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    Brook Rearrangement: Rowan Meador Fall 2016 Chem 676

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    Mahesh
    The document summarizes the Brook rearrangement reaction discovered by Adrian Brook in 1974. It describes the reaction's ability to form silyl enol ethers with retention of stereochemistry. Several recent uses of the Brook rearrangement are highlighted, including one-pot syntheses of γ-amino-β-hydroxy amides, α-hydroxy acid derivatives, arylvinyl ketones, eight-membered rings, and silyl dienol ethers. The reaction has proven useful in tandem with other reactions to form new bonds and synthesize biologically active molecules.

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    Brook Rearrangement: Rowan Meador Fall 2016 Chem 676

    Uploaded by

    Mahesh
    159 views17 pages
    The document summarizes the Brook rearrangement reaction discovered by Adrian Brook in 1974. It describes the reaction's ability to form silyl enol ethers with retention of stereochemistry. Several recent uses of the Brook rearrangement are highlighted, including one-pot syntheses of γ-amino-β-hydroxy amides, α-hydroxy acid derivatives, arylvinyl ketones, eight-membered rings, and silyl dienol ethers. The reaction has proven useful in tandem with other reactions to form new bonds and synthesize biologically active molecules.

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    The document summarizes the Brook rearrangement reaction discovered by Adrian Brook in 1974. It describes the reaction's ability to form silyl enol ethers with retention of stereochemistry. Several recent uses of the Brook rearrangement are highlighted, including one-pot syntheses of γ-amino-β-hydroxy amides, α-hydroxy acid derivatives, arylvinyl ketones, eight-membered rings, and silyl dienol ethers. The reaction has proven useful in tandem with other reactions to form new bonds and synthesize biologically active molecules.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    159 views17 pages

    Brook Rearrangement: Rowan Meador Fall 2016 Chem 676

    Uploaded by

    Mahesh
    The document summarizes the Brook rearrangement reaction discovered by Adrian Brook in 1974. It describes the reaction's ability to form silyl enol ethers with retention of stereochemistry. Several recent uses of the Brook rearrangement are highlighted, including one-pot syntheses of γ-amino-β-hydroxy amides, α-hydroxy acid derivatives, arylvinyl ketones, eight-membered rings, and silyl dienol ethers. The reaction has proven useful in tandem with other reactions to form new bonds and synthesize biologically active molecules.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 17

    Brook Rearrangement

    Rowan Meador
    Fall 2016
    Chem 676
    Discovery of Brook Rearrangement
    • Adrian Gibbs Brook discovered the
    rearrangement in 1974.
    • Brook did mechanistic studies as well.
    • He studied at the University of Toronto (PhD
    1950).
    • Also first to synthesis a silicon-carbon double
    bond.
    Adrian G. Brook
    1924- 2013

    References: Brook, Adrian G. Acc. Chem. Res. 1974. 7, 77.


    http://www.chem.utoronto.ca/_shared/images/news/thumbs/brook.jpg
    Brook Rearrangement
    • Makes silyl enol ethers
    • Pseudo-first order
    General reaction
    • Retention of stereochemistry
    • Later was found to be reversible
    • Later found to be useful in
    tandem with other reactions via
    the addition of an electrophile

    General mechanism
    Modern use of Brook rearrangement
    Overview of Recent Literature Reactions
    • vinylation, [1,2]-Brook rearrangement, vinylogous Michael cascade
    • α-Hydroxy Acid Derivatives
    • Eight-Membered Rings
    • Improved Morita-Baylis-Hillman reaction
    • α-Hydroxyproargylsilanes to Aldehydes
    • Arylvinyl Ketones
    • γ-Amino-β-Hydroxy Amides
    • 1,4-Brook Rearrangement-Wittig Reaction
    Michael Cascade Reaction
    • Regio- and diasterocontrol
    • 1,7-chirality transfer
    • Uses vinylation, [1,2]-Brook rearrangement, vinylogous Michael
    cascade

    Reference: Boyce, Gregory R. and Johnson, Jeffery S., J. Org. Chem. 2016, 81, 1712-1717
    α-Hydroxy Acid Derivatives
    • One-pot synthesis using aldehydes, PhMe2SiLi, and CO2.
    • Via 1,4-Brook Rearrangement
    • Uses CsF as a “promoter”
    • α-hydroxy acids are important in the cosmetic industry

    References: T. Mita, Y. Higuchi, Y. Sato, Org Lett., 2014, 16, 14-17.


    https://en.wikipedia.org/wiki/Alpha_hydroxy_acid
    Eight-Membered Rings
    • Synthesized functionalized, stereodefined eight-membered rings

    Reference: Takeda, Kei, Haraguchi, Hidekazu, and Okamoto, Yasushi. Org. Lett., 2003, 5, 3705-3707
    Eight-Membered Rings Overall Scheme
    α-Hydroxyproargylsilanes to Aldehydes
    • Improved Morita-Baylis-Hillman reaction
    • β-substitution of alkene tolerance
    • Z geometry preference
    • NHC-initiated method, NHC interacts with aldehyde allows for highly
    reactive allenolate

    Reference: Reynolds, Troy E., Stern, Charlotte A., Scheidt, Karl A. Org Lett, 2007, 9, 2581-2584
    Arylvinyl Ketones
    • Morita-Baylis-
    Hillman reaction
    yields a mixture
    of products
    • Using phosphine
    to arylvinyl
    ketone followed
    by 1,3-Brook
    rearrangement
    only one product
    References: Trofimov, Alexander and Gevorgyan, Vladimir. Org. Lett., 2009, 11, 253-255
    γ-Amino-β-Hydroxy Amides
    • β-hydroxy carbonyl compounds are important bioactive molecules
    • Synthesized via 1,2-Brook rearrangement
    • High diastereoselectivity (≥ 20:1)

    Reference: R. B. Lettan, II, C. V. Galliford, C. C. Woodward, K. A. Scheidt. J. Am. Chem. Soc. 2009, 131, 8805- 8814
    Lactam Synthesis
    • Can convert γ-amino-β-hydroxy amide to lactam
    • High diastereoselectivity (≥ 20:1)

    Reference: R. B. Lettan, II, C. V. Galliford, C. C. Woodward, K. A. Scheidt. J. Am. Chem. Soc. 2009, 131, 8805- 8814
    1,4-Brook Rearrangement-Wittig Reaction
    • One-pot synthesis of silyl dienol ethers

    Reference: Matsuya, Yuji; Koiwai, Azusa; Minato, Daishiro; Sugimoto, Kenji; Toyooka, Naoki. Tetrahedron
    Letters. 2012, 53, 5955-5957.
    1,4-Brook Rearrangement-Wittig Reaction

    Reference: Matsuya, Yuji; Koiwai, Azusa; Minato, Daishiro; Sugimoto, Kenji; Toyooka, Naoki. Tetrahedron
    Letters. 2012, 53, 5955-5957.
    Conclusions
    • Brook Rearrangement makes silyl enol ethers
    • Useful reaction in tandem with others to form bonds
    • Several one-pot synthesies in recent literature
    • Recent literature have used this chemistry to synthesize the following
    • γ-amino-β-hydroxy amide
    • α-hydroxy acid derivatives
    • arylvinyl ketones
    • eight-membered rings
    • silyl dienol ethers
    Questions?

    https://memegenerator.net/instance/65112981

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