Reactions of Phosphine Oxides

Oxides containing hydrogen atoms are thermally less stable than MCjPO and dimethylethylphos-phine oxide decomposes above 330°C to ethylene and dimethylphosphine oxide(6.119), but this latter product disproportionates according to (6.133) below. 

Tertiary oxides containing a hydroxy groups are less stable than simple alkyl derivatives, and undergo thermal decomposition at about 100°C to form secondary phosphine oxides (6.120). Tertiary oxides can be reduced to tertiary phosphines with lithium aluminium hydride (6.58). Alkali hydrides form phosphinite derivatives (6.121). 

The lower molecular weight tertiary phosphine oxides are highly water soluble, but are resistant to hydrolysis involving cleavage of the P-C bond. Triphenylphosphine oxide reacts very slowly with refluxing alcoholic NaOH, to give benzene and sodium metaphosphate. 

Aqueous NaOH reacts with a-hydroxyalkyl substituents to give sodium diphenylphosphinate and a ketone (6.122). This reaction proceeds via the initial production of diphenylphosphine oxide, which then disproportionates as in (6.133) below. 

Fusion of phenyl (and other aryl) tertiary oxides with NaOH at 200-300°C gives sodium diphenylphosphinate directly (6.124) while with nitric acid, the phosphoryl group acts as a meta director, and with sulphuric acid a phosphonium salt can be formed (6.123). 

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The reduction of optically active methylphenyl-n-propylphosphine sulphide with lithium aluminium hydride proceeds with 100% retention, whereas the reaction of phosphine oxides with lithium aluminium hydride leads to racemization. ... 

This year s literature has been characterized by an increasing number of papers devoted to theoretical studies of the bonding in phosphine oxides and related compounds, and these are discussed in Section 1. The chemical aspects of phosphine oxides have not shown any major new developments over the past year, and, once again, these have been sub-divided into sections on the preparation and on the reactions of phosphine oxides. 

A series of Af-(alk-l-enyl) nucleobase compounds has been prepared by Wittig-Horner reaction of phosphine oxides (165)-(167) or the Horner-Wadswor-th-Emmons reaction of the analogous phosphonates (168) and (169). Hor-ner-Wittig reactions have been utilised for the stereoselective synthesis of single... 

CAMEO, an interactive computer program for the mechanistic evaluation of organic reactions, has been extended to include the reactions of phosphine oxide-stabilised carbanions.27 A convenient route to 3-methoxy-l-trimethylsilyl-1,3-dienes (50) is available from a one-pot... 

The completion of the total synthesis is described in Scheme 47. The HW reaction of phosphine oxide 320 and 314 efficiently afforded ( )-triene 321. After hydrolysis of dimethyl acetal in 321 followed by aldol reaction, macro-lactamization was carried out under Mukaiyama macrocyclization conditions to give an 1 1 mixture of diastereomers 322. Removal of three allylcarbonates followed by treatment with the Dess-Martin reagent resulted in oxidation of the three alcohols and subsequent oxidation of the C9 methylene. Final deprotection of the resulting tetraketone with HF-py completed the total synthesis of rapamycin (2). 

A major review of stereocontrol in organic synthesis using the diphenylphos-phoryl group has appeared and includes coverage of Homer olefination and other reactions of phosphine oxide-stabilised carbanions. ... 

There has been a small reorganization in this year s Chapter in that reactions of phosphine oxide-stabilized carbanions will all be discussed in Chapter 4. 

In continuing studies of stereoselectivity in reactions of phosphine oxides, Warren has shown that the introduction of a diphenylphosphinoyl group to create a chiral centre next to the hydroxyl group in allylic alcohols allows epoxidation with high diastereoselectivity, especially in the erythro-isomers, e.g. (45) (Scheme 5).22 This high diastereoselectivity was retained when a third chiral centre was introduced. The epoxides produced could be ring-opened with thiolate anions in a highly diastereoselective manner and... 

The titanium-mediated intramolecular radical vinylations of oxirane was first reported to yield alkylidene pyrrolidines 488 via the radical (3-elimination of phosphinoyl radical. The reactions of phosphine oxide precursors 487 with a stoichiometric amount of Cp2TiQ2 were carried out at room temperature using powdered manganese as reductant, from which pyrrolidines 488 were obtained in 57-82% yields (Scheme 4.146). The procedure for the synthesis of phosphine oxide precursors 487 is also shown in Scheme 4.146. 

Phosphine oxides may be prepared by the acid-cataly2ed reaction of phosphine with carbonyl compounds such as ketones (94). 

It is possible to replace one isocyanide by triphenylphosphine, or to replace two isocyanides with diphos, giving phosphine analogues of these complexes. These species are not available from analogous reactions of phosphine-palladium(O) and (II) complexes. Reactions with active alkyl halides proceeds with oxidation nitric oxide also oxidizes these complexes. [Eqs. (31, 32)]. 

