Asymmetric Allylic Substitution-Isomerization for the Modular Synthesis of Axially Chiral N-Vinylquinazolinones |
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Authors: | Jia-Yu Zou Yu-Ying Yang Jun Gu Fei Liu Dr Zhiwen Ye Dr Wenbin Yi Prof Ying He |
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Institution: | School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing, 210094 China |
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Abstract: | Axially chiral N-substituted quinazolinones are important bioactive molecules, which are presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis are mainly limited to the axially chiral arylquinazolinone frameworks. The development of modular synthetic methods to access diverse quinazolinone-based atropisomers remains scarce and challenging. Herein, we report the regio- and atroposelective synthesis of axially chiral N-vinylquinazolinones via the strategy of asymmetric allylic substitution-isomerization. The catalysis system utilized both asymmetric transition-metal catalysis and organocatalysis to efficiently afford trisubstituted and tetrasubstituted N-vinylquinazolinone atropisomers, respectively. With the meticulous design of β-substituted allylic substrates, both Z- and E-tetrasubstituted axially chiral N-vinylquinazolinones were obtained in good yields and high enantioselectivities. |
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Keywords: | Atropisomerism Axially Chiral N-Vinylquinazolinones Kinetic Control Modular Synthesis Thermodynamic Control |
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