Phosphonate ylids, reaction with

Adducts from various quaternary salts have been isolated, in reactions with aldehydes, a-ketoaldehydes, dialkylacylphosphonates and dialkyl-phosphonates, isocyanates, isothiocyanates, and so forth (Scheme 15) (36). The ylid (11) resulting from removal of a Cj proton from 3.4-dimethyl-S-p-hydroxyethylthiazolium iodide by NEtj in DMF gives with phenylisothiocyanate the stable dipolar adduct (12) that has been identified by its NMR spectrum and reactional product, such as acid addition and thiazolidine obtention via NaBH4 reduction (Scheme 16) (35). It must be mentioned that the adduct issued from di-p-tolylcarbodiimide is separated in its halohydrogenated form. An alkaline treatment occasions an easy ring expansion into a 1,4-thiazine derivative (Scheme 17) (35). 

More general methods depend on Wittig reactions with functionalised ylids. The ylid24 from 116 and the lithium derivatives of 117-120 all react with aldehydes and ketones to give enol ethers that can be hydrolysed to chain-extended aldehydes. Yields with the ylid from 116 are not always wonderful and the phosphonate ester 120a with a chelating substituent generally does better.25... 

The reaction of triethyl phosphite with maleic anhydride has been re-investi-gated. The product is not the dimeric phosphorane (11), but the ylid (12). Reactions of alkyl or aryl diphenylphosphinites with 1-nitro-l-alkenes have been studied in detail. Radical ion-pairs are involved as shown by e.s.r. and P CIDNP experiments. Allene may be hydrophosphorylated in a radical-initiated process to give allyl- and isopropenyl-phosphonates. A phosphorane (14) has been observed during the reaction of ethyl diethylthiophosphinite (13) with methacrylic acid. ... 

The reaction of trialkylphosphines, especially triphenylphosphine, with alkyl halides is particularly useful since the resultant phosphonium salts are easily converted to the phosphonium ylid on treatment with a suitable base (sec. 8.8r kk Ylids are, of course, the reactive species in the well-known Wittig olefination reaction, which will be discussed in section 8.8.A.i. A related Sn2 process involves reaction of a trialkylphosphite with an alkyl halide, the Arbuzov reaction (sometimes called the Michaelis-Arbuzov reaction). Triethylphos-phite (70) reacts with iodomethane to give the phosphonium salt, 71. Heating generates the monoalkyl phos-phonic ester (72). This type of phosphonic ester can be converted to an ylid and used in the well-known Horner-Wadsworth-Emmons oiefination (sec. 8.8.A.iii). 

The phosphonate XXIV was converted to the respective ylid with sodium hydride and yielded on reaction with ketones or aldehydes the corresponding Schiff bases XXV. These products, in contrast to the aldehyde or ketimine adducts with their intramolecular hydrogen bonds, can easily be converted to the unsaturated carbonyl compound in good yield. 

Fluorophosphoranes can be obtained from phosphonous and phosphinous halides by reactions with arsenic or antimony obtained with KHF2 (6.518). Some phosphinous halides react with sulphur compounds to give phosphinothioites (9.420), with phenyl azide to give monophosphazenes (7.447), and with ylids fluorides (6.504, 6.505). Hydrofluorophosphoranes produces phosphonium salts (6.377). Phosphonous and phosphinous halides can be condensed to form polyphosphines or cyclic derivatives (6.660, 6.666,6.680,6.684), or reacted to give P-P linkages (6.737). 

Other functionality can be incorporated into the ylid prior to reaction with an aldehyde or ketone. Aldehyde 1.195, for example was converted 1.196 by reaction with a fluorine-bearing phosphonate ylid. 5 The ester group was reduced to an aldehyde moiety (see 1.197) with diisobutylaluminum hydride. This allowed final conversion to 5-(N-Boc amino)-4-fluoro-6-phenylhex-3E-enoic acid (1.198), in four steps (3% overall yield the first and second steps gave a combined yield of 14% and step five proceeded in 28% yield). 

Ylids are usually prepared from triphenylphosphine, but other triarylpho-sphines, trialkylphosphines, and triphenylarsine " have also been used. The Wittig reaction has also been carried out with other types of ylids, the most important being prepared from phosphonates " ... 

