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

✍ Scribed by Sai Kumar Chakka; Pher G. Andersson; Glenn E. M. Maguire; Hendrik G. Kruger; Thavendran Govender

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 227 KB
• Volume: 2010
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200901159

✦ Synopsis

Abstract

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.