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

Abstract

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.