Selective .gamma. alkylation of copper enolates derived from .alpha.,.beta.-unsaturated acids: factors affecting scope and regio- and stereoselectivity

Savu, Patricia M.; Katzenellenbogen, John A.

doi:10.1021/jo00315a003

Cited by 79 publications

(10 citation statements)

References 2 publications

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“…For example, if α,β‐unsaturated ketones or carboxylic acid derivatives are treated with an alkyl halide in the presence of alkali‐metal bases such as KO t Bu4a or lithium diethylamide (LDE),4b,c alkylation occurs at the α‐position preferentially over the γ‐ or α′‐positions. The regioselectivity of this reaction may be reversed to favor γ‐alkylation with the use of copper,4d,e germanium,4f tin,4g or zinc4h,i dienolates.…”

Section: Methodsmentioning

confidence: 99%

Palladium‐Catalyzed γ‐Arylation of β,γ‐Unsaturated Ketones: Application to a One‐Pot Synthesis of Tricyclic Indolines

Hyde¹,

Buchwald²

2007

Angewandte Chemie

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Extensive work has been carried out to develop the palladium-catalyzed a-arylation of ketones and related carbonyl functional groups, [1] providing a very simple and dependable route to a-aryl and a-vinyl ketones. However, less attention has been directed to the palladium-catalyzed arylation of dienolates, [2] which would allow for rapid construction of garyl-a,b-unsaturated ketone motifs (Scheme 1) found in a Scheme 1. Regioselective dienolate arylation.Scheme 2. Unsuccessful attempt to arylate a,b-unsaturated ketone 1.

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Section: Methodsmentioning

confidence: 99%

Palladium‐Catalyzed γ‐Arylation of β,γ‐Unsaturated Ketones: Application to a One‐Pot Synthesis of Tricyclic Indolines

Hyde¹,

Buchwald²

2007

Angewandte Chemie

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“…[14] Significantly, this building block exhibits a fully orthogonal protecting-group pattern, which does not impose any restrictions on the final stages of the synthesis. However, the ultimately successful route to 1 relied on the early installation of the unsaturated ester, which was readily accomplished by selective cleavage of the TES moiety with PPTS followed by esterification of the released alcohol with acid 16 [15] to give 17 as a fully functional surrogate of the "south-eastern" part of 1.…”

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confidence: 99%

Total Syntheses of Amphidinolide H and G

et al. 2007

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General. NMR spectra were recorded with a Bruker DPX 300, AV 400, or DMX 600 spectrometer in the solvents indicated; chemical shifts (δ) are given in ppm relative to TMS, coupling constants (J) in Hertz. The solvent signals were used as references and the chemical shifts converted to the TMS scale (CDCl 3 : δ C = 77.0 ppm; residual CHCl 3 in CDCl 3 : δ H = 7.24 ppm; CD 2 Cl 2 : δ C = 53.8 ppm; residual CH 2 Cl 2 in CD 2 Cl 2 : δ H = 5.32 ppm). Where indicated, the signal assignments are unambiguous; the numbering scheme is arbitrary and is shown in the inserts. The assignments are based upon 1D and 2D spectra recorded using the following pulse sequences from the Bruker standard pulse program library: DEPT; COSY (cosygs and Negishi carboalumination: Preparation of vinyl iodide 25.A solution of AlMe 3 (2.0 M in heptane, 21.2 mL, 42.4 mmol) was added to a suspension of Cp 2 ZrCl 2 (4.64 g, 15.9 mmol) in 1,2-dichloroethane (70 mL). After stirring for 0.5 h, a solution of alkyne 24 (3.56 g, 10.57 mmol) in 1,2-dichloroethane (15 mL) was added dropwise. The resulting yellow solution was stirred for 24 h at ambient temperature before the mixture was cooled to −20°C and a solution of iodine (16.10 g, 63.5 mmol) in THF (60 mL) was slowly added. After stirring for 20 min at −20°C and 30 min at 0°C, the reaction was carefully quenched with water (10 mL). A sat. aq. Na 2 SO 3 solution was then added and the layers were separated. The aqueous phase was extracted twice with CH 2 Cl 2 (40 mL each), the combined organic extracts were washed with brine, dried over MgSO 4 and evaporated. .7, 135.7, 134.0, 129.7, 127.8, 75.4, 61.8, 39.9, 37.7, 27.0, 20.5, 19.6, 19.3 was added dropwise to a solution of epoxide 7 (7.6 g, 30.84 mmol) in toluene (25 mL) at −78°C over the course of 1 h. The temperature was then raised to −40°C and stirring continued for 4 h before the reaction was carefully quenched at −60°C with a solution of tBuOH in THF (1:1, 25 mL). The resulting mixture was poured into an icecold solution of Rochelle's salt (85g in 250 mL water) and vigorously stirred for 2 h until a clear separation of the phases was reached. The aqueous layer was extracted with tert-butyl methyl ether, the combined organic phases were dried over Na 2 SO 4 and evaporated, and the residue was purified by flash chromatography (hexanes:EtOAc, 1:1) to give product 8 as a

