Silyl enol ethers intramolecular alkylation

Whatever the exact mechanism of the conjugate-addition reaction, it seems clear that enolate anions are formed as intermediates and they can be trapped as the silyl enol ether or alkylated with various electrophiles. For example, addition of lithium methylvinyl cuprate (a mixed-cuprate reagent) to cyclopentenone generates the intermediate enolate 166, that can be alkylated with allyl bromide to give the product 167 (1.161). The trans product often predominates, although the transxis ratio depends on the nature of the substrate, the alkyl groups and the conditions and it is possible to obtain the cis isomer as the major product. Examples of intramolecular trapping of the enolate are known, as illustrated in the formation of the ds-decalone 168, an intermediate in the synthesis of the sesquiterpene valerane (1.162). 

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

Longifolene has also been synthesized from ( ) Wieland-Miescher ketone by a series of reactions that feature an intramolecular enolate alkylation and ring expansion, as shown in Scheme 13.26. The starting material was converted to a dibromo ketone via the Mr-silyl enol ether in the first sequence of reactions. This intermediate underwent an intramolecular enolate alkylation to form the C(7)—C(10) bond. The ring expansion was then done by conversion of the ketone to a silyl enol ether, cyclopropanation, and treatment of the siloxycyclopropane with FeCl3. 

Titanium-mediated intramolecular Friedel-Crafts acylation and alkylation are important methods for construction of fused-ring systems (Scheme 29).107 As well as aromatics, olefin units also react in the same way.108 Alkylation of electron-rich olefins such as enol ethers or silyl enol ethers proceeds effectively in the presence of TiCl4.109... 

Different nucleophiles such as methanol, allylsilanes, silyl enol ethers, trimethylsilyl-cyanide, and arenes can be used in this process [62]. When the sulfide itself contains an unsaturated or aromatic fragment and the process is carried out in the absence of a nucleophile, an intramolecular anodic sub-stitution/cyclization might occur [61-63]. Methyl esters of 2-benzothiazolyl-2-alkyl or aryl-acetic acid, oxidized in MeOH/Et4 NCIO4 or H2SO4 in the presence of CUCI2, form 2,2-dimethoxy products (Eq. 7) [64]. 

In all of the cyclization reactions, Moeller has found only a small difference between the use of alkyl and silyl enol ethers. Since both styrenes and enol ethers have similar oxidation potentials, even the styrene moiety could function as the initiator for oxidative cyclization reactions. The anodic oxidation of simple styrene type precursors leads to low yields of cyclized products so that enol ether moiety seems to be the more efficient initiator for intramolecular anodic coupling reactions [93]. 

In contrast, the closely related palladium acetate-promoted intramolecular alkylation of alkenes by tri-methylsilyl enol ethers (Scheme 4)6,7 has been used to synthesize a large number of bridged carbocyclic systems (Table 1). In principle, this process should be capable of being made catalytic in palladium(II), since silyl enol ethers are stable to a range of oxidants used to carry the Pd° -> Pd11 redox chemistry required for catalysis. In practice, catalytically efficient conditions have not yet been developed, and the reaction is usually carried out using a full equivalent of palladium(II) acetate. This chemistry has been used in the synthesis of quadrone (equation 2).8 With the more electrophilic palladium(II) trifluoroace-tate, methyl enol ethers underwent this cyclization process (equation 3).9... 

On the other hand, unsaturated aldehydes and ketones were obtained using allylic alcohols as alkene components [68]. Similarly, allyl f-butyldimethylsilyl ether and N-allylamides gave silyl enol ethers [69] and enamides [70], respectively. The ruthenium-catalyzed alkene-alkyne coupling was successfully combined with the palladium-catalyzed intramolecular asymmetric allylic alkylation [71] to provide a novel one-pot heterocyclization method [72]. 

Lewis acid catalyzed intramolecular alkylations of silyl enol ethers containing 5n1-reactive functionality provide useful routes to a variety of carbocyclic systems. - Smith et al have employed an intramolecular Mukaiyama reaction of the enol derivative (76) to produce the tetracyclic system (77) (equation 7). This transformation was a key step in their elegant synthesis of jatrophone. The synthesis... 

A process that has proved valnable in synthesis is the addition of singlet oxygen to A-alkyl- and especially A-acyl-pyrroles ° prodncing 2,3-dioxa-7-aza-bicyclo[2.2.1]heptanes, which react with nncleophiles, such as silyl enol ethers, mediated by tin(II) chloride, generating 2-substitnted-pyrroles that can be nsed, as the example shows, for the synthesis of indoles via intramolecular electrophilic attack by the carbonyl group at the pyrrole P-position. 

Intramolecular alkylation accompanying desilylation of a silyl enol ether is expected in the case that a cis-decalin is formed. For acquiring the trans-isomer the cyclization must rely on activation by the nitrile group alone. 

Applications Based on Deprotonation of Selenoketals R Se CHB — alkyl) and Seleno-orthoesters. Deprotonation, usually with KDA, of selenoketals (PhSe)2CHR (R = alkyl) gives carbanions that react efficiently with common electrophiles [primary alkyP - and benzyl halides, aldehydes, ketones, and (for R = alkyl or H) epoxides ]. A few of the resulting selenoketals have been hydrolysed under very mild conditions. Carbanions derived from selenoketals undergo intramolecular reactions [e.g. (49)] when appropriately substituted, and can be used in the synthesis of silyl enol ethers, e.g. (50). ... 

The first EtAlCl2-mediated intramolecular addition of silyl enol ethers to both terminal and internal non-activated alkynes (Scheme 16), bearing alkyl and phenyl substituents at the alkyne moiety (121) -> (122), has been reported and shown to... 

Reactions of Enolates and Enolate Equivalents.— Highly crowded ketones are prepared by the Lewis acid-catalysed t-alkylation of trimethylsilyl enol ethers. Stereoselection is observed in alkylations with tertiary halides which are known to solvolyse stereoselectively owing to anchimeric assistance or other factors. The alkylation can be carried out in an intramolecular fashion, but compounds having silyl enol ether and tertiary halide functions are difficult to prepare. However, Lewis acid-mediated cyclization of trisubstituted olefinic active methylene compounds provides an alternative method for the intramolecular... 

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