Nishad, Chandra ShekharSuman, PallavSaha, HimadriBanerjee, Biplab2024-01-212024-08-132024-01-212024-08-132023-07-1822326310.1021/acs.joc.3c00987http://10.2.3.109/handle/32116/3280Visible-light-promoted metal- and photocatalyst-free radical cascade cyclization of cinnamamides with ?-oxocarboxylic acids is described for sustainable synthesis of diverse pharmaceutically important dihydroquinolinone scaffolds in one pot under mild conditions. The decarboxylative cascade cyclization proceeded efficiently at room temperature without the need for expensive photocatalysts such as Ir or Ru complexes, which indicates the practicability and environmentally benign nature of this protocol. Preliminary mechanistic studies reveal that the blue LED irradiation efficiently cleaves the I-O bond of the hypervalent iodine reagent PhI(O2CCOAr)2 formed through ligand exchange between iodobenzene diacetate and arylglyoxylic acid to initiate the cascade reaction. The synthetic value of this operationally simple and energy-efficient method is further demonstrated by late-stage functionalization of drug molecules in excellent yields. � 2023 American Chemical Society.en-USCyclizationEnergy efficiencyIridium compoundsRuthenium compoundsScaffolds1 benzyl 3 (4 bromobenzoyl) 4 phenyl 3,4 dihydroquinolin 2(1h) one1 methyl 3 (2 methylbenzoyl) 4 phenyl 3,4 dihydroquinolin 2(1h) one1 methyl 3 (4 methylbenzoyl) 4 phenyl 3,4 dihydro 1,8 naphthyridin 2(1h) one1 methyl 3 (4 methylbenzoyl) 4 phenyl 3,4 dihydroquinolin 2(1h) one1 methyl 4 phenyl 3 (thiophene 2 carbonyl) 3,4 dihydroquinolin 2(1h) one1 methyl 4 phenyl 3 [4 (trifluoromethyl)benzoyl] 3,4 dihydroquinolin 2(1h) one2 [3 (4 bromobenzoyl) 2 oxo 4 phenyl 3,4 dihydroquinolin 1(2h) yl]ethyl 2 (6 methoxynaphthalen 2 yl)propanoate2 [3 (4 methylbenzoyl) 2 oxo 4 phenyl 3,4 dihydroquinolin 1(2h) yl]ethyl 2 (6 methoxynaphthalen 2 yl)propanoate3 (4 bromobenzoyl) 1 ethyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 (4 bromobenzoyl) 1 methyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 (4 bromobenzoyl) 6 fluoro 4 (2 methoxyphenyl) 1 methyl 3,4 dihydroquinolin 2(1h) one3 (4 bromobenzoyl) 6 methoxy 1 methyl 4 (4 tolyl) 3,4 dihydroquinolin 2(1h) one3 (4 methoxybenzoyl) 1 methyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 acetyl 1 methyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 1 ethyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 1 methyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 1,5,7 trimethyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 4 (4 bromo 2 fluorophenyl) 1,5,7 trimethyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 6 bromo 1,5 dimethyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 6 fluoro 1 methyl 4 phenyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 6 fluoro 4 (2 methoxyphenyl) 1 methyl 3,4 dihydroquinolin 2(1h) one3 benzoyl 6 methoxy 1 methyl 4 phenyl 3,4 dihydroquinolin 2(1h) one4 (2,3 dimethoxyphenyl) 6 fluoro 3 (4 methoxybenzoyl) 1 methyl 3,4 dihydroquinolin 2(1h) one4 (4 bromo 2 fluorophenyl) 1,5,7 trimethyl 3 (4 methylbenzoyl) 3,4 dihydroquinolin 2(1h) one4 (4 bromo 2 fluorophenyl) 1,5,7 trimethyl 3 [4 (trifluoromethyl)benzoyl] 3,4 dihydroquinolin 2(1h) one6 methoxy 3 (4 methoxybenzoyl) 1 methyl 4 phenyl-3,4 dihydroquinolin 2(1h) one6 methyl 8 (4 methylbenzoyl) 9 [3 (trifluoromethyl)phenyl] 2,3,8,9 tetrahydro[1,4]dioxino[2,3 g]quinolin 7(6h) one8 (3,4 dimethoxybenzoyl) 6 methyl 9 [3 (trifluoromethyl)phenyl] 2,3,8,9 tetrahydro[1,4]dioxino[2,3 g]quinolin 7(6h) one8 benzoyl 6 (prop 2 yn 1 yl) 9 [3 (trifluoromethyl)phenyl] 2,3,8,9 tetrahydro[1,4]dioxino[2,3 g]quinolin 7(6h) one8 benzoyl 6 methyl 9 [3 (trifluoromethyl)phenyl] 2,3,8,9 tetrahydro[1,4]dioxino[2,3 g]quinolin 7(6h) oneacetoacetic acidamidecarboxylic acid derivativecinnamic acid derivativedihydroquinoline derivativeethyl 2 (3 benzoyl 2 oxo 4 phenyl 3,4 dihydroquinolin 1 (2h) yl]acetateethyl 2 [3 benzoyl 4 (4 bromo 2 fluorophenyl) 5,7 dimethyl 2 oxo 3,4 dihydroquinolin 1(2h) yl]acetateethyl 2 [4 (4 bromo 2 fluorophenyl) 5,7 dimethyl 3 (4 methylbenzoyl) 2 oxo 3,4 dihydroquinolin 1(2h) yl]acetatefree radicalfunctional groupglyoxylic acidiodineiodobenzeneiridium complexligandmetaln methyl 2 [3 (4 methylbenzoyl) 2 oxo 4 phenyl 3,4 dihydroquinolin 1(2h) yl] n [3 phenyl 3 [4 (trifluoromethyl)phenoxy]propyl]acetamidephenylglyoxylic acidreagentruthenium complexunclassified drugCascade cyclizationConditionEnvironmentally benignFunctionalizedIr complexesMechanistic studiesOne potRu complexesVisible lightVisible light inducedArticlechemical bondcomplex formationconjugationcontrolled studycyclizationdecarboxylationdrug synthesiselectrophilicityone pot synthesisphotocatalysisreaction analysisreaction optimizationregioselectivityroom temperatureFree radicalsArticlehttps://pubs.acs.org/doi/10.1021/acs.joc.3c00987