Synthesis and Screening of C 1 ‐Substituted Tetrahydroisoquinoline Derivatives for Asymmetric Transfer Hydrogenation Reactions

Tetrahydroisoquinoline (TIQ) derivatives exhibit good biological activity. However, utilization of TIQ compounds in asymmetric catalysis is limited. This paper presents a series of TIQ derivatives in asymmetric transfer hydrogenation (ATH) reactions. Chiral TIQ amino alcohol ligands were synthesized and screened for the ATH reaction of aromatic ketones. The effect of a cis ‐ and trans ‐phenyl substitution at the C 1 position on the ligand backbone was investigated both experimentally and computationally. The results showed that the trans orientation on the TIQ scaffold yields higher turnover rates with a selectivity of 94 % ee obtained at room temperature with an Ru complex. The cis isomer results in a high turnover rate with no selectivity. The trans isomer gave 99 % ee at lower temperatures. Furthermore, it was observed that substitution at the C 3 ‐α position results in a drop of the enantioselectivity and the reactivity of the catalyst.