- The Synthesis of N-Heterocycles using ortho-Metallated Primary Benzylamine Complexes of Palladium(II) and Platinum(II)
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The synthesis of the isoindolinimines (5) by the insertion of isocyanides into the metal-carbon bond of the ortho-palladated primary benzylamine complex (1a) is described; the novel oxidative addition and subsequent reductive elimination of the ortho-metallated primary benzylamine-platinum complex (6) yields 3-oxo-1,2,3,4-tetrahydroisoquinoline (8).
- O'Sullivan, Richard D.,Parkins, Adrian W.
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- Utilization of Borane-Catalyzed Hydrosilylation as a Dearomatizing Tool: Six-Membered Cyclic Amidine Synthesis from Isoquinolines and Pyridines
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In this study, a convenient strategy to synthesize six-membered?? cyclic amidines from isoquinolines and pyridines has been developed. Borane-catalyzed hydrosilylation of each N-heteroarene was utilized as a dearomatizing tool. Substrate scope is broad with respect to both isoquinolines and pyridines, with various reaction pathways depending on the substitution pattern of the N-heteroarenes. The reaction mechanism and reactivity of each class of N-heteroarenes has been discussed. The resulting six-membered (Z)-sulfonyl amidine products are rarely reported and are mostly unprecedented. The scalability of this method and versatility of the cyclic amidine products are also presented.
- Cao, Vinh Do,Jo, Dong Geun,Kim, Huiae,Kim, Changeun,Yun, Seula,Joung, Seewon
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- Synthetic approaches to N- and 4-substituted 1,4-dihydro-3(2H)-isoquinolinone derivatives
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Reaction of methyl-2-(2-formylphenyl)acetate with primary amines in a reductive amination/cyclisation process resulted in N-substituted 1,4-dihydro-3(2H)-isoquinolinones. With H2NCH2R sodium borohyride is a suitable reductant (11 examples), but H2NCHR1R2 required a transfer hydrogenation using ammonium formate catalysed by palladium on carbon (9 examples). 4-Substituted-1,4-dihydro-3(2H)-isoquinolinones were synthesised by deprotonation (n-butyllithium) and addition of R3CH2Br (12 examples with R3 = alkyl, Ar, CH[dbnd]CH2, C[tbnd]CH). Modest diastereoselectivity was achieved with 1,4-dihydro-3(2H)-isoquinolinones derived from H2NCHMeR2 [R2 = (η5-C5H4)Co(η4-C4Ph4) - max. dr = 1.9 : 1], but use of H2NCHMeFc (Fc = ferrocenyl) provided a new method of 1,4-dihydro-3(2H)-isoquinolinone N-deprotection with formic acid.
- O’ Sullivan, Michael J.,Hatley, Richard J.D.,Wellaway, Christopher R.,Bew, Sean P.,Richards, Christopher J.
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- Rapid and Mild Lactamization Using Highly Electrophilic Triphosgene in a Microflow Reactor
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Lactams are cyclic amides that are indispensable as drugs and as drug candidates. Conventional lactamization includes acid-mediated and coupling-agent-mediated approaches that suffer from narrow substrate scope, much waste, and/or high cost. Inexpensive, less-wasteful approaches mediated by highly electrophilic reagents are attractive, but there is an imminent risk of side reactions. Herein, a methods using highly electrophilic triphosgene in a microflow reactor that accomplishes rapid (0.5–10 s), mild, inexpensive, and less-wasteful lactamization are described. Methods A and B, which use N-methylmorpholine and N-methylimidazole, respectively, were developed. Various lactams and a cyclic peptide containing acid- and/or heat-labile functional groups were synthesized in good to high yields without the need for tedious purification. Undesired reactions were successfully suppressed, and the risk of handling triphosgene was minimized by the use of microflow technology.
- Fuse, Shinichiro,Komuro, Keiji,Otake, Yuma,Masui, Hisashi,Nakamura, Hiroyuki
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supporting information
p. 7525 - 7532
(2021/03/17)
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- Desymmetrization of Prochiral Cyclopentenes Enabled by Enantioselective Palladium-Catalyzed Oxidative Heck Reaction
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In the presence of a catalytic amount of Pd(TFA)2 and a chiral Pyox ligand under oxygen atmosphere, oxidative Heck reaction between arylboronic acids and 4-substituted or 4,4-disubstituted cyclopent-1-enes afforded the chiral arylated products with concurrent creation of two stereocenters in good yields with excellent diastereo- and enantioselectivities.
- Chen, Guihua,Cao, Jian,Wang, Qian,Zhu, Jieping
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supporting information
p. 322 - 325
(2020/01/02)
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- An Efficient Two-Step Preparation of α-, β-, γ- or δ-Amino Acids from 2-Pyrazinones, 2-Hydroxypyrimidines or 2-Pyridones Respectively
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A practical and efficient two-step procedure is reported for the preparation of a variety of α-, β-, γ- and δ-amino acids from 2-pyridone, 2-pyrazinone or 2-hydroxypyrimidine and derivatives. The procedure is amenable to scale-up and in most cases no chromatographic purification of the product is required. This approach is useful, especially in the synthesis of amino acids or deuterated amino acids that are not obtained by other methods.
