Ketones Brook rearrangement

E)-Enol silyl ethers.1 A new highly stereoselective route to (E)-enol silyl ethers involves addition of CH,Li to silyl ketones substituted at the a -position by a SC6H5 group such as 1. The adduct (a) undergoes a Brook rearrangement and... 

Silyl enol ethers have been prepared via a Brook rearrangement from the reaction of phenyldimethylsilyllithium with a-silyloxy ketones (see Scheme 68). The comparison of the rate of the base-catalysed Brook rearrangement in -substituted... 

Retro-Brook rearrangement of the [l,3]-variant will readily take place in sp and sp carbanion systems. Kuwajima and Takeda and Corey and Rticker have developed the [l,3]-retro-Brook rearrangement of silyl enol ether anions which provide a-silyl ketones (equation 100 and 101). 

Trimethylsilyloxyailenes a,f -unsaturated ketones.6 1-Trimethylsilylpropargylic alcohols (I) on treatment with a catalytic amount of n-butyllithium in THF undergo Brook rearrangement to give trimethylsilyloxyailenes (2). If 1 equivalent of n-butyllithium is used and hexane is the solvent the intermediate (b) can be alkylated to afford a./i-nnsaluralcd ketones (3) alter acidic work-up. 

The latter reaction involves the addition of the pcrfluoro(l-iodohexane) to phenyl trimethylsilyl ketone and a Brook rearrangement with lithium fluoride and fluorotrimethylsilane elimination. In the case of the corresponding magnesium derivative, which is more stable at the reaction temperature, warming up to room temperature before hydrolysis is necessary.214... 

In an interesting transformation, reaction of benzoyl trimethylsilane with lithium enolates derived from various methyl ketones gives rise to 1,2-cyclopropanediols, predominantly with the cis configuration, in good yields (Scheme 77). The reaction, which proceeds through addition, Brook rearrangement and cyclization, is also successful with a,/l-unsaturated acyl silanes vide infra, Section IV.D)187. 

Fluoride ion-catalysed addition of trifluoromethyltrimethylsilane to acyl silanes occurs to give l,l-difluoro-2-trimethylsilyloxyalkenes (silyl enol ethers of difluoromethyl ketones), through nucleophilic addition of trifluoromethyl anion, Brook rearrangement and loss of fluoride. These compounds could be isolated when tetrabutylammonium difluorotriphenylstannate was used as a catalyst use of tetrabutylammonium fluoride gave the product corresponding to subsequent aldol reaction with the difluoromethyl ketone (Scheme 78)m. 

Some /J-heteroatom substituted a,/J-unsaturated acyl silanes react with methyl ketone enolates in a stepwise stereoselective cyclopentannelation process, formally a [3 + 2] annelation, which may proceed through aldol reaction followed by Brook rearrangement and cyclization (Scheme 111)223. 

Ab initio through-space/bond interaction analysis was applied to 3 + 2-anulation based on Brook rearrangement using /i-phcnylthioacryloylsilanes with alkyl methyl ketone enolates (Scheme 103).150 The major product has the large substituents on the same side of the five-membered ring. Orbital interactions related to the carbanion... 

Oxasilacyclopentenes were shown to be competent substrates for a scandium triflate-catalyzed Mukaiyama aldol process (Scheme 7.35).104 Exposure of silacy-clopentene 121 and benzaldehyde to substoichiometric amounts of scandium triflate produced ketone 122 diastereoselectively.105 This ketone was proposed to form by addition of enolate 123, resulting from desilylation of 121,106 to benzaldehyde. A 1,3-Brook rearrangement then afforded 122 from 124.107 This ketone could be further functionalized through lithium aluminum hydride reduction followed by deprotection to afford triol 125 containing four contiguous stereocenters. Thus, the molecular complexity of silyloxyalkynes can be increased dramatically in just three operations. 

In contrast, Fleming and coworkers proposed another mechanism involving a Brook rearrangement coupled with desilylative /J-elimination for similar reactions of a-siloxy ketones 131 with phenyldimethylsilyllithium to give silyl enol ethers 132 (equation 87) no trimethylsilyl enol ether 133 was detected in the reaction mixture203. 

Similarly, the [3 + 4] annulation of the E- and Z-isomers of /1-heteroatom-substituted acryloylsilanes 156 with lithium enolates of ,/l-unsaturated methyl ketones 157 gave stereospecifically cis-5,6- and //r/w.v-5,6-disubstituted-3-cycloheptenones 160, respectively (equation 97). The stereospecificity in the annulation was explained by an anionic oxy-Cope rearrangement of the 1,2-divinylcyclopropanediol intermediate 159, which was generated through the Brook rearrangement of the initial 1,2-adduct 158219 - 223. 

