Orthogonal Synthesis of Indolines and Isoquinolines via Aryne Annulation

Gilmore, Christopher D.; Allan, Kevin M.; Stoltz, Brian M.

doi:10.1021/ja0780582

Cited by 224 publications

(88 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.

View full text Add to dashboard Cite

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...

show abstract

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.

View full text Add to dashboard Cite

show abstract

“…We began our research by an amidation of 4-aminophenol (1) with homoveratroyl chloride (2). 7 The product, amide (3), was then converted to amine by a reduction with lithium aluminium hydride in THF (83%). By treatment of amine (4) with ethyl 3-chloro-3-oxopropanoate in dichloromethane in the presence of pyridine, amide (5) was obtained in 71% yield over three steps.…”

Section: Resultsmentioning

confidence: 99%

Oxidative dearomatic approach towards the synthesis of erythrina skeleton: a formal synthesis of demethoxyerythratidinone

Pan

Liang

Yang

et al. 2011

Nat. Prod. Bioprospect.

View full text Add to dashboard Cite

show abstract

“…In addition, treatment of N-acyl enamines with arynes produces isoquinolines via the formal [4 þ 2] cycloaddition, 202,203 and this reaction has been employed in total synthesis of papaverine (70) 202 The formal [3 þ 2] cycloaddition can be applied to one-step synthesis of benzofurans (from iodonium ylides) 209 and indoles (from azidoacrylates). 210 Although oxygen (76) and nitrogen (77) anions have been reported to be a nucleophilic site as described in Scheme 64, the regiochemical outcomes of 3-substituted arynes cannot be rationally explained by the pathways, and thus other mechanisms may be operative in these cases.…”

Section: N-cycloadditionmentioning

confidence: 99%

4.09 Nucleophilic Coupling with Arynes

Yoshida

2014

Comprehensive Organic Synthesis II

View full text Add to dashboard Cite

Orthogonal Synthesis of Indolines and Isoquinolines via Aryne Annulation

Cited by 224 publications

References 27 publications

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

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

Oxidative dearomatic approach towards the synthesis of erythrina skeleton: a formal synthesis of demethoxyerythratidinone

4.09 Nucleophilic Coupling with Arynes

Contact Info

Product

Resources

About