Silyl ethers transmetallation

Aldol reactions of silyl enolates are promoted by a catalytic amount of transition metals through transmetallation generating transition metal enolates. In 1995, Shibasaki and Sodeoka reported an enantioselective aldol reaction of enol silyl ethers to aldehydes using a Pd-BINAP complex in wet DMF. Later, this finding was extended to a catalytic enantioselective Mannich-type reaction to a-imino esters by Sodeoka s group [Eq. (13.21)]. Detailed mechanistic studies revealed that the binuclear p-hydroxo complex 34 is the active catalyst, and the reaction proceeds through a palladium enolate. The transmetallation step would be facilitated by the hydroxo ligand transfer onto the silicon atom of enol silyl ethers ... 

Williams and coworkers have expanded the utility of this methodology via the application to highly functionalized substrates. transmetalation with R.R)-ot (S,S)-228 is quantitative and dependable, with a variety of allylic stannanes with C-2 substitution. Carbon chains at C-2 of the allyl component may contain additional functionality, including benzyl and allyl ethers, silyl ethers, esters, alkenes, halogens, or thioacetals, as well as stereogeificity. Asymmetric induction in the condensation with aldehydes is dominated by the chiral auxiliary. In this fashion, the allylation reaction may be designed as a convergent... 

The active intermediates of these reactions are believed to be titanium enolates formed by the transmetallation with titanium(IV) chloride. Alkylation of enol silyl ethers is also elTected by use of benzyltrimethyl ammonium fluoride, in which quaternary ammonium enolates are produced as intermediates (eq (27)) [24]. 

Reaction of enol silyl ethers with lead tetrabenzoate followed by treatment with triethylammonium fluoride leads to the a-benzoyloxyketones. In both cases, the sequence involves bisoxygenation of the double bond followed by hydrolysis. a-Acetoxylation is also possible, but the benzoate is the reagent of choice for that system. i In the cyclohexanone series, reaction of lead tetraacetate with cyclohexanone trimethylsilyl enol ether afforded also a-acetoxycyclohexanone after hydrolysis." When the same reaction was performed on the triethyltin enol ether, the main product was now a-acetoxycyclohexanone with a small amount of dimeric product. This latter result could be explained by a transmetallation followed by ligand coupling, in the major pathway. 

P, P] Tin(II) enolates of propionyl imides do not undergo uncatalyzed reactions with enones. Lewis acid catalysis results in the construction of 1,4-addition products. The stereoselectivity of this reaction has been examined by Mukaiyama and co-workers (87,88) and is summarized in Scheme 41 and Table 14. The tin(II) enolates were generated by the action of tin(II) triflate with N-ethylpiperidine on the propionyl imide. Although not examined, it is likely that this procedure results in the generation of a Z enolate (89). A process can be envisioned whereby transmetallation occurs to yield a silyl ether and a tin(II) species capable of Lewis acidic behavior. Hence, either direct conjugate addition of the tin enolate to a silyl-activated acceptor or transmetallation to... 

Preparation of enones from saturated ketones by Pd(II)-promoted dehydrosilyla-tion via silyl enol ethers was reported by Ito. Transmetallation of the silyl enol ether of cyclohexanone 519 with Pd(OAe)2 gives the oxo-TT-allylpalladium complex 520 (Pd enolate), which undergoes -H elimination to afford cyclohexenone. BQ is used as an oxidant of Pd(0) [211], However, the enone formation can be carried out using a catalytic amount of Pd(OAc)2 in DMSO under oxygen without other oxidants at room temperature. Also aldehyde 521 is converted to unsaturated aldehyde 522 via silyl ether in DMSO [4],... 

Coupling of reactive alkoxyalkenylsilanes has been applied to the synthesis of medium-sized rings. The cyclic silyl ether 54 was converted to cyclodeca-3,5-dienol (55) at room temperature [104]. In many silane coupling reactions, it has been claimed that ligandless r-allylpalladium chloride is an effective catalyst precursor. Possibly, chloride ion is essential for transmetallation as compared with unreactive Pd(OAc)2. 

