- A through halogen bond activation isoquinoline asymmetric hydrogenation method
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A through halogen bond activation isoquinoline asymmetric hydrogenation method, the catalyzing system is [...] complex, the activator is a halide. The reaction can be carried out under the following conditions, temperature: 25 - 100 °C; solvent: tetrahydr
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Paragraph 0037; 0038; 0039; 0046; 0062
(2019/03/26)
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- Dual Stereocontrol for Enantioselective Hydrogenation of Dihydroisoquinolines Induced by Tuning the Amount of N-Bromosuccinimide
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An efficient dual stereocontrol in iridium-catalyzed hydrogenation of 1-substituted 3,4-dihydroisoquinolines was realized by tuning the amount of N-bromosuccinimide using chiral ligand of single configuration, providing both enantiomers of 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 89% ee (S) and 98% ee (R), respectively. Dual activation role of N-bromosuccinimide is proposed to be responsible for the reversal of enantioselectivity under two hydrogenation conditions.
- Ji, Yue,Wang, Jie,Chen, Muwang,Shi, Lei,Zhou, Yonggui
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supporting information
p. 139 - 142
(2018/01/05)
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- A method catalyzed by iridium and used for bidirectional enantioselective synthesis of chiral tetrahydroisoquinoline
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A method catalyzed by iridium and used for bidirectional enantioselective synthesis of chiral tetrahydroisoquinoline is provided. A catalysis system adopted by the method is a chiral diphosphine complex of iridium. By utilizing a single chiral source and
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Paragraph 0035-0051; 0060; 0061; 0075
(2018/03/01)
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- Simultaneous engineering of an enzyme's entrance tunnel and active site: The case of monoamine oxidase MAO-N
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A new directed evolution approach is presented to enhance the activity of an enzyme and to manipulate stereoselectivity by focusing iterative saturation mutagenesis (ISM) simultaneously on residues lining the entrance tunnel and the binding pocket. This combined mutagenesis strategy was applied successfully to the monoamine oxidase from Aspergillus Niger (MAO-N) in the reaction of sterically demanding substrates which are of interest in the synthesis of chiral pharmaceuticals based on the benzo-piperidine scaffold. Reversal of enantioselectivity of Turner-type deracemization was achieved in the synthesis of (S)-1,2,3,4-tetrahydro-1-methyl-isoquinoline, (S)-1,2,3,4-tetrahydro-1-ethylisoquinoline and (S)-1,2,3,4-tetrahydro-1-isopropylisoquinoline. Extensive molecular dynamics simulations indicate that the altered catalytic profile is due to increased hydrophobicity of the entrance tunnel acting in concert with the altered shape of the binding pocket.
- Li, Guangyue,Yao, Peiyuan,Gong, Rui,Li, Jinlong,Liu, Pi,Lonsdale, Richard,Wu, Qiaqing,Lin, Jianping,Zhu, Dunming,Reetz, Manfred T.
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p. 4093 - 4099
(2017/07/10)
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- Asymmetric Hydrogenation of Isoquinolines and Pyridines Using Hydrogen Halide Generated in Situ as Activator
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By employing halogenide trichloroisocyanuric acid as a traceless activation reagent, a general iridium-catalyzed asymmetric hydrogenation of isoquinolines and pyridines is developed with up to 99% ee. This method avoids tedious steps of installation and removal of the activating groups. The mechanism studies indicated that hydrogen halide generated in situ acted as an activator of isoquinolines and pyridines.
- Chen, Mu-Wang,Ji, Yue,Wang, Jie,Chen, Qing-An,Shi, Lei,Zhou, Yong-Gui
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supporting information
p. 4988 - 4991
(2017/09/23)
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- Identification of an Imine Reductase for Asymmetric Reduction of Bulky Dihydroisoquinolines
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A new imine reductase from Stackebrandtia nassauensis (SnIR) was identified, which displayed over 25- to 1400-fold greater catalytic efficiency for 1-methyl-3,4-dihydroisoquinoline (1-Me DHIQ) compared to other imine reductases reported. Subsequently, an efficient SnIR-catalyzed process was developed by simply optimizing the amount of cosolvent, and up to 15 g L-1 1-Me DHIQ was converted completely without a feeding strategy. Furthermore, the reaction proceeded well for a panel of dihydroisoquinolines, affording the corresponding tetrahydroisoquinolines (mostly in S-configuration) in good yields (up to 81%) and with moderate to excellent enantioselectivities (up to 99% ee).
