22990-19-8Relevant articles and documents
Light-Promoted Dearomative Cross-Coupling of Heteroarenium Salts and Aryl Iodides via Nickel Catalysis
Nallagonda, Rajender,Musaev, Djamaladdin G.,Karimov, Rashad R.
, p. 1818 - 1829 (2022/02/07)
Partially saturated nitrogen heterocycles are versatile building blocks for the preparation of other nitrogen heterocycles. For example, dihydropyridines can be converted to pyridines, tetrahydropyridines, and piperidines through oxidation, reduction, and functionalization reactions, respectively. Dearomatization of heteroarenes is an attractive approach for the synthesis of partially saturated heterocycles such as dihydropyridines due to the wide availability of heteroarenes. Significant research efforts have been dedicated to the addition of nucleophiles to various heteroarenium salts in this direction using organoboron or organometallic reagents. The availability of organoboron and organometallic coupling partners has been an important limitation to this chemistry. Direct coupling of electrophiles with heteroareniums could significantly improve the scope of these dearomatization reactions due to the wider availability of electrophiles compared to nucleophiles such as organoboron and organometallic reagents. Herein, we report the coupling of aryl iodides with pyridinium and related heteroarenium salts catalyzed by Ni/bpp and an Ir photocatalyst using Zn as a terminal reductant. This methodology tolerates a wide range of functional groups and allows the coupling of aryl and heteroaryl iodides, thus significantly expanding the scope of nitrogen heterocycle scaffolds that could be prepared through dearomatization of heteroarenes. The reaction products have been further functionalized to prepare various nitrogen heterocycles. Initial mechanistic studies indicate that the reaction described herein goes through a unique mechanism involving dimers of dihydroheteroarenes.
Enhancement of the carbamate activation rate enabled syntheses of tetracyclic benzolactams: 8-oxoberbines and their 5- And 7-membered C-ring homologues
Kurouchi, Hiroaki
supporting information, p. 653 - 658 (2021/02/06)
A route to the direct amidation of aromatic-ring-tetheredN-carbamoyl tetrahydroisoquinoline substrates was developed. This route enabled general access to 8-oxoberberines and their 5- and 7- membered C-ring homologues. It overcomes the undesired tandem side-reactions that result in the destruction of the isoquinoline backbone, which inevitably occurred under our previously reported superacidic carbamate activation method.
Discovery of quinuclidine modulators of cellular progranulin
Burnett, Duane A.,Chen, Angela Y.-P.,Koenig, Gerhard,Lanter, James C.,Williamson, Toni,Blain, Jean-Fran?ois
, (2021/06/30)
Phenotypic screening of an annotated small molecule library identified the quinuclidine tetrahydroisoquinoline solifenacin (1) as a robust enhancer of progranulin secretion with single digit micromolar potency in a murine microglial (BV-2) cell line. Subsequent SAR development led to the identification of 29 with a 38-fold decrease in muscarinic receptor antagonist activity and a 10-fold improvement in BV-2 potency.
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.
Geometric and electronic effects on the performance of a bifunctional Ru2P catalyst in the hydrogenation and acceptorless dehydrogenation of N-heteroarenes
Shao, Fangjun,Yao, Zihao,Gao, Yijing,Zhou, Qiang,Bao, Zhikang,Zhuang, Guilin,Zhong, Xing,Wu, Chuan,Wei, Zhongzhe,Wang, Jianguo
, p. 1185 - 1194 (2021/02/16)
The development of bifunctional catalysts for the efficient hydrogenation and acceptorless dehydrogenation of N-heterocycles is a challenge. In this study, Ru2P/AC effectively promoted reversible transformations between unsaturated and saturated N-heterocycles affording yields of 98% and 99%, respectively. Moreover, a remarkable enhancement in the reusability of Ru2P/AC was observed compared with other Ru-based catalysts. According to density functional theory calculations, the superior performance of Ru2P/AC was ascribed to specific synergistic factors, namely geometric and electronic effects induced by P. P greatly reduced the large Ru-Ru ensembles and finely modified the electronic structures, leading to a low reaction barrier and high desorption ability of the catalyst, further boosting the hydrogenation and acceptorless dehydrogenation processes.
Diprotonative stabilization of ring-opened carbocationic intermediates: conversion of tetrahydroisoquinoline to triarylmethanes
Kurouchi, Hiroaki
supporting information, p. 8313 - 8316 (2020/08/17)
Superacid-promoted conversion of tetrahydroisoquinolines to triarylmethanes via tandem reactions of C-N bond scission, Friedel-Crafts alkylation, C-O bond scission, and electrophilic aromatic amidation was developed. Dication formation was important for stabilizing the ring-opened carbocationic intermediate, which is a new role for diprotonation in reaction mechanisms. This journal is
Preparation method of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline
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Paragraph 0016, (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.
Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity
Barrios-Rivera, Jonathan,Xu, Yingjian,Wills, Martin
, p. 6283 - 6287 (2020/09/02)
The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with high enantioselectivity; therefore, this approach solves a long-standing challenge for imine ATH.
(S)1-phenyl-1,2,3,4-tetrahydroisoquinoline synthesis method
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Paragraph 0040-0076, (2020/02/08)
The invention relates to a (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline synthesis method, wherein the reaction route is defined in the specification. The synthesis method comprises: 1) dissolving a rawmaterial 1 in a solvent, and adding an alkali and a catalyst; and (2) carrying out gas replacement by using hydrogen to form a hydrogen atmosphere, and carrying out an pressurization reaction to obtain (S)1-phenyl-1,2,3,4-tetrahydroisoquinoline 2, wherein the catalyst is a BIAMH system catalyst, a D-BIMAH system catalyst or a P-BIMAH system catalyst.
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.
