Metal‐Catalyzed α‐Arylation of Carbonyl and Related Molecules: Novel Trends in CC Bond Formation by CH Bond Functionalization

Johansson, Carin C. C.; Colacot, Thomas J.

doi:10.1002/anie.200903424

Cited by 680 publications

(217 citation statements)

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“…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)(34)(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)(37)(38)(39).…”

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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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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“…There are several metal-catalyzed methods to accomplish α-arylation using aryl halides, but these routes suffer from high temperatures, long reaction times and drawbacks associated with the use of heavy metals in industry. [2,99] Diaryliodonium salts and other hypervalent iodine reagents provide a means by which α-arylation can be achieved without the need for toxic or expensive transition metal reagents.…”

Section: Trifluoromethylationmentioning

confidence: 99%

“…Two intermediates, with oxygen or carbon bonded to iodine, were identified as isoenergetic. These form the product through different reductive elimination mechanisms; [2,3] rearrangement or [1,2] rearrangement, respectively, where the first pathway is the favored one. [117] The most important finding was that the isomerization barrier between the C-I and O-I intermediate was low enough (16 kJ⋅mol -1) to give a fast equilibration.…”

Section: Mechanistic Studies Of α-Arylationmentioning

confidence: 99%

“…[1] Despite the success of organocatalysis in α-heterofunctionalization, α-arylation of carbonyl compounds is dominated by transition metal catalysis. [2] Hypervalent iodine compounds have recently received considerable attention as mild, non-toxic and selective reagents in organic synthesis. [3] They are efficient alternatives to toxic heavy metal-based oxidants and expensive organometallic catalysts in many organic transformations.…”

Section: Introductionmentioning

confidence: 99%

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α-Functionalization of Carbonyl Compounds Using Hypervalent Iodine Reagents

Merritt¹,

Olofsson²

2010

Synthesis

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“…3 is a commonly used mechanism for the insertion of low valence transition metals. 3,22 In the intramolecular hydroarylation reaction of formation of coumarin, this metal insertion involves the cleavage of the aryl C-H bond by attaching a Pd(II) catalyst to phenylpropiolate (oNC to oC, Fig. 3), followed by a six-membered ring closure and then the attachment of a hydrogen to the ethynyl group, toward the products, oRP.…”

Section: Introductionmentioning

confidence: 99%