Phosphonium ylides 2+2 -cycloadditions

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... 

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). 

Cycloaddition of selenoxophosphane 47 and phosphonium ylide 48 leads to 1,2,4-selenadiphosphetane 49. However, product 49 was not isolated but identified on the basis of its 31P-NMR spectral data (Equation 7)... 

A number of 2-iminothietanes have been prepared from ketenimines and thio-benzophenone ° or thioxanthone. Addition of carbon oxysulfide or carbon disulfide to the phosphonium ylide of a ketenimine 312 gives an imino- 3-dithiolactone as previously noted.Arylsulfonylisothiocyanates undergo cycloaddition at 50°C to vinyl ethers to give 2-iminosulfonylthietanes in 50-76% yields.A ( 2g -I- 2 ) process involving zwitterions was suggested on the basis of the observed stereochemistry. 

An aldehyde or a ketone reacts with a phosphonium ylide in a Wittig reaction to form an alkene. A Wittig reaction is a concerted [2 + 2] cycloaddition reaction it is completely regioselective. Stabilized ylides form primarily E isomers unstabilized ylides form primarily Z isomers. 

The enantioselective 3 + 3-cycloaddition reaction of aromatic azomethine imines with donor-acceptor cyclopropane diesters produced 6,6,6-tricyclic dihydroquinolines in high yields (99%) and up to 98% ee. The side-arm-modified In-TOX/Ni(II) complex was shown to be an effective stereoselective catalyst for this reaction. The formal 3 + 3-cycloaddition reaction of allylic phosphonium ylides (127) to a, -unsaturated carbonyls (128) formed multi-substituted benzenes (129) in high yields (36-93%) (Scheme 38). °... 

It is now accepted that the oxaphosphetane intermediate is formed directly by a [2-1-2] cycloaddition of the phosphonium ylide with the aldehyde (or ketone) through a four-center transition state, in which the formation of the carbon-carbon bond is more advanced than that of the phosphorus-oxygen bond (Scheme 2, Path b). Although there are some exceptions [25, 26], the oxaphosphetane formation step is generally nonreversible [27, 28] and decides the stereoselectivity. 

Heteroatom Wittig chemistry also includes reactions of N-sulfonyl imines. It was demostrated that these compounds underwent olefination reactions with nonstabilized phosphonium ylides under mild conditions to afford an array of both Z- and E-isomers of 1,2-disubstituted alkenes, allylic alcohols, and allylic amines.Additionally, studies of the reactions of 5-bromo-4,6-dimethyl-2-thioxo-l,2-dihydropyridine-3-carboni-trile and thiazolidinone with phosphorus ylides have proved the formation of new phosphonium ylides. Annulations via P-ylides are a common occurrence in the literature. For example, on photochemical irradiation, phosphonium-iodonium ylides were shown to undergo 1,3-dipolar cycloaddition reactions with triple bonds, via a carbene intermediate, to yield furans. " Even more common are the reactions of Morita-Baylis-Hillman (MBH) acetates and carbonates. Zhou et al. demostrated that these substrates were able to generate very reactive 1,3-dipoles in the presence of tertiary phosphines the dipoles then underwent cycloaddition reactions to yield annulation products (Scheme 16). ... 

The symmetrical bis(ylidyl)phosphenium chlorides 103, obtained from the reaction of trimethylsilyl ylides 102 with PCI3 are the first phosphenium salts which do not need counterions of low basicity such as AICI4 to be isolated (Scheme 30) [119]. The explanation of their stability lies in the delocalisation of the phosphenium charge in the two phosphonium parts. The reactivity study of these species is reported and for example the phosphenium 103 (R=Ph) adds ortho quinones to the central phosphorus to give the corresponding dioxaphospholenium salts 104 via a [4-1-1] cycloaddition. 

In the first step a Wittig transformation is performed. The a-position of the phosphonium salt 12 is C,H-acidic, and therefore the strong base NaHMDS abstracts a proton forming the labile ylide 38. This ylide is a carbon nucleophile, which attacks the ketone moiety of Segment B (7) forming the oxaphosphetane intermediates cw-39 and trans-39. The mode of action is thought to proceed via a [2+2]-cycloaddition. 

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. 

In the reaction of OH-, NH-, SH- and CH-acidic compounds with phosphacumulene ylides the anion Nu of the initially formed phosphonium salt (c/. equation 101) is so nucleophilic, that addition of the anion to give a new alkylidenephosphorane is faster than cycloaddition of a second mole of starting ylide (equation 105). ° ... 

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