Palladium enolates from silyl enol ethers

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Silyl enol ethers and ketene acetals derived from ketones, aldehydes, esters and lactones are converted into the corresponding o/i-unsaturated derivatives on treatment with allyl carbonates in high yields in the catalytic presence of the palladium-bis(diphenylphosphino)ethane complex (32). A phosphinc-free catalyst gives higher selectivity in certain cases, such as those involving ketene acetals. Nitrile solvents, such as acetonitrile, are essential for success. 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

An interestingly short total synthesis of quadrone was developed by Kende and coworkers who made application of Pd(II)-mediated cycloalkenylation of silyl enol ethers (Scheme LV) Their point of departure was 609 which was converted directly to 610, Reaction of this silyl enol ether with palladium acetate in acetonitrile gave predominantly 6JI which could be cyclized to 612. From this intermediate, it was possible to prepare the known keto acid. 

In 1998, a new type of Pd(II) binuclear complex was reported which was effective for Mannich reactions of an imine derived from glyoxylate and anisidine with silicon enolates [38,39]. In these reactions, use of solvents including a small amount of water was essential. It was shown that water played an important role in this system water not only activated the Pd(II) complex to generate a cation complex, but also cleaved the N-Pd bond of the intermediate to regenerate the chiral catalyst. This reaction reportedly proceeded via an optically active palladium enolate on the basis of NMR and ESIMS analyses. A unique binuclear palladium-sandwiched enolate was obtained in the reaction of the p-hydroxo palladium complex with the silyl enol ether [(Eq. (9)]. 

The imines 12 (X = 4-CH3-QH4-SO2 (Ts), Ar, C02R, COR, etc.) preformed or generated in situ from N,0- or N,N-acetals or hemiacetals are another important class of Mannich reagents frequently used for diastereo- and/or enantioselective aminoalkylation reactions catalyzed by chiral Lewis acids (usually copper or palladium BINAP complexes such as 13). Among other things excellent results were obtained in the aminoalkylation of silyl enol ethers or ketene acetals [24], A typical example is the synthesis of Mannich bases 14 depicted in Scheme 5 [24b], Because of their comparatively high electrophilicity imines 12 could even be used successfully for the asymmetric aminoalkylation of unactivated alkenes 15 (ene reactions, see Scheme 5) [24h, 25], and the diastereo- and/or enantioselective aminoalkyla-... 

The neutral palladium(II) compound 43 is transformed by addition of AgOTf into the cationic complex 44. In the presence of water an exchange of the triflate anion to hydroxide occurs (44 — 45). Finally, the palladium enolate 46 is formed from the palladium complex and the silyl enol ether. 

In the last years several publications appeared describing palladium-catalyzed a-arylations of ketone enolates for the synthesis of a-aryl ketones, involving ketone eno-lates, silyl enol ethers and intramolecular a-aiylation of ketone enolates . In this process, an enolate is generated from a ketone in the presence of an aryl halide, and a palladium catalyst couples this enolate with the aryl halide. Iwama and Rawal proposed... 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

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. 

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. 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

An alternative approach to the protonation of silyl enol ethers involves the use of palladium catalysts which proceed via intermediate palladium enolates. The asymmetry can either be provided by ligands on the palladium or from an enantiomerically pure acid. °... 

The in situ formation of silyl enol ether intermediates appears to be a valuable strategy to accomplish further transformations. That is what happens for the palladium(II) acetate-mediated preparation of indenones from indanones (eq 41), or for diastereo-selective enol silane coupling reactions (eq 42). ... 

Heck-type reactions with enol carboxylates (e.g., vinyl acetate) are generally complex. Most common are reactions in which vinyl acetate is employed as an ethylene equivalent (see Scheme 24). However, an example of a preparatively useful reaction with an intact acetate function is given in entry 44.The reaction of vinyl triflates with vinyl phosphonates affords the corresponding conjugate dienylphosphonates (entry 45).f A new access to reactive nonaflates via a one-pot nonaflation-Heck reaction was recently reported (entry 46). " This reaction sequence starts from silyl enol ethers and provides functionalized 1,3-dienes in a simple manner, lodonium salts can be used as RPd precursors (entry 47). It is notable that the palladium(O) insertion preferentially occurs inbetween the iodonium ion and the vinylic, rather than the arylic sp -hybridized carbon (entry 47). Some years ago, Jeffery used acetylenic halides to achieve (JiJ-enynoates and (Ji)-enynones in fair yields at room temperature (entry 48). ... 

Takasago Perfumery Ltd. manufactures optically pure (Jl)-muscone from the racemic compound by way of its silyl enol ether which is dehydrosUylated with palladium acetate to the pure (Z)-enone. [202] The enantioselective hydrogenation with ruthenium-BINAP catalysts finally gives the enantiomericaUy pure product. [203]... 

The first gold-catalyzed addition reactions of carbon nucleophiles to allenes were only first disclosed in 2006, and the number of examples is still small. Toste and co-workers showed that allenic silyl enol ethers undergo a 5-endo- ng cyclization to hexahydroindenone derivatives in the presence of a cationic gold catalyst (Scheme 4-10). In these transformations, water or methanol is used as an external proton source for protodeauration of an intermediate vinylgold species. In an analogous manner, cyclopentenes were obtained in good yields from allenic P-ketoesters. In the presence of a palladium catalyst and an allylic halide, these substrates afford functionalized 2,3-dihydroflirans. 

Some synthetic modification for Pd(II)-catalyzed oxidation of silyl enol ethers is also developed. Silyl enol ethers prepared from aldehydes and ketones are converted to the corresponding a,/3-unsaturated carbonyl compound in good yields by 10 mol % of palladium(II) acetate in the presence of 1 atm pressure of O2 in DMSO as solvent (Scheme... 

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