Phosphonium ylides with carbonyls

Condensation of Phosphonium Ylides with Carbonyl Compounds Wittig Reaction... 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

TABLE 11 Comparison of Yields from the Reaction of Carbonyl Compounds Carbomethoxymethylene Triphenylarsorane and with the Corresponding Phosphonium Ylides WITH... 

Reactions of arsonium ylides with carbonyl compounds take place much more readily than with phosphonium or sulphonium ylides. The nature of the products depends upon the character of the substituents on the ylide carbon atom, where electron-withdrawing substituents favour alkene formation, and of substituents on the arsenic atom, where... 

Volatron, F., Eisenstein, O. Theoretical study of the reactivity of phosphonium and sulfonium ylides with carbonyl groups. J. Am. Chem. 

The Wittig reaction of phosphorus ylides derived from phosphonium salts with carbonyl compounds to form alkenes is widely used in synthetic chemistry. The alkylation of phosphorus ylides offers a route to a variety of phosphonium salts which can be further manipulated. Bestman and coworkers - have been responsible for a large number of reports based upon this and other aspects of phosphorus chemistry. Their work includes many examples of the intramolecular alkylation of ylides derived from phosphonium salts to form cyclic compounds. The salts can be prepared from dihalides either with triphenylphos-... 

We study the Wittig reaction in two stages first, the formation and structure of phosphonium ylides and, second, the reaction of a phosphonium ylide with the carbonyl group of an aldehyde or a ketone to give an alkene. The Wittig reaction is especially valuable as a synthetic tool because it takes place under mild conditions... 

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. 

NMR spectroscopic studies f111,13C, and 31P) are consistent with the dipolar ylide structure and suggest only a minor contribution from the ylene structure.234 Theoretical calculations support this view.235 The phosphonium ylides react with carbonyl compounds to give olefins and the phosphine oxide. 

Whereas phosphonium ylides normally react with carbonyl compounds to give alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides undergo intramolecular displacement of the sulfur substituent by oxygen. In this reaction, the sulfur substituent serves both to promote anion formation and as the leaving group. 

Y (as confirmed by results with triafulvenes (see p. 101)). With phosphonium ylides 2-pyrone formation competes with Wittig olefination of the cyclopropenone carbonyl group. 

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). 

Phosphonium ylides form complexes with almost every metal of the periodic table [8-13]. The first ylide complexes involved carbonyl-stabilized ylides at Pd (II) and Pt(II) metal centers. One early example was reported by Amup and Baird in 1969 [61]. The scope of the ylide coordination chemistry was then extensively investigated by Schmidbaur [8]. 

The difluoromethylene ylides react with carbonyl derivatives (aldehyde, lactone) to afford gem-difluoromethylene compounds.They are generated starting from halogenodifluoromethane with triphenylphosphine (or trisaminophosphine) or starting from zinc and a phosphonium salt (or a phosphine oxide)." ° ... 

When artemisinin 9a was treated with 2-lithiothiazole followed by in situ O-acetylation, the thiazole carbonyl adduct 161 was formed chemoselectively in good yield (Scheme 22) the same reaction with PhLi produced a mixture of uncharacterized products. When this acetyl adduct 161 was exposed to TMSOTf, the corresponding elimination product 162 was formed, which was converted in three steps without purification of intermediates into aldehyde 163. This was reacted with high chemoselectivity in reactions with organometallics ( -BuLi, PhMgBr) and with phosphonium ylides in a Wittig procedure <1999T3625>. 

Fluoroolefins may be prepared by the reaction of Wittig reagents and other pho sphorus-contaimng ylides with fluorinated carbonyl compounds. (A discussion of the fluorinated Wittig reagents or other fluorinated phosphorus reagents with nonfluonnated carbonyl compounds is on page 581.) Tnphenylphosphoranes, derived from alkyltriphenyl phosphonium salts, react with 1,1,1-trifluoroacetone [3/] or other trifluoromethyl ketones [32, 33] (equation 26) (Table 10). 

Phosphonium ylides react with carbonyl compounds to give olefins whereas sulfonium ylides aflFord epoxides. In their behavior toward car-... 

Ylides of other elements have been used much less commonly than sulfur ylides in cyclopropanations. Rather, other ylides are better known for their uses in other types of reactions, the best example being the use of phosphonium ylides in the Wittig reaction with carbonyl compounds to give alkenes. Nonetheless, some cases of cyclopropanations have been reported with phosphonium ylides and the related arsenic derivatives. Examples are given in Table 9. 

Application of the Wittig reaction in the carbohydrate field is accompanied by certain difficulties. A correct choice of the initial sugar components is the main problem, owing to the basicity of phosphoranes and, especially, to the drastically basic conditions employed with phosphonium ylides (2a). It is not surprising, therefore, that protected (acetalated and aeetylated) aldehydo sugars and resonance-stabilized phosphoranes were used at first,3-5 although partially protected, and even unprotected, aldoses were shown to be amenable to the reaction with various resonance-stabilized phosphoranes, thanks to the presence of the carbonyl form in the mobile equilibrium. The latter reactions, however, are extremely complicated (see Section IV, p. 284). 

The retinoid-like compound bexarotene (63) is approved for treating skin lesions associated with T-cell lymphomas. The starting tetralin (60) is probably obtained by alkylation of toluene with dichloride (54). Fiiedel-Crafts acylation with the acid chloride (57), gives the ketone (61). This intermediate is then treated with the ylide from triphenylmethyl-phosphonium bromide. The carbonyl oxygen in the product (62) is now replaced by a methylene group. Saponfication of the ester affords the free acid and thus 63. °... 

Sulfonium salts react in several ways. They may behave as a leaving group, undergoing substitution by a nucleophile or fragmenting with the formation of an alkene. However, the most important reaction of sulfonium salts involves the formation of an ylide in the presence of a base. The carbanion of this sulfur ylide is stabilized by the adjacent positively charged sulfonium ion. The reaction of the carbanion with a carbonyl group parallels that of a phosphonium ylide in the Wittig reaction. However, the decomposition of the intermediate dipolar species is different and leads to the formation of an epoxide (oxirane) rather than an alkene. 

Reactions of Phosphonium Ylides. - 2.3.1 Reactions with Carbonyl Compounds. This year we are able to report several variations of the traditional Wittig olefination which employ the addition of catalysts to effect the reaction. For example, Lebel et al. have reported a new salt-free process for the methyl-enation of aldehydes, in which the phosphorane is generated in situ from triphenylphosphine and a diazo precursor with either a rhodium- or rhenium-based catalyst (Scheme 6). It was found that the most effective combination of catalyst and diazo-compound were Wilkinson s catalyst [RhCl(PPh3)3] and... 

In the Wittig reaction an aldehyde or ketone is treated with a phosphorus ylid (also spelled ylide and called a phosphorane) to give an alkene. The conversion of a carbonyl compound to an alkene with a phosphorus ylid is called the Wittig reaction. Phosphorus ylids are usually prepared by treatment of a phosphonium salt with a base, and phosphonium salts are usually prepared from a triaryl phosphine and an alkyl halide (10-31) ... 

In order to study possible side reactions which may reduce the yield in the Woodward method of annulation of azetidin-2-ones (Scheme 31) similar reactions of ylides (214), which do not contain groups capable of conversion to carbonyl by DMSO-acetic anhydride treatment, have been investigated. 30 A range of products, e.g. (215) and (216), were obtained. A mild, four-carbon homologation of the 4-formyl-substituted azetidinone (217) involving reaction with the phosphonium ylide (218) has been used to synthesize (219), a useful intermediate in the synthesis of carbacephem antibiotics. 3 ... 

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