Deprotonation of phosphonium salts

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. 

All P ylides for Wittig reactions are obtained by deprotonation of phosphonium salts. Depending on whether one wants to prepare a nonstabilized, a semistabilized, or a stabilized ylide, certain bases are especially suitable (see Table 11.1 an unusual, i.e., base-free, generation of ylides is described in Side Note 11.1). In stereogenic Wittig reactions with aldehydes, P ylides exhibit characteristic stereoselectivities. These depend mainly on whether the ylide involved is nonstabilized, semistabilized, or stabilized. This can also be seen in Table 11.1. 

Sodium hydride itself, not only its reaction product with DMSO, is also suitable for deprotonation of phosphonium salts and preference has been given to this base over sodium ethoxide. ... 

Because of the strong basicity of the fluoride ion, in nucleophilic Sn2 reactions elimination usually occurs as a dominant side-reaction. On the other hand, the basicity of the naked fluoride can be used for synthetic purposes, e. g. for deprotonation of phosphonium salts to the corresponding ylides in a system based on potassium fluoride with catalytic amounts of 18-crown-6 in acetonitrile. 

Deprotonation of phosphonium salts can give rise either to phosphino or to phosphido derivatives. ... 

Deprotonation of phosphonium salts by liquid ammonia is another method (7.450) of preparation. 

Other recent uses of LHMDS as base for the deprotonation of phosphonium salts include the final coupling in the total synthesis of (+)-spongistatin and the assembly of the subunit C31-C40 of... 

Deprotonation of phosphonium salts gives phosphorus ylides... 

Silyl migrations readily occur in silylated ylides to give the ylides of optimum stability. Thus, deprotonation of the salts (21) and (23) gave the ylides (22) and (24), respectively. Intermolecular silyl transfers, from one ylide (or the corresponding phosphonium salt) to another, also lead to maximum stabilization. Silyl transfer does not occur in the product (26) from methylenetrimethylphosphorane and the chlorodisilane (25), pre-... 

The reaction of trialkyl- and triaryl-phosphines with 1,3-benzodithiolylium salts leads to formation of phosphonium salts which are deprotonated by treatment with n-butyllithium to produce (69). The similar reaction of trialkyl phosphites in the presence of sodium iodide yields dialkyl phosphonates which can be deprotonated to (70). Both (69) and (70) can react further with ketones to give the 2-alkylidene-l,3-dithiole derivatives (71) (80AHC(27)151>. The ylide (72) has also been prepared (80H(l4)27l>. 

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 diphosphinomethanes (70 R = Me, Ph) react with 1,2-xylylene dibromide to give the bis(phosphonium) salts (71 R = Me, Ph) <820M1266>. By stepwise deprotonation of the salts, the mono-, bis- <81CB1428>, and tris-ylides <820M1266> (72)-(74) have been prepared (74) has been used as a ligand for transition metal ions <820M1266,83AG(E)907>. 

The acidity of the proton on the a-carbon atom determines how strong a base is required to deprotonate a phosphonium salt. The range of bases used extends from aqueous potassium carbonate solution to organometallic compounds. Phosphonium salts that are substituted by strong electron acceptors on the a-carbon atom can be deprotonated by bases as weak as dilute aqueous alkali, even in two-phase systems, to give stable ylides. Even amines such as triethylamine can be used as proton acceptors in such cases. On the other hand, to deprotonate... 

The reactivity of the ultrasonically formed butyllithiums was also examined. Thus, sec-BuLi was used to deprotonate a phosphonium salt and the resulting ylide used in the standard Wittig reaction. Similarly, ortho-lithiation of anisole could be effected in a one-pot process (Scheme 22). However, deprotonation of terminal alkynes or 1,3-dithianes requires use of lithium containing at least 2% sodium, in contrast to the previous examples, which were all carried out using low-sodium content lithium wire (<0.02%). There is no satisfactory explanation for this observation as yet. 

Generation of Phosphorus Ylides and Phosphonate Anions. NaHMDS is the most utilized base for the deprotonation of a variety of phosphonium salts to generate the corresponding ylides, which then undergo Wittig reaction with a carbonyl compound. More recently, it was shown that such a base is compatible with a variety of other systems. For instance, it was shown that aUenes and dienes could be prepared, respectively, from aromatic... 

In general, nonstabilized and semistabilized phosphonium ylides are prepared by deprotonation of the corresponding phosphonium salts with strong bases that are incompatible with aldehydes or ketones. However, some studies have shown that these phosphonium ylides can be generated in the presence of aldehydes by treatment of the corresponding phosphonium salts with a weaker base such as l,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) [100], NaOH, LiOH [101, 102], KOH [103], or K2CO3 [49, 104, 105] (Scheme 20). In addition, these bases promote the one-pot Wittig reaction of phosphonium salts with aldehydes in a number of solvents such as toluene, tetrahydrofuran, dimethyl sulfoxide, isopropanol, and water. 

Fluonnated ylides have also been prepared in such a way that fluonne is incorporated at the carhon P to the carbamonic carbon Vanous fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyUithium or hthium dusopropy-lamide did not lead to yhde formation, rather, deprotonation was accomparued by loss of fluonde ion Flowever deprotonation with hydrated potassium carbonate in thoxane was successful and resulted in fluoroolefin yields of45-S0% [59] (equation 54) P-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydnde The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyUithium to form a new yhde, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [6/j such as an acetyhde to form a fluonnated enyne [62] (equation 56)... 

This accounts for the considerable discrepancy between the alkene Z/E ratio found on work-up and the initial oxaphosphetan ais/trans ratio. By approaching the problem from the starting point of the diastereomeric phosphonium salts (19) and (20), deprotonation studies and crossover experiments showed that the retro-Wittig reaction was only detectable with the erythreo isomer (19) via the cis-oxaphosphetan (17). Furthermore, it was shown that under lithium-salt-free conditions, mixtures of (19) and (20) exhibited stereochemical drift because of a synergistic effect (of undefined mechanism) between the oxaphosphetans (17) and (18) during their decomposition to alkenes. 

Phosphoniosilylotion. This combination reacts with acyclic or cyclic enones to give phosphonium salts, formed by addition of P(C6H,)3 to the p-position of the enone and silylation of the carbonyl group. The products can be converted into p-substituted enones by deprotonation (BuLi), a Wittig reaction, and hydrolysis. 

Alternatively, phosphine imines 266 were treated with various phenylacetyl chlorides 270 (method B). Surprisingly, phosphonium salts 271 were isolated with 25 to 97% yield, which could be deprotonated by means of a base to build up the corresponding phosphoranes 272 (66-89% yield). Upon heating to... 

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