Stereoselective synthesis of carane-based chiral β- and γ-amino acid derivatives via conjugate addition

Michael addition of dibenzylamine to (−)-tert-butyl isochaminate, prepared in three steps from (−)-perillaldehyde, furnished a carane-based β-amino acid derivative in a highly stereospecific reaction. The resulting amino ester was transformed to the bicyclic amino acid, a promising building block for the synthesis of 1,3-heterocycles and peptidomimetics. The conjugate addition of nitromethane to α,β-unsaturated methyl ester likewise resulted in nitro esters in stereospecific reactions. Catalytic reduction of the nitro group yielded a γ-amino ester. Under acidic conditions, the hydrolysis of the methyl ester resulted in an unexpected aminolactone-type product through rearrangement of the bicyclic carane system, whereas an alternative synthetic pathway through α,β-unsaturated benzyl ester furnished the desired γ-amino acid.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide