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?

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