- Li, Hao,Tian, Ping,Xu, Jian-He,Zheng, Gao-Wei
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supporting information
p. 3151 - 3154
(2017/06/23)
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- Enantioselective hydrogenation of cyclic imines catalysed by Noyori-Ikariya half-sandwich complexes and their analogues
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A method for enantioselective hydrogenation of cyclic imines with gaseous hydrogen has been developed. Easily accessible Noyori-Ikariya Ru(ii) and Rh(iii) complexes can be used directly without an inert atmosphere. Substrate activation has been achieved by trifluoroacetic acid. A new hydroxyl-functionalized complex is reported, showing high activity in transfer hydrogenation.
- Vilhanová,Václavík,?ot,Pechá?ek,Zápal,Pa?out,Maixner,Kuzma,Ka?er
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supporting information
p. 362 - 365
(2016/01/09)
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- Enhancing effects of salt formation on catalytic activity and enantioselectivity for asymmetric hydrogenation of isoquinolinium salts by dinuclear halide-bridged iridium complexes bearing chiral diphosphine ligands
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Asymmetric hydrogenation of 1- and 3-substituted and 1,3-disubstituted isoquinolinium chlorides using triply halide-bridged dinuclear iridium complexes [{Ir(H)(diphosphine)} 2(μ -Cl)3]Cl has been achieved by the strategy of HCl salt formation of isoquinolines to afford the corresponding chiral 1,2,3,4-tetrahydroisoquinolines (THIQs) in high yields and with excellent enantioselectivities after simple basic workup. The effects of salt formation have been investigated by time-course experiments, which revealed that the generation of isoquinolinium chlorides clearly prevented formation of the catalytically inactive dinuclear trihydride complex, which was readily generated in the catalytic reduction of salt-free isoquinoline substrates. Based on mechanistic investigations, including by 1H and 31P{1H} NMR studies and the isolation and characterization of several intermediates, the function of the chloride anion of the isoquinolinium chlorides has been elucidated, allowing us to propose a new outer-sphere mechanism involving coordination of the chloride anion of the substrates to an iridium dihydride species along with a hydrogen bond between the chloride ligand and the N-H proton of the substrate salt.
- Kita, Yusuke,Yamaji, Kenta,Higashida, Kosuke,Sathaiah, Kandula,Iimuro, Atuhiro,Mashima, Kazushi
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p. 1915 - 1927
(2015/01/30)
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- Concise Redox Deracemization of Secondary and Tertiary Amines with a Tetrahydroisoquinoline Core via a Nonenzymatic Process
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A concise deracemization of racemic secondary and tertiary amines with a tetrahydroisoquinoline core has been successfully realized by orchestrating a redox process consisted of N-bromosuccinimide oxidation and iridum-catalyzed asymmetric hydrogenation. This compatible redox combination enables one-pot, single-operation deracemization to generate chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 98% ee in 93% yield, offering a simple and scalable synthetic technique for chiral amines directly from racemic starting materials.
- Ji, Yue,Shi, Lei,Chen, Mu-Wang,Feng, Guang-Shou,Zhou, Yong-Gui
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supporting information
p. 10496 - 10499
(2015/09/28)
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- Robust cyclometallated Ir(iii) catalysts for the homogeneous hydrogenation of N-heterocycles under mild conditions
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Cyclometallated Cp*Ir(N∧C)Cl complexes derived from N-aryl ketimines are highly active catalysts for the reduction of N-heterocycles under ambient conditions and 1 atm H2 pressure. The reaction tolerates a broad range of other potentially reducible functionalities and does not require the use of specialised equipment, additives or purified solvent.
