Li Panpan, Zheng En, Li Guanlin, Luo Yicong, Huo Xiaohong, Ma Shengming, Zhang Wanbin
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai 200032, China.
Science. 2024 Aug 30;385(6712):972-979. doi: 10.1126/science.ado4936. Epub 2024 Aug 29.
The precise control of and configurations of the carbon-carbon double bond in alkene synthesis has long been a fundamental challenge in synthetic chemistry, even more pronounced when simultaneously striving to achieve enantioselectivity [(,), (,), (,), (,)]. Moreover, enantiopure non-natural α-amino acids are highly sought after in organic and medicinal chemistry. In this study, we report a ligand-controlled stereodivergent synthesis of non-natural α-quaternary amino acids bearing trisubstituted alkene moieties in high yields with excellent enantioselectivity and / selectivities. This success is achieved through a palladium/copper-cocatalyzed three-component assembly of readily available aryl iodides, allenes, and aldimine esters by simply tuning the chiral ligands of the palladium and copper catalysts.
长期以来，在烯烃合成中精确控制碳 - 碳双键的Z和E构型一直是合成化学中的一项基本挑战，当同时努力实现对映选择性时（[(Z),(E),(Z),(E)]），这一挑战更为突出。此外，对映纯的非天然α - 氨基酸在有机化学和药物化学中备受关注。在本研究中，我们报道了一种配体控制的立体发散合成方法，可高产率、高对映选择性和Z/E选择性地合成带有三取代烯烃部分的非天然α - 季铵氨基酸。这一成功是通过钯/铜共催化的、由易得的芳基碘化物、丙二烯和醛亚胺酯组成的三组分组装反应实现的，只需调节钯和铜催化剂的手性配体即可。
