Phosphorin oxides

That this oxidation leads to the radical cation 55 and not to a X -phosphorin-oxide radical 59 was evidenced by the observation that labelled triphenyl-phenoxy radicals do not lead to any coupling pattern, but rather to precisely the same ESR spectrum as before. Nevertheless, the possibility of an equilibrium with the neutral radical 5P cannot be excluded with certainty since the coupling may be quite small and the P-coupling may not be changed very much. 

Alkylation with triethyl oxonium tetrafluoroborate yields two products (in the proportion 3 1) 1.2-dihydro-l-ethoxy-2-ethyl-2-4.6-triphenyl-phosphorin oxide 92 m.p. 161-162 °C, and l.l-diethoxy-2.4.6-triphenyl-X -phosphorin 71, m.p. 106 "C. 71 is known from Stade s synthesis (p. 84), 92 was identified by H-NMR. No diastereoisomers were isolated... 

Phospha-Michael reactions are useful to establish a P-C bond. The addition of >P(0)H species (e.g., dialkyl phosphites and secondary phosphine oxides) at the end of electron-poor double bonds may be facilitated by bases, like NaOR, NaOH, or DBU [56]. The addition of P-heterocyclic nucleophiles was also studied. Dibenzo[c.e][l,2]oxa-phosphorine oxide (36) added easily on the double bond of methyl vinyl ketone xmder MW conditions in the absence of any solvent (Scheme 12) [57]. 

The synthesis of the planar, tricyclic- A5-phosphorin (179) has been described.161 It reacts with methyl iodide to give the salt (180) as a mixture of stereoisomers, and is in equilibrium with the ylide (181), which reacts with benzaldehyde to give the oxide (182). 

The lithium salt of enantiomerically pure (2S,65)-6-methyl-tetrahydro-2//-l,3,2-oxaza-phosphorine-2-oxide was also alkylated with high diastcrcosclcctivity, whereas in the case of the (2/ ,6S)-isomer only moderate selectivities were observed. With the 3-isopropyl derivative even higher selectivities (97-98% de) were observed. 

Electrophilic attack occurred on the Re-face of lithiated (25,6S)-tetrahydro-2W-l,3,2-oxaza-phosphorine 2-oxides to give 7 -configurated products, as was confirmed by X-ray crystallo-... 

In contrast to pyridine derivatives, aryl- and alkyl-substituted A -phosphorins cannot be protonated by strong, non-oxidizing acids such as trifluoroacetic acid. Addition of trifluoroacetic acid to cyclohexane solutions of various A -phosphorins fails to produce any change in the UV spectra Similarly, alkylation by such strong agents as oxonium salts or acylation by acylchlorides cannot be induced at the P atom or any ring C atom. This behavior has also been discussed theoretically 55a)... 

Addition of a few drops of 60% perchloric or cone, sulfuric acid to a solution of 2.4.6-triphenyl-X -phosphorin 22 affords a deep blue compound which is soluble in polar solvents. This new compound is not the protonated form of the X -phosphorin, but rather a cation which results from oxidation of the X -phosphorin (see p. 50). 

The position of phosphorus with respect to nitrogen in the periodic table led to the expectation that it should be much easier to remove one electron from X -phos-phorins than from pyridines (see also p. 37). Indeed, soon after the synthesis of 2.4.6-triphenyl-X -phosphorin 20 by Markl, we discovered that addition of 2.4.6-triphenoxyl 57 in benzene induces oxidation to the very stable radical cation 55... 

According to Weber the coiuse of the oxidation of 2.4.6-triphenyl-X -phosphorin with tetracyanoethylene is similar. 

As Mach has found, oxidation of 2.4,6-tri-tert-butyl-X -phosphorin 24 in glacial acetic acid with a mixture of equal parts of cone, nitric and sulfuric acids yields... 

Analogous results were found in hydrogen peroxide oxidation of 2.6-di-tert-butyl-4(4-methoxyphenyl)-X -phosphorin 87. The crystalline 2-hydrophosphinic acid 88, m.p. 176-178 °C, on esterification with diazomethane, leads to a mixture of two diastereoisomeric esters, 89 E and 89 Z, which could be separated by thin-layer chromatography but not crystallized. 

Triphenyl-X -phosphorin 22, when oxidized with hydrogen peroxide, leads to the noncrystallized 2-hydrophosphinic acid 90b. The tautomers 90a and c are minor components of an equilibrium, as we suppose from the spectroscopic... 

Hydrogen peroxide oxidation of other X -phosphorins produces analogous hydrophosphinic acids. Chatzidakis in oxidizing the dihydrophenanthren-X -... 

Method A From X -phosphorins by oxidation with H2O2. Method B From 2-hydro-phosphinic-90 with diazomethane. Method C From l.l-dialkoxy-X -phosphorins with BBr3. Method D From pyrylium sMts with phenyl phosphine... 

Tri-tert-butyl-X -phosphorin24 readily reacts with bromine and with chlorine. Mach oxidizing with bromine in CCI4, could not isolate a crystalline product. The brown colour of the addition product of one mole Br2 to one mole 24 disappeared with water and the crystalline 2-hydro-phosphinic acid 85b could be isolated in 45% yield. Methyl-magnesium-iodide or red phosphorus yielded 2.4.6 tri-tert-butyl-X -phosphorin 24. It seems reasonable to suppose that on bromination l.l-dibromo-2.4.6-tri-tert-butyl-X -phosphorin was formed. 