- Wu, Jianjun,Barnard, Jonathan H.,Zhang, Yi,Talwar, Dinesh,Robertson, Craig M.,Xiao, Jianliang
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supporting information
p. 7052 - 7054
(2013/09/02)
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- A highly efficient and enantioselective access to tetrahydroisoquinoline alkaloids: Asymmetric hydrogenation with an iridium catalyst
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Efficient and enantioselective: Using the iodine-bridged dimeric iridium complex [{Ir(H)[(S,S)-(f)-binaphane]}2(μ-I)3] +I- (1) a wide range of tetrahydroisoquinoline alkaloids, including the substructure of the pharmaceutical drug solifenacin, were obtained with excellent enantioselectivities and high turnover numbers (see scheme). Copyright
- Chang, Mingxin,Li, Wei,Zhang, Xumu
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p. 10679 - 10681
(2011/12/05)
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- Asymmetric hydrogenation of cyclic imines with an ionic Cp*Rh(III) catalyst
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When associated with a noncoordinating bulky counteranion, a cationic Cp*Rh(III)-diamine catalyst displayed excellent enantioselectivities in asymmetric hydrogenation of cyclic imines, affording bioactive tetrahydroisoquinolines and tetrahydro-β-carboline
- Li, Chaoqun,Xiao, Jianliang
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supporting information; experimental part
p. 13208 - 13209
(2009/02/06)
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- 4,5-Dihydrothiazoline - A new protecting and activating group for generation of α-aminocarbanions of secondary amines
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4,5-Dihydrothiazoline has been successfully used as a protecting and activating group for synthesis of various 1-substituted 1,2,3,4- tetrahydroisoquinolines via a lithiation-electrophillic substitution reaction sequence. Copyright Taylor & Francis Group, LLC.
- Singh, Kamal Nain,Singh, Paramjit,Kaur, Amarjit
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p. 3339 - 3343
(2007/10/03)
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- Prototype Pictet-Spengler reactions catalyzed by superacids. Involvement of dicationic superelectrophiles
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The Pictet-Spengler reaction, an acid-catalyzed intramolecular cyclization of intermediate imines of 2-arylethylamine to give 1,2,3,4- tetrahydroisoquinolines, has long been limited to active substrates which bear strongly electron-donating groups such as a methoxy or a hydroxy group on the cyclizing benzene ring. In this paper, we present superacid-catalyzed Pictet-Spengler reactions of imines of 2-phenethylamine, including the prototype Pictet-Spengler reaction of N-methylene-2-phenethylamine, to give the parent and 1-substituted 1,2,3,4-tetrahydroisoquinolines in moderate to high yields. The yields are dependent on the acidity of the media. A linear relationship was found between the rate of the cyclization and the acidity of the reaction media in kinetic studies of N-methylene-2-phenethylamine and related imines, strongly supporting the intervention of an additional protonative activation of the N-protonated imines, that is, the involvement of dicationic superelectrophiles, N,N-diprotonated imines (ammonium- carbenium dications). We further found that the prototype cyclization of the parent N-methylene-2-phenethylamine is also catalyzed by TFA to give 1,2,3,4- tetrahydroisoquinoline in good yield, although the cyclization is significantly slower than that catalyzed by superacids. The prototype Pictet- Spengler cyclization of N-methylene-2-phenethylamine can thus take place both through the monocation (the N-monoprotonated imine) and the dication (the N,N-diprotonated imine), the latter reaction being predominant in superacids.
- Yokoyama, Akihiro,Ohwada, Tomohiko,Shudo, Koichi
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p. 611 - 617
(2007/10/03)
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- Free-Radical Chemistry of Imines
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Aryl radicals bearing an aldimino functional group as part of an ortho substituent cyclized by addition to C and/or N of the imino group.When the choice was between 5-exo closure to C and 6-endo closure to N, the former predominated.However, 6-endo closure to C predominated over 5-exo cyclization to N in isomeric imines.Absolute values of cyclization rate constants were determined and an explanation for the unusual 6-endo preference is offered.Chiral induction in 6-endo cyclization to C of an aldimine from D-glyceraldehyde acetonide was observed, and its sense was determined.
