Aza-henry reactions of 3,4-dihydroisoquinoline

Muneer Ahamed, Thiru Thirukkumaran, Wing Yan Leung, Paul Jensen, Jade Schroers, Matthew H. Todd

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The aza-Henry reaction of 3,4-dihydroisoquinoline is reported. The reaction is favourable in excess nitromethane under ambient conditions. Isolation of the unstable reaction product is achieved by acylation or alkylation, allowing the synthesis of Reissert-like compounds in good yields from a one-pot, three-component coupling. The rates of reaction for dihydroisoquinoline and the corresponding benzylisoquinolinium ion have been investigated in the presence and absence of base. The reaction with dihydroisoquinoline probably proceeds via an azinic acid tautomer of nitromethane, a reaction pathway unavailable to the isoquinolinium ion. The traditionally problematic reduction of two of the resulting β-nitroamine derivatives was achieved, providing access to a number of new chiral vicinal diamines. 3,4-Dihydroisoquinoline reacts with nitromethane, likely via a cyclic mechanism employing nitromethane's azinic acid tautomer. The product may be alkylated or acylated. Alternatively a Reissert-like one-pot, three-component coupling may be used to generate a range of β-nitroamines which may be reduced to give new isoquinoline-derived chiral, vicinal diamines.

Original languageEnglish
Pages (from-to)5980-5988
Number of pages9
JournalEuropean Journal of Organic Chemistry
Issue number31
DOIs
Publication statusPublished or Issued - Nov 2010
Externally publishedYes

Keywords

  • aza-Henry reaction
  • nitro-Mannich reaction
  • Nitroalkanes
  • Nitrogen heterocycles

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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