Asymmetric Arylation of Ketone Enolates

Åhman, Jens; Wolfe, John P.; Troutman, Malisa V.; Palucki, Michael; Buchwald, Stephen L.

doi:10.1021/ja973794z

Cited by 278 publications

(136 citation statements)

References 7 publications

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“…The reactions of the cyclohexanone derivative with two different aryl triflates (Table 2, entries 10, 11) formed the product in a modest 78 and 77% ee, but these values are presumably higher than the "very low ee's" obtained in previous work with BINAP as ligand. 4 The reaction of 2-methyl 6-benzylidene cyclopentanone with phenyl triflate (Table 2, entry 12) occurred in 95% ee, this result is still slightly higher than the value (92%ee) obtained in previous work with BINAP as ligand. 4 (4) To determine the absolute configuration of one of the α-aylation products, we synthesized an iodide derivative of 2-methyl-2-(3,4-di-methoxyphenyl)-tetralone (Eq 4) and obtained X-ray structural data.…”

Section: Scope Of the Palladium-catalyzed α-Arylations With Aryl Trifmentioning

confidence: 62%

“…4 The reaction of 2-methyl 6-benzylidene cyclopentanone with phenyl triflate (Table 2, entry 12) occurred in 95% ee, this result is still slightly higher than the value (92%ee) obtained in previous work with BINAP as ligand. 4 (4) To determine the absolute configuration of one of the α-aylation products, we synthesized an iodide derivative of 2-methyl-2-(3,4-di-methoxyphenyl)-tetralone (Eq 4) and obtained X-ray structural data. To obtain crystalline samples, the iodination product was subjected to demethylation conditions to produce an iodo, hydroxyphenyl derivative.…”

Section: Scope Of the Palladium-catalyzed α-Arylations With Aryl Trifmentioning

confidence: 62%

“…The reaction of a 2-methylcyclopentanone derivative with a number of aryl bromides occurred with high enantioselectivity, 5 but the reactions of a 2-methylcyclohexanone derivative occurred with low enantioselectivity. 4 Likewise, the α-vinylation of five-membered cyclic ketones occurred in high ee with electron rich, sterically-hindered versions of Hayashi's MOP ligand, but reactions of six-membered cyclic ketones were not reported. 6 In addition to these limitations on reaction scope, little information has been gained on the factors that control stereoselectivity.…”

Section: Introductionmentioning

confidence: 99%

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Enantioselective α-Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel

2007

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The asymmetric α-arylation of ketones with aryl triflates is described, and the use of this electrophile with nickel and palladium catalysts containing a segphos derivative increases substantially the scope of highly enantioselective arylations of ketone enolates. The combination of aryl triflates as reactant, difluorphos as ligand, palladium catalysts for reactions of electron-neutral to (or) electron-rich aryl triflates, and nickel catalysts for reactions of electron-poor aryl triflates led to a series of α-arylations of tetralone, indanone, cyclopentanone, and cyclohexanone derivatives with electron-rich and electron poor aryl electrophiles. Enantioselectivities ranged from 70-98% with ten examples over 90%. Systematic studies on these α-arylations have revealed a number of factors that affect enantioselectivity. Ligands containing biaryl backbones with small dihedral angles generate catalysts that react with higher enantioselectivity than related ligands with larger dihedral angles. In addition, faster rates for reactions of aryl triflates vs those for reactions of aryl bromides allow the α-arylations of aryl triflates to be conducted at lower temperatures, and this lower temperature improves enantioselectivity. Finally, studies that compare the enantioselectivities of catalytic reactions to those of stoichiometric reactions of isolated [(segphos)Pd(Ar)(Br)], [(segphos)Pd(Ar)(I)] and [(segphos) Ni(C 6 H 4 -4-CN)Br] suggest that catalyst decomposition affects enantioselectivity.