Tsai and coworkers89,91,246,247 reported the synthesis of cyclic silyl enol ethers and silyl ethers by using a radical cyclization followed by the radical Brook rearrangement (equation 111). The cyclization of 4-bromo-4-stannylbutyl silyl ketones 188 in benzene with a catalytic amount of tributyltin hydride and AIBN gave cyclic silyl enol ethers 18989 91 247. The whole catalytic cycle proposed is shown in equation 112. 

By contrast, the similar phosphate-phosphonate rearrangement proceeds with retention, whether it proceeds via a tertiary56 or a secondary57 organolithium 57 or 58, as does the related amide-ketone rearrangement of 59.58 These retentive rearrangements presumably involve C=0-Li or P=0-Li coordination not possible in the Brook rearrangement. 

Allenyl trialkylsilyl ethers 771 can be a-deprotonated with f-BuLi in THF at — 78 °C to give the allenyllithiums 77210901091. They underwent reverse Brook rearrangement to afford the silaacrolein enolates 773, which react with aldehydes and ketones to yield the a,/9-unsaturated acyl silanes 774 (Scheme 200). For enolizable aldehydes transmetallation with ZnCl2-TMEDA, and MgBr2 for ketones, provided better yields. 

A highly useful twofold reaction of silyl dithioacetals with epoxides was described by Tietze and coworkers (Scheme 2.107) [249]. Treatment of 2.2equiv. of enan-tiopure epoxides 2-463 with lithiated silyldithiane 2-458b in the presence of a crown ether led to 2-467 after aqueous work-up. It can be assumed that by attack of the lithium compound 2-462 at the sterically less-hindered side of the epoxide 2-463, the alkoxide 2-464 is formed which in a subsequent Brook rearrangement produces the lithium dithioacetal 2-465. This reacts again with an epoxide to give 2-466 and furthermore 2-467. Treatment with NaF then leads to the diol 2-468 which can be converted into the dihydroxy ketones 2-469 and the corresponding 1,3,5-triols, respectively. 

The experimental results and the known facility of O-desilylation of silyl enol ethers, such as 3-acetoxy-2-trimethylsiloxypropenes, under the given reaction conditions led Trost ° to suggest the intermediacy of an oxatrimethylenemethanepalladium complex 4 addition to the alkene at the less-substituted terminal carbon atom of 4 followed by tautomerism and ring closure would give rise to the cyclopropane. Since the palladium complex that is prepared from tris(dibenzylideneacetone)palladium(0)-chloroform complex [Pd2(dba)j CHClj] and triphen-ylphosphane also catalyzes the Brook rearrangement of an a-silyl ketone to a silyl enol ether, (2-oxo-3-silylpropyl) acetates can also serve as precursors of intermediate palladium complexes 4, and the same cyclopropanation reactions as with 3-acetoxy-2-trimethylsiloxypropenes can be carried out. 

Tandem Carbon-Carbon Bond Formation via Brook Rearrangement Takeda et al. have reported that the reactions of benzoyl- and crotonylsilanes with hthium enolates of methyl ketones produce 1,2-cyclopropanediol monosilyl ethers via the Brook rearrangement of the initial 1,2-adduct 158 and the subsequent internal nucleophilic addition (Scheme 10.225) [587]. No formation of the corresponding cyclopropanes with alkanoylsilanes implies fhat fhe Brook rearrangement is accelerated by the phenyl or vinyl group. 

Various other preparative methods, such as the trap of enolates formed by dissolving metal reduction of a.P-unsaturated ketones or a-halo ketones (eq (53)) [48], the 1,4-hydrosilation of a,P-unsaturated ketones (eq (54)) [49], and the addition of organometallic compounds to a-silyl ketones followed by the Brook rearrangement (eq (55)) [50], have been investigated. 

The kinetic enolate of a conjugated ketone generated by LDA reacts with a conjugated acylsilane to form the monosilylated 1,3-cycloheptanedione. A Brook rearrangement following the initial C-acylation delivers an allyl anion that is poised to return an attack on the enone that ie-emerges/°... 

A controlled opening of a,(3-epoxy ketones involves reaction with Ph(Me)2SiLi and mild hydrolysis. Attack of the silyllithium reagent on the ketone groups is followed by a Brook rearrangement and p-elimination. " ... 

The synthetic route can be shortened, if a sterically demanding silyl ketone is used as the synthetic equivalent of acetaldehyde, according to Bouffard and Salzmann. The lithium alkoxide is then transformed stereoselectively in a Brook rearrangement into the silyl ether. This is of advantage, since during the down-stream-processing no separate protection step is needed. [59]... 

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