Two contrasting conclusions have been reported in the reactions of lithium aluminium hydride in THF with phosphine oxides and phosphine sulphides respectively. The secondary oxide, phenyl-a-phenylethylphos-phine oxide (42), has been found to be racemized very rapidly by lithium aluminium hydride, and this observation casts some doubt on earlier reports of the preparation of optically active secondary oxides by reduction of menthyl phosphinates with this reagent. A similar study of the treatment of (/ )-(+ )-methyl-n-propylphenylphosphine sulphide (43) with lithium aluminium hydride has revealed no racemization. These results have been rationalized on the basis of the preferred site of attack of hydride on the complexed intermediate (44), which, in the case of phosphine oxides (X = O), is at phosphorus, and in the case of the sulphides (X = S), is at sulphur. Such behaviour is comparable to that observed during the reduction of phosphine oxides and sulphides with hexachlorodisilane. ... 

Even under the most inert atmosphere conditions, the 31CP/MAS spectrum of the immobilized ligand showed a major signal at 6 = 42 ppm (wrt 85% H3POO characteristic of phosphine oxide rather than phosphine. This could be quantitatively reduced by HSiCl3 and this surface reaction monitored by NMR but the subsequent exchange reaction (equation [5]) generated substantial quantities of phosphine oxide and a number of different isomeric complexes were f ormed. 

A Michael-type addition reaction of phosphine generated from red phosphorus in concentrated aqueous KOH solution has been noted to provide moderate isolable yields of pure organophosphorus products.27 For example, tris-(2-cyanoethyl)phosphine is produced in 45% isolable yield from acrylonitrile, and tris-(2-[y-pyridyl]ethyl) phosphine oxide is isolated in 40% yield from 4-vinylpyridine under these conditions. Excellent yields of the tertiary phosphine oxide, tris-(2-cyanoethyl)phosphine oxide, have been reported using white phosphorus in absolute ethanol with KOH at ice/salt-bath temperatures.28 A variety of solvent systems were examined for this reaction involving a Michael-type addition to acrylonitrile. Similarly, tris-(Z-styryl)phosphine is produced from phenylacetylene under these conditions in 55% isolated yield. It is noteworthy that this last cited reaction involves stereospecific syn- addition of the phosphine to the alkyne. 

Finally, Cristau and coworkers have reported on a quite efficient preparation of triphenylphosphine oxide (Figure 2.13) by a similar addition-elimination reaction of red phosphorus with iodobenzene in the presence of a Lewis acid catalyst followed by oxidation of an intermediate tetraarylphosphonium salt.42 This approach holds the potential for the preparation of a variety of triarylphosphine oxides without proceeding through the normally used Grignard reagent. Of course, a variety of approaches is available for the efficient reduction of phosphine oxides and quaternary phosphonium salts to the parent phosphine, including the use of lithium aluminum hydride,43 meth-ylpolysiloxane,44 trichlorosilane,45 and hexachlorodisilane.46... 

The reaction of phosphines and alkyl halides presents an alternative way to generate phosphonium electrophiles (Scheme 3.8). In particular, the combination of a phosphine and carbon tetrabromide (the Appel reaction) allows for in situ formation of a phosphonium dibromide salt (48, X = Br). Treatment of a hemiacetal donor 1 with the phosphonium halide 48 initially provides the oxophosphonium intermediate 38 (X = Br). However, the oxophosphonium intermediate 38 can react with bromide ion to form the anomeric bromide intermediate 49 (X = Br) with concomitant generation of phosphine oxide. With the aid of bromide ion catalysis (i.e. reversible, catalytic formation of the more reactive P-anomeric bromide 50) [98], the nucleophile displaces the anomeric bromide to form the desired glycoside product 3. The hydrobromic add by-product is typically buffered by the presence of tetramethyl urea (TMU). 

Furthermore, even the ligand, necessary to stabilize the catalyst, can reduce Pd(II) to Pd(0) complexes and formation of phosphine oxides [62-64], In the preparation of [Pd(AcO)2(dppp)], from Pd(AcO)2 and dppp in MeOH, phosphine oxides have been found to form together with methyl acetate and palladium metal [65]. The reaction can be schematized as follows ... 

Several reports have appeared on the effect of additives on the Pauson-Khand reaction employing an alkyne-Co2(CO)6 complex. For example, addition of phosphine oxide improves the yields of cyclopentenones 119], while addition of dimethyl sulfoxide accelerates the reaction considerably [20]. Furthermore, it has been reported that the Pauson-Khand reaction proceeds even at room temperature when a tertiary amine M-oxide, such as trimethylamine M-oxide or N-methylmorpholine M-oxide, is added to the alkyne-Co2(CO)6 complex in the presence of alkenes [21]. These results suggest that in the Pauson-Khand reaction generation of coordinatively unsaturated cobalt species by the attack of oxides on the carbonyl ligand of the alkyne-Co2(CO)6 complex [22] is the key step. With this knowledge in mind, we examined further the effect of various other additives on the reaction to obtain information on the mechanism of this rearrangement. 

As well as for the preparation of alkali phosphides, the reaction of phosphine with the elements, their oxides or halides, at higher temperatures in quartz tubes have been much used recently for the preparation of other phosphides, in particular those which play important roles in semi-conductor technology. The preparations of the following phosphides using these methods have been described for example, NdP 3s> 36) 3p 137,138) Q p 139.140) SmP, LaP 136,141) TiP, Ti2P (possibly TisP) and InP See also Section IV.9. 

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