Methylenetriphenylphosphorane1

Ph3P=CH2

[3487-44-3]  · C19H17P  · Methylenetriphenylphosphorane  · (MW 276.33)

(methylenating agent for aldehydes and ketones;1 can convert lactols into hydroxy alkenes;2 can form a lithio derivative;3 can be transformed into a b-ketophosphorus ylide4-6)

Physical Data: mp 96 °C; yellow crystals turning white in air.

Solubility: sol ether, THF, DME, benzene, toluene, DMSO; water and protic solvents destroy the reagent completely.

Form Supplied in: not available commercially; prepared as a solution immediately prior to use.

Analysis of Reagent Purity: ylide concentration can be calibrated by color end-point titration of an aliquot with PhCHO in ether or PhCO2H in THF at -20 °C under N2.

Preparative Methods: usually prepared by treatment of a suspension of Methyltriphenylphosphonium Bromide (or iodide) in an appropriate solvent with a strong base. Butyllithium, dimsylsodium, t-BuOK, and sodamide are commonly used. Typically, a suspension of dry methyltriphenylphosphonium bromide in dry ether or THF is treated with n-Butyllithium at 0 °C under N2 and the resulting solution is stirred at rt for 1 h. A yellow to deep orange color indicates the ylide formation. The dimsylsodium (Sodium Methylsulfinylmethylide) procedure7 requires heating a suspension of NaH in dry DMSO at 75-80 °C for 1 h followed by ice-cooling prior to the addition of phosphonium bromide. A salt-free ylide is usually prepared using Sodium Amide in liquid ammonia8 or in refluxing THF.9

Handling, Storage, and Precautions: should always be handled under N2 or Ar. The ylide should be used as prepared for best results.

Methylenation of Aldehydes and Ketones.

The most versatile utility of Ph3P=CH2 is Wittig methylenation10 of aldehydes and ketones.1,10 Under salt-free conditions, 1,2-oxaphosphetanes have been observed as the only intermediate in the methylenation of aldehydes and ketones.8 Even in cases where a lithium base is used, the classically favored betaine intermediate could not be observed. Decomposition of 1,2-oxaphosphetanes upon warming then provides terminal alkenes from aldehydes and 1,1-disubstituted alkenes from ketones. Hydroxy aldehydes11a and ketones11b can be directly converted to hydroxy alkenes when excess reagent is employed (eqs 1 and 2). Often one-carbon homologation of an alcohol can be achieved through a sequence of oxidation, Wittig methylenation, and hydroboration (eq 3).12

Vinyl cyclopropanes13a and cyclobutanes13b are conveniently prepared from corresponding cyclopropyl and cyclobutyl carbonyl compounds. Likewise, vinyl epoxides14 and aziridines15 can be prepared (eqs 4 and 5). a,b-Unsaturated aldehydes and ketones are readily converted to 1,3-dienes (eqs 6 and 7).16

Substituted 1,3-dienes can be prepared by the treatment of corresponding enals and enones with Ph3P=CH2. Some examples include dienyl iodide,17a silyldiene,17b and dienyltin17c (eqs 8-10). Under carefully controlled reaction conditions, dienol ethers and sulfides are obtained from vinylogous formates and thioesters, respectively (eqs 11 and 12).18 The 1,3-dienes prepared this way are often used as Diels-Alder dienes.

a-Thioalkoxy aldehydes give rise to allylic sulfides in reaction with Ph3P=CH2.19 Wittig methylenation can also be effected even in the presence of unusual functional groups such as a phosphonate ester,20 O-silyl oxime,21 peracetal,22 and ketene dithioacetal23 (eqs 13-16).

However, sterically hindered and enolizable ketones are not readily methylenated with Ph3P=CH2.24 Methylenation of a sterically hindered ketone generally requires a substantial excess of the reagent at elevated temperature and a minimum amount of solvent, as demonstrated in a modhephene synthesis (eq 17).24a In this particular example, it was necessary to add the ketone to a preheated (92 °C) solution of a sevenfold excess of Ph3P=CH2 in toluene. One practical modification used to increase the yield of methylenation of enolizable ketones is the repeated additions of stoichiometric amounts of water and the reagent.24b Cyclooctanone was therefore methylenated in ether in 89% yield (44%, otherwise) after five cycles of additions (eq 18).

