Synthesis of optically active 6-amino-2-cycloheptenone as a convenient chiral building block for the preparation of 6-alkyl-2-cycloheptenone

Abstract

Optically active 6-amino-2-cycloheptenone 5 has been prepared from ethyl 2( E),6-heptadienoate where the Michael addition of a chiral amine, Ti(II)-mediated intramolecular nucleophilic acyl substitution reaction and FeCl 3-mediated ring expansion are the key steps. The compound 5 undergoes highly diastereoselective conjugate addition of a Grignard reagent in the presence of a catalytic amount of Li 2Cu(CN)Cl 2 to provide the corresponding cis-adducts which, in turn, are converted in to 6-alkyl substituted 2-cycloheptenones by treatment with p-TSA.