Brook Rearrangement and Retro-Brook Rearrangement
The anionic [1,2]-migration of silicon groups from carbon to oxygen atoms occurs in the presence of bases. This process was later expanded to include the migration of silicon from [1,n]-carbon to oxygen, and it is commonly referred to as the Brook rearrangement. It has now developed into [1,5]-Brook rearrangement reaction. The opposite process, that is, the intramolecular migration of silicon groups from oxygen to carbon, can also occur, which is called retro-Brook rearrangement reaction. Brook rearrangement reaction and its reverse reaction both go through the same silicon anion intermediate.
- Reagents: Bases.
- Reactants: Silanyl alcohols.
- Products: Alkyl silyl ethers.
- Reaction Type: Rearrangement reaction.
- Related Reaction: Peterson olefination.
Fig 1. Brook rearrangement and its mechanism. [1]
Mechanism of Brook Rearrangement
First, the base captures the hydrogen on the hydroxyl group to generate an alkoxy anion, which then attacks the silicon atom. After the cyclic silicon anion transition state, the negative charge is transferred to the carbon atom, the Si-C bond is broken to generate a carbon anion, and finally the carbon anion captures a proton from the proton donor to generate the product silyl ether.
Experimental Tips
- Silicon Substituents (R3): Trialkylsilyl groups (TMS, TES, TIPS) are standard. Migration rate generally decreases with increasing steric bulk of R3 (TMS > TES > TBDMS > TIPS). Aryl or hydrido substituents can alter reactivity.
- The substituent on the silicon atom can be an aliphatic group or an aromatic group, and the alcohol can be a secondary alcohol, a tertiary alcohol or a phenol.
- Commonly used bases include amines, sodium hydroxide, organolithium reagents (e.g., n-BuLi, PhLi), amide bases (e.g., LDA, LiTMP), alkoxides (e.g., t-BuOK), or alkali metal alloys (e.g., Na/K alloy).
- Anhydrous, aprotic solvents are essential (THF, Et2O, DME, toluene, hexanes). Traces of water or protic solvents can protonate the carbanion prematurely or hydrolyze silicon groups.
- [1,3]- and [1,4]-silicon migrations show significant solvent effects. For example, the [1,4]-Brook rearrangement reaction of formula (1) cannot proceed in ether, but can proceed in tetrahydrofuran at -40°C. The addition of hexamethylphosphoramide (HMPA) can accelerate the reaction. [2]
Fig 2. Solvent effects of Brook rearrangement.
Application Examples of Brook Rearrangement
- Example 1: In the presence of NaHMDS/THF, enolized N-tert-butanesulfinyl imidates were added to acylsilanes, followed by a [1,2]-Brook rearrangement and intramolecular cyclization of β-silyloxy anion intermediates to successfully prepare polysubstituted cyclopropanes. In the presence of potassium tert-butoxide/toluene, the reaction produced β-silyloxy imidates as the protonation product of the β-siloxy anion intermediate. [3]
- Example 2: Azusa Kondoh and colleagues created an effective technique for synthesizing tetrasubstituted furans through a Brønsted base-catalyzed [1,2]-phosphoric acid-Brook rearrangement. The method involves the nucleophilic addition of the propargyl anion generated by the [1,2]-phospho-Brook rearrangement to an aldehyde, followed by an intramolecular cyclization mediated by N-iodosuccinimide to give 2,4,5-trisubstituted-3-iodofurans. [4]
![Fig 3. Brook rearrangement used for preparation of polysubstituted cyclopropanes; [1,2]-phospho-Brook rearrangement used for synthesis of tetrasubstituted furans.](/upload/image/brook-rearrangement-3.jpg)
Fig 3. Synthetic examples via Brook rearrangement.
Related Products
References
- Jie Jack Li. Name Reactions-A Collection of Detailed Mechanisms and Synthetic Applications, Sixth Edition, 2021, 47-49.
- Shinokubo, Hiroshi. Tetrahedron Lett, 1996, 37, 6781.
- Tang, Fan, et al. Chemical Communications, 2019, 55(26), 3777-3780.
- Kondoh, Azusa, et al. Organic Letters, 2020, 22(5), 2105-2110.
