Highly Regioselective 5-endo-tet Cyclization of 3,4-Epoxy Amines into 3-Hydroxypyrrolidines Catalyzed by La(OTf)3
Highly Regioselective 5-endo-tet Cyclization of 3,4-Epoxy Amines into 3-Hydroxypyrrolidines Catalyzed by La(OTf)3
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DOI：
10.1002/chem.202004455
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发表时间：
2020-12-30
影响因子：
4.3
通讯作者：
Iwabuchi, Yoshiharu
中科院分区：
文献类型：
--
作者：
Kuriyama, Yuse;Sasano, Yusuke;Iwabuchi, Yoshiharu
实现了3，4-环氧胺的高区域选择性分子内氨解反应。该反应的主要特点是(1)在La(OTf)(3)催化剂作用下，在相同分子中无保护脂肪胺存在的情况下，环氧化物被化学选择性地活化；(2)对于反Baldwin 5-Endo环化反应具有良好的区域选择性。该反应高产率地立体定向合成了3-羟基-2-烷基吡咯烷。密度泛函理论计算表明，这种区域选择性可能归因于环氧胺底物的扭曲能。首次对映体选择性合成抗痉挛药普非溴铵证明了该反应的用途。
Highly regioselective intramolecular aminolysis of 3,4-epoxy amines has been achieved. Key features of this reaction are (1) chemoselective activation of epoxides in the presence of unprotected aliphatic amines in the same molecules by a La(OTf)(3) catalyst and (2) excellent regioselectivity for anti-Baldwin 5-endo-tet cyclization. This reaction affords 3-hydroxy-2-alkylpyrrolidines stereospecifically in high yields. DFT calculations revealed that the regioselectivity might be attributed to distortion energies of epoxy amine substrates. The use of this reaction was demonstrated by the first enantioselective synthesis of an antispasmodic agent prifinium bromide.