brook rearrangement -...

Brook RearrangementRowan 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. Brook1924- 2013

References: Brook, Adrian G. Acc. Chem. Res. 1974. 7, 77. http://www.chem.utoronto.ca/_shared/images/news/thumbs/brook.jpg

Brook Rearrangement

General reaction

General mechanism

• Makes silyl enol ethers• Pseudo-first order• Retention of stereochemistry• Later was found to be reversible• Later found to be useful in tandem with other reactions viathe addition of an electrophile

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 arylvinylketone 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. TetrahedronLetters. 2012, 53, 5955-5957.

1,4-Brook Rearrangement-Wittig Reaction

Reference: Matsuya, Yuji; Koiwai, Azusa; Minato, Daishiro; Sugimoto, Kenji; Toyooka, Naoki. TetrahedronLetters. 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