Phosphonium ylides with electrophiles

Treatment of P-oxido ylides with electrophiles other than proton donors provides a route to stereospecific trisubstituted alkenes. For example, trapping the P-oxido phosphonium ylide B with formaldehyde (generated from paraformaldehyde) leads to dioxido phosphonium derivative D to yield, after elimination of triphenylphosphine oxide, the trisubstituted allylic alcohol... 

Step 1 Make a new bond between a nudeophile and an electrophile. Reaction of a nucleophilic phosphonium ylide with the electrophilic carbonyl carbon of an aldehyde or a ketone gives a dipolar intermediate called a betaine. 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

The phosphanes useful in this process are built from acyl derivatives of compounds such as those shown in Figure 17.22. During the Staudinger ligation process, once the azide reactant forms the aza-ylide with the phosphine, electrophilic attraction induces the nitrogen to attack the electron deficient carbonyl, which in turn causes release of the phosphonium group and forms the amide bond (Figure 17.23). 

In the reactions with phosphonio-a-methoxycarbonyl-alkanides, the products of type 261 derived from 1,3-cycloaddition can rearrange to the tautomeric lif-pyrazolo-triazole (87MI2). The reaction of 3-diazopyra-zoles and 3-diazoindazole with acyl-substituted phosphonium ylides led to pyrazolo-triazine and indazolo-triazine derivatives 266 instead of the expected triazole compounds (8IJHC675). In this case, the ylides, which can exist as phosphonium enolates, possess nucleophilic and electrophilic centers in a /8-relationship, giving [7 + 2] or [11 -I- 2]cycloaddition reactions. With dimethylsulfonio-a-aroyl-methanides, very complex, temperature-dependent mixtures were obtained, in some cases with sulfur retention (87MI3). 

Ylide formation by capture of electrophilic carbenes with tertiary phosphines has been shown to be a symmetry-breaking allowed pathway. The reverse process, dissociation of a phosphonium ylide into carbene and phosphine, is in agreement with the concept of phosphonium ylides as phosphine-carbene complexes."... 

Deprotonation of a phosphonium salt by an ylide is a transylidation reaction,- which is of importance especially in those cases where ylides are reacted with electrophiles (see Section 1.6.1.3), but may also be applied to isolated phosphonium salts. For an unequivocal reaction the two involved ylides must differ sufficiently with respect to their base strength (as for example in equation 14). 

Phosphonium ylides carrying at least one proton at the a-carbon atom react with various electrophilic reagents with formation of a-substituted phosphonium salts or zwitterionic intermediates, from which a-substituted ylides are generated by deprotonation or proton migration, the former reaction being more important (equation... 

Besides protons a series of heteroligands in the a-position of phosphonium ylides can also be substituted, giving rise to the formation of new alkylidenephosphoranes. Halogen atoms have been substituted by carbon groups (with lithium organyls or acyl chlorides) or another halogen. Reaction of a-lithiated ylides (see equation 35) or ylide anions with electrophiles may be considered as substitution of an alkali metal substituent at the ylide carbon atom. 

Synthesis and Characterisation of Phosphonium Ylides. - We start this section with a phosphanylidene-o -phosphorane (14) which, although not strictly an ylide, has a P-P bond which displays many of the properties of more conventional phosphonium ylides. A crystal structure of (14) revealed a P-P bond length of 2.084(2) A, which is similar to those found in other phos-phanylidene-o( -phosphoranes and is certainly shorter than a typical P-P single bond ca. 2.22 A), indicative of multiple bond character. Compound (14) undergoes reactions with electrophiles (Scheme 1) which demonstrate its nucleophilic... 

Olefins with electrophilic substituents, but not those with electron-donating substituents, add tertiary phosphines 61 the phosphonium betaines first formed stabilize themselves under some circumstanes by forming their tautomers, the alkylidenephosphoranes. Thus, for example, the ylide (5) is obtained in more... 

Intramolecular Wittig reactions can be used for the preparation of cyclic alkenes. The formation of the phosphonium ylide must be compatible with other functionality in the molecule and thus stabilized ylides are used most commonly. Wittig reactions with carbonyl groups other than aldehydes or ketones, such as carboxylic esters, are known. For example, a route to the indole or penem ring systems uses a carboxylic amide or a thioester respectively as the intramolecular electrophile (2.77). 

Where the substituent R is capable of conjugation with the P=C bond (e.g. R = CN, CO R, COR, aryl), the ylide is stabilized both against electrophilic and also against nucleophilic attack. Such stabilized ylides are much less prone to oxidation, alcoholysis or hydrolysis. They can be generated, for example, by treating appropriate phosphonium salts with alkali metal alkoxides in alcohols. This is convenient, as lithium alkyls would react with groups such as CO R or COR leading to side products. 

Many alkylidenephosphoranes can be transformed into new phosphonium ylides by reactions which take place in the side chain of a parent ylide, the a-C atom of the ylide group not being involved. Allylidenetriphenylphosphoranes react with a series of chloro compounds (alkyl chloioformates, acyl chlorides, 3-chloroacrylates, 2-chlorovinyl ketones, phosphorus chlorides) and other electrophilic compounds at the 7-C atom. Abstraction of a proton from the 7-position of the resulting phosphonium salts by a second mole of starting ylide (or proton migration) gives rise to the formation of -substituted derivatives of the original allylidenephosphoranes (equation 90). 

The mechanism for both methods is similar and has been proposed to begin with the conjugate addition of the phosphine to the Michael electrophile (i.e., allenoate or2-aUcynoate). In Scheme 33 the mechanism describing the transformation of 2-aIkynoate is presented. After Michael addition, protons shift of the Michael adduct leads eventually to phosphonium ylide 57 that would react in a Wittig reaction with an aldehyde and displace the previous equilibria. Note that, despite the elevated temperature of the reaction with 2-aIkynoate, no isomerization of the double bond allowing the conjugation of the ester with the double bonds was observed. 

The preparation of norbomadiene-fused thiophene (17) involved a double-Wittig reaction of 1,2-dione 15 with the bis-ylide derived from phosphonium salt 16 <99BCSJ1597>. The effect of the fused heteroaromatic ring of 17 (neighboring group participation) on electrophilic substitution of the norbomadiene ring was examined. 

In a synthesis of PGEt reported by Corey 89) for the preparation of the 0,S-acetal-protected dienol thioether aldehyde 122, the ylide generated from phosphonium salt 119 was used as an electrophile in the alkylation of 118. The following Wittig reaction of the resulting phosphonium salt 120 with the thioenolether aldehyde 121 in the presence of phenyllithium as the base gave intermediate 122 in 35% yield. 

Addition of an electrophile to the lone pair of oxo-, thioxo- and imino-vinylidenephosphoranes transforms the nucleophilic system into the dipolar ir -ir system of a ketene. The resulting phosphonium salt becomes a true dipolar ketene which, as such, reacts in a known manner (equation 101). Whenever the anion Nu is a stronger nucleophile than the original cumulated ylide, the new alkylidene-phosphorane will be formed, in which compound ElNu has added to the parent vinylidenephosphorane. If the starting phosphacumulene ylide is a stronger nucleophile than Nu , the intermediate salt always reacts with a second molecule of unreacted ylide in a [2 + 2] cycloaddition to give 1,3-cyclobutanedione derivatives. 

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