- Tomaszewski, Miroslaw J.,Warkentin, John,Werstiuk, Nick H.
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p. 291 - 322
(2007/10/02)
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- New strategies for enantioselective syntheses of 1-alkyl- and 1,4-dialkyl-1,2,3,4-tetrahydroisoquinolines: Diastereoselective additions of nucleophiles and electrophiles to isoquinoline mediated by an easily resolved and recycled chiral transition metal auxiliary
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The chiral rhenium isoquinoline complex [(η5-C5H5)Re(NO)(PPh 3)(iso-NC9H7)]+ TfO- (1) and (CH3)3-SiCH2Li give the addition product (η5-C5H5)Re(NO)(PPh3)(N?CH = CHC(CH)4CCHCH2Si(CH3)3) (2) in 71% yield as a 94:6 SS,RR/SR,RS diastereomer mixture. Similar reactions with RMgX (R = (CH3)2CH, CH3CH2, C6H5CH2, CH3(CH2)2, CH3, CH3(CH2)3) give analogous adducts (3-8) as 89-82:11-18 diastereomer mixtures. Reactions of 2 and ROTf (R = H/D, (CH3)3SiCH2, CH3) give alkyl-1,4-dihydroisoquinoline complexes [(η5-C5H5)Re(NO)-(PPh3)(N = CHCHRC(CH)4CCHCH2Si(CH3)3)] + TfO- in 84-72% yields as 94:6 diastereomer mixtures. Related complexes are prepared from 3-5 and HOTf. These react with NaBH4/CH3OH to give alkyl-1,2,3,4-tetrahydroisoquinoline complexes, which are in turn treated with (CH3CH2)4N+ CN- to give (η5-C5H5)Re(NO)(PPh3)(CN) (17) and the title compounds. A reaction sequence starting with (+)-(S)-1 and (CH3)3SiCH2Li yields (+)-(SS)-NHCH2-CH(CH2Si(CH3) 3)C(CH)4CCHCH2Si(CH3)3 (84% overall, 88% ee) and (+)-(S)-17 (82%, >98% ee). Other optically active alkyl tetrahydroisoquinolines are similarly prepared. Complexes 17 and (+)-(S)-17 are converted to (η5-C5H5)Re(NO)(PPh3)(CH 3) (CH3OTf/NaBH4; 88-53%) and thence to 1 or (+)-(S)-1 (92-74%, >98% ee). A crystal structure and other data confirm the configurations assigned to the preceding compounds.
- Richter-Addo, George B.,Knight, D. Andrew,Dewey, Michael A.,Arif, Atta M.,Gladysz
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p. 11863 - 11873
(2007/10/02)
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- O,O'-Bistributyltin Benzopinacolate (1,1,2,2-Tetraphenylethane-1,2-bisolate) as Thermal Source of Tributylstannyl Radicals
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The previously unknown bistributyltin benzopinacolate was prepared by photolysis of benzophenone in the presence of bistributyltin and used for thermal formation of aryl radicals that undergo subsequent intramolecular addition to an imine bond in an ortho-substituent.
- Tomaszewski, Miroslaw J.,Warkentin, John
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p. 1407 - 1408
(2007/10/02)
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- Rate constants for aryl radical cyclization of aldimines: Synthesis of tetrahydroisoquinolines by fast 6-endo closures to carbon
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Aryl radicals cyclize to an imino functional group in a competition involving 6-endo closure to C and 5-exo closure to N. there is a large 6-endo preference forming tetrahydroisoquinolinyl radicals with k(6-endo) (80°C) > 108 s-1.
- Tomaszewski,Warkentin
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p. 2123 - 2126
(2007/10/02)
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- Phencyclidine-like Effects of Tetrahydroisoquinolines and Related Compounds
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A series of 1,2,3,4-tetrahydroisoquinolines, tetrahydrothienopyridines, and related compounds were evaluated for their ability to inhibit binding of -1--N-allylnormetazocine to phencyclidine (PCP) and ? receptors, respectively.A representative series of compounds was evaluated in behavioral assays to determine the ability of the compounds to induce PCP-like stereotyped behavior and ataxia.All of the compounds caused stereotyped behavior and ataxia, indicating their agonist actions at the PCP site.
