One‐Pot Synthesis of Isoquinolinium Salts by Rhodium‐Catalyzed CH Bond Activation: Application to the Total Synthesis of Oxychelerythrine

Jayakumar, Jayachandran; Parthasarathy, Kanniyappan; Cheng, Chien‐Hong

doi:10.1002/ange.201105755

Cited by 96 publications

(18 citation statements)

References 47 publications

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“…In particular, the rhodium-catalyzed coupling reactions of (hetero)aromatic substrates with alkynes have offered a unique platform for atom-economical and straightforward annulation [6][7][8][9][10][11][12][13][14] . Recently, the research groups of Cheng and co-workers 8 , Glorius and co-workers 9 and Jeganmohan and co-workers 10 have disclosed the synthesis of indenols through the rhodium-or rutheniumcatalyzed carbonyl-assisted aromatic C-H activation/cyclization of aryl ketones with internal alkynes via a proposed fivemembered metallocyclic intermediate (Fig.…”

mentioning

confidence: 99%

Unexpected regioselective carbon–hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles

Liu

Song

et al. 2014

Nat Commun

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Rhodium-catalyzed carbon-hydrogen bond activation has attracted great interest in the construction of carbon-carbon and carbon-heteroatom bonds. In recent years, transition metal-mediated oxygen transposition through a 'dehydration-rehydration' process has been considered as a promising strategy towards oxygen-functionalized compounds. Here we describe an unexpected rhodium-catalyzed regioselective carbon-hydrogen bond activation/ cyclization of easily available indolyl aldehydes or ketones with alkynes to afford benzo-fused oxindoles, involving the sequential carbonyl-assisted carbon-hydrogen activation of the indole ring at the 4-position, [4 þ 2] cyclization, aromatization via dehydration, nucleophilic addition of water to iminium and oxidation. Isotopic labelling experiments disclose the occurrence of apparent oxygen transposition via dehydration-rehydration from the indolyl-3-carbonyl group to the 2-position of pyrrole to forge a new carbonyl bond. The tandem reaction has been used as the key step for the concise synthesis of priolines, a type of alkaloid isolated from the roots of Salvia prionitis.

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confidence: 99%

Unexpected regioselective carbon–hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles

Liu

Song

et al. 2014

Nat Commun

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“…It is also imperative to develop routes to highly-substituted isoquinolines to fully explore this chemical space, for example, for potential pharmaceutical targets. While recent synthetic efforts have greatly expanded the diversity of isoquinoline motifs available (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), new routes to isoquinolines are still highly desirable, particularly ones with the ability to directly access the isoquinoline moiety in a range of oxidation levels and which do not require highly-specialized starting materials.…”

mentioning

confidence: 99%

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

Donohoe

Pilgrim

Jones

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The utilization of sequential palladium-catalyzed α-arylation and cyclization reactions provides a general approach to an array of isoquinolines and their corresponding N-oxides. This methodology allows the convergent combination of readily available precursors in a regioselective manner and in excellent overall yields. This powerful route to polysubstituted isoquinolines, which is not limited to electron rich moieties, also allows rapid access to analogues of biologically active compounds.T he isoquinoline motif and its derivatives form the cores of numerous natural products (1, 2), are the central components of a number of pharmaceutical agents (3-5), and can provide the scaffold for chiral ligands (6, 7) and valuable organic materials (8). However, traditional isoquinoline syntheses such as the Bischler-Napieralski (9, 10), 12), and Pomeranz-Fritsch reactions (13-15) all centre around the lynchpin of electrophilic aromatic substitution and are thus often limited to electron-rich carbocycles (Scheme 1A). It is also imperative to develop routes to highly-substituted isoquinolines to fully explore this chemical space, for example, for potential pharmaceutical targets. While recent synthetic efforts have greatly expanded the diversity of isoquinoline motifs available (16-29), new routes to isoquinolines are still highly desirable, particularly ones with the ability to directly access the isoquinoline moiety in a range of oxidation levels and which do not require highly-specialized starting materials.Originally reported by Palucki and Buchwald (30), Hamann and Hartwig (31), and Miura and coworkers (32), the palladiumcatalyzed α-arylation of enolates has recently emerged as a powerful new reaction in synthetic organic chemistry (33-35). Key to its success has been the design of appropriate ligands for palladium that have precisely engineered steric and electronic properties to enable the various steps in the catalytic cycle to proceed with maximum efficiency (36-39). The reaction's utility has also been greatly enhanced by the development of robust preformed palladium catalysts. Properties such as air stability and very high reactivity in a range of systems have greatly expanded the potential uses of these catalysts (40-43). However, the α-arylation reaction has seen limited use in the de novo construction of aromatic compounds (44-51) and is still greatly underused in this regard, especially because the bond forming abilities provided by this powerful reaction can greatly simplify the design of routes to heavily-substituted aromatic compounds. Hence, we decided to explore the scope of this new catalytic method in the synthesis of important heteroaromatic ring systems, beginning our investigations with the isoquinoline nucleus. ResultsIn our disconnection approach we envisaged that key pseudo-1,5-dicarbonyl intermediates 3 could be accessed via the palladiumcatalyzed α-arylation of ketones 1 with aryl halides 2 possessing a protected aldehyde or ketone in the ortho-position (52). Subsequent treatment of these inter...

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“…[74][75][76][77][78][79] Because of these relevant properties, many synthetic approaches towards the creation of an isoquinoline or THIQ core have been described so far. [80][81][82][83][84][85][86][87] The well-known procedures are the Pictet-Spengler, Bischer-Napieralski, and Pomeranz-Fritsch-Bobbit cyclizations, which are widely-applied synthetic methodologies to create a number of important isoquinoline alkaloids. [80] Fluorine-containing tetrahydroisoquinoline or isoquinoline derivatives constitute an important area of fluorinated molecules either as pharmaceuticals or agrochemicals.…”

Section: Synthesis Of Fluorine-containing 1234-tetrahydro-isoquinomentioning

confidence: 99%

Stereocontrolled Synthesis of Functionalized Azaheterocycles from Carbocycles through Oxidative Ring Opening/Reductive Ring Closing Protocols

Kiss

Ouchakour

Ábrahámi

et al. 2019

The Chemical Record

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Fluorine‐containing organic scaffolds are of significant interest in medicinal chemistry. The incorporation of fluorine into biomolecules can lead to remarkable changes in their physical, chemical, and biological properties. There are already many drugs on the market, which contain at least one fluorine atom. Saturated functionalized azaheterocycles as bioactive substances have gained increasing attention in pharmaceutical chemistry. Due to the high biorelevance of organofluorine molecules and the importance of N‐heterocyclic compounds, selective stereocontrolled procedures to the access of new fluorine‐containing saturated N‐heterocycles are considered to be a hot research topic. This account summarizes the synthesis of functionalized and fluorine‐containing saturated azaheterocycles starting from functionalized cycloalkenes and based on oxidative ring cleavage of diol intermediates followed by ring expansion with reductive amination.

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One‐Pot Synthesis of Isoquinolinium Salts by Rhodium‐Catalyzed CH Bond Activation: Application to the Total Synthesis of Oxychelerythrine

Cited by 96 publications

References 47 publications

Unexpected regioselective carbon–hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles

Unexpected regioselective carbon–hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

Stereocontrolled Synthesis of Functionalized Azaheterocycles from Carbocycles through Oxidative Ring Opening/Reductive Ring Closing Protocols

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