Asymmetric Transfer Hydrogenation of 1‐Aryl‐3,4‐Dihydroisoquinolines Using a Cp*Ir(TsDPEN) Complex

Abstract

We report herein a simple alternative method for the asymmetric transfer hydrogenation (ATH) of 1‐aryl‐3,4‐dihydroisoquinolines (1‐Ar‐DHIQs) that are known to be challenging substrates owing to their poor reactivity. The hydrogenation protocol employs the readily available Cp*Ir(TsDPEN) {where Cp* = pentamethylcyclopentadienyl and TsDPEN = (S,S)‐HNCHPhCHPhNTs2–} catalytic complex, 2‐propanol and HCOOH/triethylamine mixture as the solvent and hydrogen donor, and anhydrous phosphoric acid as an inexpensive additive. The series of examined substrates shows a favorable tolerance to various functional groups. Unlike 1‐alkyl‐DHIQs, where the enantiomeric excess (ee) starkly changes during the course of hydrogenation, 1‐Ar‐DHIQs exhibit a constant ee value, which makes the method practical and useful for the production of fine chemicals containing the 1,2,3,4‐tetrahydroisoquinoline motif.

Introduction of chirality at C1 position of 1-substituted-3,4-dihydroisoquinoline by its enantioselective reduction: synthesis of chiral 1-substituted-1,2,3,4-tetrahydroisoquinoline – a review

“…24) complexes in ACN, IPA, DCM, DMSO, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), HCOOH/TEA hydrogen-donor solvents for 24 h but no combinations gave full conversion to 52a from 51a (Scheme 41). 59 ACN gave a very low conversion of 2–3% with (1 S ,2 S )- 47d , (1 S ,2 S )- 47c′ but a good conversion of 87% with (1 S ,2 S )- 47d′ (10% ee). IPA had an increasing conversion rate with the complexes (64%, 66%, and 83% respectively) but moderate ee (60%) with (1 S ,2 S )- 47d′ only.…”

Asymmetric Hydrogenation of 1-aryl substituted-3,4-Dihydroisoquinolines with Iridium Catalysts Bearing Different Phosphorus-Based Ligands

“…The traditional organic methods for the synthesis of tetrahydroquinoline are based on condensation, the cyclization/reduction sequence and intramolecular nucleophilic addition [18][19][20][21][22][23]. Many efforts have been made to improve the synthetic approach via catalytic methods [7,[24][25][26][27][28][29][30][31]. Considering the convenience in terms of efficiency and atom economy, asymmetric hydrogenation (AH) of prochiral imines, using phosphine-based metal complexes as catalysts, was evinced as the most practical application.…”

Enantioselective Imine Reduction of Dihydro-β-carbolines by Fe-Thiosquaramide Catalyst

“…However, the enantioselective imine reduction is more favorable than asymmetric Pictet–Spengler cyclization because the imine reduction can be performed at room temperatures or low temperatures while the Pictet–Spengler cyclization occurs at elevated temperatures and/or requires strong acid catalysts . In recent years, numerous protocols have been developed for the synthesis of chiral THBCs through enantioselective imine reduction employing asymmetric organocatalysis and metal-chiral auxiliary complexes. , Moreover, excellent stereoselectivities observed with metal complexes such as Ru, Rh, Ir, and Pd associated chiral auxiliaries (Figure ). Despite their high catalytic potential, they are very expensive and highly toxic to living species as well as the environment .…”