The asymmetric construction of polycyclic spiroindolines featuring one or more quaternary stereocenters remains a significant challenge in synthetic chemistry.We report a highly chemoselective and stereoselective casc...The asymmetric construction of polycyclic spiroindolines featuring one or more quaternary stereocenters remains a significant challenge in synthetic chemistry.We report a highly chemoselective and stereoselective cascade cycloadditions of newly designed oxazepino indolones with 5-methylene-1,3-dioxanones,employing an iridium catalyst in combination with the Carreira ligand for the divergent synthesis of chiral polycyclic spiroindolines.This strategy enables the construction of a series of pentacyclic spiroindolines featuring two chiral quaternary stereocenters and one tertiary stereocenter in good yields with excellent chemoselectivity and stereocontrol(30 examples,up to 81%yield,>20:1 dr,99%ee).The process was scalable,and synthetic transformations of the products were performed to demonstrate their practical utility.展开更多
An annulation reaction of tryptamine-derived isocyanides with hydrazonyl chlorides in the presence of bases was developed.Controlled by different bases,[1+2+3]annulation and[1+2+3]/[2+3]annulation cascade were realize...An annulation reaction of tryptamine-derived isocyanides with hydrazonyl chlorides in the presence of bases was developed.Controlled by different bases,[1+2+3]annulation and[1+2+3]/[2+3]annulation cascade were realized.In the latter reaction,five new chemical bonds as well as three new heterocycles were formed in one step.It showed extremely high efficiency,relatively broad substrate scope,milder reaction conditions,good tolerance of functional groups and good chemoselectivity.展开更多
The dearomatization of indole derivatives bearing amide functionalities presents a significant challenge due to the inherent stability of the amide carbonyl group,resulting from nitrogen lone-pair delocalization that ...The dearomatization of indole derivatives bearing amide functionalities presents a significant challenge due to the inherent stability of the amide carbonyl group,resulting from nitrogen lone-pair delocalization that imparts increased resonance stabilization.In this study,we report a visible-light photocatalytic intramolecular dearomatization of indole derivatives with amide groups,achieving the synthesis of spiroindolines via energy transfer.This method enables the efficient formation of a range of hydroxyl-substituted spiroindolines in moderate to high yields,with excellent diastereoselectivity(>20:1)under mild reaction conditions.Control experiments confirmed the involvement of an energy transfer pathway in the reaction mechanism.Density Functional Theory(DFT)calculations further revealed r-stacking interactions between the indole core and pyridine ring,along with the strengthening of hydrogen bonding between the pyridine nitrogen and hexafluoroisopropanol(HFiP)in the excited state.These interactions facilitated the energy transfer-mediated triplet excited state intermolecular proton transfer(T-ESPT),crucial for activating the otherwise amide functionality.This protocol represents a rare example of harnessing the reactivity of amide groups for dearomative transformations.展开更多
基金support for this work from the National Natural Science Foundation of China(21901142,22201161)the Natural Science Foundation of Shandong Province(ZR2024MB004,ZR2022QH294)+4 种基金the Medical and Health Science and Technology Development Program of Shandong Province(202102070368)the Fundamental Research Funds of Shandong University(2020QNQT007 and 2020QNQT009)Funded by Basic Research Program of Jiangsu(BK20220097)Open Research Fund Program of Key Laboratory of Marine Drugs,Ministry of Education(Ocean University of China,MDME2308-03)the Open Project of Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development(2024GCUKLACTRD003).
文摘The asymmetric construction of polycyclic spiroindolines featuring one or more quaternary stereocenters remains a significant challenge in synthetic chemistry.We report a highly chemoselective and stereoselective cascade cycloadditions of newly designed oxazepino indolones with 5-methylene-1,3-dioxanones,employing an iridium catalyst in combination with the Carreira ligand for the divergent synthesis of chiral polycyclic spiroindolines.This strategy enables the construction of a series of pentacyclic spiroindolines featuring two chiral quaternary stereocenters and one tertiary stereocenter in good yields with excellent chemoselectivity and stereocontrol(30 examples,up to 81%yield,>20:1 dr,99%ee).The process was scalable,and synthetic transformations of the products were performed to demonstrate their practical utility.
基金the National Natural Science Foundation of China(Nos.21772138 and 21672157)the Natural Science Foundation of Jiangsu Province,the Project of the Scientific and Technologic Infrastructure of Suzhou(No.SZS201708)and PAPD.
文摘An annulation reaction of tryptamine-derived isocyanides with hydrazonyl chlorides in the presence of bases was developed.Controlled by different bases,[1+2+3]annulation and[1+2+3]/[2+3]annulation cascade were realized.In the latter reaction,five new chemical bonds as well as three new heterocycles were formed in one step.It showed extremely high efficiency,relatively broad substrate scope,milder reaction conditions,good tolerance of functional groups and good chemoselectivity.
基金supported by the National Natural Science Foundation of China(22001220)Sichuan Science and Technology Program(2023NSFSC1086)+1 种基金the Collaborative Fund of Luzhou Government and Southwest Medical University(2024LZXNYDJ016)Ningbo Key Scientific and Technological Project(2023ZI58)。
文摘The dearomatization of indole derivatives bearing amide functionalities presents a significant challenge due to the inherent stability of the amide carbonyl group,resulting from nitrogen lone-pair delocalization that imparts increased resonance stabilization.In this study,we report a visible-light photocatalytic intramolecular dearomatization of indole derivatives with amide groups,achieving the synthesis of spiroindolines via energy transfer.This method enables the efficient formation of a range of hydroxyl-substituted spiroindolines in moderate to high yields,with excellent diastereoselectivity(>20:1)under mild reaction conditions.Control experiments confirmed the involvement of an energy transfer pathway in the reaction mechanism.Density Functional Theory(DFT)calculations further revealed r-stacking interactions between the indole core and pyridine ring,along with the strengthening of hydrogen bonding between the pyridine nitrogen and hexafluoroisopropanol(HFiP)in the excited state.These interactions facilitated the energy transfer-mediated triplet excited state intermolecular proton transfer(T-ESPT),crucial for activating the otherwise amide functionality.This protocol represents a rare example of harnessing the reactivity of amide groups for dearomative transformations.
