Phosphorus acid derivatives nucleophilic reactions

A review (91 references) on electrophilic and nucleophilic reactions of trivalent phosphorus acid derivatives, reactions of two-coordinate phosphorus compounds, and miscellaneous reactions has appeared.228 Earlier in this review we looked at the heavy-atom isotope effects on reactions of Co(III)-bound /vnitrophenyl phosphate,186 the uranyl ion hydrolysis of /vnitrophcnyl phosphodiesters (218)-(220),190 and the Th(IV) hydrolysis of these.191... 

To get a broader concept of the nucleophilic reactivity of phosphorus acid derivatives towards organosilanes we studied mechanism of reactions of triorganosilyl halides with esters of tricoordinate and tetracoordinate phosphorus having the general formulae ... 

Tervalent phosphorus acid derivatives (1) are compounds with three covalent bonds to phosphorus and at least one electronegative atom bound directly to the phosphorus atom. Such compounds are able to undergo a diversity of reactions since they are nucleophiles due to the lone pair on phosphorus and also electrophiles because of the presence of a leaving group X. They are generally reactive towards water and often easily oxidized. They are therefore mainly used as intermediates for the preparation of more stable phosphorus compounds, such as phosphine oxides, phosphates and phosphonates. 

All tervalent phosphorus acid derivatives have a lone pair on phosphorus and are therefore nucleophiles, but their reactivity depends on the electronegativity of the group(s) bound to phosphorus. Aminophosphines are the most reactive and chlorophosphines the least reactive, with the phosphinites, phosphonites and thio analogues in between. In principle they are ambident nucleophiles because there are lone pairs both on the heteroatoms and on phosphorus, but apart from the thio analogues these heteroatom lone pairs do not participate in the common reactions discussed below. 

Nucleophilic attack of tervalent phosphorus acid derivatives on the carbon atom of alkyl halides is the normal process, but sometimes the attack occurs at the halogen atom instead. This reaction is most pronounced when a stabilized carbanion may be formed, e.g. in the reaction with tetrachloromethane (equation 147). The extent of debromination of a-bromo ketones has been found to decrease in the series R2POR > RP(OR)2 > P(OR)3. Ethyl di- erf-butylphosphinite has been shown to react preferentially at the halogen atom of chloroacetonitrile, 1,2-dibromoethane and diiodomethane, to give in each case a mixture of products, e.g. equation 148. Aminophosphines are also very reactive in this respect... 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

Note that the reaction at the phosphorus atom is postulated to occur by an SN2 (no intermediate formed) rather than by an addition mechanism such as we encountered with carboxylic acid derivatives (Kirby and Warren, 1967). As we learned in Section 13.2, for attack at a saturated carbon atom, OH- is a better nucleophile than H20 by about a factor of 104 (Table 13.2). Toward phosphorus, which is a harder electrophilic center (see Box 13.1), however, the relative nucleophilicity increases dramatically. For triphenyl phosphate, for example, OH- is about 108 times stronger than H20 as a nucleophile (Barnard et al., 1961). Note that in the case of triphenyl phosphate, no substitution may occur at the carbon bound to the oxygen of the alcohol moiety, and therefore, neutral hydrolysis is much less important as compared to the other cases (see /NB values in Table 13.12). Consequently, the base-catalyzed reaction generally occurs at the phosphorus atom leading to the dissociation of the alcohol moiety that is the best leaving group (P-0 cleavage), as is illustrated by the reaction of parathion with OH ... 

Step 1 Reaction of the diphosphate oxygen of GDP with the phosphorus of the acyl phosphate to produce an intermediate similar to the intermediates formed in nucleophilic acyl substitutions of carboxylic acid derivatives. 

