Stereoselective Synthesis of Tetrahydroisoquinolines from Chiral 4-Azaocta-1,7-diynes and 4-Azaocta-1,7-enynes

The N-propargylation of enantioenriched homopropargylic amine derivatives 3 proceeds in high yields under basic conditions. The resulting 4-azaocta-1,7-dynes 5 were transformed into 1,2,3,4-tetrahydrosioquinolines 7 bearing substituents at 3-, 6- and 7-positions, upon reaction with symmetrical alkynes, through a [2+2+2] cyclotrimerization promoted by Wilkinson catalyst. Ruthenium-catalyzed ring closing metathesis of azaocta-1,7-enynes 9a and 15a gave 1,3-dienes 10a and 16a, respectively, in high yields. Tetrahydroisoquinolines 12a and 18a, with a substitution pattern in the aromatic ring different to that of compounds 7, were prepared by a [4+2] cycloaddition of dimethyl acetylenedicarboxylate with dienes 10a and 16a, respectively.