Synthesis and Screening of C1‐Substituted Tetrahydroisoquinoline Derivatives for Asymmetric Transfer Hydrogenation Reactions

Abstract

AbstractTetrahydroisoquinoline (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 C1 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 C3‐α position results in a drop of the enantioselectivity and the reactivity of the catalyst.