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 beta-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 alpha,beta-unsaturated methyl ester likewise resulted in nitro esters in stereospecific reactions. Catalytic reduction of the nitro group yielded a gamma-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 alpha,beta-unsaturated benzyl ester furnished the desired gamma-amino acid. (C) 2015 Elsevier Ltd. All rights reserved.