Silyl enol ethers vinyl substitution

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

Chromene acetals 39 are accessible from 2-vinyl-substituted phenols via the allylic acetals 38 through oxypalladation of benzyloxypropa- 1,2-diene and a subsequent Ru-catalysed RCM. 2-Substituted chromenes can be derived from the acetals 39 by conversion into the 1-benzopyrylium salts which are then trapped by nucleophiles (Scheme 26) <00TL5979>. In a like manner, 2-aIkoxychromans have been converted into various 2-substituted chromans by sequential treatment with SnCl4 and a silyl enol ether <00TL7203>. 

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. 

Vinyl substitution with silyl enol ethers 840... 

S-Substituted a-lithiated silyl enol ether 557 has been prepared by reductive lithia-tion of vinyl tellurides834 and sulfides835,836 with lithium 1 -(dimethylamino)naphthalenide (LDMAN). This intermediate 557 gave, after inverse Brook rearrangement, the enolate 558 and after hydrolysis the corresponding acylsilane (Scheme 151). 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

This is a mild, simple and practical procedure for 1,4-addition of an aldehyde to methyl vinyl ketone, without converting the aldehyde into an enamine or a silyl enol ether. The products, substituted 5-ketoaldehydes, are important compounds, especially for the preparation of substituted 2-cyclohexen-1-one derivatives, which have been versatile starting materials for syntheses of natural products such as terpenoids. These 5-ketoaldehydes have been prepared previously by the 1,4-addition of modified aldehydes, i.e., morpholinoenamines of aldehydes,trimethylsilyl enol ethers of aldehydes in the presence of a Lewis acid, or diethylallylamine in the presence of a catalytic amount of a Ru complex, to methyl vinyl ketones. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

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. 

Narasaka found that optically enriched oxabicydic substrate 277 bearing a vinyl sulfide moiety reacts with a silyl enol ether or ketene silyl acetal in the presence of a Lewis acid to afford the protected cyclohexenols 278a and 278b, Eq. 175 [18]. The reaction was proposed to occur via a ring-opening and alkylation sequence which is equivalent to overall nucleophilic substitution with retention of configuration. Presumably, the nucleophile attacked the carbocationic intermediate from the exo face, because the methylene-OTIPS substituent was blocking the endo side. 

The presence of two substituents (generally both at the /3-carbon) still allows the reaction to occur in good yields [25,26], and the same is true when three substituents are present. Thus Verlhac et al. described the alkylation of stannylated silyl enol ethers and, after workup, obtained aryl ketones in moderate to good yields (Scheme 4-4) [27], Booth et al. [28] (Scheme 4-5) and Casson and Kocienski [29] reported couplings of heterofunctionalized vinyl tins, Takeda et al. [30] prepared a series of highly substituted aj3-unsaturated ketones (Scheme 4-6) and Shi et al. [31] a number of /3-fluoro-a-keto acid derivatives. 

Normally, the A-arylimine is obtained by reaction of aldehyde and aniline in acidic condition. Either tetrahydroquinoline or its corresponding substituted quinoline can be generated in the Povarov reaction, depending on the reaction conditions. For instance, DDQ-promoted dehydrogenation, vacuum distillation under acidic condition, oxidation by air or Mn(OAc)3, and Pd/C-catalyzed aromatization of tetrahydroquinoline, provides the corresponding substituted quinolines in good to excellent yield. Since some tetrahydroquinolines are unstable under the reaction conditions, the corresponding substituted quinolines could be isolated as the sole products. Electron-rich olefin, such as vinyl enol ethers, vinyl sulfides, and silyl enol ethers, are widely used as dienophiles in the cycloaddition of A-aryl aldimines to obtain substituted tetrahydroquinolines. To access natural... 

Silyl enol ethers of P-amido substituted cyclohexanone give [2+2] cyclisadons to form N-heterocycles, fluoroalkyl amides convert cyclohexanones to the enol ether, C N02)4 witii benzocyclohexanone gives a-nitroketones, and with diazoesters give optically active siloxycyclopropanes. Pb(OAc)4 gives acetoxy derivatives, deracemisation by enantioselective protonation demonstrated, methyl vinyl ketones added to give a,e-diones, and... 

Application of this reaction to cyclic vinylsiloxanes results in fi-substitution at each of the vinyl groups on the cyclic siloxanes. Enol ethers, silyl enol ethers, and styrene all effectively functionalize cyclic siloxanes in high yield. The combination of 04 with styrene under silylative functionalization conditions provides tetrastyryltetramethylcyclotrisiloxane (9) in 92% yield with the phenyl subsituent exclusively at the 8-carbon (eq 8), while the same reactants under standard mthenium cross-metathesis conditions afford only monofunctionalization in 10% conversion. Moreover, the reaction of D4 or and styrene affords only the E-isomer, whereas the combination of and an enol ether provides a mixture of the E- and Z-isomers. 

Silyl ketones are hydrolytically unstable and can be converted to the desilylated ketone by simple acid or base treatment, or used in a Peterson alkenation reaction to provide enones. They are also precursors to silyl enol ethers by rearrangement. Reaction of the /3-silyl ketone with a vinyl Grignard reagent provides a rapid entry to 2-substituted 1,3-dienes by a Peterson protocol. ... 

The second method involves end-quenching of living polymers with appropriate nucleophiles. Although this approach appears to be more attractive than the first one, in situ end funaionali-zation of the living ends is limited to nucleophiles that do not react with the Lewis add coinitiator. Because the ionization equilibrium is shifted to the covalent spedes, the concentration of the ionic active species is very low. Quantitative functionalization can only be accomplished when ionization takes place continuously in the presence of nudeophile. Quenching the vinyl ether polymerization with the malonate anion,certain silyl enol ethers " and silyl ketene acetals have been successfully used to synthesize end-functionalized poly(vinyl ethers). Alkyl amines, " ring-substituted anilines, " " alcohols, " and water " have also been used to quench the vinyl... 

For example, substituents in terminal olefins (43) in the resulting nitronates (35) are generally adjacent to the C-6 atom. The alkoxy and siloxy substituents from vinyl ethers and silyl enolates respectively, as well as the amino group from enamines, are oriented in the same positions. In the case of tris-substituted olefins, C-6 is the most crowded atom in the resulting nitronates. 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

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