Brook rearrangement alkoxides

Brook rearrangements may be carried out with either catalytic or stoichiometric base. With catalytic base, the reaction can be considered an equilibrium between 41 and 42. The strength of the Si-0 bond (about 500-520 kJ mol-1) compared with the Si-C bond (about 310-350 kJ mol-1) means that, provided the anion 33 forms reasonably rapidly (some degree of stabilisation is required), Brook rearrangement (alkoxide formation) is favoured over retro-Brook. Organolithiums 33 may be present as intermediates in the catalytic Brook rearrangement, but their reactivity cannot be exploited under these conditions. 

Conversely, were nucleophilic attack of the alkoxide ion to occur at the carbonyl group of 31, then the species formed (35) should undergo Brook rearrangement to 36 with retention of configuration at silicon (Path A). Reduction of 36 with lithium aluminium hydride would then produce (S)-(—)-l-naphthyl phenyl methyl silane (37). 

An alternative disconnection of the alkoxide requires the addition of a silyllithium reagent to an enone. Addition of stoichiometric base to the alcohol 51 produces an alkoxide 52, but no evidence of Brook rearrangement to generate 53 was found on protonation of the product. However, alkoxide 52 must exist in equilibrium with some of the organolithium 53, since alkylation with a soft electrophile (Mel) produced 54.41 The equilibrium concentration of the organolithium 53 is lessened in this case by the impossibility of O-Li coordination. 

Trimethylsilyloxy)vinyllithium 548 has been prepared by tin-lithium exchange from the vinylstannane 552, which is generated from acetyltri-n-butyltin 551 (Scheme 149)830. This vinyllithium suffers a reverse Brook rearrangement to generate the alkoxide 553 used for the synthesis of acylsilanes831. 

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 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]... 

SYNTHETIC REACTIONS USING BROOK REARRANGEMENTS IN a-SILYL ALKOXIDES GENERATED VIA REGIOSELECTIVE [I-RING-OPENING OF g.p-EPOXYSILANES BY A NUCLEOPHILE... 

Scheme 6.19 Enantioselective cyanation/Brook rearrangement/C-acylation of acylsilanes catalyzed hy chiral metal alkoxides.

Reactions of acylsilanes with a nucleophile (Scheme 6.4. Eq. 1) are among the most common and versatile methods for generation of an a-silyl alkoxide because various combinations of the two components for facilitating Brook rearrangement are possible. 

A carbanion generated at the y-position of a,p-epoxysilanes via a process such as deprotonation can cause (3-ring opening to provide a-silyl alkoxides fScheme 6.4. Eq. 5). Taking into consideration the ready availability of enantiomerically pure epoxides, this method opens the possibility for using epoxides as a source of chiral carbanions via Brook rearrangement. 

Scheidt recently reported that a-silyl alkoxides generated from a-silyl silylethers 79 by fluoride-induced desilylation instead of deprotonation of a-silyl alcohol can be trapped by primary alkyl and by allylic and benzylic electrophiles via a Brook rearrangement (Scheme... 

Linderman and Ghannam have utilized EtsSiOTf to trap the alkoxide formed from the addition of stannyl anion to aldehydes (eq 7). Upon treatment with excess butyllithium, these adducts undergo a reverse Brook rearrangement to afford a-hydroxysilanes. 

In contemporaneous studies by Kuwajima, the 1-silyloxy allyl anions were generated from 1-trimethylsilyl allylic alcohols such as 24. Treatment with a catalytic amount of base led to silyl enol ether 25 in excellent yield and (Z)-selectivity. The alkene geometry was proposed to arise from chelate 26, a structure consistent with Reich s results. Protonation of anionic intermediate 26 by alcohol 24, would provide product 25 and the alkoxide of 24, poised for Brook rearrangement. ... 

Marek and co-workers found that magnesium-to-zinc transmetalation of the alkoxides derived from addition of acetylenic Grignard reagents to acyl silanes promoted the 1,2-Brook rearrangement. The resulting propargyl zinc intermediates (e.g., 37), in equilibrium with the silyl allenol ethers of type 38, underwent diastereoselective carbocyclization in suitable systems, providing cyclopentanol 39, for example, after acid quench and desilylation. ... 

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