palladium-catalyzed intermolecular arylation of ketones and amides tiansheng mei brandeis university march 7, 2007

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2. 2 I.) Introduction II.) Palladium-Catalyzed Arylation of Alkali Metal Ketone Enolates A. Initial Discoveries B. Mechanism and Catalyst Improvement C. Asymmetric Arylation III.) Palladium-Catalyzed Arylation of Silyl Enol Ethers A. Initial Discoveries B. Palladium Catalyzed Arylation of Diphenylsilyl Enol Ethers C. Palladium Catalyzed Arylation of Trimethyl Silyl Enol Ethers IV.) Palladium-Catalyzed Arylation of Amides IV.) Summary

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5. 5 I.) Introduction II.) Palladium-Catalyzed Arylation of Alkali Metal Ketone Enolates A. Initial Discoveries B. Mechanism and Catalyst Improvement C. Asymmetric Arylation III.) Palladium-Catalyzed Arylation of Silyl Enol Ethers IV.) Palladium-Catalyzed Arylation of Amides IV.) Summary

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11. 11 I.) Introduction II.) Palladium-Catalyzed Arylation of Alkali Metal Ketone Enolates A. Initial Discoveries B. Mechanism and Catalyst Improvement C. Asymmetric Arylation III.) Palladium-Catalyzed Arylation of Silyl Enol Ethers IV.) Palladium-Catalyzed Arylation of Amides IV.) Summary

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22. 22 I.) Introduction II.) Palladium-Catalyzed Arylation of Alkali Metal Ketone Enolates A. Initial Discoveries B. Mechanism and Catalyst Improvement C. Asymmetric Arylation III.) Palladium-Catalyzed Arylation of Silyl Enol Ethers IV.) Palladium-Catalyzed Arylation of Amides IV.) Summary

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27. 27 Advantages: 1. The palladium-catalyzed arylation of alkali metal ketone enolates has provided a general way to prepare arylated ketones. 2. The use of bulky, electron-rich phosphine ligands not only increases the rate of arylation but also allows the use of aryl chlorides as substrates. Drawbacks: 1. Difficult to selectively couple at the more hindered of two enolizable positions 2. Difficult to form acidic tertiary stereocenters Palladium-catalyzed arylation of silyl enol ethers might solve these problems.

28. 28 I.) Introduction II.) Palladium-Catalyzed Arylation of Alkali Metal Ketone Enolates III.) Palladium-Catalyzed Arylation of Silyl Enol Ethers A. Initial Discoveries B. Palladium Catalyzed Arylation of Diphenylsilyl Enol Ethers C. Palladium Catalyzed Arylation of Trimethyl Silyl Enol Ethers IV.) Palladium-Catalyzed Arylation of Amides IV.) Summary

29. 29 Kuwajima, I.; Urabe, H. J. Am. Chem. Soc. 1982, 104, 6831. Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita. T. Bull. Chem. Soc. Jpn. 1984, 57, 242.

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39. 39 I.) Introduction II.) Palladium-Catalyzed Arylation of Alkali Metal Ketone Enolates A. Initial Discoveries B. Mechanism and Catalyst Improvement C. Asymmetric Arylation III.) Palladium-Catalyzed Arylation of Silyl Enol Ethers A. Initial Discoveries B. Palladium Catalyzed Arylation of Diphenylsilyl Enol Ethers C. Palladium Catalyzed Arylation of Trimethyl Silyl Enol Ethers IV.) Palladium-Catalyzed Arylation of Amides IV.) Summary

40. 40 IV. Palladium-Catalyzed Intermolecular a-Arylation of Amides

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46. 46 Coupling of Zinc Enolates of N,N-Dialkylacetamides Generated via Lithium Enolates.

47. 47 Summary 1. The palladium-catalyzed arylation of alkali metal ketone enolates has provided a general way to prepare arylated ketones. 2. The use of bulky, electron-rich phosphine ligands not only increases the rate of arylation but also allows the use of aryl chlorides as substrates 3. Using silyl enolates and zinc enolates can avoid strongly basic conditions, allowing functional group tolerance and formation of a tertiary carbon center without racemization. These methods expand the application of the palladium-catalyzed arylation of carbonyl compounds.

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