Catalytic Asymmetric Vinylation of Ketone Enolates

Chieffi, A.; Kamikawa, Ken; Åhman, Jens; Fox, Joseph M.; Buchwald, Stephen L.

doi:10.1021/ol0159470

Cited by 164 publications

(88 citation statements)

References 11 publications

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“…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. To date, the development of these reactions has been largely empirical.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

2007

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“…[4] However, despite the synthetic potential, there exist only a few reports that describe the coupling of vinylic compounds. [5] Furthermore, examples of such asymmetric reactions with electron-deficient alkenes [Eq. (1); EWG = electron-withdrawing group] have, to the best of our knowledge, been absent until now.…”

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confidence: 99%

Organocatalytic Enantioselective Nucleophilic Vinylic Substitution

et al. 2006

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“…[5] Finally, it is worth mentioning that isolated examples of the alkenylation reaction have also been reported in the studies of the Pd(0)-catalyzed intermolecular arylation of ester [6] and alanine-derived azlactone [7] enolates.…”

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confidence: 94%

Palladium‐Catalyzed Intramolecular Coupling of Amino‐Tethered Vinyl Halides with Ketones, Esters, and Nitriles Using Potassium Phenoxide as the Base

2004

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Vinyl halides undergo intramolecular coupling with amino-tethered ketones, esters, and nitriles in the presence of a palladium catalyst and potassium phenoxide as the base. This reaction constitutes a useful methodology for the synthesis of monocyclic, bridged, and spirocyclic nitrogen-containing compounds.Keywords: alkenylation; enolates; homogeneous catalysis; nitrogen heterocycles; palladium During the past decade there has been a growing interest in the palladium-catalyzed coupling reactions of aryl and vinyl halides with enolates and related anions. However, while the reactions of aryl halides have been extensively studied, and it is now possible to introduce an aromatic unit to a broad range of enolate-type nucleophiles, [1] the coupling reactions involving vinyl halides have received little attention and deal almost exclusively with the a-alkenylation of ketone enolates.The first examples of such palladium-catalyzed coupling reactions involving vinyl halides were reported by Piers at the beginning of the 1990s, when he described the intramolecular alkenylation of ketone enolates and then applied the reaction to the synthesis of the diterpenoid crinipellin B.[2] Some years later, another example of this coupling process was reported by Cook in the context of the total synthesis of the alkaloid (þ)-vellosimine, [3] and we reported our studies on the synthesis of nitrogen heterocycles by the Pd(0)-catalyzed intramolecular coupling of amino-tethered vinyl halides and ketone enolates.[4] Later on, Buchwald described the intermolecular vinylation of ketone enolates. [5] Finally, it is worth mentioning that isolated examples of the alkenylation reaction have also been reported in the studies of the Pd(0)-catalyzed intermolecular arylation of ester [6] and alanine-derived azlactone [7] enolates.In our previous work, we established that the use of Pd(PPh 3 ) 4 (0.2 equivs.) and KO-t-Bu (1.5 equivs.) in THF at reflux effectively promotes the intramolecular coupling of amino-tethered vinyl halides and ketones to afford bridged, condensed, and monocyclic nitrogen-containing compounds.[4] However, for some substrates side reactions such as the elimination of HX leading to alkynes which may undergo subsequent coupling with the starting vinyl halides to afford dimeric compounds, and dealkylation at the nitrogen, resulted in low or moderate yields of the cyclization products.[4b]As these side reactions can mainly be attributed to the use of a strong base, a more general protocol for the intramolecular a-alkenylation of ketones could be found if, instead of KO-t-Bu, a milder base was used. In this context, it should be noted that the intramolecular coupling of amino-tethered vinyl halides and ketones was also accomplished in some cases by using Cs 2 CO 3 as the base, although these reaction conditions were only suitable for the construction of five-membered ring systems and afforded moderate or low yields. [4b] Continuing our studies on this palladium chemistry, [8] we have recently reported that both vinyl an...

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Catalytic Asymmetric Vinylation of Ketone Enolates

Abstract: [see reaction]. A protocol for the catalytic asymmetric vinylation of ketone enolates has been developed. Key to the success of this process was the development of new electron-rich chiral monodentate ligands.

Cited by 164 publications

References 11 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

Organocatalytic Enantioselective Nucleophilic Vinylic Substitution

Palladium‐Catalyzed Intramolecular Coupling of Amino‐Tethered Vinyl Halides with Ketones, Esters, and Nitriles Using Potassium Phenoxide as the Base

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