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Section: Scope Of the Palladium-catalyzed α-Arylations With Aryl Trifmentioning

confidence: 62%

Section: Scope Of the Palladium-catalyzed α-Arylations With Aryl Trifmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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Enantioselective α-Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel

2007

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“…The palladium-or nickel-catalyzed asymmetric a-arylation [3] and a-alkenylation [4] of carbonyl compounds provides an efficient method for the synthesis of chiral ketones substituted with quaternary stereogenic centers, but their application to the asymmetric synthesis of products containing hydrogen at the chiral carbon should present a problem due to the difficulty in keeping the stereogenic character of the chiral carbon center bound to an acidic hydrogen under basic conditions at a high reaction temperature. Another important method of providing a-chiral ketones is the catalytic asymmetric protonation of enolates, [5][6][7] but the asymmetric synthesis at the stage of carbon-carbon bond formation is more desirable.…”

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confidence: 99%

Asymmetric 1,4‐Addition of Organoboron Reagents to Quinone Monoketals Catalyzed by a Chiral Diene/Rhodium Complex: A New Synthetic Route to Enantioenriched 2‐Aryltetralones

Tokunaga

Hayashi

2007

Adv Synth Catal

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A novel synthetic approach to 2-aryltetralones with high ee has been developed through asymmetric 1,4-addition of arylboronic acids to naphthoquinone monoketals catalyzed by a rhodium complex with the (R,R)-Ph-bod* ligand. The asymmetric addition proceeded in high yields with excellent enantioselectivity.Keywords: asymmetric catalysis; boron; chiral diene ligands; conjugate addition; quinone monoketals; rhodium Enantiomerically pure carbonyl compounds bearing aryl or alkenyl groups at the a position to the carbonyl moiety, which are represented by the 2-aryltetralones, constitute key intermediates to biologically important compounds.[1] Although their preparation using a stoichiometric amount of chiral reagents has been reported, [1,2] their catalytic asymmetric synthesis has not been well developed. The palladium-or nickel-catalyzed asymmetric a-arylation [3] and a-alkenylation [4] of carbonyl compounds provides an efficient method for the synthesis of chiral ketones substituted with quaternary stereogenic centers, but their application to the asymmetric synthesis of products containing hydrogen at the chiral carbon should present a problem due to the difficulty in keeping the stereogenic character of the chiral carbon center bound to an acidic hydrogen under basic conditions at a high reaction temperature. Another important method of providing a-chiral ketones is the catalytic asymmetric protonation of enolates, [5][6][7] but the asymmetric synthesis at the stage of carbon-carbon bond formation is more desirable. Our approach is to apply the rhodium-catalyzed asymmetric 1,4-addition [8,9] to the asymmetric synthesis of a-aryl ketones. Herein we report that the asymmetric 1,4-addition of aryl-and alkenylboron reagents to quinone monoketals [10] is efficiently catalyzed by a chiral diene/rhodium complex [11][12][13][14] and one of the enantioenriched addition products (96-99 % ee) is readily converted into a 2-aryltetralone without loss of enantiomeric purity.

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“…[2] This reaction has been reported using Pd and Ni salts in the presence of chiral phosphine ligands, which are often expensive, toxic and sensitive. [3] In addition, a chiral heterogeneous catalyst, Pd/Fe 3 O 4 nanoparticles modified by a chiral N-heterocyclic carbene (NHC), has been successfully employed in the asymmetric a-arylation. [4] In the past 30 years, the naturally occurring Cinchona alkaloids have been widely applied by themselves or as versatile precursors for organocatalysts in asymmetric synthesis, chromatographic selectors and NMR discriminating agents.…”

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confidence: 99%

Enantioselective α‐Arylation of Cyclic Ketones Catalyzed by a Combination of an Unmodified Cinchona Alkaloid and a Palladium Complex

2012

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A palladium/Cinchona alkaloid-catalyzed a-arylation between cyclic ketones and aryl halides under phosphine-free conditions is presented. The use of a simple, unmodified Cinchona alkaloid results in high levels of activity and selectivity with up to 93% ee. These enantioinduction levels are comparable or even higher than the ones reported using palladium/BINAP complexes. To the best of our knowledge, this represents the first use of unmodified Cinchona alkaloids as ligands/catalysts in asymmetric transition metal complex-catalyzed crosscoupling reactions.

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Asymmetric Arylation of Ketone Enolates

Cited by 278 publications

References 7 publications

Enantioselective α-Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel

Enantioselective α-Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel

Asymmetric 1,4‐Addition of Organoboron Reagents to Quinone Monoketals Catalyzed by a Chiral Diene/Rhodium Complex: A New Synthetic Route to Enantioenriched 2‐Aryltetralones

Enantioselective α‐Arylation of Cyclic Ketones Catalyzed by a Combination of an Unmodified Cinchona Alkaloid and a Palladium Complex

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