- Direct Synthesis of Indoles from Azoarenes and Ketones with Bis(neopentylglycolato)diboron Using 4,4′-Bipyridyl as an Organocatalyst
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Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (B2nep2) with a catalytic amount of 4,4′-bipyridyl under neutral reaction conditions, where 4,4′-bipyridyl acted as an organocatalyst to activate the B-B bond of B2nep2 and form N,N′-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of N,N′-diboryl-1,2-diarylhydrazines with ketones afforded N-vinyl-1,2-diarylhydrazines, which rearranged to the corresponding indoles via the Fischer indole mechanism. This organocatalytic system was applied to diverse alkyl cyclic ketones, dialkyl, and alkyl/aryl ketones, including heteroatoms. Methyl alkyl ketones gave the corresponding 2-methyl-3-substituted indoles in a regioselective manner. This protocol allowed us to expand the preparation of indoles having high compatibility with not only electron-donating and electron-withdrawing groups but also N- and O-protecting functional groups.
- Misal Castro, Luis C.,Sultan, Ibrahim,Nishi, Kohei,Tsurugi, Hayato,Mashima, Kazushi
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p. 3287 - 3299
(2021/03/01)
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- Iron-catalyzed reductive coupling of nitroarenes with olefins: Intermediate of iron-nitroso complex
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Using a single half-sandwich iron(II) compound, CpFe(1,2-Ph2PC6H4S)(NCMe) (Cp- = C5Me5-, 1) as a catalyst, reductive coupling of nitroarenes with olefins has been achieved by a well-defined iron(II)/(EtO)3SiH system. Through either inter- or intramolecular reductive coupling, various branched amines and indole derivatives have been directly synthesized in one-pot. Mechanistic studies showed that the catalysis is initiated by activation of nitroarenes by the iron(II) catalyst with silane, generating iron-nitrosoarene intermediate for the C-N bond coupling.
- Song, Heng,Yang, Zhuoyi,Tung, Chen-Ho,Wang, Wenguang
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p. 276 - 281
(2019/12/24)
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- Catalytic Asymmetric N-Alkylation of Indoles and Carbazoles through 1,6-Conjugate Addition of Aza-para-quinone Methides
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Catalytic asymmetric N-alkylation of indoles and carbazoles represents a family of important but underdeveloped reactions. Herein, we describe a new organocatalytic strategy in which in situ generated aza-para-quinone methides are employed as the alkylating reagent. With the proper choice of a chiral phosphoric acid and an N-protective group, the intermolecular C?N bond formation with various indole and carbazole nucleophiles proceeded efficiently under mild conditions with excellent enantioselectivity and functional-group compatibility. Control experiments and kinetic studies provided important insight into the reaction mechanism.
- Chen, Min,Sun, Jianwei
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supporting information
p. 4583 - 4587
(2017/04/11)
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- Aqueous Titanium Trichloride Promoted Reductive Cyclization of o-Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine
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Treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles through a formal reductive C(sp2)-H amination process. A range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxy, and amino groups were tolerated. From β,β-disubstituted o-nitrostyrenes, 2,3-disubstituted indoles were formed by a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterize the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine. Mild and efficient treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles through a formal reductive C(sp2)-Hamination process. A concise synthesis of a marketed drug (rizatriptan) and a formal total synthesis of aspidospermidine featuring this novel N-heterocyclization process are reported.
- Tong, Shuo,Xu, Zhengren,Mamboury, Mathias,Wang, Qian,Zhu, Jieping
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p. 11809 - 11812
(2015/10/05)
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- A Convenient Modification of the Fischer Indole Synthesis with a Solid Acid
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(Chemical Equation Presented). A new one-pot version of the titled reaction involves heating a mixture of a carbonyl compound, a phenylhydrazine, and the cation exchange resin Amberlite IR 120 in refluxing ethanol. A variety of enolizable aldehydes, and ketones and several substituted phenylhydrazines could thus be converted to the corresponding indoles in excellent yields (70-88%). Reaction times were typically 6-10 h, with the resin being then filtered off and the product isolated after minimal workup.
