118864-75-8Relevant articles and documents
Asymmetric Transfer Hydrogenation of 1-Aryl-3,4-Dihydroisoquinolines Using a Cp*Ir(TsDPEN) Complex
Václavíková Vilhanová, Bea,Budinská, Alena,Václavík, Ji?í,Matou?ek, Václav,Kuzma, Marek,?erveny, Libor
, p. 5131 - 5134 (2017)
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
The development of an asymmetric hydrogenation process for the preparation of solifenacin
Ruzic, Milos,Pecavar, Anica,Prudic, Darja,Kralj, David,Scriban, Corina,Zanotti-Gerosa, Antonio
, p. 1293 - 1300 (2012)
The successful development of a catalytic imine asymmetric hydrogenation process for the reduction of the hydrochloride salt of 1-phenyl-3,4- dihydroisoquinoline to 1-(S)-phenyl-1,2,3,4-tetrahydroisoquinoline is described. This represents a novel approach to the key intermediate in preparing the urinary antispasmodic drug solifenacin, (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl-3, 4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate. Suitable reaction conditions were identified through an extensive screen of catalysts and combination of solvents and additives. The best reaction conditions: [Ir(COD)Cl] 2-(S)-P-Phos, molar substrate to catalyst ratio (S/C) of >1000/1, THF, 1-2 equiv of H3PO4, 60 °C, 20 bar H2, were reproduced on a 200 g scale (95% isolated yield, 98% ee and >99% HPLC product purity).
Enantioselective synthesis of 1-Aryl-substituted tetrahydroisoquinolines employing imine reductase
Zhu, Jinmei,Tan, Hongqun,Yang, Lu,Dai, Zheng,Zhu, Lu,Ma, Hongmin,Deng, Zixin,Tian, Zhenhua,Qu, Xudong
, p. 7003 - 7007 (2017)
Tetrahydroisoquinolines (THIQs) with a C1-aryl-substituted groups are common in many natural and synthetic compounds of biological importance. Currently, their enantioselective synthesis are primarily reliant on chemical catalysis. Enzymatic synthesis using imine reductase is very attractive, because of the cost-effectiveness, high catalytic efficiency, and enantioselectivity. However, the steric hindrance of the 1-aryl substituents make this conversion very challenging, and current successful examples are mostly restricted to the simple alkyl-THIQs. In this report, through extensive evaluation of a large collection of IREDs (including 88 enzymes), we successfully identified a panel of steric-hindrance tolerated IREDs. These enzymes are able to convert meta- and para-substituted chloro-, methyl-, and methoxyl-benzyl dihydroisoquinolines (DHIQs) into corresponding R- or S- THIQs with very high enantioselectivity and conversion. Among them, the two most hindrance-tolerated enzymes (with different stereospecificity) are also able to convert ortho-substituted chloro-, methyl-, and methoxyl-benzyl DHIQs and dimethoxyl 1-chlorobenzyl-DHIQs with good enantiometric excess. Furthermore, using in silico modeling, a highly conserved tryptophan residue (W191) was identified to be critical for substrate accommodation in the binding cavity of the S-selective IRED (IR45). Replacing W191 with alanine can dramatically increase the catalytic performance by decreasing the Km value by 2 orders of magnitude. Our results provide an effective route to synthesize these important classes of THIQs. Moreover, the disclosed sequences and substrate binding model set a solid basis to generate more-efficient and broad-selective enzymes via protein engineering.
Ferritin encapsulation of artificial metalloenzymes: Engineering a tertiary coordination sphere for an artificial transfer hydrogenase
Hestericová, Martina,Heinisch, Tillmann,Lenz, Markus,Ward, Thomas R.
, p. 10837 - 10841 (2018)
Ferritin, a naturally occuring iron-storage protein, plays an important role in nanoengineering and biomedical applications. Upon iron removal, apoferritin was shown to allow the encapsulation of an artificial transfer hydrogenase (ATHase) based on the streptavidin-biotin technology. The third coordination sphere, provided by ferritin, significantly influences the catalytic activity of an ATHase for the reduction of cyclic imines.
Low-Temperature Nickel-Catalyzed C?N Cross-Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N-Heterocyclic Carbene Ligand
Hong, Xin,Shi, Shi-Liang,Wang, Zi-Chao,Xie, Pei-Pei,Xu, Youjun
supporting information, p. 16077 - 16084 (2021/06/17)
The transition-metal-catalyzed C?N cross-coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low-temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low-temperature (as low as ?50 °C), enantioselective Ni-catalyzed C?N cross-coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N-heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ-bonds on the C2-symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal-catalyzed asymmetric cross-coupling reactions.
Preparation method of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline
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, (2020/11/26)
The invention discloses a preparation method of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. Benzophenone and aminoacetaldehyde dimethyl acetal are used as raw materials, which carry out a reaction under a heating condition to obtain N-(diphenylmethylene)-2,2-dimethoxyethylamine; N-(diphenylmethylene)-2,2-dimethoxyethylamine carries out cyclization under an acid heating condition to obtain 1-phenylisoquinoline, 1-phenylisoquinoline is reduced by using a Pd/C or Ni catalyst to obtain racemic 1-phenyl-1,2,3,4-tetrahydroisoquinoline, and finally 1-phenyl-1,2,3,4-tetrahydroisoquinoline is split byL-mandelic acid to obtain (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. Compared with the prior art, benzophenone and aminoacetaldehyde dimethyl acetal are creatively and directly used for reaction,the raw materials are cheap and easy to obtain, and the production cost is greatly reduced. Phosphorus-containing wastewater is not generated, so that the preparation method is safer and more environment-friendly; L-mandelic acid is used for replacing traditional tartaric acid, the crystallization speed is high, the yield is high, the splitting efficiency is improved, and the production period isshortened.
Synthesis method of (S)-1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline
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Paragraph 0068; 0073-0075; 0080-0082; 0087-0089; 0094-0096, (2021/01/15)
The invention relates to a synthetic method of (S) 1-phenyl -1, 2, 3, 4-tetrahydroisoquinoline. The method comprises the following steps: mixing 1-phenyl-3, 4-dihydroisoquinoline, a chiral catalyst, an acid and a solvent, and reacting, wherein the structural formula of the chiral catalyst is shown as a formula (I). further forming (S)-1phenyl -1, 2, 3, 4-tetrahydroisoquinoline with high chiral purity in one step in the hydrogenation reduction process, meanwhile, the product is easy to separate and purify, and the yield is high. In addition, the invention is mild in reaction condition, stable in process, simple, convenient and safe in reaction operation, low in production cost, simple and feasible in three-waste treatment, environment-friendly, simple in equipment used in the reaction process, easily available in raw materials, low in production cost and suitable for industrial production.