Wittig reaction enol ethers

Review articles of synthetic importance have featured eliminations involving carbon-halogen bonds and leading to highly strained rings, elimination and addition-elimination reactions, enol ether formation from unsaturated acetals, and the Wittig reaction and related methods. " ... 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

Table 12. Fluorinated Esters and Amides in the Wittig Reaction to Form Enol Ethers [47 and Enamines 48 ...

For references to the use of the Wittig reaction to give enol ethers or enol thioethers, which are then hydrolyzed, see Ref. 58, pp. 715, 726. 

The protection of the hemiacetal hydroxyl in Step B-2 was followed by a purification of the dominant stereoisomer. In Step C-l, the addition of the C(6) methyl group gave predominantly the undesired a-stereoisomer. The enolate was trapped as the trimethylsilyl ether and oxidized to the enone by Pd(OAc)2. The enone from sequence C was then subjected to a Wittig reaction. As in several of the other syntheses, the hydrogenation in Step D-2 was used to establish the configuration at C(4) and C(6). 

Ally vinyl ethers. Enol ethers of aldehydes ean be obtained in moderate to high yield by a Wittig Horner reaction of aliphatic ketones with I and an alcohol in the presence of a base (equation I).2... 

Trifluoromethyl ketones can also be synthesized from 1-trifluoromethyl-substituted enol ethers, which are readily prepared from aldehydes via a Wittig reaction (Scheme 9). Similar to Ruppert s procedure (Section 15.1.4.3.4), this method has thus far only been used to prepare trifluoromethyl compounds. The a-amino trifluoromethyl ketones produced in the reaction scheme are much less stable than the corresponding a-amino ketones, which leads to the formation of byproducts (a-hydroxy ketones) during attempts to purify the a-amino trifluoromethyl ketones by chromatography on silica gel. 35 ... 

Acyl silanes can display disparate behaviour when treated with carbon nucleophiles, even of related types5,61149. For example, when aroyl silanes were treated with a Wittig reagent, none of the expected alkenes was obtained, and the only reaction products isolated were silyl enol ether and triphenylphosphine (Scheme 73)182,183. When alkanoyl silanes were treated with Wittig reagents, however, only the normal olefinated vinyl silane products were isolated (Scheme 74)182-184 Under soluble lithium salt conditions, Z-vinyl silanes were produced with very high selectivities the reaction was used to prepare a pheromone component (50) of the sweet potato leaf folder moth (Scheme 75)183. 

The major advantage of this reagent is its ability to react with carbonyl compounds that do not react with Wittig reagents. Thus it was used to convert the ketone group of 2 into the isomeric enol ethers (4), a reaction that failed with a number of other reagents.2... 

Wittig-type alkenation of the carbonyl group is possible with Ti carbene compounds [56], The reaction is explained by the formation of nucleophilic carbene complexes of Ti, although they are not isolated. In the carbonyl alkenation, the oxametallacyclo-butane intermediate 182 is formed by [2+2] cycloaddition of the carbene complex 181 with the carbonyl group. This intermediate is converted to the new alkene 183 and the Ti(IV) oxo species 184, which is a stable compound, and hence the carbonyl alkenation requires a stoichiometric amount of the Ti complex. Also, ester 185 is converted to the enol ether 187 via 186. 

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]. 

The ketodiester 88 was made from furfural 78 by a Wittig reaction and treatment of the product 87 with acidic methanol.14 The central carbon atom in 88 can be seen as an enol ether in 87. You might like to try to draw a mechanism for this extraordinary reaction which is described in detail in the workbook. 

The Wittig olefination of 1,5-oxazocine 416 with [(methoxy)methylene]triphenylphosphorane led to the formation of the enol ether 431a (88% yield) as an inseparable mixture of E and Z isomers (2.5 1 ratio). Instead, when the reaction was carried out using methyltriphenylphosphorane as Wittig reagent, the as 3,5-disubstituted diastereoisomer 431b was exclusively formed in 85% yield (Scheme 84) <1998JOC3492>. 

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