Studies on 1, 2, 3, 4-Tetrahydroisoquinolines. VI. Reutilization of the Unwanted (R)-Isomer of (S)-(-)-5, 7-Dihydroxy-1-(3, 4, 5-trimethoxybenzyl)-1, 2, 3, 4-tetrahydroisoquinoline (TA-073)

Abstract

Racemization of the unwanted isomer (R-1) of (S)-(-)-5, 7-dihydroxy-1-(3, 4, 5-trimethoxybenzyl)-1, 2, 3, 4-tetrahydroisoquinoline (TA-073) via the imine 6 was examined. Reduction of 6 with NaBH₄ followed by hydrogenolysis over 10% Pd-C gave (±)-TA-073 in a good yield. Asymmetric reduction of 6 to S-4, the precursor of TA-073, by the use of the chiral reducing agent (I), prepared from NaBH₄ (1 eq) and (S)-N-benzyloxycarbonylproline (3 eq), was also investigated. Treatment of 6 with I in a halogenated alkane such as CHCl₂CH₃ or CHCl₂CHCl₂ at -30°C afforded S-4 in an excellent optical yield (87% e.e.).