- Gray, Nancy M.,Cheng, Brian K.,Mick, Stephen J.,Lair, Cecelia M.,Contreras, Patricia C.
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p. 1242 - 1248
(2007/10/02)
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- CARBON DOIXIDE: A REAGENT FOR THE PROTECTION OF NUCLEOPHILIC CENTERS AND THE SIMULTANEOUS ACTIVATION OF ELECTROPHILIC ATTACK. PART II. A NEW SYNTHETIC METHOD FOR THE 1-SUBSTITUTION OF 1,2,3,4-TETRAHYDROISOQUINOLINES.
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Tetrahydroisoquinoline was converted into several 1-substituted derivatives by using carbon dioxide both for N-protection and to give an intermediate carbanion stabilizing group. t-Butyllithium was used as a lithating agent at the alpha-carbon atom of the secondary amino group.The resulting 1-substituted 1,2,3,4-tetrahydroisoquinoline-2-carboxylic acids underwent smooth acid-catalysed decarboxylation under mild conditions.
- Katritzky, Alan R.,Akutagawa, Kunihiko
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p. 2571 - 2574
(2007/10/02)
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- ALKYLATION OF THE ISOQUINOLINE SKELETON IN THE 1-POSITION: LITHIATED 2-PIVALOYL- AND 2-BIS(DIMETHYLAMINO)-PHOSPHINOYL-1,2,3,4-TETRAHYDROISOQUINOLINES
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Nucleophilic reactivity in the 1-position of 1,2,3,4-tetrahydroisoquinoline is generated by lithiation of the N-pivaloyl- (16a) and N-phosphinoyl-derivatives (17a).The organolithium compounds (16b, 17b) thus obtained are highly nucleophilic and can be alkylated even with poor alkylating reagents such as secondary halides, neopentyl bromide and cyclopentanone.Hydrolysis of the phosphorylamide products with hydrochloric acid leads to 1-substituted tetrahydroisoquinolines in excellent yields (Table 2).
- Seebach, Dieter,Lohmann, Jean-Jacques,Syfrig, Max A.,Yoshifuji, Masaaki
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p. 1963 - 1974
(2007/10/02)
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- 2-Bis(dimethylamino)phosphinoyl-1-lithio-1,2,3,4-tetrahydro-isoquinoline. A Highly Nucleophilic d1-Reagent for the Preparation of 1-Substituted Tetrahydroisoquinolines
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The title compound 4 is generated from the phosphoric amide 5 in tetrahydrofuran with butyllithium.The lithium reagent 4 is stable at room temperature; its reactions with electrophiles furnish the products 6-22, 26,27, see Table 1 and the Scheme.A second alkylation is also possible, see 23-25.The cleavage to tetrahydroisoquinolines is accomplished in refluxing aqueous-methanolic hydrochloric acid, see Table 2.Phosphinoylation, lithiation, reaction with electrophiles and cleavage constitute an efficient sequence for 1-alkylation of the isoquinoline nucleus.
- Seebach, Dieter,Yoshifuji, Masaaki
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p. 643 - 647
(2007/10/02)
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- REDUCTION OF 1-ISOQUINOLYL-DIMETHYLMETHANOL AND 1-(1-ISOQUINOLYL)CYCLOHEXANOL
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Reduction of alcohols Ia and IIa with zinc and formic acid afforded 1-isopropylisoquinoline (Ib) and 1-cyclohexylisoquinoline (IIb), respectively, reduction with sodium in 1-butanol led to the 1,2,3,4-tetrahydroisoquinoline derivatives III, IV and Va and electrolytical reduction gave 1-isopropyl-1.2.3.4-tetrahydroisoquinoline (Vd) and the 1-cyclohexyl derivative Ve, respectively.
- Ferles, Miloslav,Sputova, Michaela,Tegza, Marian
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p. 262 - 265
(2007/10/02)
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