As Schaffer has found 2.4.6-triphenyl-X -phosphorin 22 and other 2.4.6-tri-substituted X -phosphorins react smoothly with aryl diazonium salts in benzene. Nitrogen develops and the aryl residue bonds with the phosphorus. In presence of alcohols as nucleophiles, l-alkoxy-l-aryl-2.4.6-triphenyl-X -phosphorins 100 can be isolated. The aryl diazonium-tetrafluoroborate without any nucleophile in DMOE yields l-aiyl-l-fluoro-2.4.6-triphenyl-X -phosphorin 70i. As with other oxidants like halogen or mercury-Il-acetate, we suppose that in the first step triphenyl-X -phosphorin radical cation is formed. This could be shown by ESR spectroscopy. The next step may be a radical-radical addition to the X -phosphorin cation or a nucleophileradical addition respectively ... 

These reactions are related to the reaction of aryl diazonium salts with iodide yielding iodoaryls, the mechanism of which seems to be a one-electron transfer (radical) reaction and not a nucleophilic displacement. Just as iodide is easily oxi- zed to iodine by the aryl diazonium cation, 2.4.6-triphenyl-X -phosphorin is oxidized to the radical cation 58. 

As it is clear from the preceding paragraphs, there are four different positions where X -phosphorins are attached by oxidants ... 

Table 14. 1.1-Disubstituted X -phosphorins from X -phosphorins by diazonium salt oxidation...

The physical and chemical properties of the X -phosphorins 118 and 120 are comparable to those of phosphonium ylids which are resonance-stabilized by such electron-pulling groups as carbonyl or nitrile substituents Thus they can be viewed as cyclic resonance-stabilized phosphonium ylids 118 b, c, d). As expected, they do not react with carbonyl compounds giving the Wittig olefin products. However, they do react with dilute aqueous acids to form the protonated salts. Similarly, they are attacked at the C-2 or C-4 positions by alkyl-, acyl- or diazo-nium-ions Heating with water results in hydrolytic P—C cleavage, phosphine oxide and the hydrocarbon being formed. 

Oxidation of X -phosphorins with hydrogen peroxide (Dimroth and Vogel). 

Oxidation of 1-substituted phosphorin radicals with mercuric acetate (Dimroth and Hettche). 

Oxidation of 1-substituted 1,2-dihydro-X -phosphorins with mercuric acetate or triphenylcarbonium salts (Markl). 

A third reaction path, which again has no analog in pyridine chemistry, involves the stable X -phosphorin cation radical55 as an intermediate. It is easily formed by oxidation of X -phosphorins ... 

If the oxidation is carried out with a radical R in the presence of a nucleophile R , an equilibrium reaction forming the neutral radical 135 may take place. 135 could lead to the X -phosphorin 129 via oxidation to 127 and addition of the anion R , or by simple coupling with the radical R. ... 

Oxidation of dihydro-X -phosphorin 147 with triphenyl-methyl-perchlorate leads to an intermediate which most likely has the structure 127. Addition of phenyl-lithium to this cation affords the deep red 1,1,2,4,6-pentaphenyl-X -phosphorin... 

One of the most versatile methods for the preparation of 1,1-disubstituted X -phosphorins 124 was discovered by Stade who found that X -phosphorins 2 can be oxidized (mercuric acetate gives the best results) in the presence of alcohols or phenols in benzene to 1.1-dialkoxy- or l.l-diphenoxy-X -phosphorins 124. The first step is probably a reaction of the soft X -phosphorin- jr-system with the soft acid Hg which by electron transfer leads to the weakly electrophilic radical cation 58. This is then attacked by alcohol or phenol - or as Hettche has found by other nucleophiles such as an amine to form by loss of a proton the neutral X -phosphorin radical 59. This radical is oxidized once again by mercury ions leading to the formation of elemental mercury and the strongly electrophilic, short-lived X -phosphorin cation 127, which is immediately attacked by alcohol, phenol or amine. Loss of a proton then leads to the X -phosphorin 124. It is also conceivable that 59 can couple directly with a radical to form 124 (Method E, p. 82). 

If 1-alkyl- or l-aryl-l,2-dihydro-X -phosphorins 147 (obtained by Method B, p. 78) are oxidized with mercuric acetate in the presence of alcohols or phenols as nucleophiles, it is possible to isolate X -phosphorins 156 in which the phosphorus bears a carbon substituent besides an alkoxy or phenoxy group (Markl ° ). 

Price obtained in the presence of water a crystalline product (m. p. 256—257 °C) and an amorphous material from which Markl could isolate the X -phosphine oxide 158 (m. p. 156-158 °C) and the 4-hydroxy-phosphine oxide 160 (m. p. 239-241 °C) which probably was formed by autoxidation. 158 is also formed by HaO2-oxidation of 147 The tautomeric form of 158 would be the 1-hydroxy-X -phosphorin 159. Indeed, treatment with base affords a bright red anion which probably has the structure 161 (see p. 60 and 87). 

This reaction can also be used to convert the phosphine oxide 158. (Method I, p. 86) to 1-aiyl-l-alkoxy-X -phosphorin 156... 

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