Brook isomerization

The Brook isomerization is the migration of a silyl group from a carbon atom to an oxygen anion as illustrated in its simplest [1,2] form (e.g. 27 to 28 in equation 11). ... 

In this section, we will concentrate on the chemistry of the Brook isomerization mediated by organolithium compounds and on their unusual routes to potentially useful carbanions. 

Allenyl silyl ethers 40 have also been prepared by the reaction of 2-lithiofurans 38 with acylsilanes 39 via the Brook isomerization (equation 15) . 

Even the starting acylsilane 39 can be easily prepared via a Brook isomerization by the reaction of silylmethyllithium 41 with carbon monoxide " °. Initially, the reaction gives the corresponding unstable acyllithium 42 which underwent the Brook isomerization affording the stable lithium enolate (equation 16). 

This strategy was very recently used for the total synthesis of 5-Araneosene. In the first step of the synthesis, methyl rert-butyldimethylsilyl ketone 47 was treated with 2-propenyllithium 48 in ether and then with 2-isopropylallyl bromide 49 in THF to give the (Z)-enol silyl ether 50 in 82% yield. The sequence of reactions that leads to 50 includes (1) carbonyl addition of 48, (2) Brook isomerization and (3) allylation of the resulting ally lie lithium reagent (equation 18) ". ... 

Similarly, the [3-1-4] annulation of the E- and Z-isomers of /3-hetero-substituted acryloylsilanes 52 with lithium enolates of a,-unsaturated methyl ketones 54 gave stereospecifically the c -6,7-cyclopentyl-5-trimethylsilyl-3-cycloheptenone 55 (equation 20). The stereospecificity in the annulation was explained by an anionic oxy-Cope isomerization of the 1,2-divinylcyclopropanediol intermediate 56, which was generated through the Brook isomerization of the initial 1,2-adduct (equation 20). 

Metalloaldimines 57 bearing a silicon linked to a carbon can be alkylated with a range of carbon electrophiles. When 57 is treated with an aldehyde, the resulting adduct 58 undergoes the Brook isomerization providing a new lithioaldimine intermediate 59. Reaction of this lithioaldimine with electrophiles such as chlorotrimethylsilane provides a new imidoylsilane 60 in 62% yield (equation 21). ... 

In contrast to 1,2-migrations between C and O, there are few reports on the Brook isomerization of a-silylamine (aza-Brook isomerization). The reaction of (a-silylallyl)amine 61 with n-C4H9Li in THF at low temperatnre followed by the addition of HMPA and CH3I gives the methylated prodnct 62 in qnantitative yield. These resnlts indicate that an aza-Brook isomerization occnrs, i.e. the silyl group of 61 migrates from carbon to nitrogen and the lithinm salt of an aUyl anion 63 is produced (equation 22) . 

Thus, only few reports were disclosed for the [1,3] Brook isomerization Utimoto, Oshima and coworkers have reported that the treatment of tert-butyldimethyl(dibromomethyl)silane 64 with LDA followed by the addition of an excess of benzaldehyde lead to the 1,3-diol monosilyl ether 66 via the intermediacy of lithium carbenoid 65 (equation 24) . The rate of isomerization was dependent on the solvent used and HMPA was found to be the best solvent. ... 

However, this process requires a reaction time of 2 days and is inapplicable to unsymmetrical couplings (two different epoxides). As the study described in equation 24 revealed a dramatic solvent effect on similar Brook isomerizations in the adduct of lithio dihalo(triaIkylsilyl)methanes with epoxides (isomerization did not occur following metalation and initial alkylation in THF but proceeded readily upon addition of HMPA), the effect of HMPA for promoting the Brook isomerization was studied once the first alkylation was complete (equation 28) . ... 

Thus, metalation of 78 and alkylation with epoxide Ej in Et20 or THF likewise furnished the unrearranged carbinols exclusively. Then, addition of ITMPA or DMPU induced the 1,4-Brook isomerization (equation 28) and addition of a second epoxide leads to 79... 

Finally, addition of the carbanions derived from 83 to non-enolizable aldehydes is a facile process. Aryl and tertiary alkyl aldehydes gave trimethylsilyl allyl ethers 85 by a [1,4]-Brook isomerization (equation 30). The stereochemistry of the intermediate alkoxides 84 dramatically influences the reaction conditions required . 

Reactions between silyl ketones (acylsilanes) and nucleophiles again proceed without being imparted by steric or electronic effects. However, the adducts may undergo Brook isomerization before being trapped. ... 

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