Alkylation phosphonium ylides

Allylic alkylation of 3-acetoxy-l,3-diphenylpropene by sodium dimethytmalonate, catalysed by the Pd-allyl complex 115, bearing the non-symmetric phosphonium ylide NHC ligand (5 mol%), proceeds to completion with 100% regioselectivity. 

Phosphonium ylides are usually prepared by deprotonation of phosphonium salts. The phosphonium salts that are used most often are alkyltriphenylphosphonium halides, which can be prepared by the reaction of triphenylphosphine and an alkyl halide. The alkyl halide must be reactive toward Sw2 displacement. 

The metal-free eyclobutane-1,2-dioxime can be generated by oxidative displacement. It is interesting to note that, unlike ketene dimerization, head-to-head dimerization takes place here. The chromium ketenimine complex 20 is prepared by reaction of the Fischer-type chromium carbene complex with alkyl isocyanides.60 A cyclobutane-1,2,3,4-tetraimine 24 has been reported from the reaction of the ketenimine phosphonium ylide 22.61 Bisimine 23 has been proposed as the intermediate in this transformation. 

Conversion of phosphines via phosphonium salts into phosphonium ylides induces a deshielding of the a alkyl and aryl carbons (Table 4.49). Considerable shielding of the ylide sp2 — C = P carbon nucleus reflects the presence of a large electron density, thus indicating a significant contribution of the ylide dipole to the actual state of the molecule. 

A limited number of other anionic species have been employed as Michael donors in tandem vicinal difunctionalizations. In a manner similar to sulfur ylides described above, phosphonium ylides can be used as cyclopropanating reagents by means of a conjugate addition-a-intramolecular alkylation sequence. Phosphonium ylides have been used with greater frequency261-263 than sulfur ylides and display little steric sensitivity.264 Phosphorus-stabilized allylic anions can display regiospecific 7-1,4-addition when used as Michael donors.265... 

The Wittig Reaction allows the preparation of an alkene by the reaction of an aldehyde or ketone with the ylide generated from a phosphonium salt. The geometry of the resulting alkene depends on the reactivity of the ylide. If R is Ph, then ihe ylide is stabilized and is not as reactive as when R=alkyl. Stabilized ylides give ( )-alkenes whereas non-stabilized ylides lead to (Z)-alkenes. 

The same trans-selectivity can be observed with the condensation of aldehydes with phosphonium ylides of the type Ph3P -CH -C(=0)-alkyl or Ph3P -CH -C(=0)-H, which is illustrated in Figure 11.9, using as an example the preparation of the O, /T unsaturated ketone C and the preparation of the o ,/Tun saturated aldehyde D, although the latter does not work that smoothly (see below). 

The Wittig reaction is a C,C-forming olefin synthesis from phosphonium ylides and carbonyl compounds (see also Section 4.7.4). In more than 99% of all Wittig reactions, ylides of the structure Ph3P+—CH-—X (i.e., triphenylphosphonium ylides) are used. Therein, X usually stands for H, alkyl, aryl, or C02-alkyl and seldom for other substituents. 

The alkylation of an anion of 347, obtained by treatment with lithium diethylamide, with methyl iodide has been reported briefly. p-Nitrobenzaldehyde undergoes the Wittig reaction with phosphonium ylide 345 to give the red-black derivative 354. The acid-catalyzed ring-expansion of several 2-iminothietanes, for example, 355, has been described. ... 

Stereoselctive synthesis of fluorinated (E)- and (Z)-allylphosphonates involves treatment of phosphonium ylides (236) with methyllithium derivative (237) giving, after protonation and elimination of PhaPO, (Z)-allylphosphonates (238), whereas with alkyl lithium derivative (239), (E)-allylphosphonates (240) result (Scheme 62). ... 

In the Wittig reaction an aldehyde and a phosphonium-ylide are coupled to give a new C=C double bond and triphenylphosphine oxide. Depending on the nature of the phosphonium ylide the Wittig reaction is either Z-selective if a labile ylide is employed or E-selective if a stable ylide is used. A labile phosphonium-ylide PhsP-CH-X possesses a substituent X (e.g. alkyl), which is not able to stabilize the negative charge at the carbon atom, whereas a stable ylide... 

In addition to the generation of phosphonium ylides from phosphonium salts by deprotonation with bases in some instances ylides may result from pyrolysis of phosphonium salts, especially silylated salts (equation 17). Similar fluoride ion induced desilylation (equation 18) of phosphonium salts proved to be a very useful alternative for the synthesis of ylides which are difficult to synthesize by the conventional salt method (as in the case of R, R = alkyl). - The most effective fluoride source is cesium fluoride and the reaction proceeds at room temperature. 

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-... 

Axelrod et alP have describe the synthesis of 1,5-dienes by alkylation of an allylic phosphonium ylide with an allylic bromide. The method was used to synthesize pure all-( )-squalene from ( , )-fame-syl bromide and its tributylphosphonium salt. No isomerization occurred during the reaction and reduction of the resulting phosphonium salt with lithium in ethylamine gave squalene in 65% yield. 

Alkylation chemistry has also been reported for alkylphosphine oxides and dialkyl phosphonates. The phosphonate carbanions are often preferred as they offer many advantages over the phosphonium ylides. In particular, the phosphonate group is highly acidifying and the resulting organolithium can be smoothly alkylated. 

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

Stable phosphorus ylides (50) and (51) have been prepared from the reaction of electron-deficient acetylenic esters, such as dialkyl acetylenedicarboxylates or alkyl propiolates and triphenylphosphine in the presence of 3-chlorotetrahyd-rofuran-2,4-dione (Scheme 10). These reactions are thought to proceed via vinylphosphonium salt intermediates which undergo Michael addition with the conjugate base of the CH-acid. Similar methodology has been used to prepare phosphonium ylide (52) from triphenylphosphine, isatin (indoline-2,3-dione) and dimethyl acetylenedicarboxylate. " ... 

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