- Chandrasekhar, Sosale,Mukherjee, Somnath
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supporting information
p. 1018 - 1022
(2015/03/30)
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- Fischer indole synthesis in low melting mixtures
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Functionalized indoles are synthezised under mild conditions in a tartaric acid-dimethylurea melt. The melt serves as the solvent and as the catalyst. Under these reaction conditions, sensitive functional groups such as N-Boc, N-Cbz, or azides are stable, and indolenines are obtained regioselectively in excellent yields. The practical use of the method is demonstrated in the synthesis of the hormone melatonin.
- Gore, Sangram,Baskaran, Sundarababu,K?nig, Burkhard
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supporting information
p. 4568 - 4571
(2012/10/30)
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- One-pot approach to installing eight-membered rings onto indoles
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Ring fusion: The Pd0-catalyzed reaction of 2-allyl-3-iodo-1- tosyl-1H-indoles and propargylic bromides affords dihydrocycloocta[b]indoles (see scheme; M.S.=molecular sieves, TFP=tris(2-furyl)phosphine, Ts=4-toluenemethanesulfonyl), and proceeds
- Zhu, Can,Zhang, Xue,Lian, Xiongdong,Ma, Shengming
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p. 7817 - 7820
(2012/09/08)
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- Enantioselective N-H functionalization of indoles with α,β- unsaturated γ-lactams catalyzed by chiral Bronsted acids
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Nitrogen revives: Cyclic N-acyliminium ions were generated from α,β-unsaturated γ-lactams (1) and underwent intermolecular addition by indole nucleophiles (2) under the catalysis of a chiral Bronsted acid (3). A variety of N-functionalized indole derivatives containing a pyrrolidinone moiety (4) were assembled with high enantioselectivity. Bn=benzyl. Copyright
- Xie, Yinjun,Zhao, Yingwei,Qian, Bo,Yang, Lei,Xia, Chungu,Huang, Hanmin
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supporting information; experimental part
p. 5682 - 5686
(2011/08/03)
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- Rhodium-catalyzed synthesis of 2,3-disubstituted indoles from β,β-Disubstituted stryryl azides
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Rings la carte: Rhodium carboxylate complexes catalyze selective cascade reactions to produce a range 2,3-disubstituted indoles from β,β- disubstituted stryryl azides. The selective migration of aryl groups appears to originate from a putative phenonium ion reactive intermediate (see scheme).
- Sun, Ke,Liu, Sheng,Bec, Patryk M.,Driver, Tom G.
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p. 1702 - 1706
(2011/04/24)
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- Fischer indole synthesis with organozinc reagents
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Updated classic: Primary and secondary alkylzinc reagents add to various aryldiazonium salts leading regioselectively to polyfunctional indoles by means of a [3,3]-sigmatropic shift and subsequent aromatization. This organometallic variation of the Fischer indole synthesis tolerates a wide range of functional groups and displays absolute regioselectivity. Copyright
- Haag, Benjamin A.,Zhang, Zhi-Guang,Li, Jin-Shan,Knochel, Paul
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supporting information; experimental part
p. 9513 - 9516
(2011/02/24)
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- A study on the synthesis of structural analogs of bis-indole alkaloid caulerpin: a step-by-step synthesis of a cyclic indole-tetramer
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The syntheses of structural isomers of bis-indole alkaloid caulerpin are investigated. Construction of the caulerpin skeleton is based on the Fisher indolization reaction of the appropriate cyclooctane-diones or cyclooctanone. In addition, a step-by-step
- Talaz, Oktay,Saracoglu, Nurullah
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experimental part
p. 1902 - 1910
(2010/04/06)
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- 2,3-Disubstituted indoles from olefins and hydrazines via tandem hydroformylation-Fischer indole synthesis and skeletal rearrangement
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The tandem hydroformylation-Fischer indolisation protocol is used in the synthesis of 2,3-disubstituted indoles. After hydroformylation of selected olefins to form α-branched aldehydes in a one-pot procedure these are condensed with phenylhydrazine to give hydrazones. Upon acid-promoted [3,3]-sigmatropic rearrangement indolenine intermediates with quaternary centres in the 3-position are formed, which, after selective Wagner-Meerwein-type rearrangement of one of the substituents from the 3- to the 2-position, lead to 2,3-disubstituted indoles. Several olefins, bearing substituents with various functional groups, as well as cyclic olefinic systems are investigated. The Royal Society of Chemistry 2006.
