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

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 NiII complex in the presence of sodium hydride. The resulting hydroaminated NiII complexes were isolated in 55–82 % yields with excellent diastereoselectivity (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 NiII complexes via aqueous HCl treatment of the NiII complexes and isolated with excellent enantioselectivity (> 99 % ee). The chiral auxiliary [(S)-BPB = (S)-2-(N-benzylprolyl)aminobenzophenone] and NiII ions can be easily recovered after the acidic complex cleavage step and reused for the synthesis of the starting NiII complex. Moreover, the indole′s preference for nucleophilic attack via its N1- over its C3-position was rationalized by DFT calculations. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Larionov V.A. 1, 2 , Savel'yeva T.F.1 , Medvedev M.G.1, 3, 4, 5 , Stoletova N.V.1 , Smol'yakov A.F. 1, 6 , Gugkaeva Z.T. 1 , Cruchter T.7 , Maleev V.I. 1
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  • 1 A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilov Str. 28, Moscow, 119991, Russian Federation
  • 2 Department of Inorganic Chemistry, Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya Str. 6, Moscow, 117198, Russian Federation
  • 3 N. D. Zelinsky Institute of Organic Chemistry of Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russian Federation
  • 4 Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow, 119991, Russian Federation
  • 5 National Research University Higher School of Economics (HSE), Myasnitskaya Str. 20, Moscow, 101000, Russian Federation
  • 6 Plekhanov Russian University of Economics, Stremyanny Per. 36, Moscow, 117997, Russian Federation
  • 7 Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, Marburg, 35043, Germany
Ключевые слова
Amino acids; Asymmetric synthesis; Aza-Michael addition; Indoles
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