Isoquinoline Synthesis via Rhodium-Catalyzed Oxidative Cross-Coupling/Cyclization of Aryl Aldimines and Alkynes

Guimond, Nicolas; Fagnou, Keith

doi:10.1021/ja904380q

Cited by 445 publications

(132 citation statements)

References 35 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…However, the oxidative alkenylation of heteroarenes is named the Moritani-Fujiwara reaction. [8,9] In this regard, different palladium [10][11][12][13] and rhodium catalysts [14][15][16] have already been used to promote the oxidative alkenylation of heteroarenes with a variety of directing groups, namely, imines, [17,18] amines, [19] and carboxylates. [20,21] Rutheniumcatalyst-directed arylation of unactivated C-H bonds with phenols was reported by Ackermann.…”

Section: Introductionmentioning

confidence: 99%

Solvent‐Free Ruthenium(II)‐Catalyzed C–H Activation: Synthesis of Alkenylarylpyrazole Derivatives

Shome

Singh

2015

Eur J Org Chem

View full text Add to dashboard Cite

Keywords: C-H activation / Ruthenium / Alkenylation / Nitrogen heterocyclesThe Ru II carboxylate complex Ru(MesCO 2 ) 2 (p-cymene) (Mes = mesityl) was found to be an efficient catalyst for the direct dehydrogenative alkenylation of N-arylpyrazoles by using styrenes and acrylates in the presence of Cu(OAc) 2 ·H 2 O in open air. The highly step-economical C-H bond functionalization process is characterized by a wide substrate scope and significant chemoselectivity, which allowed direct alkenylation to be performed either under solvent-free reaction con-

show abstract

Section: Introductionmentioning

confidence: 99%

Solvent‐Free Ruthenium(II)‐Catalyzed C–H Activation: Synthesis of Alkenylarylpyrazole Derivatives

Shome

Singh

2015

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…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

“…However, Fagnou and coworkers convincingly demonstrated that most probably the C-N reductive elimination occurs directly from Rh(III), generating isobutene as side product. 35 Scheme 17. Rh-catalyzed synthesis of isoquinolines from tert-butyl imines.…”

Section: (4+2) Annulationsmentioning

confidence: 99%

Metal‐Catalyzed Annulations through Activation and Cleavage of C−H Bonds

2016

View full text Add to dashboard Cite

Abstract:The exponential increase in the number of catalytic transformations that involve a metal-promoted activation of hitherto considered inert C-H bonds is promoting a paradigmatic change in the field of synthetic chemistry. While most reactions involving C-H activations consist of simple functionalizations or additions, recent years have witnessed a boost on related transformations that can be formally considered as cycloaddition processes. These transformations are particularly appealing from a synthetic perspective because they allow the conversion of readily available substrates into highly valuable cyclic products in a rapid and sustainable manner. In many cases, these annulations involve the formation of metallacyclic intermediates that resemble those proposed for standard metalcatalyzed cycloadditions of unsaturated precursors.

show abstract

Isoquinoline Synthesis via Rhodium-Catalyzed Oxidative Cross-Coupling/Cyclization of Aryl Aldimines and Alkynes

Cited by 445 publications

References 35 publications

Solvent‐Free Ruthenium(II)‐Catalyzed C–H Activation: Synthesis of Alkenylarylpyrazole Derivatives

Solvent‐Free Ruthenium(II)‐Catalyzed C–H Activation: Synthesis of Alkenylarylpyrazole Derivatives

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

Metal‐Catalyzed Annulations through Activation and Cleavage of C−H Bonds

Contact Info

Product

Resources

About