Synthesis of Pummerer’s ketone and its analogs by iodosobenzene-promoted oxidative phenolic coupling

First Evidence of Pheomelanin-UVA-Driven Synthesis of Pummerer’s Ketones by Peroxidase-Mediated Oxidative Coupling of Substituted Phenols

“…The oxidation of compound 5 performed at both pH 6 and pH 7 afforded 4a,9b-dihydro-1,7,8,9b-tetramethyl-3­(4 H )-dibenzofuranone 5a as the main reaction product, in addition to 2,2′-dihydroxy-5,5′-6,6′-tetramethyldiphenyl 5b , and the spirobenzo­[1,3]-dioxol trimer 5c (Scheme and Table , entries 1 and 2). The formation of compound 5c was unexpected . It showed a structure similar to compound II (Scheme , highlighted structure) previously isolated after anodic oxidation of 2,4-dimethylphenol .…”

“…Note that the reaction was ineffective in a dark reactor, under anaerobic conditions (argon atmosphere), and in the absence of HRP, as well as in the presence of alternative organic solvents lacking a tertiary C–H bond, such as petroleum ether or n -hexane (S3). Pummerer’s ketone 2 showed all the characteristic NMR signals expected for the tricyclic structure . In particular, the presence of the H-4 hydrogen signal at 4.71 ppm (multiplet) coupled with the adjacent CH 2 group (double doublet centered at 3.05 ppm) confirmed the closure of the central tetrahydrofuran ring.…”

“…Pummerer’s ketone 2 showed all the characteristic NMR signals expected for the tricyclic structure. 39 In particular, the presence of the H-4 hydrogen signal at 4.71 ppm (multiplet) coupled with the adjacent CH 2 group (double doublet centered at 3.05 ppm) confirmed the closure of the central tetrahydrofuran ring. In this latter case, the oxidative coupling proceeded by coupling of the ortho - and para -radical mesomeric forms of the substrate followed by internal Michael addition ( Figure 2 , panel A).…”

“…We developed a novel photobiocatalytic system in which pheomelanin works as an antenna for the UVA-driven activation of HRP in the oxidative coupling of substituted phenols to yield bioactive Pummerer’s ketones. Examples of natural substances bearing the Pummerer’s ketone-like tricyclic structure are galantamine, codeine, and usnic acid . In the designed system, singlet oxygen produced by pheomelanin was converted into 2-MeTHF hydroperoxide, while the superoxide anion was dismutated to H 2 O 2 .…”

PhIO-Mediated Oxidative C═C Bond Cleavage and Reassembly toward Highly Functionalized Oxazolones

“…Yu’s group developed an iodosobenzene diacetate (PhI­(OAc) 2 ) mediated formal oxidative CC double bond cleavage and reassembly for the synthesis of oxazoline and isothiazoline derivatives with high regioselectivity (Scheme b) . Iodosylbenzene (PhIO), a unique and benign hypervalent iodine reagent, can achieve group-transfer reactions, cross-coupling reactions, and oxidative dearomatization of phenols . Additionally, PhIO can also serve as an oxygen source and transfer the oxygen atom to the metal center or the products, realizing epoxidation, 1,2-difunctionalization of olefins, α-oxidation of carbonyls, and C–H activation .…”