The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, College of Chemistry and Materials Science, Shanghai Normal University, Shanghai, 200234, China.
State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Angew Chem Int Ed Engl. 2021 May 3;60(19):10588-10592. doi: 10.1002/anie.202017306. Epub 2021 Mar 30.
Direct α-functionalization of NH -free glycinates with relatively weak electrophiles such as α,β-unsaturated esters still remains a big challenge in organic synthesis. With chiral pyridoxal 5 d as a carbonyl catalyst, direct asymmetric conjugated addition at the α-C of glycinate 1 a with α,β-unsaturated esters 2 has been successfully realized, to produce various chiral pyroglutamic acid esters 4 in 14-96 % yields with 81-97 % ee's after in situ lactamization. The trans and cis diastereomers can be obtained at the same time by chromatography and both of them can be easily converted into chiral 4-substituted pyrrolidin-2-ones such as Alzheimer's drug Rolipram (11) with the same absolute configuration via tert-butyl group removal and subsequent Barton decarboxylation.
在有机合成中，直接将游离氨基的甘氨酸盐与相对较弱的亲电试剂（如α,β-不饱和酯）进行α-功能化仍然是一个巨大的挑战。在手性吡哆醛 5 d 作为羰基催化剂的作用下，甘氨酸盐 1 a 与α,β-不饱和酯 2 之间的直接不对称共轭加成反应得以成功实现，原位环化后可得到各种手性焦谷氨酸酯 4，产率为 14-96%，对映选择性为 81-97%ee。通过色谱分离可以同时得到顺式和反式非对映异构体，并且它们都可以通过叔丁基的脱除和随后的 Barton 脱羧反应很容易转化为具有相同绝对构型的手性 4-取代吡咯烷-2-酮，如阿尔茨海默病药物罗利普兰（11）。
