Hydroxyphosphonate

Figure 2.7 Use of red phosphorus for direct formation of a 1-hydroxyphosphonous acid.

Keywords 1-hydroxyphosphonate, Cr03/alumina, microwave irradiation, a-keto phosphonate... 

The procedure of isotope effect studies will be illustrated on several examples. First one concerns studies of phosphonate-phosphate rearrangement (Scheme 1). Phosphite 3 reacts in the presence of triethylamine with o-nitrobenzaldehyde (Pudovik reaction) to form 1-hydroxyphosphonate 4 as mixture of two diastereo-isomers, 1 1. Amine also catalyses the reverse refro-phospho-aldol (retro-Abramov) reaction of 1-hydroxyphosphonate to phosphite and aldehyde and rearrangement to phosphate 5. In acetonitrile at 65°C Pudovik reaction is much faster than of retro-Abramov reaction and phosphonate-phosphate rearrangement, which rates are comparable. Important fact for the mechanism elucidation was experimental evidence that rearrangement occurs with retention of configuration at phosphorus atom.49... 

For example, two reports of preparation of such species from elemental (red) phosphorus have been noted. The direct preparation of 1-hydroxyphosphonous acids, albeit in moderate yield, is accomphshed by the treatment of elemental phosphorus with aldehydes in aqueous basic medium (equation 12). Using polar aprotic solvents, the double direct addition of elemental phosphoms to arylalkenes proceeds to form phosphinous acids in better yields. Further, acid chloride derivatives are available also by the controlled reaction of elemental phosphoms with chloroalkanes. ... 

Dialkyl acylphosphonates have been reduced to 1-hydroxyphosphonates using... 

Burke, T.R., Jr., Smyth, M.S., Nomizu, M., Otaka, A., and Roller, PP, Preparation of fluoro- and hydroxy-4-(phosphonoinclhyl)-i),L-phcnylalanine suitably protected for solid-phase synthesis of peptides containing hydrolytically stable analogues of O-phosphotyrosine, J. Org. Chem., 58, 1336, 1993. Ganzhorn, A.J., Hoflack, J., Pelton, P.D., Strasser, E, Chanal, M.-C., and Piettre, S.R., Inhibition of myoinositol monophosphatase isoforms by aromatic phosphonates, Bioorg. Med. Chem., 6, 1865, 1998. Kaboudin. B., Surface-mediated sohd-phase reactions. The preparation of acyl phosphonates by oxidation of 1-hydroxyphosphonates on the solid surface, Tetrahedron Lett., 41, 3169, 2000. Kaboudin, B., and Nazari, R., A convenient and mild procedure for the preparation of a-keto phosphonates of 1-hydroxyphosphonates under solvent-free conditions using microwave, Synth. Commun., 31, 2245, 2001. 

All substituted alkylphosphonates lA-IJ and IVC-IVE studied or reported previously were only based on their racemic forms. Considering the importance of chirality for herbicidal active, the synthesis and the biological activities of their optical counterparts would be very important. The methods of asymmetric synthesis of both chiral 1-hydroxyphosphonates and cyclic 1-hydroxy phosphonates, and several optically active 1 -(substituted phenoxyacetoxy)alkylphosphonates were hence set up. So far, several series of optically active 1-(substituted phenoxyacetoxy) alkylphosphonates including lA, IC, IE, IF series were prepared (Scheme 1.34) and their biological activities were evaluated. Their asymmetric synthesis, enantiomeric selectivity in herbicidal activity, acute aquatic toxicity, and SAR discussion are summarized in Chap. 6. 

The (E/Z) ratio of the product can often be changed by a change in solvent or by the addition of salts. Another way of controlling the stereochemistry of the product is by use of the aforementioned phosphonic acid bisamides. In this case the betaine (42) does form and when treated with water gives the (3-hydroxyphosphonic... 

It is worthy of note that a-sulfanyl phosphonic acids, which can now be obtained enantioselectively from corresponding a-hydroxyphosphonates, are analogues of the a-sulfanyl carboxylic acids, which, for some of them, are metallo- -lactamases inhibitors [ 112]. To our knowledge, it does not seem that biological activities of a-sulfanyl phosphonic acids have been examined so far. 

A study of the decomposition in basic media of the erythro- and threo-isomers of the /8-hydroxyphosphonate (169) showed that the first step in the phosphonate olefin synthesis is reversible and that the diastereo-isomers of (169) can also interconvert directly, presumably via the a-car-banion. 

Reaction of a phosphorus halide with a 2-alkynol and subsequent rearrangement to generate a hydroxyphosphonate... 

Of course, the use of tris(trimethylsilyl) phosphite213 214 provides facile access to the free a-hydroxyphosphonic acids. These silyl reagents have been used for the preparation of a wide range of a-substituted phosphonates and -phosphonic acids, starting with ketene,215 a-ketophosphonates,216 ketoesters,217 218 and a,P-unsaturated carbonyl compounds,207/219-221 as well as simple aldehydes and ketones.205 210/219 224 Their use for the preparation of compounds of significant biological interest has been reviewed.125... 

