Wittig reaction catalysed

Scheme 7.7 Domino Michael-Wittig reaction catalysed by chiral amine catalysis and copper catalysis.

The chloromethyl derivatives of 1 and 2 can be converted to the corresponding phosphonium salts by treatment with triphenyl-phosphine.19 A subsequent phase transfer catalysed Wittig reaction of these salts with formaldehyde introduced pendant vinyl groups. 

The [2,3] sigmatropic Wittig reaction, as exemplified by the rearrangement of fluorenyl allyl ethers under solidrliquid basic conditions is catalysed by tetra-n-butyl-ammonium bromide [14]. 

Other Degraded Carotenoids. A new synthesis of the fungal sex hormone ( )-(7 , 9 )-trisporic acid B methyl ester (114) utilized as the key step a Michael-aldol sequence on the /3-keto-ester (115) to yield the highly functionalized cyclo-hexenone (116). The latter underwent Wittig reaction with the phosphonium salt (117) to give (114). After basic alumina-catalysed hydrogen exchange in tritiated... 

Good results have been achieved in phosphonio-catalysed alkylation of active methylene compounds and imides which may be steroselective873 (equation 269). Aqueous sodium hydroxide deprotonation of the phosphonium salt itself in view of a Wittig reaction is... 

How can the Z selectivity in Wittig reactions of unstabilized ylids be explained We have a more complex situation in this reaction than we had for the other eliminations we considered, because we have two separate processes to consider formation of the oxaphosphetane and decomposition of the oxaphosphetane to the alkene. The elimination step is the easier one to explain—it is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state (as in the base-catalysed Peterson reaction). Addition of the ylid to the aldehyde can, in principle, produce two diastere-omers of the intermediate oxaphosphetane. Provided that this step is irreversible, then the stereospecificity of the elimination step means that the ratio of the final alkene geometrical isomers will reflect the stereoselectivity of this addition step. This is almost certainly the case when R is not conjugating or anion-stabilizing the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z-alkene that results reflects this. The Z selective Wittig reaction therefore consists of a kinetically controlled stereoselective first step followed by a stereospecific elimination from this intermediate. 

In this case, the Wittig reaction is not entirely Z-selective, and it generates some E-isomer. Lindlar-catalysed reduction, on the other hand, generates pure Z-alkene. 

The method used by Coates and Robinson" involved the copper-catalysed decomposition of trans,trans-farnesyl diazoacetate (4) to the cyclopropyl-lactone (5) having the stereochemistry shown. This was transformed into the cis-aldehyde-ester (6) by standard methods. Base epimerization gave the more stable transcompound (7). A Wittig reaction between the trans-aldehyde-ester (7) and the phosphorane (8), followed by lithium aluminium hydride reduction, yielded presqualene alcohol (1) as the major product accompanied by the minor isomer (9). 

The product must be formed by a Wittig reaction of the usual sort (probably E-selective as this 5 a stabilized ylid) followed by base-catalysed isomerization of the alkene into conjugation with thi... 

If the diene is unsymmetrical, particularly if the monoepoxide of the less substituted and therefore less nucleophilic alkene is wanted, alternative methods are required. The enone 269 provides both epoxides 270 and 267. The sulfur ylid route converts the enone directly to one epoxide while base-catalysed epoxidation followed by a Wittig reaction provides the other. 

A protected version of the aldehyde 174 comes from acetal formation and reduction of the remaining C02H group. Acid catalysed hydrolysis of the acetal gives the lactone 177 that is protected as 178. Hydrolysis and oxidation give 179 ready for the Wittig reaction. 

Marshall and Ruden have reported a stereoselective synthesis of nootkatone (298) in which the keto-ester (299) was annelated with tmns-pent-3-en-2-one to give the bicyclic keto-ester (300). The ethylidene moiety was converted to the 7 -acetyl group by epoxidation, acid-catalysed rearrangement, and basic equilibration. After bis-ketalisation of the diketo-ester (301) the carbomethyoxy-group was converted to the 5a-methyl group in three steps and a subsequent Wittig reaction yielded racemic nootkatone (298). An earlier synthesis of noot-... 

Sun and Fraser-Reid reported a synthesis of methyl (-)-nonactate starting from D-ribose, C-4 of which (sugar numbering) provided C-6 (nonactin numbering) of the tetrahydrofuran ring (Scheme 36) (64). The ribose-derived aldehyde 260, was converted to the ketone 261 by a Wittig reaction followed by hydrolysis of the enol ether. Raney nickel catalysed hydrogenation of the ketone 261... 

In another approach to the technical synthesis of the apocarotenoids 286, 287 and 292 [118] the C25-aldehyde 12 -apo-p-caroten-12 -al (293) is the key intermediate. Several ways to synthesize this compound have been developed, applying the Wittig reaction to couple the building blocks. By the reaction of the Cas-aldehyde 293 with the protected Cs-phosphonium salt 294 the Cao-aldehyde is obtained [119,120], and this can be transformed by a base-catalysed aldol condensation with acetone (295) to give the Css-ketone citranaxanthin (292) [121]. Alternatively the C2s-aldehyde 293 can be reacted in a Horner-Emmons reaction with the Cs-phosphonate 296 to give 292 [122] Scheme 61). 

Wittig reaction. Among other unusual olefin syntheses is the formation of the six-membered olefin (29) from the five-membered ketone (27) and an excess of ethylidenephosphorane in DMSO, This probably involves initial base-catalysed isomerization of (27) to the six-membered ketone (28). 

An interesting synthesis of dictamnine (22) is initiated by lithiation of the quinoline (20) (Scheme 2) which is followed by formylation to give (21). Wittig reaction followed by two acid-catalysed steps gives dictamnine (22). The related alkaloids, pteleine and evolitrine, were similarly synthesized. 

Carotenoids, Retenoids, Pheromones and Polyenes.-A convenient route to exclusively ( )-allylic phosphonates (e.g. 165), compounds which are useful in polyene synthesis, is provided by the base-catalysed isomerisation of the corresponding vinylphosphonates. " The bis(trifluoromethyl) analogue (167) of a known, potent squalene synthase inhibitor has been synthesised using the Wittig reaction of (166) with hexafluoroacetone as a key step. ... 

The first synthesis of (-)-lipstatin came from Jean-Marc Pons and Philip Koden-ski. [266] The key step is a Lewis acid-catalysed, diastereoselective [2 + 2]-cy-cloaddition of an aldehyde with a ketene. The unsaturated side-chain is formed by two Wittig reactions. 

---