Highly Stereoselective Synthesis of γ,δ-Unsaturated Quaternary α-Amino Esters via the Tandem N-Alkylation/Claisen Rearrangement of α-Imino Allylesters
Highly Stereoselective Synthesis of γ,δ-Unsaturated Quaternary α-Amino Esters via the Tandem N-Alkylation/Claisen Rearrangement of α-Imino Allylesters
复制标题
通过 α-亚氨基烯丙酯的串联 N-烷基化/克莱森重排高度立体选择性合成 γ,δ-不饱和季 α-氨基酯
DOI：
10.1002/ajoc.202300063
复制
发表时间：
2023
影响因子：
2.7
通讯作者：
Makoto Shimizu
中科院分区：
文献类型：
--
作者：
Isao Mizota;Toshikazu Fukaya;Yumi Miwa;Yoshinari Kobayashi;Tomoki Ejima;Mizuki Yamaguchi;Makoto Shimizu
γ、δ‐不饱和氨基酸是各种天然产物和药物的主干，而季α‐氨基酸也是强大的酶抑制剂，两者都是生物有机化学中非常重要的化合物。利用α -亚胺烯基酯的串联umpolung/Claisen重排，高效合成了γ，δ‐不饱和季氨基酯。考虑到Hammett规则，该方法具有广泛的底物范围，并且通过DMSO或亚胺碳的理论取代基的作用实现了高度立体选择性的Claisen重排。此外，通过同位素标记实验、动力学同位素效应和交叉实验对反应机理进行了详细的阐述。
γ,δ‐Unsaturated amino acids are the backbone of various natural products and pharmaceuticals, while quaternary α‐amino acids are also powerful enzyme inhibitors, and both are very important compounds in bioorganic chemistry. A highly efficient synthesis of γ,δ‐unsaturated quaternary amino esters utilizing the tandem umpolung/Claisen rearrangement for α‐iminoallyl esters was developed. This method has a wide range of substrates taking account of the Hammett rule, and highly stereoselective Claisen rearrangement were achieved by the effect of DMSO or theortho‐substituents of imino carbon. Furthermore, product functionalization also showed the usefulness of this reaction and the detailed reaction mechanism was elucidated from isotopic labeling experiments, kinetic isotope effects and crossover‐experiments.