Other problems commonly observed in Wittig methylenation are b-elimination,25a,b retro-aldol,25c,d and a-ketol rearrangement,25e all of which are caused by the basic nature of Ph3P=CH2 (eqs 19-21).

Methylenation of Lactols and Carbinollactams.

Lactols readily undergo methylenation with excess Ph3P=CH2 to give hydroxy terminal alkenes (eqs 22 and 23).2 g-Lactones,26 as well as d-lactones,27 can be converted to acyclic alkenic products via reductive methylenation (eq 24). a-Substituted lactols are sometimes disposed to a rapid equilibration with the more stable conformers through their acyclic tautomers, giving rise to the epimerized product (eq 25).26e o-Carbinollactams also undergo methylenation to give corresponding alkenic amides (eq 26).28

Reaction with Esters and Carbonyl Equivalents.

Ph3P=CH2 can react with esters to give either acetylated or isopropenyl compounds, depending on the nature of the ester and the reaction conditions.29 Aromatic esters usually give rise to isopropenyl compounds, while aliphatic esters result in a mixture of both (eqs 27 and 28).29a Polar aprotic solvents and salt-free conditions favor the formation of isopropenyl compounds.29b This method has been used recently in the synthesis of the unnatural enantiomer of rothrockene (eq 29).30

Carbonyl equivalents such as mixed acetals31 and b-acyloxy enol esters32 also react with Ph3P=CH2 to provide corresponding alkenic products (eqs 30 and 31).

Formation of Allylic and Homoallylic Alcohols via Oxido Ylides.

Ph3P=CH2 can be activated by lithiation with t-Butyllithium (or s-Butyllithium) in ether.3 a-Lithiomethylenetriphenylphosphorane (Ph3P=CHLi) thus formed reacts with a hindered ketone, which is unaffected by Ph3P=CH2, to give a methylenated compound. Reaction of Ph3P=CHLi with 2 equiv of aldehyde results in formation of a trans-allylic alcohol via a b-oxido ylide (eq 32). Ph3P=CHLi also reacts with an epoxide to give a g-oxido ylide which in turn couples with an aldehyde to provide a trans-homoallylic alcohol (eq 33). b-Oxido ylides are also formed in a SCOOPY reaction33a in which a mixture of cis- and trans-allylic alcohols is usually obtained (eq 34).33b

Formation of Extended Phosphorus Ylides.

Various phosphorus ylides can be produced by reaction of Ph3P=CH2 with electrophiles. b-Ketophosphorus ylides are prepared by acylation of Ph3P=CH2 with an ester,4 thioester,5 acid chloride,6 acylimidazole,34 or even with a 5(4H)-oxazolone35 (eqs 35-39). b-Thiocarbonylphosphorus ylides can be prepared in a similar manner.36

On the other hand, alkylation of Ph3P=CH2 with alkyl halides provides novel phosphonium salts which in turn can yield ylides upon treatment with a base (eq 40).37 Likewise, four- through seven-membered cyclic phosphorus ylides can be prepared by alkylation of corresponding alkyl dihalides with Ph3P=CH2 followed by deprotonation (eq 41).38 Alkylation can also be effected with 1-alkylbenzotriazole,39a epoxide,39b,c or lactone.39d In the latter case, lactones may undergo either alkylation or acylation depending upon the reaction conditions used.39d,e

Other electrophiles which can be reacted with Ph3P=CH2 include a disulfide,40 sulfonyl halide,41 halosilane,42 selenenyl halide,43 and cyanate44 to yield various ylides after treatment with a base. Transylidation45 of phosphonium salts with Ph3P=CH2 provides yet another entry to extended ylides (eq 42).46 Phosphacumulene ylides have been prepared via double transylidation with Ph3P=CH2 (eq 43).47 Allylidenephosphoranes are also formed from the reaction of Ph3P=CH2 with dialkylaluminum alkylidenamides (eq 44).48


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Kevin C. Lee

DuPont Agricultural Products, Newark, DE, USA



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