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“…Our final objective was to install the remaining carbon atoms of the pendant side chain as a single unit. Since the alkylation of extended enolates with alkyl halides is recognized to favor α-substitution overwhelmingly, iodide 30 (Scheme ) was not serviceable in this capacity. However, this intermediate proved to be highly crystalline, thereby permitting complete corroboration of the earlier stereochemical assignments by X-ray crystallographic analysis (Figure )…”

Section: Resultsmentioning

confidence: 99%

Studies Directed toward the Total Synthesis of Cerorubenic Acid-III. 5. A Radical Cyclization Route Leading to the Methyl Ester of the Natural Isomer¹

Paquette

Dyck

1998

J. Am. Chem. Soc.

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The first total synthesis of cerorubenic acid-III methyl ester is detailed. Enantiopure 4, obtained by anionic oxy-Cope rearrangement of 3, was transformed via diol 11 into lactol 20. Following proper establishment of both side chains as in 25, a 6-exo radical cyclization was employed to set the configuration of the remaining stereogenic centers. This very useful process set the stage for construction of the pendant side chain. The complete route to 2 from 3-methylcyclohexenone required 30 steps (0.3% overall yield) confirmed the initial complex structural assignment and established the absolute configuration of the natural kairomone.

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Selective .gamma. alkylation of copper enolates derived from .alpha.,.beta.-unsaturated acids: factors affecting scope and regio- and stereoselectivity

Cited by 79 publications

References 2 publications

Palladium‐Catalyzed γ‐Arylation of β,γ‐Unsaturated Ketones: Application to a One‐Pot Synthesis of Tricyclic Indolines

Palladium‐Catalyzed γ‐Arylation of β,γ‐Unsaturated Ketones: Application to a One‐Pot Synthesis of Tricyclic Indolines

Total Syntheses of Amphidinolide H and G

Studies Directed toward the Total Synthesis of Cerorubenic Acid-III. 5. A Radical Cyclization Route Leading to the Methyl Ester of the Natural Isomer¹

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Selective .gamma. alkylation of copper enolates derived from .alpha.,.beta.-unsaturated acids: factors affecting scope and regio- and stereoselectivity

Cited by 79 publications

References 2 publications

Palladium‐Catalyzed γ‐Arylation of β,γ‐Unsaturated Ketones: Application to a One‐Pot Synthesis of Tricyclic Indolines

Palladium‐Catalyzed γ‐Arylation of β,γ‐Unsaturated Ketones: Application to a One‐Pot Synthesis of Tricyclic Indolines

Total Syntheses of Amphidinolide H and G

Studies Directed toward the Total Synthesis of Cerorubenic Acid-III. 5. A Radical Cyclization Route Leading to the Methyl Ester of the Natural Isomer1

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Studies Directed toward the Total Synthesis of Cerorubenic Acid-III. 5. A Radical Cyclization Route Leading to the Methyl Ester of the Natural Isomer¹