Wittig rearrangement compounds

The rearrangement of an ether 1 when treated with a strong base, e.g. an organo-lithium compound RLi, to give an alcohol 3 via the intermediate a-metallated ether 2, is called the Wittig rearrangement. The product obtained is a secondary or tertiary alcohol. R R can be alkyl, aryl and vinyl. Especially suitable substrates are ethers where the intermediate carbanion can be stabilized by one of the substituents R R e.g. benzyl or allyl ethers. 

In contrast to the intermediate hydroxystannanes, O-protected stannanes 7 are stable compounds which can be distilled or chromatographed and stored under nitrogen for months. Treatment of 7 with butyllithium in tetrahydrofuran at — 78,JC results in rapid tin/lithium exchange (< 1 min). No products resulting from Wittig rearrangement or formation of an ate complex 8 could be detected9. 

In order to establish the correct absolute stereochemistry in cyclopentanoid 123 (Scheme 10.11), a chirality transfer strategy was employed with aldehyde 117, obtained from (S)-(-)-limonene (Scheme 10.11). A modified procedure for the conversion of (S)-(-)-limonene to cyclopentene 117 (58 % from limonene) was used [58], and aldehyde 117 was reduced with diisobutylaluminium hydride (DIBAL) (quant.) and alkylated to provide tributylstannane ether 118. This compound underwent a Still-Wittig rearrangement upon treatment with n-butyl lithium (n-BuLi) to yield 119 (75 %, two steps) [59]. The extent to which the chirality transfer was successful was deemed quantitative on the basis of conversion of alcohol 119 to its (+)-(9-methyI mande I ic acid ester and subsequent analysis of optical purity. The ozonolysis (70 %) of 119, protection of the free alcohol as the silyl ether (85 %), and reduction of the ketone with DIBAL (quant.) gave alcohol 120. Elimination of the alcohol in 120 with phosphorus oxychloride-pyridine... 

Attempts to isolate 1,3-dilithiated propargylic ethers with two equivalents of BuLi at temperatures above -20 give unsatisfactory results, because the dilithio compounds are unstable. In the case of HCsCCH2Or-Bu, HCsCCH(-f-Bu)OH is found after aqueous hydrolysis, possibly as a result of a Wittig-rearrangement [2]. At temperatures below -20 C the dilithiation is too sluggish to be of practical interest. With the super-basic reagent BuLi.t-BuOK in a THF-hexane mixture dipotassiation can be effected in a relatively short time at low temperatures. 

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... 

A novel entry into the field of isobenzofurans was reported by Maddaford et al. The Wittig rearrangement of 76 with n-BuLi yields a dihydroisobenzo-furan which, with silica gel, gave 77. Probably because of the TBS substituent, this compound is remarkably stable at room temperature (96JA10766). 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

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 Wittig rearrangement has been used in the synthesis of a wide range of compounds that rely on this versatile protocol,455 ranging from large antibiotics,456-457 to dihydrofurans,458459 to steroid derivatives.460 62 However, the use of strongly basic conditions is the major hindrance to the implementation of this reaction at scale. 

The Wittig rearrangement of these anions afforded the alkoxides 35, which upon hydrolysis produced the alcohols 36. This type of reaction constitutes an alternative to new organolithium compounds that are difficult to obtain by traditional methods. 

Grindley, T B, Wickramage, C, A novel approach to the synthesis of C-glycosyl compounds the Wittig rearrangement, J. Carbohydr. Chem., 1, 661-685, 1988. 

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