Asymmetric Hydrogenation of Isoquinolines and Pyridines Using Hydrogen Halide Generated in Situ as Activator

Chen, Mu‐Wang; Ji, Yue; Wang, Jie; Chen, Qing‐An; Shi, Lei; Zhou, Yong‐Gui

doi:10.1021/acs.orglett.7b02502

Cited by 62 publications

(22 citation statements)

References 64 publications

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“…The products were analyzed by 1 H NMR to determine the molar conversion, whereas the enantiomeric excess was evaluated by HPLC analysis, and the absolute configuration was assigned by comparison with literature references [25,55].…”

Section: Analytical Conditionsmentioning

confidence: 99%

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

et al. 2020

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Starting from the chiral 5,6,7,8-tetrahydroquinolin-8-ol core, a series of amino-phosphorus-based ligands was realized. The so-obtained amino-phosphine ligand (L1), amino-phosphinite (L2) and amino-phosphite (L3) were evaluated in iridium complexes together with the heterobiaryl diphosphines tetraMe-BITIOP (L4), Diophep (L5) and L6 and L7 ligands, characterized by mixed chirality. Their catalytic performance in the asymmetric hydrogenation (AH) of the model substrate 6,7-dimethoxy-1-phenyl-3,4-dihydroisoquinoline 1a led us to identify Ir-L4 and Ir-L5 catalysts as the most effective. The application of these catalytic systems to a library of differently substituted 1-aryl-3,4-dihydroisoquinolines afforded the corresponding products with variable enantioselective levels. The 4-nitrophenyl derivative 3b was obtained in a complete conversion and with an excellent 94% e.e. using Ir-L4, and a good 76% e.e. was achieved in the reduction of 2-nitrophenyl derivative 6a using Ir-L5.

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Section: Analytical Conditionsmentioning

confidence: 99%

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

et al. 2020

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“…[4c] Although asymmetric reduction of substituted isoquinolines has been proved to be one of the most challenging hydrogenation transformations, there are still a few successful examples reported by the hard-working chemists in the past decades. [5][6][7][8][9][10][11][12][13][14] Since the pioneering work by Zhou, who reported the first asymmetric hydrogenation of 1-substituted isoquinolines using an Ir/(S)-segphos catalyst system in 2006, [5] development of this attractive reaction paradigm has attracted numerous attentions. In order to obtain high reactivity and stereoselectivity, numbers of strategies, including substrate activation and catalyst modification, have been developed.…”

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confidence: 99%

Iridium‐Catalyzed Enantioselective Hydrogenation of 3‐Substituted Isoquinolinium Salts

Wang

et al. 2021

Asian J Org Chem

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Chiral tetrahydroisoquinolines (THIQ) is a highly important molecular skeleton in natural alkaloids and biologically active compounds, and its derivatives are often used as key intermediates for the synthesis of drugs. Herein, we described an efficient enantioselective hydrogenation of 3‐substituted isoquinolinium salts catalyzed by a bromine‐bridged dimeric complex [{Ir(H)[(R,S,Sax)‐Ph‐ax‐Josiphos]}2(μ‐Br)3]+Br−. This efficient enantioselective transformation could provide a series of useful chiral cyclic amines, which were of great potential value in natural product modification and drug molecular preparation in high yields and moderate to excellent enantioselectivities (68–97% ee). Additionally, turnover number experiments and a gram‐scale synthesis of chiral 3‐phenyltetrahydroisoquinoline were conducted.

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“…The development of convenient methods for the enantioselective preparation of chiral 1-substituted THIQs has attracted the attention of many researchers over the past several decades . Because of its efficiency and convenience, the catalytic hydrogenation of1-substituted 3,4-dihydroisoquinolines (DHIQs) has been demonstrated as one of the most straightforward and cost-effective methods . Although considerable progress has been made in the asymmetric hydrogenation of DHIQs, almost all of the substrates of this asymmetric transformation were the less hindered DHIQs which possessed relatively small substituents, such as 1-methyl, 1-ethyl, 1-benzyl, and 1-aryl groups and so on .…”

mentioning

confidence: 99%

Iridium-Catalyzed Asymmetric Hydrogenation of Sterically Hindered Cyclic Imines for Enantioselective Synthesis of Tetrahydroisoquinolines

Liu

Yang

et al. 2020

Org. Lett.

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An efficient enantioselective hydrogenation of sterically hindered cyclic imines catalyzed by the Ir- t Bu-ax-Josiphos complex has been described, producing a series of useful chiral bulky tetrahydroisoquinoline analogs in high isolated yields (85–96%) with good to excellent enantioselectivities (74–99% ee). This transformation provided highly straightforward access to the useful derivatives of tetrahydroisoquinolines, which are of great potential value in drug molecule and natural product research.

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Asymmetric Hydrogenation of Isoquinolines and Pyridines Using Hydrogen Halide Generated in Situ as Activator

Cited by 62 publications

References 64 publications

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

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

Iridium‐Catalyzed Enantioselective Hydrogenation of 3‐Substituted Isoquinolinium Salts

Iridium-Catalyzed Asymmetric Hydrogenation of Sterically Hindered Cyclic Imines for Enantioselective Synthesis of Tetrahydroisoquinolines

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