Substrates usefully employed in Mannich reactions are, in general, XH compounds having nucleophilic properties, with X being equal to C, N, or other heteroatoms (Fig. 4). In particular, CH compounds are suitably activated saturated and unsaturated derivatives, and NH substrates may be amines, amides, hetcrocyclcs, etc. Out of OH sub-stratcs, alcohols are mainly able to give stable Mannich products. Sulfur- and phosphorus-containing substrates are XH derivatives having the H atom bonded to the hetcroatom in the lower oxidation state, i.e., thiols, sulfinic acids, and, respectively, phosphine and phosphorous acid derivatives. As and Se compounds have also been successfully used. All these substrates are listed in more detail in Sec. D of this chapter. 

A review on the chemistry of thio derivatives of trivalent phosphorus acids which covers the literature to 1986, includes a section on pentaco-ordinate phosphorus compounds derived from addition to a-diketones and unsaturated systems activated to nucleophilic attack by electron withdrawing groups. Chemical bonding in hypervalent molecules has been discussed and qualitative bonding concepts developed to supersede the dsp and d sp models. A review on the mechanism and stereochemistry of the Wittig olefination reaction inevitably includes a discussion of the equilibrium between betaine and 1,2-oxaphosphetane intermediates. A correction has been published to reference 19 of Chapter 2 in SPR14, Vol.21, concerning the Mitsunobu Reaction. ... 

The two terminal linkages of the triphosphate are phosphoric acid anhydrides i.e. they are activated phosphoric acid derivatives and nucleophilic attack at the electrophilic y OT P phosphorus is thermodynamically very favourable. The advantage of phosphoric anhydride derivatives over acyl derivatives is that the former are kineti-cally stable in neutral aqueous solution unless a suitable enzyme is present to catalyse its reactions. 

The displacement reactions of the anhydride from O-ethyl phenylphosphonothioate and O-ethyl 0-phenyl phosphorothioic acid have been the subject of separate investigations. The (R,R)-(+)-anhydride 100 was subjected to reactions with a variety of nucleophiles. The latter, which included HO ,NH3 and HS , all appeared to attack the phospho-nothioic phosphorus centre, and the reactions proceeded with inversion of configuration, with the exception of that with HS , from which a racemic product was obtained since it consisted of the ion Ph(EtO)PS2". The principle difference between this substrate example and those considered earlier is that both phosphorus centres are chiral, and hence the thio-phosphoric derivatives, formed concomitantly, are also optically active. 

The formation of aryl ethers of (hydroxyalkyl)-phosphonic or -phosphinic derivatives from the corresponding haloalkyl phosphorus(V) acid derivative and a metal phenate may present unfortunate difficulties depending on the particular halogen, but these have been overcome by the use of sulphonate substrates, in particular the 0-4-chlorobenzenesulphonyl esters of the phosphonic or phosphinic derivative, in reactions with sodium phenates. A study of the alcoholysis reactions of the O-p-tosylates of the cis and trans isomers of diethyl (2-hydroxycyclo-hexyl)phosphonate, has shown that with a 60° dihedral angle between the two functions, the rate of reaction is sensitive to solvent nucleophilicity, and the evidence supports a bimolecular displacement. When the dihedral angle is 180°, the lack of dependence of rate on solvent and other features, support the involvement of carbocationic intermediates, with their stabilization by the phosphono group . ... 

Cases of the S-coordinated rhodium and iridium are quite scarce. To complete the picture, we next consider the possibilities of S-coordination using complicated derivatives of thiophene. 2,5-[Bis(2-diphenylphosphino)ethyl]thiophene is known to contain three potential donor sites, two phosphorus atoms and the sulfur heteroatom, the latter being a rather nucleophilic center (93IC5652). A more typical situation is coordination via the phosphorus sites. It is also observed in the product of the reaction of 2,5-bis[3-(diphenylphosphino)propyl]thiophene (L) with the species obtained after treatment of [(cod)Rh(acac)] with perchloric acid (95IC365). Carbonylation of [Rh(cod)L][C104]) thus prepared yields 237. Decarbonylation of 237 gives a mixture of 238 and the S-coordinated species 239. Complete decarbonylation gives 240, where the heterocycle is -coordinated. The cycle of carbonylation decarbonylation is reversible. 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

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