- Linnepe, Petra,Schmidt, Axel M.,Eilbracht, Peter
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p. 302 - 313
(2007/10/03)
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- A flexible, palladium-catalyzed indole and azaindole synthesis by direct annulation of chloroanilines and chloroaminopyridines with ketones
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The "ringmaster" [Pd(tBu3P)2] serves as the catalyst in the direct synthesis of indoles by annulation of ortho-chloroanilines with ketones (see picture). This versatile method can be used to synthesize a variety of functionalized indoles and azaindoles. DMA = dimethylacetarnide.
- Nazare, Marc,Schneider, Claudia,Lindenschmidt, Andreas,Will, David William
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p. 4526 - 4528
(2007/10/03)
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- The first method for protection-deprotection of the indole 2,3-π bond
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(Matrix presented) The scope and generality of a new reaction of indoles with MTAD is discussed. In most cases the ene-type reaction proceeds within seconds or minutes at 0°C to provide the urazole adducts in high yield. This reaction provides the first method for protecting the indole 2,3-double bond since the urazole adducts can be reconverted to the starting indole (retro-ene) simply by heating.
- Baran, Phil S.,Guerrero, Carlos A.,Corey
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p. 1999 - 2001
(2007/10/03)
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- Indole as a tool in synthesis. Algorithmic construction of a family of compounds with all ring sizes ranging from 10 to 16
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An iterating two-step ring extension process including indolisation-oxidation by ozone applied to an eight membered cyclanone allowed the preparation of seven compounds with ring sizes ranging from 10 to 16. The structure of all derivatives were assigned
- Sigaut, Fran?oise,Didierdefresse, Betty,Lévy, Jean
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p. 9641 - 9646
(2007/10/03)
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- Rate acceleration of Fischer-indole cyclization by microwave irradiation
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Rate acceleration in Fischer-indole synthesis has been observed in a microwave oven and the reaction goes to completion within 28 sec in good yield in one-pot.
- Sridar, V.
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- Rate acceleration of Fischer-indole cyclization by microwave irradiation
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Rate acceleration in Fischer-indole synthesis has been observed in a microwave oven and the reaction goes to completion within 28 sec furnishing good yield in one-pot.
- Sridar
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p. 737 - 738
(2007/10/03)
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- Addition Reactions ofHeterocyclic Compounds. Part 79. Reaction of Dimethyl Acetylenedicarboxylate with some Cycloheptindoles and Cyclo-octindoles
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The reactions of dimethyl acetylenedicarboxylate with N-methyl- and pyridoindoles which have either a penta- or hexa-methylene chain linking positions 2 and 3, have been found to give rise to a very similar array of products.Nineteen new adducts were isolated and their structures established by 1H and 13C n.m.r. spectral comparisons, and in some cases also by chemical transformations.The structures include five new classes of adducts not previously encountered: two types of (1+1 DMAD) adducts, one of which is a cyclobutene and the other a 3-maleate; two types of (1+2 DMAD) adducts, one with two side chains, and the other having a ring-expanded nine- or ten membered ring and one side chain; and a (1+2 DMAD - CH4O) adduct, all examples of which exhibit fragmentation on heating to give a carbazole and a spiro-cycloalkyl-keten dimer.The isolation of the two (1+1 DMAD) adducts is important as both adduct types have been postulated as intermediates in the formation of more complex adducts.
- Letcher, Roy M.,Choi, Michael C.K.,Acheson, R.Morrin
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p. 515 - 526
(2007/10/02)
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- Rearrangement of the N-(3-Oxo-1-butenyl) Derivatives of Hexahydrocycloheptindole and Hexahydrocyclooctindole
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The N-(3-oxo-1-butenyl) derivatives 1,2 of hexahydrocyclohept- and -octindole are rearranged by methanolic hydrochloric acid to give 3a and 4a.Additionally, 3b, 4b, and 5 result. 3a and 4a are transformed into typical derivatives (6,7) and stereoselect
- Teuber, Hans-Joachim,Gholami, Abbas,Reinehr, Ulrich
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p. 152 - 164
(2007/10/02)
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