Nucleophiles phosphoranes

The mechanism is stiU not fiJly understood. Hydrogen peroxide formally transfers oxygen to the nucleophilic phosphorane, which then cleaves off triphenylphosphane oxide to give the aldehyde this finally reacts in a normal Wittig reaction to produce /5-carotene. 

Surprisingly carbonyl-substituted carbanions of phosphonates, in which the negative charge is delocalized over two oxygen atoms, are much more nucleophilic than the corresponding phosphoranes. This effea has first been observed by Homer, and has often been utilized in the synthesis of acylated olefins (R.D. Clark, 1975). 

Extension of the Phosphorane Route. Ample evidence of the versatihty of the phosphorane synthesis strategy is provided by the proliferation of penems that followed. Nucleophilic displacement of the acetate function of the acetoxy-azetidinone (51, R = OCOCH ) [28562-53-0] (86) provided azetidinones where R = SCOCH, SCSSC2H, and SCSOC2H, which on elaboration gave the penems (52, R = CH ) (87), (52, R = SC2H ) (88), (52, R = 0C2H ) (89). Similar treatment of 3-substituted (or disubstituted) acetoxyazetidinones allowed the synthesis of a number of 2-substituted- 6-alkyl-and 6,6-dialkylpenems (90). 

The reactivity of fluoro(organyl)phosphanes depends on the nucleophilicity of phosphorus For mstance the phosphanes may add to the carbonyl carbon to form phosphiniio phosphoranes (equation 36) or may react with acid fluondes to form acyldifhiorophosphoranes [37] (equation 37)... 

Zincke s aldehyde (61) and cyanomethyltriphenylphosphonium chloride in acetic anhydride at 100 °C gave the salt (62), isolated as the perchlorate, whereas the same reagents in pyridine gave the phosphorane-phosphonium salt (63), presumably via nucleophilic addition of cyanomethylenephos-phorane to the terminal carbon of (62). 

A mechanism for this reaction involving nucleophilic attack of the ylide on the cyanide group and formation of the P=N linkage via a four-centred intermediate was formulated. The structure of this phosphazene was confirmed by its synthesis from the vinyl azide, Ph(N3)C=CHPh, and triphenylphosphine. Phosphoranes stabilized by electron-withdrawing... 

Both neutral and anionic phosphorus compounds are good nucleophiles toward alkyl halides. We encountered examples of these reactions in Chapter 2 in connection with the preparation of the valuable phosphorane and phosphonate intermediates used for Wittig reactions. 

Finally, a reaction should be mentioned in which a nucleophile gives support to another reacting species without appearing in the final product. Diphenyl cyclopropenone interacts with 2,6-dimethyl phenyl isocyanide only in the presence of tri-phenylphosphine with expansion of the three-ring to the imine 344 of cyclobutene-dione-1,2229,230 Addition of the isocyanide is preceded by formation of the ketene phosphorane 343, which can be isolated in pure formss 231 it is decomposed by methanol to triphenyl phosphine and the ester 52. 

The best results were achieved by employing N-(3-dimethylaminopropyl)-N -ethylcar-bodiimide hydrochloride (EDC) as coupling agent. After Fmoc deprotection with piperidine in N,N-dimethylformamide, additional diversity could be introduced by acylation of the liberated amine position. Finally, the acyl cyano phosphoranes could be efficiently cleaved by ozonolysis at -78 °C or by utilizing freshly distilled 3,3-dimethyloxirane at room temperature [65]. The released compounds constituted highly activated electrophiles, which could be further converted in situ with appropriate nucleophiles. 

In another approach, 2-(alkylamino)alcohol is employed as starting material for aziridine syntheses with the aid of dihalogenophosphoranes (70BCJ1185). Intramolecular transformation of 3-azidopropyloxirane 73 results in a simultaneous formation of a condensed aziridino[l,2-a]pyrrol-idine system (Scheme 39). The azide group is first transformed into imino-phosphorane 74, the nucleophilic N atom cleaves the oxirane to form betaine 75 [as in the Mitsunobu reaction (81S1)], and the phosphorus is shifted from N to O and then eliminated as phosphane oxide under simultaneous cyclization to bicyclic 76 (89JA7500). 

