Asymmetric addition of nucleophiles to C-1 position of isoquinolines using (S)-alanine derivatives as chiral auxiliaries

5,8-Dibromoisoquinoline derivatives were allowed to react with a nucleophile (silyl enol ether or allyltributyltin) in the presence of an acyl chloride derived from (S)-alanine to afford the 1,2-addition products in good chemical yields and high stereoselectivity. The bromo groups were readily removed by a reduction process in which the double bond at C3–C4 was also reduced. Thus the reaction system provided a general method to synthesize asymmetric 1-substituted tetrahydroisoquinolines. In order to determine the absolute configuration of the reaction product, (−)-homolaudanosine was synthesized in an enantiopure form. The stereoselectivity was rationally understood from the conformation of intermediary N-acylated isoquinolinium salts.