The Selective N-functionalization of Indoles via aza-Michael Addition in the Ligand Sphere of a Chiral Ni(II) Complex: Asymmetric Synthesis of (S)-1H-Indole-Alanine Derivatives

Larionov, V.A.; Savel’yeva, T.F.; Medvedev, M.G.; Stoletova, N.V.; Smol’yakov, A.F.; Gugkaeva, Z.T.; Thomas, C.; Maleev, V.I.

Авторы: Larionov Vladimir A., Savel’yeva Tat’yana F., Medvedev Michael G., Stoletova Nadezhda V., Smol’yakov Alexander F., Gugkaeva Zalina T., Thomas Cruchter, Maleev Victor I.
Журнал: European Journal of Organic Chemistry
Номер: 22
Год издания: 2019
Издательство: John Wiley & Sons Ltd.
Местоположение издательства: United Kingdom
Первая страница: 3699
Последняя страница: 3703
DOI: 10.1002/ejoc.201900650
Аннотация: The selective addition of electrophilic C=C double bonds to the N–H bond of indoles is a challenging task due to the high nucleophilicity of indoles at their C3-position. Herein, we report the successful selective intermolecular N-functionalization of various indoles via aza-Michael addition of C=C double bond of a dehydroalanine Schiff base, which takes place in the ligand sphere of a chiral Ni(II) complex in the presence of sodium hydride. The resulting hydroaminated Ni(II) complexes were isolated in 55–82% yields with excellent diastereselectivity (dr >99:1) (8 examples). And the actual products of interest, namely (S)-2-amino-3-(1H-indol-1-yl)propanoic acids, were subsequently released from the Ni(II) complexes via aqueous HCl treatment of the Ni(II) complexes and isolated with excellent enantioselectivity (>99% ee). The chiral auxiliary ((S)-BPB = (S)-2-(N-benzylprolyl)aminobenzophenone) and Ni(II) ions can be easily recovered after the acidic complex cleavage step and reused for the synthesis of the starting Ni(II) complex. Moreover, the indole's preference for nucleophilic attack via its N1- over its C3-position was rationalized by DFT calculations.
Добавил в систему: Ларионов Владимир Анатольевич

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The Selective N-functionalization of Indoles via aza-Michael Addition in the Ligand Sphere of a Chiral Ni(II) Complex: Asymmetric Synthesis of (S)-1H-Indole-Alanine Derivativesстатья Исследовательская статья

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