Brook rearrangement is a reaction in organic chemistry in which an organosilyl group migrates from a carbon atom to an oxygen atom of an adjacent hydroxyl group . The final product is silyl ether. This process proceeds under the action of the base [1] . The reaction is named for the Canadian chemist Adrian Gibbs Brook (born 1924).
The substituents on the silicon atom can be aliphatic (e.g. methyl) or aromatic (phenyl). Alcohol can be secondary or tertiary with aliphatic or aromatic groups. The base may be an amine , sodium hydroxide , an organolithium compound or an alkali metal alloy (for example, sodium - potassium ).
Content
Reaction Mechanism
The first stage of this process is the removal of a proton from a hydroxyl group with a base. Further, the formed alkoxy anion acts as a nucleophile and replaces the methylene group at the silicon atom. As a transition state for this stage, a three-membered ring was proposed with an increasing order of the Si β O bond and a breaking Si β C bond. The resulting carbanion quickly attaches a proton from a suitable source, for example, a solvent, and turns into a neutral product - silyl ether.
It was found that the activation enthalpy for the reaction of (trimethylsilyl) methylphenylmethanol is relatively small, and at the same time, the activation entropy has a large negative value. This confirms the assumption of a cyclic transition state. Hammett's constants for a number of para-substituted phenylmethanols indicate that the introduction of acceptors stabilizes the negative charge in the intermediate and accelerates the reaction.
The driving force behind Brook's rearrangement is the formation of a strong Si β O bond. During the reaction, 451 + 427 = 878 kJ / mol is spent on breaking Si-C and OH bonds, but 809 (Si-O) + 338 (CH) = 1147 kJ / mol is released.
The rearrangement takes place while maintaining the configuration of the silicon atom, which is proved by the following Waldenov cycle:
(+) - Silyl hydride reacts with chlorine to form the corresponding silyl chloride while maintaining the configuration of the chiral center . Then follows the reaction of nucleophilic substitution with diphenylmethyl lithium, which proceeds with the reversal of the configuration. Further, during bromination and hydrolysis, the configuration does not change. The next step is actually Brook's regrouping. Finally, reduction with lithium aluminum hydride (proceeding without changing the configuration of the reaction center) leads to the (-) - enantiomer of the starting compound.
Variations
There are known cases of Brook rearrangement in acylsilanes [2] . For some silyl ethers, Brook's rearrangement is possible [3] .
Application
K. Takeda developed a method for stereoselective synthesis of eight-membered cycles (one of the most difficult to obtain) using a tandem from Brook rearrangement and [3 + 4] cancellation [4] .
Notes
- β AG Brook. Molecular rearrangements of organosilicon compounds (English) // Accounts of Chemical Research : journal. - 1974. - Vol. 7 , no. 3 . - P. 77-84 . - DOI : 10.1021 / ar50075a003 .
- β Patrocinio, Amauri F. and Moran, Paulo JS Acylsilanes and their applications in organic chemistry . J. Braz. Chem. Soc., 2001, vol. 12, no.1, p.07-31. ISSN 0103-5053. Online Article
- β Stereochemistry of the cyclization of 4- (t-butyldimethyl) siloxy-5-hexenyllithium: cis-selective ring-closure accompanied by retro- [1,4] -Brook rearrangement William F. Bailey and Xinglong Jiang ARKIVOC 2005 (vi) 25 -32 Article online (inaccessible link)
- β Takeda, K., Savada, Y., Sumi, K. Stereoselective formation of eight-membered carbocycles by Brook rearrangement-mediated [3 + 4] annulation (Eng.) // Org. Lett. : journal. - 2002. - Vol. 4 . - P. 1031-1033 . - DOI : 10.1021 / ol0256318 .