Stereoselective Synthesis and Modelling-Driven Optimisation of Carane-Based Aminodiols and 1,3-Oxazines as Catalysts for the Enantioselective Addition of Diethylzinc to Benzaldehyde

Z. Szakonyi, Árpád Csor, A. Csámpai, Ferenc Fülöp

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16 Citations (Scopus)

Abstract

The reductive amination of (-)-2-carene-3-aldehyde, prepared in two steps from (-)-perillaldehyde, furnished 2-carene-based allylamines. tert-Butyloxycarbonyl (Boc) or carbobenzyloxy (Cbz) protection of the resulting amines, followed by stereoselective dihydroxylation in highly stereospecific reactions with OsO4 and subsequent deprotection, resulted in N-benzylaminodiols, which were transformed to primary and tertiary aminodiols. The reactions of the N-benzyl- and N-(1-phenylethyl)-substituted derivatives with formaldehyde led to highly regioselective ring closure, resulting in carane-fused 1,3-oxazines. The aminodiols and their 1,3-oxazine derivatives were applied as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. The best (R) enantioselectivity was observed in the case of the N-((R)-1-phenylethyl)-substituted aminodiol, whereas the opposite chiral direction was preferred when the 1,3-oxazines were applied. Through the use of molecular modelling at an ab initio level, this phenomenon was interpreted in terms of competing reaction pathways. Molecular modelling at the RHF/LANL2DZ level of theory was successfully applied for a mechanism-based interpretation of the stereochemical outcome of the reactions leading to the development of further 1,3-oxazine-based ligands, which display excellent (S) enantioselectivity (95 and 98%ee) in the examined transformation.

Original languageEnglish
JournalChemistry - A European Journal
DOIs
Publication statusAccepted/In press - 2016

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Keywords

  • Aminodiol
  • Diethylzinc
  • Molecular modelling
  • Perillaldehyde
  • Stereoselective catalysis

ASJC Scopus subject areas

  • Chemistry(all)

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