A novel combination of (diacetoxyiodo)benzene and tert-butylhydroperoxide for the facile oxidative dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

“…The white LED was preferred over a 36 W LED (460 nm, matching the absorption wavelength of the Ru(II)-photoinitiator), w afforded lower conversion (Table 2, entries 6,7), appearing to enhance formation of a radation product of the phenyldiazonium precursor. Keeping the fore-mentioned parameters fixed, we carried out investigations of effect of the solvent, additive, and photoredox initiator on reaction conversion (Tab entries [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Some bases were included in this screening in hope of facilitating the C activation step by sequestering AcOH.…”

“…Systematic and meticulous 1 H and 13 C NMR analysis was used for structural elucida-Ethyl 4-methyl-2,6-diphenylpyrimidine-5-carboxylate substrates 8a-s were submitted in parallel to the C-H arylation reaction (Scheme 4). To the best of our knowledge, this is the first time that functionality-rich 2,6-diphenylpyrimidines (comprising ester, alkoxide, amide, tertiary amine, fluoride, and cyanide substituents) have been examined in a C-H arylation.…”

“…Previous efforts have led to the discovery of Biginelli products exhibiting a diverse range of biological activities, including anti-inflammatory, anti-viral, anti-cancer, anti-mitotic, anti-microbial, anti-tubercular, anti-fungal, anti-diabetic, anti-oxidant, anti-hypertensive, adrenoreceptor antagonistic, and calcium channel blocking [8,9]. Moreover, another biologically significant N-based scaffold, the 2-hydroxypyrimidine (2-HP, Scheme 1), can be readily obtained by oxidative dehydrogenation of 3,4-DHPMs and ensuing aromatization [10][11][12][13][14]. Notably, 2-hydroxypyrimidines may serve as synthetic precursors to nucleobases, vitamins, synthetic/unnatural amino-acids, natural products, and pharmaceuticals [15][16][17][18][19].…”

“…Access to multi-substituted pyrimidines, by means of C2 modification of 3,4-DHPMs, to eventually form a C-heteroatom or C-C bond, requires prior aromatization of Biginelli products [10][11][12][13][14] and conversion of the resulting C2-OH to a good leaving group, such as halide or sulfonate (Scheme 1) [31][32][33]. This is eventually replaced by nucleophiles [34][35][36] or submitted to cross-coupling reactions [37][38][39][40].…”

Oxidation of Biginelli Reaction Products: Synthesis of 2-Unsubstituted 1,4-Dihydropyrimidines, Pyrimidines, and 2-Hydroxypyrimidines

“…These shortcomings were improved significantly by the recent discovery of oxidation using a combination of tert-butylhydroperoxide with either copper(II) catalyst 18 or stoichiometric (diacetoxyiodo)benzene. 19 In contrast to the established oxidation of the Biginelli product, dihydropyrimidin-2(1H)-one to 2-hydroxypyrimidine, there is no report on the oxidation of dihydropyrimidin-2(1H)-thiones, which might provide a new route towards the valuable pharmacophore of 2-unsubstituted pyrimidines via desulfurative oxidation. This class of compounds has only been accessible from the condensation of b-alkoxy-a-acylacrylates with amidines in poor yield of 10-60%.…”