Highly Regioselective 5-endo-tet Cyclization of 3,4-Epoxy Amines into 3-Hydroxypyrrolidines Catalyzed by La(OTf)3 |
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Authors: | Yuse Kuriyama Dr Yusuke Sasano Yoshihiko Hoshino Dr Shun-ichiro Uesugi Aoto Yamaichi Prof Dr Yoshiharu Iwabuchi |
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Institution: | Department of Organic Chemistry, Graduate School of, Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578 Japan |
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Abstract: | 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. |
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Keywords: | amines chemoselectivity cyclization regioselectivity synthetic methods |
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