Two reports have been made of the preparation of P-chiral phosphine oxides through reaction of chiral f-butylphenylphosphine oxide treated with LDA and electrophiles. The electrophiles included aldehydes,355 ketones,355 and benzylic-type halides.356 Optically active a-hydroxyphosphonate products have also been generated from aldehydes and dialkyl phosphites using an asymmetric induction approach with LiAl-BINOL.357... 

Texier-Boullet, F., Synthesis of a-hydroxyphosphonates in a heterogeneous solid-liquid medium and at the surface of inorganic solids. Study of factors of their formation in some two-phase systems, Bull. Soc. Sci. Bretagne, 56, 57, 1984. 

Schultz s group employed an a-hydroxyphosphonate hapten [99] and subsequently isolated 20 cell lines of which 5 catalysed the hydrolysis of the model substrate p-nitrophenyl phosphate [100] above background (Fig. 34) (Scanlan et al., 1991). Antibody 38E1 was characterized in more detail and kinetic parameters were afforded by Lineweaver-Burke analysis. This antibody exhibited 11 turnovers per binding site with no change in Vmax, and thus acted as a true catalyst. Moreover, examination of substrate specificity showed that catalysis was entirely selective for p-substituted species (Appendix entry 6.6). 

Fig. 34 (above) Antibody 38E1, generated from the a-hydroxyphosphonate hapten [99], catalysed the hydrolysis of p-nitrophenyl phosphate [100]. 

The oxidation of alcohols with metal dichromates, other than sodium or potassium dichromate, has been little explored. Hydrated zinc dichromate (ZnCr207 3H20)367 368a and ferric dichromate [Fe2(Cr207)3],368b—which are very easy to prepare as stable solids—are able to oxidize alcohols in organic solvents.368 Zinc dichromate is particularly efficient in the transformation of a-hydroxyphosphonates into a-ketophosphonates.369... 

The chlorohydrin 87 was obtained with 97% ee by the Ru-catalyzed hydrogenation of y-chloroacetoacetate (86) at 100°C. The % ee was lower at lower temperature. The chlorohydrin 87 was converted to (R)-camitine (88) [58], Asymmetric hydrogenation of the z-bromo-/M[Pg.404]

Hammerschmidt, F. Schmidt, S. Deprotonation of secondary benzylic phosphates. Configurationally stable benzylic carbanions with a diethoxyphosphoryloxy substituent and their rearrangement to optically active tertiary a-hydroxyphosphonates. Chem. Ber. 1996, 329, 1503-1508. 

With I (X-Nalk R =H) the intermediate hydroxyphosphonate(III) is rather stable and undergoes the expected cycloelimination only poorly or not at all. However, III upon acidification undergoes a semi-pinacol type rearrangement to give aldehydes... 

As expected, the reaction of the lithium salts of phosphonates with oxygen results in the formation of dialkyl phosphoric acids-8 and carbonyl products i.e. the cleavage of the C-P bond takes place (, 5). However, when the halomagnesiurn salts of phosphonates Z were oxidized, a-hydroxyphosphonates 2 were formed. 

An unexpected result was obtained [82, 83] with isatin and dialkyl phosphite in a ratio of 2 1. At room temperature in the presence of sodium alkoxide 3-dialkylphosphoryl-3 -hydroxy-3,3 -di(2-indolinone) 90 is formed. In boiling ethanol with the reagents in the same ratio hydroxyphosphonates 89 were obtained. 

Sodium borohydride reduction of cyclic ketone 109 produced alcohol 110 <1997BMC1327> (Equation 19). Biheterocyclic 2-hydroxyphosphonates 111 were synthesized by reactions of phospha-bicyclodecanones 112 with dimethylphosphonates in the presence of NaOH/MeOH <1996RJC567> (Equation 20). 1-Cyclohexylphosphin-4-one 113 was reduced to the corresponding alcohol 114 by sodium borohydride <2004TL407> (Equation 21). 

The reduction of yff-ketoesters to aldols is one of the most important applications of Ru(II)-BlNAP catalysts [7]. As a special bonus, the chirally labile C2 stereogenic center can be exploited in a dynamic kinetic resolution such that racemic reactants yield only one of the four conceivable stereoisomers in high diastereomeric and enantiomeric excess. This strategy has been extended to the reduction of -ketophosphonates 10. The 3-hydroxyphosphonic acids 7 which are accessible by this route constitute promising starting materials for the synthesis of peptide analog and antibiotics [8]. 

Styrene-furfural and acetylated styrene-furfural copolymers on phosphorylation afford phosphonic acid (SFP) and hydroxyphosphonic acid (SFAP) cation-exchange resins, respectively. The equilibrium studies reveal that both resins have a high affinity for hydrogen and divalent ions. The values of the separation factor... 

---