α-Carbonyl Nucleophilesstaff.uny.ac.id/sites/default/files/pendidikan/Dr. Sri...Aldol condensation...

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1 α-Carbonyl Nucleophiles Michael and Stork reactions Aldol condensation Claisen condensation The Michael Reaction Addition of any β-dicarbonyl compound to any α,β-unsaturated carbonyl compound, in the β position. Disampaikan oleh : Dr. Sri Handayani 2013 Edited with the trial version of Foxit Advanced PDF Editor To remove this notice, visit: www.foxitsoftware.com/shopping

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Transcript of α-Carbonyl Nucleophilesstaff.uny.ac.id/sites/default/files/pendidikan/Dr. Sri...Aldol condensation...

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    α-Carbonyl Nucleophiles

    Michael and Stork reactionsAldol condensationClaisen condensation

    The Michael Reaction

    Addition of any β-dicarbonyl compound to any α,β-unsaturated carbonyl compound, in the β position.

    Disampaikan oleh : Dr. Sri Handayani 2013

    Edited with the trial version of Foxit Advanced PDF Editor

    To remove this notice, visit:www.foxitsoftware.com/shopping

    http://www.foxitsoftware.com/shopping

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    The Michael Reaction

    Addition of any β-dicarbonyl compound to any α,β-unsaturated carbonyl compound, in the β position.

    Generic “Michael” addition

    “Michael” addition

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    Mechanism of the Michael Reaction

    The Stork Enamine Reaction

    O OCH2CH2CH

    Oa. b. c. H+/H2O

    N H

    CH2 CH CH

    O

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    Mechanism of the Stork Enamine Reaction

    Enolates react with carbonyls

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    The Aldol addition and its products

    Mechanism of the Aldolreaction

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    The Aldol condensation makes α,β-unsaturated carbonyls

    The Aldol intermediate is not always isolated

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    What’s the mechanism?

    The mixed Aldol can be a mess

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    Mixed Aldol works if one has no α-hydrogens

    Mixed aldol works if enolate is pre-formed

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    The Claisen condensation makes β-keto esters

    Mechanism

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    The essential difference between Aldol and Claisen

    leaving group

    Why the Claisen only happens once: acidity of β-dicarbonyl

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    Mixed Claisen in which one component has no α-hydrogens

    Mixed Claisenbetween ketone and ester

    Why don’t we get Aldol with ester enolatenucleophile?

    pKa ~ 20 pKa ~ 25

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    Mixed Claisen with formic or carbonate ester

    Synthesis problem, from cyclohexanone

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    Solution

    Synthesis problem, from cyclohexanone

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    Solution

    The Dieckmann Condensation: an intramolecular Claisen condensation

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    Mechanism

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    Intramolecular Aldol can give two possible ring sizes

    Intramolecular Aldol can give two possible ring sizes

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    Six-membered rings are preferred

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    The Robinson Annulation: Michael Addition, then intramolecular Aldol condensation

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    Retrosynthetic breakdown

    Robinson retrosynthesis

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    Retrosynthetic breakdown

    Robinson retrosynthesis