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

Addition of alkyllithium to cyclobutanones and transmetallation with VO(OEt)Cl2 is considered to give a similar alkoxide intermediates, which are converted to either the y-chloroketones 239 or the olefinic ketone 240 depending on the substituent of cyclobutanones. Deprotonation of the cationic species, formed by further oxidation of the radical intermediate, leads to 240. The oxovanadium compound also induces tandem nucleophilic addition of silyl enol ethers and oxidative ring-opening transformation to produce 6-chloro-l,3-diketones and 2-tetrahydrofurylidene ketones. (Scheme 95)... 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[601] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of silyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

The silyl enol ether 940 is prepared from the a-bromo ketone 939 by the transmetallation with trimethylsilyltributyltin[784j. 

Pd(II)-cataIyzed cyclization of the siloxyhexatriene 34 offers a cyclohexe-none annulation method. The Pd enolate 35, formed by transmetallation of the silyl enol ether with Pd(II), is an intermediate which undergoes intramolecular endo-alkene insertion. Then Pd(II) is regenerated to give 36, and finally cyclohexenone is formed[38]. 

Although simple ketones and esters can not be allylated by Pd catalysts, they are allylated with allyl carbonates via their enol ethers of Si and Sn. In the allylation of the silyl enol ether 202 with allyl carbonate 200, transmetallation of 202 with the n-allylpalladium methoxide 201, generated from allyl methyl carbonate (200), takes place to generate the Pd enolates 203 and 204. Depending on the reaction conditions, allyl ketone 205 is formed by the reductive elimination of 203 [100]. When the ratio of Pd Ph3P is small, the a,/i-unsaturated ketone 206 is obtained by -elimination [101]. For example, the silyl enol ether 208 of aldehyde 207 is allylated with allyl carbonate (200) to give a-allylaldehyde 210 via 209. The a-allyl carboxylate 213 is obtained by allylation of ester 211 with allyl carbonate (200), after conversion of ester 211 to the ketene silyl acetal 212 [102], As the silyl group is trapped in these... 

Transmetallation of silyl enol ethers of ketones and aldehydes with Pd(II) generates Pd(II) enolates, which are usefull intermediates. Pd(II) enolates undergo alkene insertion and -elimination. The silyl enol ether of 5-hexen-2-one (241) was converted to the Pd enolate 242 by transmetallation with Pd(OAc)2, and 3-methyl-2-cyclopentenone (243) was obtained by intramolecular insertion of the double bond and -elimination [148], Formally this reaction can be regarded as carbopalladation of alkene with carbanion. Preparation of the stemodin intermediate 246 by the reaction of the silyl enol ether 245, obtained from 244, is one of the many applications [149]. Transmetallation and alkene insertion of the silyl enol ether 249, obtained from cyclopentadiene monoxide (247) via 248, afforded 250, which was converted to the prostaglandin intermediate 251 by further alkene insertion. In this case syn elimination from 250 is not possible [150]. However, there is a report that the reaction proceeds by oxypalladation of alkene, rather than transmetallation of silyl enol ether with Pd(OAc)2 [151]. 

Elimination of the Pd enolate 253, formed by the transmetallation of 252, is a good synthetic method of the enones 254 [152], The silyl enol ether 255, prepared by trapping the conjugate addition product of cyclohexenone, is dehydrogenated with... 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Relatively less acidic ketones compared to 1,3-dicarbonyl compounds are also suitable substrates for the palladium catalyzed coupling. a-Aryl ketones are obtained as products. In the early examples, masked ketone enolates such as silyl enol ethers [42] and enol acetates [43-45] were used in the presence of a tin source. These reactions involve tin enolates or acylmethyltins as intermediates and thus proceed by transmetalation (mechanism B in Scheme 1). 

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