The arylethylamine framework is a prevalent motif in a great range of biologically important organic compounds.One intractable task for frontline drug discovery is to find structurally new medicine candidates instead ...The arylethylamine framework is a prevalent motif in a great range of biologically important organic compounds.One intractable task for frontline drug discovery is to find structurally new medicine candidates instead of opioid,based on the construction of a rich chemical space of arylethylamine motif In this report,a practical protocol for the synthesis of arylethylamine functionality common in pharmaceutical chemicals has been developed.It proceeds by Mn-catalyzed anti-Markovnikov hydroarylation of electron-rich enamides under mild conditions without the use of ligands.In spite of mismatched electronic effects during the manganese-mediated migratory insertion process,both terminal and internal enamides can be regioselectively hydroarylated with various aryl boronic acids in 15 min.Also,the successful hydroalkenylation of enamides with alkenyl boronic acids in air atmosphere affords an elegant route to synthetically useful β-alkenylated amines in satisfactory yields.The synthetic robustness and practicality of the reaction reveal its simple operation,short reaction time,viability on a gram-scale and its value in late-stage modification of complex molecules.展开更多
基金We gratefully acknowledge the National Natural Science Foundation of China(22122103,22101130,22001116,21971108,21971111,21732003)the National Key Research and Development Program of China(2021YFC2101901)+3 种基金the Fundamental Research Funds for the Central Universities(020514380252)the Natural Science Foundation of Jiangsu Province(Grant No.BK20190006)the Guangdong Basic and Applied Basic Research Foundation(2020A1515110816)the"Innovation&Entrepreneurship Talents Plan"of Jiangsu Province.Nian Li,Chuan-Gang Zhao,Junheng Liu are warmly acknowledged to reproduce experimental procedures for products 3ii,5p and 3a.
文摘The arylethylamine framework is a prevalent motif in a great range of biologically important organic compounds.One intractable task for frontline drug discovery is to find structurally new medicine candidates instead of opioid,based on the construction of a rich chemical space of arylethylamine motif In this report,a practical protocol for the synthesis of arylethylamine functionality common in pharmaceutical chemicals has been developed.It proceeds by Mn-catalyzed anti-Markovnikov hydroarylation of electron-rich enamides under mild conditions without the use of ligands.In spite of mismatched electronic effects during the manganese-mediated migratory insertion process,both terminal and internal enamides can be regioselectively hydroarylated with various aryl boronic acids in 15 min.Also,the successful hydroalkenylation of enamides with alkenyl boronic acids in air atmosphere affords an elegant route to synthetically useful β-alkenylated amines in satisfactory yields.The synthetic robustness and practicality of the reaction reveal its simple operation,short reaction time,viability on a gram-scale and its value in late-stage modification of complex molecules.
