Enolates 1,2 -Wittig rearrangements

Disubstituted alkenes with a trans double bond can be generated routinely from Wittig rearrangements in the case of ester enolate Wittig rearrangements, cis selectivity can be achieved. For trisub-stituted alkenes, ( )- and (Z)-selective syntheses are known. 

Table 2 Counterion Effects on the cis/trans Selectivity of Ester Enolate Wittig Rearrangements ...

Most examples of [1,2]-Wittig rearrangements involve relatively basic carbanions. However, a few reports have demonstrated that enolates derived from a-alkoxy carbonyl compounds can also participate in [1,2]-Wittig rearrangements. For example, a-benzyloxy lactam 34 was converted to 35 in 63% yield upon treatment with LiHMDS. Related enolate Wittig rearrangements have also been used in tandem processes as described below. 

The [1,4]-Wittig rearrangement is potentially useful not only for the carbon-carbon bond formation but also for enolate formation. However, synthetic applications have been rather limited, because of the low yields and restricted range of substrates. Schlosser s group have developed a practical approach to aldehydes based on a [1,4]-rearrangement/ enolate trapping sequence. In contrast, standard aqueous workup gave poor yield of aldehyde. This protocol was employed as the key step in a synthesis of pheromone (102) from 99 via 100 and 101 (equation 56f. ... 

Snider and colleagues have developed the sequential ene reaction/thia-[2,3]-Wittig reaction which provide appropriately functionalized product 152 at allylic position on simple alkene 150 in two steps involving intermediate 151 (equation 87) . Thia-[2,3]-Wittig rearrangement was often utilized as a key step of natural product synthesis. Masaki and colleagues have demonstrated that the potassium enolate thia-[2,3]-rearrangement of aUyl sulfide 153 to 154 is useful for the synthesis of terpenoid diol component 155 of the pheromonal secretion of the queen butterfly (equation 88) . 

As described above, the desired compound 17 with high degree of anti selectivity could be obtained from the starting materials, propargylic alcohols in only three steps. Thus,ester-enolate [2,3]-Wittig rearrangement can be considered as one of the most attractive synthetic methods for new types of trifluoromethyla-ted intermediates. However, switching of ( )- and (Z)-substrates did not lead to the diastereoselective construction of the different stereoisomers. The next... 

Table 8. Stereoselective Ester Enolate [2,3] Wittig Rearrangement of Substituted Methyl (Z)-2-[(4,4,4-Trifluorobut-2-enyl)oxy]acetates (Z)-25 to y.ti-U nsaturated anti-( )-a-Hydroxy-/3-(trifluoromethyl) Esters (E)-2617...

The lithium enolate formed from methyl S-trityl mercaptoacetate (8) has been C-alkylated in high yield at or below —40 °C (Scheme 4).37 At higher temperatures, the [ 1,2]-thio-Wittig rearrangement of the enolate was the predominant process. ESR evidence has indicated that the rearrangement occurred by a radical mechanism. 

It has been shown that treatment of o -benzyloxyallyltrimethylsilane with strong base (s-BuLi) at low temperatures results in exclusive formation of the [1,4]-Wittig rearrangement product, the enolate of 4-phenylbutanoyltrimethylsilane, which can be protonated or trapped with a range of electrophiles. By contrast, when weaker bases... 

Metal alkoxides, such as sodium benzylate, in catalytic amounts promote the [2,3]-Wittig rearrangement of silyl enolates (34), to afford the corresponding rearrangement product (35) in good yields at room temperature (Scheme 8).23... 

It has been demonstrated that the oxygen anion of initially formed product (36) effectively catalysed the [2,3]-Wittig rearrangement as a Lewis base. Other Lewis-base catalysts such as lithio or sodio 2-pyrrolidone promote the same [2,3]-Wittig rearrangement of silyl enolates generated from a-allyloxy ketones, whereas rearrangements of enolates from a-allyloxy esters were efficiently catalysed by ammonium 4-methoxybenzoate.24... 

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]. 

Silyl enolates generated from a-allyloxy esters undergo the [2,3]-Wittig rearrangement on treatment with Lewis base such as tetrabutylammonium acetate or tetrabuty-lammonium 4-methoxybenzoate (Scheme 10).14... 

A Lewis-base-catalyzed [2,3]-Wittig rearrangement of the silyl enolate 1113 exclusively affords the chroman-4-one 1114 (Equation 436) <2005CL588>. 

Cyclisation onto the enol ether 315 transiently generates a tetrahydrofuran 316, but this undergoes rapid elimination to 317 - a transformation which is overall equivalent to a [1,4]-Wittig rearrangement.154... 

We also observed similar phenomena in the reaction of silyl enol ethers with cation radicals derived from allylic sulfides. For example, oxidation of allyl phenyl sulfide (3) with ammonium hexanitratocerate (CAN) in the presence of silyl enol ether 4 gave a-phenylthio-Y,5-un-saturated ketone 5. In this reaction, silyl enol ether 4 reacts with cation radical of allyl phenyl sulfide CR3 to give sulfonium intermediate C3, and successive deprotonation and [2,3]-Wittig rearrangement affords a-phenylthio-Y,6-unsaturated ketone 5 (Scheme 2). Direct carbon-carbon bond formation is so difficult that nucleophiles attack the heteroatom of the cation radicals. 

Generally, ester enolates of structure (202 R = M, R = Oalkyl) rearrange via a 3,3-shift, whereas the corresponding amide enolates (202 R = M, R = N(alkyl)2) and acid dianions (202 R = M, R = OM) prefer the 2,3-pathway (equation 20). Both pathways have been observed with ketone enolates (202 R = M, R = alkyl). With substrate (179), Koreeda and Luengo observed only traces of Wittig rearrangement product (205), except for the lithium enolate, where (205) accounted for up to 20% of the reaction mixture (equation 21). ° Thomas and Dubini, however, reported predominant formation of 2,3 Wittig products (207) and (209) under base treatment of ketones (206) and (208) (equation 22). ... 

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