Multicomponent alkene 1,2-dicarbofunctionalizations(DCFs)have emerged as a powerful strategy to rapidly incorporate both two carbon subunits across one C-C double bond in one step for enhancing molecular complexity an...Multicomponent alkene 1,2-dicarbofunctionalizations(DCFs)have emerged as a powerful strategy to rapidly incorporate both two carbon subunits across one C-C double bond in one step for enhancing molecular complexity and diversity.To the best of our knowledge,there is only one report on photoredox-catalyzed three-component DCFs with malonates through the radical−radical cross-coupling,while photoredox-catalyzed radical-polar crossover(RPC)-type DCFs with malonates were still rare.Herein,we describe a redox-neutral RPC-type 1,2-dialkylation of styrenes with malonates and aldehydes through the synergistic Brønsted base/photoredox catalysis system.This transition-metal-free strategy provides an efficient and clean approach to a broad variety ofδ-hydroxy esters and also features exceptionally mild conditions,wide compatibility of substrate scope and functional groups,and high atomic economy.Moreover,three-component 1,2-alkylacylation from the same starting materials was achieved in one-pot manner through such RPC-type coupling and subsequent two-electron oxidation process,providing a set ofδ-keto esters of interest in pharmaceutical research.展开更多
Background and Originality Content,3,4-Dihydroquinazoline frameworks have frequently been encountered in natural products and bioactive molecules.In the past decades,these key structures prompted the development of cr...Background and Originality Content,3,4-Dihydroquinazoline frameworks have frequently been encountered in natural products and bioactive molecules.In the past decades,these key structures prompted the development of creative pharmaceuticals owing to their prominent biological properties,including trypanothione reductase(TryR)inhibitor,Hepatitis B virus(HBV)inhibitive activities,anticancer activities,etc.(Scheme 1A).[1]Notably,the chirality of the C4 atom is crucial for drug design.For example,the DPC-083 is a potent reverse transcriptase inhibitor for the treatment of HIV infection but the undesired enantiomers exhibit virtually no activity.[ia]Therefore,developing synthetic methods for innovative chiral 4-substituted 3,4-dihydroquinazolines is significant and essential for drug discovery.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22101237,22171233)the Science and Technology Program of Sichuan Province(No.2022NSFSC1219)+1 种基金the Science and Technology Program of Luzhou City(Nos.2021-SYF-34,2023LZXNYDJ019)and the Open Project Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province(No.HYX21003).
文摘Multicomponent alkene 1,2-dicarbofunctionalizations(DCFs)have emerged as a powerful strategy to rapidly incorporate both two carbon subunits across one C-C double bond in one step for enhancing molecular complexity and diversity.To the best of our knowledge,there is only one report on photoredox-catalyzed three-component DCFs with malonates through the radical−radical cross-coupling,while photoredox-catalyzed radical-polar crossover(RPC)-type DCFs with malonates were still rare.Herein,we describe a redox-neutral RPC-type 1,2-dialkylation of styrenes with malonates and aldehydes through the synergistic Brønsted base/photoredox catalysis system.This transition-metal-free strategy provides an efficient and clean approach to a broad variety ofδ-hydroxy esters and also features exceptionally mild conditions,wide compatibility of substrate scope and functional groups,and high atomic economy.Moreover,three-component 1,2-alkylacylation from the same starting materials was achieved in one-pot manner through such RPC-type coupling and subsequent two-electron oxidation process,providing a set ofδ-keto esters of interest in pharmaceutical research.
基金financial support from NSFC(Grant No.92156022)Anhui Provincial Natural Science Funds(Grant Nos.2308085MB43,2308085QB44)Shennong Scholar Program of Anhui Agricultural University,and National Undergraduate Training Program for Innovation and Entrepreneurship.
文摘Background and Originality Content,3,4-Dihydroquinazoline frameworks have frequently been encountered in natural products and bioactive molecules.In the past decades,these key structures prompted the development of creative pharmaceuticals owing to their prominent biological properties,including trypanothione reductase(TryR)inhibitor,Hepatitis B virus(HBV)inhibitive activities,anticancer activities,etc.(Scheme 1A).[1]Notably,the chirality of the C4 atom is crucial for drug design.For example,the DPC-083 is a potent reverse transcriptase inhibitor for the treatment of HIV infection but the undesired enantiomers exhibit virtually no activity.[ia]Therefore,developing synthetic methods for innovative chiral 4-substituted 3,4-dihydroquinazolines is significant and essential for drug discovery.
