Study on medium ring heterocycles: Synthesis and structure of novel condensed pyrazolo[1,4]diazocinones including single enantiomers

Ádám Gyömöre, Antal Csámpai, Tamás Holzbauer, Mátyás Czugler

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

By means of a base-catalysed ring enlargement of triazapentalenoindenes resulting from diasteroselective anhydride-induced ring transformation of chiral aminoalcohol-derived zwitterionic 2,3-dihydroimidazo[2,1-a]phthalazinium- olates, a series of pyrazolo[1,5-d][1,4]diazocin-7(6H)-ones with central and conformational chirality were obtained in enantiomerically pure form. The possible reasons of the characteristic substrate- and reagent-dependency observed for the diasteroselective ring transformations of the zwitterions were interpreted in terms of the relative energetics of the crucial alternative imidazolinium intermediates disclosed by B3LYP/6-31G(d,p) calculations. The trans-annular opening of three epimeric pairs of triazapentalenoindanones afforded identical pyrazolodiazonine products. This finding suggests that the primarily formed diastereomers, having different asymmetric conformations but the same element of central chirality, undergo ring inversions in one- and two steps, respectively, involved in pathways previously established for the facile racemisation of pyrazolodiazocines with conformational chirality and hydrogen- or methyl-substituent at C1-position. The ring enlargement of triazapentalenoindanones resulted from butyric anhydride-mediated ring transformation of zwitterions with symmetrical substitution pattern afforded highly rigid 1-ethylpyrazolodiazocines in racemic form potentially separable without thermal racemisation. The constitution, conformation and relative configuration of the novel compounds were determined by 1H-, 13C- and 15N-NMR methods including 2D-HSQC, 2D-HMBC and DNOE measurements and the structure of a pyrazolodiazocine was supported by single crystal X-ray diffraction.

Original languageEnglish
Pages (from-to)2979-2990
Number of pages12
JournalTetrahedron
Volume67
Issue number16
DOIs
Publication statusPublished - Apr 22 2011

Keywords

  • Conformational chirality
  • DFT
  • DNMR
  • Diastereoselectivity
  • Pyrazolodiazocine
  • Ring inversion
  • trans-Annular ring enlargement

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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