Photocatalyst-Free Singlet Oxygen-Induced Oxygenation: A Strategy for the Preparation of 5-Cyano-2-pyridones Driven by Blue-Light Irradiation

Abstract

A mild, catalyst- and metal-free photochemical protocol for the oxygenation of 3-cyano-1,4-dihydropyridines to 5-cyano-2-pyridones was developed. Utilizing molecular oxygen from the air as the oxidant and a cheap blue LED lamp as the light source, a variety of 3-cyano-1,4-dihydropyridines were converted into the corresponding 5-cyano-2-pyridones in moderate to excellent yields. Exploration of the substrate scope revealed that 3-cyano and 4-aryl groups play an important role in the formation of 2-pyridone.

Construction of 3,12-Diazatetracyclododecane-dienes through Unexpected Visible-Light-Induced Radical Cascade Cyclization

“…Then, obviously, when 1b is exposed to the air for photoreaction, the yield is significantly reduced. The reason is molecular oxygen in the air acted as the oxidant under the mediation of blue light to convert a large amount of 3-cyano-1,4-dihydropyridine, which converted to the corresponding 5-cyano-2-pyridone 5a , and the research results have also been published by our group (Figure b) . Finally, because photocyclization reactions proceed via the free radical pathway, we performed our model reaction in the presence of the radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) under optimized reaction conditions.…”

Photooxidation of 2-(tert-Butyl)-3-Methyl-2,3,5,6,7,8-Hexahydroquinazolin-4(1H)-one, an Example of Singlet Oxygen ene Reaction

“…Coordinates for selected structures and thermochemistry data are given in the Supplementary Material. Quinazolinone (8) was prepared according to a known procedure [19] from isatoic anhydride (6 g, 30.68 mmol), methylamine in isobutanol (18.2 mL, 122.7 mmol), and ethyl acetate (50 mL). The resulting material was filtered and concentrated in a rotavapor.…”

“…Photooxidative reactions involve initial light absorption by so-called photosensitizers, which then transfer the absorbed energy to other molecules, including dissolved oxygen ( 3 O 2 ) [5][6][7]. Olefins containing allylic hydrogen could form allylic hydroperoxides under the action of singlet oxygen [8,9]. Direct and selective oxygenation of C-H bonds to C-O bonds are still associated with challenges, such as harsh reaction conditions, as well as the use of expensive transition metal catalysts and the use of oxidant reagents in stoichiometric amounts.…”

“…Previously, our research was focused on the preparation of the starting material (8) following the methodology reported in [19] where a reaction between isatoic anhydride 1 and methylamine in ethyl acetate at 40 • C results in the corresponding aminobenzamide 2 in 92% yield. In this work, instead, 8 is produced by the cyclocondensation of 2 with pivalaldehyde in dichloromethane and p-toluenesulfonic acid monohydrate with 90% yield (Scheme 4).…”

“…The result is confirmed by a X-ray diffraction from suitable single-crystal where the tert-butyl group of quinazolinone ( 8) is shown to adopts a pseudo-axial conformation (Figure 1). The Birch reduction of quinazolinone (8) was carried out (stage 1), without purification, and we proceeded with stage 2 (catalytic hydrogenation). When the product of step 2 was purified by column chromatography and characterized by 1 H-NMR, hexahydroquinazolinone (11) (yield 28%, Scheme 5) was obtained instead of 10.…”