Palladium-catalyzed enantioselective (2-naphthyl)methylation of azaarylmethyl amines

Shuguang Chen,Jiahong Tan,Dan Xiong,Yongjia Shang,Jianyou Mao*a andPatrick J. Walsh

aTechnical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis, Schoolof Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu

Road, Nanjing 211816, P.R. China

Abstract:Enantioenriched azaarylmethyl amine derivatives are useful building blocks in synthetic and medicinal chemistry. To access these valuable motifs, an enantioselective palladium-catalyzed benzylation of azaarylmethyl amine pronucleophiles is introduced. Of note, this is a rare application of asymmetric (2-naphthyl)methylation of pro-nucleophiles with high pKa values (pKa≈34 in DMSO). Control experiments support the notion that the coordination of Li+ to the azaaryl nitrogen plays a critical role in the substitution process. With this procedure, enantioenriched (2-naphthyl)methylene azaarylmethyl amines with a variety of azaaryl groups (pyridyl, pyrazine, quinoxaline and isoquinoline) and cyclic and acyclic amines are readily obtained with good yields and enantioselectivities up to 99%.

Organic Chemistry Frontiers (2022), 9(10), 2721-2727(2022年影响因子5.456)

论文链接：https://pubs.rsc.org/en/content/articlelanding/2022/qo/d2qo00273f