Transmetalation silyl enol ethers

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... 

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). 

SnCU is also the principal source of alkyltin chlorides, R SnCl4 [51]. Allyltrialkyl-tin reagents react with SnCU to produce allyltrichlorotin species through an Se2 pathway (Eq. 32) [52-56], Allyltrimethylsilanes react with SnCU to produce the corresponding allyltrichlorotin (Eq. 33) [57]. Silyl enol ethers react with SnCU to give a-tri-chlorotin ketones (Eq. 34) [58]. Transmetalation or metathesis reactions of this type... 

The ( )/ (Z) substrate-dependent absolute stereochemistry and the steric influence of 5n-substituents on the enantioselectivity observed in these reactions suggest that the mechanism is essentially different from that of silyl enol ethers. Although the detailed stereochemical course has not been ascertained, it is possible that the protonation occurs via a two-chlorine-bridged intermediate between allyltrimethyltin and LBA. Keck et al. have reported that transmetalation between allyltributyltin and free... 

If the electrophile is a vinyl triflate, it is essential to add LiCl to the reaction so that the chloride may displace triflate from the palladium o-complex. Transmetallation takes place with chloride on palladium but not with triflate. This famous example illustrates the similar regioselectivity of enol triflate formation from ketones to that of silyl enol ether formation discussed in chapter 3. Kinetic conditions give the less 198 and thermodynamic conditions the more highly substituted 195 triflate. 

A more convenient method for the preparation of functionalized organozinc species is hydroboration of an alkene followed by transmetalation with Et2Zn [36]. In this scheme, a wider range of functional organozincs is readily synthesized. For example, Knochel et al. reported that a dialkylzinc, prepared from a dienic silyl enol ether, enantiomerically added to various aldehydes in the presence of the chiral disulfonamide-titanium system (Scheme 12) [37]. 

In contrast, Sodeoka and coworkers reported Pd-catalyzed asymmetric Mannich-type reactions (Scheme 47) [189-191]. In this case, the Pd(II)/tol-BI-NAP hydroxo complex 68 did not act as a Lewis acid, but formed the chiral Pd enolate generated from the silyl enol ether 65 through transmetalation to give the product 67b in high enantioselectivity (90% ee). The Pd(II)/tol-BINAP hydroxo complex 65a is effective to suppress the generation of strong protic acid HBF4 that catalyzed the racemic reaction. 

Asymmetric aldol reactions. The chiral N-propionyloxazolidinone (1), prepared in several steps from (lR)-(—)-camphorquinone, undergoes highly diastereoselective aldol reactions with the additional advantage of high crystallinity for improving the optical purities of crude aldols. Either the lithium enolate or the titanium enolate, prepared by transmetalation with ClTi(0-(-Pr)3, reacts with aldehydes to form syn-adducts with diastereomeric purities of 98-99% after one crystallization. The observed facial selectivity is consistent with metal chelation of intermediate (Z)-enolates (supported by an X-ray crystal structure of the trapped silyl enol ether). The lithium enolate also exhibits... 

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],... 

In the presence of a double bond, its intramolecular insertion to Pd enolate in 528 takes place. For example, the silyl enol ether 527 undergoes transmetallation with Pd(OAc)2 to give the Pd enolate 528, or the oxy-7r-allylpalladium, which undergoes 6-exo cyclization to generate 529. The subsequent jS-H elimination gives the 3-methylcyclohexenone (530) [215]. The reaction is called cycloalkeny-lation [216]. 

Sodeoka found that Pd(II) hydroxide complexes of BINAP derivatives 18 are excellent catalysts for asymmetric synthesis. Pd enolates are generated from silyl enol ethers by transmetallation. The asymmetric Mannich-type reaction of silyl enol ether of acetophenone (15) with the imine 16 proceeded smoothly using Pd complex of Tol-BINAP, and the ester of amino acid 17 with 90 % ee was obtained in 95 % yield [3]. 

Corey has utilized the Brook-generated allyl anion alkylation in several syntheses. A recent example was in the preparation of ZF-cation cyclization precmsor 28. Chemoselective addition of 2-propenyllithium to the acyl silane carbonyl of 27, followed by transmetalation and alkylation provided the (Z)-silyl enol ether 28. ... 

In the allylation of the silyl enol ethers with allyl carbonates, the transmetallation of the silyl enol ethers with the 7r-allylpalladium methoxides, generated from allyl methyl carbonates, gives the 7r-allylpalladium enolates. Depending on the reaction conditions, allyl ketones are formed by reductive elimination (Scheme When a ratio... 

Bismuth(in) triflate appears to act as an efficient catalyst, although transmetalation with the silyl enol ether may mean that trimethylsilyl fiiflate (MesSiOTO is the real catalyst." The system is more catalytic than rare earth fiiflates and, as the bismuth reagent is water-soluble, it is easily recovered. 

Oshima and coworkers reported reactions of aldehyde enolates with ketones [11]. They used enolates generated from silyl enol ether 14 with meth-yllithium and transmetalated with titanium tetrabutoxide. Representative examples are shown in Table 2.2. Selectivity was minimal, except for 1,1,1-trichloroacetone (entry 5), for which the anti isomer was formed almost exclusively. 

The cleavage of silyl enol ethers by Lewis acidic metal salts may also be categorized as a transmetallation. Kuwajima and coworkers have shown that silyl enol ethers react with titanium tetrachloride under formation of the corresponding titanium enolates 174, which were characterized by NMR spectroscopy (Scheme 2.51). Whereas (Z)-enolsilanes of acyclic ketones retain their configuration in the titanium enolates, the ( )-silyl enol ethers lead to a mixture of... 

Mukaiyama aldol reactions of silyl enol ethers are generally rationalized by a Lewis acid activation of the carbonyl group by in situ formation of a complex that reacts with the silyl enol ether or the silyl ketene acetal [99,167]. Transmetallation mechanisms according to which silicon is replaced under formation of a metal enolate have been discussed as well for catalytic versions of the reaction [168], in particular for late transition metals [169]. 

Scheme 2.52 O-bound palladium enolate 177 generated in situ from silyl enol ether 176 by transmetallation.

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