Strong nucleophilic character of dithizone could assist in the generation of such dipolar intermediates (422, 423, and 424), and there is plenty of general analogy for such intermediates. Particular reference may be made to the closely related cycloaddition reactions of meso-ionic 1,2-diazoles 373 and 382. The transformation 424 - 421 could well involve a pentacovalent phosphorane intermediate as well. 

Scheme 43 shows the details of the different steps involved in the equilibrium. The nucleophilic attack of the P(III) derivative on the acetylenic bond yields a 1,3-dipole which, after a fast protonation, frees aZ ion. If the subsequent addition of this ion occurs on the P atom (reaction a), a P(V) phosphorane is formed, but the addition of Z on the ethylenic C atom (reaction b) results in the formation of an ylide. Both of these reactions occur under kinetic control and, in both cases, X is always an OR group from the initial acetylene dicarboxylic ester. When the acetylenic compound is a diketone and X is an alkyl or aryl moiety, the C=0 group is much more electrophilic and the attack by the Z ion produces an alcoholate (reaction c), a new intermediate which can cyclize on to the P+ to form a phosphorane, or attack the a-C atom to form an ylide as in Scheme 42. Hence, reactions a and c can coexist, and are strongly dependent on the nature of the trapping reagent and of the P compound, but reaction b is blocked, whatever the reagent. This is well illustrated by the reaction of the 2-methoxytetramethylphospholane 147 on diben-zoylacetylene in the presence of methanol as trapping reagent. The proportions of the vinylphosphorane 157 and spirophosphorane 158 formed (Figure 24) are 13% and 84%, respectively.

One of the interesting points connected with this type of coordination springs from the fact that nucleophilic substitution on phosphoranes probably occurs via the formation of an octahedral complex242-245. Further, it should be recalled that the mechanism of irregular stereomutations of pentacoordinated structures in basic media may also involve a hexacoordinated intermediate. Figure 26 shows just a few of the numerous and diverse structures known (196-203) but, even then, some general observations can be made. 

Cyclic 1,3,2-dioxaphosphorinanes (P-CN = 4) react with nucleophiles, probably by initial addition of the nucleophile to the phosphorus atom, giving phosphoranes (P-C1V = 5) as intermediates (or transition states). This holds not only for P=0 derivatives but also for quaternary 1,3,2-dioxaphosphorinanium salts (81JA5894). By steric rearrangement of the phosphoranes the configuration of the P atom can be changed (retention or inversion) (see Section 1.17.5). 

The most interesting properties of phosphoranes, i.e. their role as intermediates or transition states of nucleophilic addition reactions of four-coordinate phosphorus compounds and their intramolecular rearrangements according to BPR or TR, have already been fully considered. The synthetic potential of stable phosphoranes has been reviewed by Burger in great detail (B-79MI11702), and only some special aspects need be mentioned in this chapter. 

Hexacoordinate phosphorus compounds are also considered as transition states in nucleophilic diplacements of phosphoranes in a manner similar to an 2 displacement in carbon chemistry (see Scheme 38) (72MI11704, 73AG(E)9l>. 

This observation, that the aptitude of X to be displaced with inversion, is parallel to the tendency of the Si—X bond to be stretched under the influence of an attacking nucleophile, does not agree with the apicophilic-ity order stated from dynamic NMR studies on stable pentacoordinate phosphoranes (42), which is as follows ... 

Vinylphosphonium salts accept nucleophiles by addition in a Michael reaction to form phosphoranes, which may subsequently react with a carbonyl group to form an alkene (see Scheme 10). This reaction, discovered by E. E. Schweizer in 1964,80 was developed into a widely applicable cycliza-tion method.81 The reaction of 2-formyIpyrrole with vinyltriphenylphos-phonium bromide to give 87% of 3/f-pyrrolizine (1) is among the first to... 

---