Phosphorus ylides synthesis

The synthesis of vitamin Dj from a sensitive dienone was another etu-ly success of phosphorus ylide synthesis (H.H. Inhoffen, 1958 A). This Wittig reaction could be carried out without any isomerization of the diene. An excess of the ylide was needed presumably because the alkoxides formed from the hydroxy group in the educt removed some of the ylide. 

Gautam DR, Litinas KE, Fylaktakidou KC, Nicolaides DNJ (2003) Reactions of o-quinones with a-methyl- (or methylene) substituted phosphorus ylides. Synthesis of benzo[b]furan derivatives. Heterocycl Chem 40 399-404... 

The exploration of the chemistry of azirines has led to the discovery of several pyrrole syntheses. From a mechanistic viewpoint the simplest is based upon their ability to behave as a-amino ketone equivalents in reactions analogous to the Knorr pyrrole synthesis cf. Section 3.03.3.2.2), as illustrated in Schemes 91a and 91b for reactions with carbanions. Parallel reactions with enamines or a-keto phosphorus ylides can be effected with electron-deficient 2//-azirines (Scheme 91c). Conversely, electron-rich azirines react with electron deficient alkynes (Scheme 91d). 

An interesting application of a phosphorus ylide in heterocyclic synthesis is in a ring annulation. The diazopyrazole (592) when treated with various phosphorus ylides gave the 3//-pyrazolo[5,l-c][l,2,4]triazole derivatives (593) with elimination of triphenylphosphine (79TL1567). 

Wittig reaction (Section 17.12) Method for the synthesis of alkenes by the reaction of an aldehyde or a ketone with a phosphorus ylide. 

This review concerns in the first part the works published during the last three years on the synthesis and reactivity of stabilized ylides C-substituted by electron-withdrawing groups (COR, CO2R, CN, etc.). The second part deals with the works published in the same period on the chemistry of phosphorus ylides mainly C-substituted by heteroatoms of groups 1-16 (metals, metalloids and nonmetal elements Li, Ba, Ca, Ti, Zr, Nb, Mo, Re, Fe, Ru, Rh, Pd, Pt, Au, Zn, Hg, B, Si, Sn, N, P, As, Sb, O, S, Te). 

Further, Wasserman and coworkers developed a direct acylation of stabilized phosphonium ylides by carboxylic acids in presence of the EDCI/DMAP (way c). This last method allows the introduction of a-aminoacid structures into the resulting P-oxo phosphorus ylides [19-25],opening the way to the total synthesis of depsipeptide elastase inhibitors [22,24] or cyclic peptidic protease inhibitor EurystatinA [20]. 

For group 14, C-tin-substituted phosphorus ylides have been studied in the past but less than the corresponding C-silyl ylides which, owing to their stability and reactivity, are of considerable interest. Indeed a recent review concerning the silylphosphanes with one part concerning the synthesis and applications of silylated phosphorus ylides has been published [112]. 

Phosphorus ylides C-substituted and stabifized by elements of group 16 are often used for the synthesis of natural substances. For example, the synthesis of simpHfied analogs of artemisinin, used against chloroquine-resistant malaria, has been recently described from methoxymethylphosphonium yhde 120 [127,128]. The later is able to convert afiphatic nitriles into a-functionafized ketones 122 which are the precursors of the target compounds. Starting from the aromatic ni-... 

Kolodiazhnyi 01 (1999) Phosphorus ylides chemistry and application in organic synthesis. Wiley-VCH, p 73... 

Decomposition with the elimination of arsenic or phosphorus ylide and formation of silylene (germylene, stannylene) Me2E14, which represents the process inverse to the synthesis of these betaines. 

Kolodiazhnyi, O. I. Phosphorus Ylides. Chemistry and Application in Organic Synthesis, Wiley-VCH, Weinheim-New York-Chichester, 1999. 

The most useful methods for the formation of C-C bonds are based on the addition of C-nucleophiles to carbonyl compounds. Among the many variations of this basic scheme phosphorus ylides, capable of olefinating aldehydes or ketones in a single step, have proven to be exceedingly valuable reagents in organic synthesis. 

Sakamoto et al. reported the synthesis of hyellazole (245) and carazostatin (247) based on the benzannulation of indoles. This method involves an electrocyclization of the 3-(l,3-butadienyl)indoles 685, which derive from the indolin-3-one 686 and the phosphorus ylides 687 (Scheme 5.59). 

As well as the Bingel reaction and its modifications some more reactions that involve the addition-elimination mechanism have been discovered. 1,2-Methano-[60]fullerenes are obtainable in good yields by reaction with phosphorus- [44] or sulfur-ylides [45,46] or by fluorine-ion-mediated reaction with silylated nucleophiles [47]. The reaction with ylides requires stabilized sulfur or phosphorus ylides (Scheme 3.9). As well as representing a new route to l,2-methano[60]fullerenes, the synthesis of methanofullerenes with a formyl group at the bridgehead-carbon is possible. This formyl-group can be easily transformed into imines with various aromatic amines. 

With no major research on the reaction of phosphorus ylides and aliphatic or alicyclic thiones prior to their investigation, Krapcho et where able to elaborate a useful method for the synthesis of the thietane ring system in addition to the preparation of novel types of thiocarbonyl stabilized ylides (Eq. 1). 

A phosphorus ylide serves as the carbanionic component in a synthesis of pyran-2-ones from 1,3-diketones (70ACS343). A Wittig reaction between the ylide and one of the carbonyl groups is envisaged as the first step in the sequence and the resulting keto ester spontaneously cyclizes. The reaction is conducted under pressure and yields are low. 

A further illustration of the reaction of carbanionic species with o-hydroxybenzaldehydes is provided by the use of phosphorus ylides in coumarin synthesis. Thus, ethoxycarbonyl-methylenetriphenylphosphorane affords simple coumarins via the ester (380 R = H), whilst with o-hydroxyacetophenone a 4-methylcoumarin results (381 R = Me) (77S464), and 4-methylsulfinylmethylcoumarin (381 R = CH2SOMe) is obtained from o-hydroxy-a>-methylsulfinylacetophenone (Scheme 120) (72JHC175). 

Compounds containing phosphorus can be both valuable synthetic intermediates and target compounds of solid-phase synthesis. Important synthetic intermediates include phosphonium salts and phosphorus ylides, which are key intermediates in carbonyl olefinations. Their preparation is discussed in Section 5.2.2.1. The preparation of oligonucleotides, these being the most important phosphorus-containing target molecules in solid-phase synthesis, is considered in Section 16.2. In this chapter, the preparation of phosphines, phosphonic acid derivatives, and phosphinic acid derivatives is discussed. 

The comparison between the reactions of a carbonyl compound with a phosphorus ylide (Wittig s reagent) on one hand and a sulfur ylide on the other shows clearly the complementarity of these reagents in the strategy of synthesis. 

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