Derivatives of the general formula (7) in Table 6 have been successfully used as probases and their properties in this context are being further explored. In common with the azobenzenes and ethenetetracarboxylate esters, the fluoren-9-ylidene derivatives usually display two reversible one-electron peaks in cyclic voltammetric experiments. Although disproportionation is possible (cf. Scheme 12) it is the dianions which are the effective bases. It was shown early on that the radical-anions of such derivatives are long-lived in relatively acidic conditions (e.g. in DMF solution the first reduction peak of Ph C -.QCN) remains reversible in the presence of a 570-fold molar excess of acetic acid, at 0.1 V s ). Even the dianions are relatively weak bases, useful mainly for ylid formation from phosphonium and sulphonium salts (pKj s 11-15) they are not sufficiently basic to effect the Wittig-Homer reaction which involves deprotonation of phosphonate esters... 

Further reports have appeared on the reaction of trivalent phosphorus compounds with acetylene dicarboxylates. In the first, alkyl diphenylphosphinites (e.g.57) are shown to react with dialkylacetylene dicarboxylates (e.g.58) in the presence of carbon dioxide to form 1,2-oxaphosphol-3-enes (e.g.59) which in the presence of excess phosphinite decompose via (60) to give di-ylids (e.g.61). On the other hand, the phosphoranes (62) from phosphonites and phosphites react with a further phosphorus component to give the ylids (63) which are readily converted by treatment with alcohol into phosphonates (65) apparently via ketene intermediates (64) as evidenced by and isotopic tracer studies. ... 

The extra stabilisation makes the ylid rather unreactive and phosphonate esters 91 are often used instead of phosphonium salts in these reactions. Treatment with a base (NaH or RO is often used, BuLi will certainly not do) gives an inherently more reactive enolate anion 92 rather than an ylid. These Horner-Wadsworth-Emmons reagents (H WE as we shall call them, though they go under many other names) react with ketones as well as aldehydes and the product is normally the E-alkcnc16 93. 

Monocyclic Phosphoranes. - Further studies of the reaction of P-fluoro-ylids (53) with carbonyl compounds (54) reveals formation of P-fluoro-oxaphosphetans (55) as the initial addition products. These may decompose in a conventional Wittig reaction to form alkenes (56)21 ajgo lose HF to form alkyl phosphonates (57).22... 

A.iu. Phosphine Oxides and Phosphonate Esters. Many extensions of the Wittig reaction have been introduced that improve or modify the reactivity and/or stereoselectivity of the ylid. Horner et al. showed that a-lithiophosphine oxides such as that derived from 552 react with aldehydes or ketones to give a p-hydroxy phosphine oxide (553) as an isolable species. Subsequent treatment with base liberates the alkene, (554). Wadsworth and Emmons modified the Horner reaction to use phosphonate ester derivatives such as... 

The major product of olefination with phosphonate carbanions is usually the ( )-isomer.304 However, a (Z)-selective reaction has recently been developed that uses sodium iodide and DBU as the base.305 Speziale and Ratts suggested that increased amounts of (Z) alkene were obtained by increasing the steric bulk of the L and l1 groups in 557 and 560, formed by reaction of the phosphonate ester ylid with a carbonyl compound. This equilibrium favors the anti conformation(557 over 560 and elimination gives more of the (Z) product, 559.306 jjjjg model assumes that steric encumbrance is more important in 557 and 560 than in oxaphos-phetanes 558 and 561, respectively, that are required for syn elimination to the alkene. This equilibrium generally favors 559 over 562 due to the stereochemical preferences in the initially formed ylid products. 

Some 2,3-epoxyamides of aldonic acids have been prepared by reaction of acyclic aldose derivatives with sulfur ylids (Scheme 1). 5y -epoxidation of some racemic 2-benzyloxy-4-alkenamides by way of iodohydrin formation and subsequent base treatment has afforded epoxides such as 2. Epoxidation of hex-2-enopyranosyl phosphonates has been effected with H202/sodium tungstate. ... 

Ylids are also convenient sources of carbanions and they react with aldehydes and ketones to give alkenes. With a suitable reactant, alkenyl amino acids can be prepared using this approach. One example used a phosphonate ester ylid in a Homer-Wadsworth-Emmons reaction 12 with amino aldehyde 1.189. The product... 

FIGURE 10.16 Synthesis of higher sugar enones hy reaction of sngar aldehydes with stabilized sugar ylids or sugar phosphonates. 

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