- Zacharie, Boulos,Abbott, Shaun D.,Baigent, Christopher B.,Doyle, Christopher,Yalagala, Ravi Shekar
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p. 6486 - 6493
(2018/11/23)
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- Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors
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A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Bronsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids.
- Shi, Shi-Liang,Wei, Xiao-Feng,Shimizu, Yohei,Kanai, Motomu
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supporting information
p. 17019 - 17022,4
(2012/12/12)
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- Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors
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A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Bronsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids.
- Shi, Shi-Liang,Wei, Xiao-Feng,Shimizu, Yohei,Kanai, Motomu
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supporting information
p. 17019 - 17022
(2013/01/15)
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- Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase
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The design, synthesis, and evaluation of novel γ-aminobutyric acid aminotransferase (GABA-AT) inhibitors and inactivators can lead to the discovery of new GABA-related therapeutics. To this end, a series of aromatic amino acid compounds was synthesized to aid in the design of new inhibitors and inactivators of GABA-AT. All compounds were tested as competitive inhibitors of GABA-AT. The amino acids with benzylic amines were also tested as substrates for GABA-AT. It was found that these compounds were all poor competitive inhibitors of GABA-AT, but some were substrates of the enzyme, suggesting their utility as scaffolds for potential GABA-AT mechanism-based inactivators. Computer modeling was used to rationalize the substrate activity of the various compounds.
- Clift, Michael D.,Silverman, Richard B.
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p. 3122 - 3125
(2008/12/22)
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- Superacidic activation of 1- and 3-isoquinolinols and their electrophilic reactions
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Isomeric 1- and 3-isoquinolinols (11 and 12) when activated in CF3SO3H-SbF5 acid system undergo selective ionic hydrogenation with cyclohexane to give 5,6,7,8-tetrahydro-1(2H)- and 5,6,7,8-tetrahydro-3(2H)-isoquinolinones (22 and 27). Under the influence of aluminum chloride similar products were also obtained along with 3,4-dihydro-1(2H)- and 1,4-dihydro-3(2H)-isoquinolinones (23 and 28), respectively. Compounds 11 and 12 also condense with benzene in the presence of aluminum halides, under mild conditions, to give 3,4-dihydro-3-phenyl-1(2H)- and 1,4-dihydro-1-phenyl-3(2H)-isoquinolinones (24 and 29), respectively. Prolonged reaction time or catalysis under strongly acidic HBr-AlBr3 provides an alternative reaction pathway to yield 5,6-dihydro-6,8-diphenyl-1(2H)- and 5,6,7,8-tetrahydro-6,8-diphenyl-3(2H)-isoquinolinones (25 and 30), respectively. Products 24 and 29 were also found to revert back to 11 and 12 in the presence of aluminum halides in o-dichlorobenzene. The mechanism of these intriguing reactions, which involves superelectrophilic dicationic intermediates, is discussed.
- Koltunov, Konstantin Yu.,Prakash, G. K. Surya,Rasul, Golam,Olah, George A.
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p. 8943 - 8951
(2007/10/03)
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- (2-Azidomethyl)phenylacetyl as a new, reductively cleavable protecting group for hydroxyl groups in carbohydrate synthesis
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The (2-azidomethyl)phenylacetyl group (AMPA) is described as a new protecting group for carbohydrates. AMPA was introduced to carbohydrate hydroxyl groups in the presence of DCC, while its removal was conveniently achieved via Lindlar catalyst-catalyzed hydrogenation that had no influence on other protecting groups including benzyl, acyl, acetal and ketal.
- Xu, Jinghua,Guo, Zhongwu
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- Preparation of amides from acids and resin bound azides: Suppression of intramolecular lactam formation
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A new method for the formation of amides on solid phase has been developed. The procedure involves the reaction between activated acids in solution and resin bound iminophosphoranes generated from the corresponding azides and tributylphosphine. The method is particularly attractive when starting from δ azido acids since amides can form without internal cyclization to the lactam.
- Tang, Zhilian,Pelletier, Jeffrey C.
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p. 4773 - 4776
(2007/10/03)
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- PREPARATION OF TETRAHYDROISOQUINOLINES FROM N-(TERT-BUTOXYCARBONYL)-2-METHYLBENZYLAMINES
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Dilithiation of N-(tert-butoxycarbonyl)-2-methylbenzylamine (1a) followed by treatment with N,N-dimethylformamide affords 2-(tert-butoxycarbonyl)-3-hydroxy-tetrahydroisoquinoline (3a).Dehydration and reduction of 3a afford BOC-tetrahydroisoquinoline (5a).The methodology is also applicable to synthesis of chloro and fluoro substituted tetrahydroisoquinolines (5b,c), 3 and 4-substituted derivatives (8,10), and the hexahydro-2H-benzoquinolizine ring system (13).
