oxidation of α-CH group of free amines is hard to achieve due to the higher reactivity of amine moiety. Therefore, oxidation of amines involves the use of sophisticated metallic reagents/catalyst in the presence or absence of hazardous oxidants under sensitive reaction conditions. A novel method for direct C-H oxygenation of aliphatic amines through a metal-free activation of molecular oxygen has been developed. Both activated and unactivated free amines were oxygenated efficiently to provide a wide variety of amides (primary, secondary) and lactams under operationally simple conditions without the aid of metallic reagents and toxic oxidants. The method has been applied to the synthesis of highly functionalized amide-containing medicinal drugs, such as O-Me-alibendol and -buclosamide.

Different roles for the acyl chain and the amine leaving group in the substrate selectivity of N-Acylethanolamine acid amidase

“…1 H-NMR (400 MHz, Chloroform-d): δ 5.35 ppm (2H, br), 2.22 ppm (2H, t, J = 7.5 Hz), 1.64 ppm (2H, quint, J = 7.5 Hz), 1.40–1.14 ppm (24H, m), 0.88 ppm (3H, t, J = 7.1 Hz). Analytical data are consistent with those previously reported in the literature 48 .…”

“…MS calc. : 255.26, found: Analytical data are consistent with those previously reported in the literature 48 .…”

Visible‐Light‐Induced Oxidation of Diazenyl‐Protected Tetrahydroisoquinolines and Isoindolines for the Synthesis of Functionalized Lactams

“…In the recent developments in this field, the direct α‐oxidation of tetrahydroisoquinolines and isoindolines is receiving a great deal of attention and proved to be a useful, efficient and direct strategy (Scheme 1a) [8] . Nevertheless, most protocols require harsh reaction conditions (e. g., higher reaction temperature [8d] and longer reaction times [8c] ) or using environmentally undesirable organic or inorganic oxidants such as TBHP, [8b,f] hypervalent iodine [8h] or chlorite, [8e] and transition metal catalyst (e. g., copper, [8a,g] manganese, [9] cobalt, [10] rhodium, [11] or iron [12] ). Compared to the use of common environmentally unfriendly organic and inorganic oxidants, the molecular oxygen has been suggested as an alternative to oxides organic substrates due to its atom‐economical, environmentally benign, and inexpensive character [13] .…”

Recent Advances in Synthesis of 3,4‐Dihydroisoquinolin‐1(2H)‐one

“…The cyclic amine 116 under goes oxidation to 3,4-dihydroisoquinolin-1(2H)-one 118 in 76 to 82% yield in presence of 9-Fluorene-imine 117 under oxygen at reflux (Scheme 47). [66] N. J. Turner et al synthesized the 3,4-dihydroisoquinolin-1(2H)-one 1 by enzymatic oxidation of amino alcohol 119 using the Galactose Oxidase. The reaction proceed at 37°C, at buffer pH = 7.0 (Scheme 48).…”