Phosphonium salts preparing ylides from

The phosphonium salt X derived from 1,2 3,A-di-0-isopropylidene-a-D-galactopyranose was readily prepared ( ), and the ylide derived from it was condensed effectively with both aliphatic and aromatic aldehydes. The products all had the a-D-galacto configuration, and the aliphatic aldehydes afforded only the Z-isomers. The less constrained permethylated phosphonium salt XI was also prepared, and... 

Other carbon bases that have been used successfully to convert phosphonium salts into ylides include sodium methylsulfinate and the corresponding potassium compound (prepared from alkali metal hydride and DMSO), tritylsodium, sodium acetylide and other strongly basic ylides. 

Since electron-donating substituents at the phosphorus atom favor addition reactions over olefination reactions, addition of 9 to aldehydes leads to the exclusive formation of the silyl-pro-tected allylic alcohols 10. No reaction products arising from Wittig alkenylation could be detected. The ylides (R,S)-9 and (S.S)-9 and their enantiomers were prepared from the corresponding optically pure l-[2-(diphenylphosphino)ferrocenyl]-A,A -dimethylethanamine diastereomers 7 via the phosphonium salts 8. 

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. 

Salt-free ylides have been prepared from phosphonium chlorides and bromides by treatment with sodamide in refluxing THF. The sodium halide precipitates and is removed by filtration. Allylidene- and benzylidene-trimethylphosphoranes have been obtained as low melting distillable solids from the phosphonium chlorides and butyl-lithium in ether. The allylidenephosphorane on standing at room temperature slowly decomposed to give methylenetrimethylphosphorane. 

Preparation.—It has been shown that the stability of the ylide solution formed from the reaction of dihalogenodifluoromethanes with tertiary phosphines is due to a dynamic equilibrium which lies on the side of phosphine and phosphonium salt (Scheme 1). Ylide solutions generated from chlorodifluoroacetate are unstable since no such equilibrium is possible.1... 

A series of conjugated polyenes capped with chromophores and containing an androstane spacer were synthesized by Wittig or Wittig-type olefinations from epi-androsterone 5150. For example, vinyl carboxaldehyde 52, prepared from 51 in 60% yield as shown in equation 32, was treated with 9-anthrylmethylphosphonium bromide and n-butyllithium to give diene 53. Exocyclic diene 53 was subsequently oxidized to vinyl carboxaldehyde 54. The androsterone vinyl aldehyde intermediate could either be treated with a tetraphenylporphyrinpolyenyl phosphonium ylide, or, as shown below, the phosphonium salt of the androsterone (55) could be reacted with TPP polyeneal 56. The desired all-(E) isomer, 57, was obtained from the ( )/(Z)-isomeric mixture by chromatographic purification. 

As an example of a o-arabino phosphonium salt, XVIa was prepared. Simple Wittig reactions with the ylide derived from XVIa did not proceed as smoothly as with the other ylides, and for that reason salt XVIb, which proved to be much better behaved (results not shown), was also prepared. 

The preparation of norbomadiene-fused thiophene (17) involved a double-Wittig reaction of 1,2-dione 15 with the bis-ylide derived from phosphonium salt 16 <99BCSJ1597>. The effect of the fused heteroaromatic ring of 17 (neighboring group participation) on electrophilic substitution of the norbomadiene ring was examined. 

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) ... 

This method, sometimes called the Horner-Emmons, Wadsworth-Emmons, or Wittig-Hor-ner reaction,658 has several advantages over the use of phosphoranes.659 These ylides are more reactive than the corresponding phosphoranes, and when R is an electron-withdrawing group, these compounds often react with ketones that are inert to phosphoranes. In addition, the phosphorus product is a phosphate ester and hence soluble in water, unlike PhjPO, which makes it easy to separate it from the olefin product. Phosphonates are also cheaper than phosphonium salts and can easily be prepared by the Arbuzov reaction ... 

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). 

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. 

When generating the ylide from the corresponding phosphonium salt, the choice of the method of formation is important for the stereochemistry of the reaction. With the original application of lithium alkyls as bases one equivalent of lithium halogenide is always formed this lowers the stereoselectivity. Not before the development of methods for the preparation of salt-free ylide solutions, such as the sodium amide... 

In a synthesis of PGEt reported by Corey 89) for the preparation of the 0,S-acetal-protected dienol thioether aldehyde 122, the ylide generated from phosphonium salt 119 was used as an electrophile in the alkylation of 118. The following Wittig reaction of the resulting phosphonium salt 120 with the thioenolether aldehyde 121 in the presence of phenyllithium as the base gave intermediate 122 in 35% yield. 

A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

Explain why ylides such as this one can be prepared from phosphonium salts using a base such as NaOH rather than BuLi ... 

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. 

Similar types of alkylation have been applied in syntheses of other steroidal side-chains, including that of 22-trans-26,27-dinorergosta-5,22-dien-3j8-ol (387), a novel marine sterol. In addition, the Wittig reaction has been used to prepare various possible polyene intermediates in phytosterol biosynthesis. The aldehydes (389) and (390) were prepared (Scheme 26) from stigmasterol acetate (388b) by modification of a known procedure. These aldehydes were then alkylated with a variety of ylides derived from phosphonium salts, leading to a series of polyenes (391) and (392). ... 

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 . 

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