- Clark, Robin D.,Jahangir
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p. 1699 - 1703
(2007/10/02)
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- STUDIES ON THE SYNTHESIS OF BENZOLACTAM RINGS. II SYNTHESIS OF 1,4-DIHYDRO-3(2H)-ISOQUINOLINONE DERIVATIVES
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A new synthesis of 1,4-dihydro-3(2H)-isoquinolinones by the amidomethylation with acrylacetamide or acrylacetonitrile and paraformaldehyde in some acid-catalysts is described.
- Kamochi, Yasuko,Watanabe, Yasuo
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p. 2385 - 2391
(2007/10/02)
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- Photoinduced Cyclizations of Mono- and Dianions of N-Acyl-o-chloroanilines and N-Acyl-o-chlorobenzylamines as General Methods for the Synthesis of Oxindoles and 1,4-Dihydro-3(2H)-isoquinolinones
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Formation of the monoanions of a series of N-acyl-N-alkyl-o-chloroanilines by means of LDA in THF followed by irradiation with near-UV light affords 1,3-dialkyloxindoles in good yields.Similar photoinduced cyclizations of dianions derived from N-acyl-o-chloroanilines leads to 3-alkyloxindoles.Photocyclizations of mono- and dianion prepared from α,β-unsaturated o-haloanilides proceed to form 3-alkylideneoxindoles.Carbanions derived from N-acyl-o-chlorobenzylamines also undergo photoassisted ring closure to afford 1,4-dihydro-3(2H)-isoquinolinones.The influence of near-UV light and the effect of inhibitors implicate a radical-chain mechanism as the major reaction pathway in this convenient new method for oxindole and isoquinolinone synthesis.
- Goehring, R. Richard,Sachdeva, Yesh P.,Pisipati, Jyothi S.,Sleevi, Mark C.,Wolfe, James F.
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p. 435 - 443
(2007/10/02)
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- (HYDROXYIMINO)-3(2H)-ISOQUINOLINONES, III. DETERNINATION OF THE STRUCTURE OF PHENYL-SUBSTITUTED 1,4-DIHYDRO-3(2H)-ISOQUINOLINONE OBTAINED IN THE CYCLIZATION REACTION OF 3-BIPHENYL-N-METHYLACETAMIDE BY 1H-NMR SPECTROSCOPIC STUDY OF THE 4-(HYDROXYIMINO)-DERIVATIVE
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By means of 1H NMR spectroscopic investigations it has been established that the compound prepared from 3-methylbenzyl cyanide and benzaldehyde and described earlier as 8-methyl-1-phenyl-1,4-dihydro-3(2H)-isoquinolinone is actually the 6-methyl derivative.The isoquinoline derivative carrying the substituent at position 6 was also obtained when the cyclization reaction took place between 3-biphenyl-N-methyl-acetamide and formaldehyde.
- Tikk, I.,Toth, G.,Deak, Gy.
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p. 355 - 360
(2007/10/02)
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- A NEW SYNTHESIS OF 1,4-DIHYDRO-3(2H)-ISOQUINOLINONES BY THE CYCLIZATION OF N-HYDROXYMETHYLARYLACETAMIDES
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A new and facile synthesis of 1,4-dihydro-3(2H)-isoquinolinones by the intramolecular amidomethylation with pyrophosphoric acid is described.
- Watanabe, Yasuo,Kamochi, Yasoko,Miyazaki, Tokumitsu
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p. 609 - 611
(2007/10/02)
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- Basically substituted 1,4-dihydro-2H-isoquinoline derivatives and process for preparing them
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1,4-Dihydro-2H-isoquinoline derivatives of the general formula I SPC1 in which R1 represents hydrogen or straight chain or branched alkyl of 1 to 6 carbon atoms, R2 represents low molecular dialkylaminoalkyl, in which both alkyl groups of the dialkylamino group together with the nitrogen atom may also form a 5-, 6- or 7-membered saturated ring in which one carbon atom may be substituted by an oxygen atom, a sulfur atom or another nitrogen atom which may be substituted by hydrogen, C1 -C4 -alkyl or phenyl, or R1 and R2 together may form a 5- or 6-membered saturated ring containing 1 nitrogen atom, R3 represents phenyl which may be mono- or di-substituted by halogen, nitro, amino or sulfamoyl, or acylamino or alkyl each containing 1 to 4 carbon atoms, or pyridyl R4 and R5, which may identical or different, represent hydrogen or alkoxy of 1 to 4 carbon atoms, and X represent oxygen or sulfur, Their physiologically tolerated salts, process for preparing them. The compounds are active on the coronary circulation and are distinguished in particular by an anti-arrhythmic action and may, therefore, be used in the treatment of disorders of the heart rhythm.
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