Alkyl halides phosphonium ylides

Wittig reactions are versatile and useful for preparing alkenes, under mild conditions, where the position of the double bond is known unambiguously. The reaction involves the facile formation of a phosphonium salt from an alkyl halide and a phosphine. In the presence of base this loses HX to form an ylide (Scheme 1.15). This highly polar ylide reacts with a carbonyl compound to give an alkene and a stoichiometric amount of a phosphine oxide, usually triphenylphosphine oxide. 

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. 

Alkyl halide reacts with triphenylphospine to give a phosphonium salt, which is an important intermediate for the preparation of phosphorus ylide (see Section 5.3.2). 

In the Wittig reaction an aldehyde or ketone is treated with a phosphorus ylide (also called aphosphorane) to give an olefin.638 Phosphorus ylides are usually prepared by treatment of a phosphonium salt with a base,639 and phosphonium salts are usually prepared from the phosphine and an alkyl halide (0-43) ... 

Quaternisation of triphenylphosphine with an alkyl halide gives a quaternary phosphonium halide (4) which under the influence of a strong base eliminates hydrogen halide to give an alkylidenephosphorane [(5), an ylide]. The latter reacts with an aldehyde or ketone to give first an intermediate betaine (6), which rearranges to the oxaphosphetane (7), which then under the reaction conditions eliminates triphenylphosphine oxide to form an alkene. 

The phosphorus-stabilized carbanion is an ylide (pronounced ilL-id )—a molecule that bears no overall charge but has a negatively charged carbon atom bonded to a positively charged heteroatom. Phosphorus ylides are prepared from tri-phenylphosphine and alkyl halides in a two-step process. The first step is nucleophilic attack by triphenylphosphine on an unhindered (usually primary) alkyl halide. The product is an alkyltriphenylphosphonium salt. The phosphonium salt is treated with a strong base (usually butyllithium) to abstract a proton from the carbon atom bonded to phosphorus. 

Phosphorus ylides are prepared from phosphonium salts by deprotonating them with a strong base. The method consists of the alkylation of triphenylphosphine with alkyl halide. The resulting phosphonium salt is treated with a strong base (phenyUithium or n-butyllithium) to give a phosphorus ylide. The simplest ylide is methylenetriphenylphos-phorane (3.50), which is prepared by the abstraction of a proton from methyltriphenylphos-phonium iodide. 

A publication discussing the uses of reactive arsonium ylides for the stereospecific preparation of epoxides draws attention to the fact that arsonium salts are less readily prepared than phosphonium salts because of the poorer nucleophilicity of arsenic compared to phosphorus, and suggests methods for obtaining them. Primary salts were made from alkyl triflates, while a-branched salts were prepared from alkyldiphenylarsines, obtained from iodo compounds as, for example, in equation 23. Reaction of alkyl halides with arsines to form arsonium salts is also promoted by the presence of silver tetra-fluoroborate . 

The trivalent phosphorus atom bears a lone pair of electrons and therefore can be used as a nucleophilic reagent for substitution. Triphenylphosphine displacements on alkyl halides give phosphonium salts which, after the conversion into phosphorus ylides by strong bases. 

Nonstabilized Ylides. These ylides are devoid of electron-v ithdrawing substituents at the anionic center they carry hydrogen or electron-donating alkyl groups on the ylide carbon and phenyl groups on the phosphorus. Nonstabilized ylides are very nucleophilic and react with CO2, O2, and H2O hence they must be handled in an inert atmosphere. Primary as well as secondary alkyl halides may be used for the preparation of phosphonium salts and subsequently ylides. 

Ethylene oxide or 1,2-epoxybutane may also be used for the synthesis of ylides. The resulting ylide is in equilibrium with its conjugated salt (equation 15). The use of ethylene oxide offers some advantages over more conventional bases used in Wittig reactions. The application is simple since ylides and most often also phosphonium salts (from phosphine and alkyl halide) need not to be prepared separately. The reaction medium is neutral, so that base-induced side reactions fail to appear. The method is however less applicable to weakly acid phosphonium salts, since deprotonation requires high temperatures (150 C). 

The reaction of ylides with saturated aliphatic alkyl halides (like methyl iodide, ethyl iodide etc.) usually stops at the stage of the alkylated salt because the +/ effect of the aliphatic substituent causes the resulting salt to be a weaker acid than the conjugated salt of the original ylide (which would result in the course of a transylidation reaction). However since partial transylidation also occurs between al-kylidenephosphoranes and phosphonium salts with equal or not very different base and acid strength, mixtures may result from Ae reaction with saturated aliphatic alkyl halides. At this point it should be mentioned that the synthesis of dialkylated ylides via the salt method is also difficult since the preparation of the necessary phosphonium salt is accompanied by -elimination. The successful synthesis of dialkylated ylides may be achieved by fluoride ion induced desilylation of a-trimethylsilylphosphonium salts (see equation 18). There is no doubt about the course of ylide alkylation in cases where the inductive effect of the new substituent leads to complete transylidation (e.g. equation 54). ... 

The phosphonium ylide needed for a particular synthesis is obtained by an Sn2 reaction between triphenylphosphine and an alkyl halide with the appropriate number of carbon atoms. A proton on the carbon adjacent to the positively charged phosphorus atom is sufficiently acidic (p/fa = 35) to be removed by a strong base such as butyl-lithium (Section 12.11). 

SOLUTION TO 34b (1) The alkyl halide required depends on which phosphonium ylide is used it would be either 1-bromobutane or 2-bromopropane. 

Phosphonium ylides (alkyhdene phosphoranes) can be prepared by a number of methods, but in practice they are usually obtained by action of a base on (alkyl)triphenylphosphonium salts, which are themselves readily available from an alkyl halide and triphenylphosphine. The phosphonium salt can usually be isolated and crystallized, but the phosphonium ylide is generally prepared in solution and used without isolation. Formation of the phosphonium ylide is reversible, and the reaction conditions and the strength of the base required depend entirely on the nature of the ylide. A common procedure is to add a stoichiometric amount of a solution of n-butyllithium to a solution or suspension of the phosphonium salt in ether or THF, followed, after an appropriate interval, by the carbonyl compound. Other bases, such as sodium hydride or sodium or potassium alkoxides, in solution in the corresponding alcohol or in dimethylformamide, are used commonly. 

Among the other developed approaches to novel P-ylides, the synthesis of a-sulfanyl-a-phosphonyl phosphonium ylides (58) in quantitative yields via the addition of two equivalents of trialkylphosphites to phosphonodithio-formates should be mentioned. The subsequent reaction of these ylides with alkyl or benzyl halides gives stabilized sulfonium ylides (59) while their heating (18-150 h, 110 °C) leads to a-sulfanyl methylene bis-phosphonates through protonation-dealkylation intramolecular reactions. The synthesis... 

Phosphorus ylides are most commonly prepared by deprotonation of phos-phonium salts with strong base. The phosphonium salts, in turn, are prepared by the reaction of trialkyl- or triarylphosphines with alkyl halides ... 

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