Extension of a One-Pot Synthesis of Bicyclo[n.4.0]alkanols; Indications of Scope and Limitations for Formation of Substituted Bicyclo[n.4.0]alkanols

Abstract

Novel bicyclo[n.2.0]alkan-1-ols with incorporation of methyl substitution at the C6 bridgehead and C2 position on a six-member ring, and incorporation of methyl substitution at the C2 position on a five-member ring were obtained. The presence or absence of a group at these positions had a role in the preference of the major stereochemical isomer observed. Potential limitations of the cyclisation methodology was observed when the ketone was hindered (camphor), and where conjugation was present in the enolate. By contrast, another functional group, as illustrated with 1,4-cyclohexanedione mono-ethylene ketal 24, can be incorporated in the bicyclo[4.2.0]octan-1-ol, and the ketal group converted to a ketone, as in 28, without disrupting the bicyclo[4.2.0]octan-1-ol ring.

Key words

bicyclic compounds - cyclisations - ketones - sulfoxides - sulfones

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12

Crystals were grown for example by the slow evaporation of a hexane-EtOAc (90:10) solution of pure 13 or 14, and from the slow diffusion of Et₂O into a solution of 13 or 14 in CH₂Cl₂.

17

The bicyclo[2.2.2]octanones 34-36 were characterised by interpretation of spectral data from ¹H and ¹³C 1D NMR and gCOSY, gHSQC and gHMBC 2D NMR, FT-IR spectroscopy and mass spectrometry. With four stereocentres present, eight racemic diastereomers could potentially form in a non-selective reaction process. However the individual stereochemistries of bicyclo[2.2.2]octanones 34-36 were unable to be assigned. Two-dimensional ROESY NMR spectra of 34-36 provided ambiguous information. Likewise ¹H-¹H coupling information drawn from the ¹H NMR spectra was inconclusive.