Phosphonates hydroxyphosphonates

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. 

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... 

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

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]

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. 

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... 

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... 

It has been shown that metallation of diisopropyl phosphates derived from primary aliphatic alcohols, except methanol, takes place at the alkyl as well as the isopropyl group in a ratio which is strongly influenced by steric effects. It was proposed that short-lived alkyllithium compounds were configurationally stable up to — 50°C and rearrange, with retention of configuration, into the corresponding a-hydroxyphosphonates (phosphate-phosphonate rearrangement) (Scheme 21). ... 

Catalytic hydrogenation (Pd-on-carbon) of N-Boc aziridine 2-phosphonates (253) derived from 3-amino-2-hydroxyphosphonates affords N-Boc a-aminophosphonic esters (254) in high enantiomeric purity (Scheme 68). 

The mechanism of phosphonate anion (135) addition to carbonyl derivatives is similar to the phosphonium ylide addition however, there are several notable features to these anion additions that distinguish the reactions fix)m those of the classical Wittig. The addition of the anion gives a mixture of the erythro (136 and 137) and threo (139 and 140) isomeric p-hydroxyphosphonates (Scheme 24). In the case of phosphine oxides, the initial oxyanion intermediates may be trapped. The anion intermediates decompose by a syn elimination of phosphate or phosphinate to give the alkene. The elinunation is stereospecific, with tile erythro isomer producing the ci.r-alkene (138), and the threo addition adduct producing the... 

Several studies have described the successful enhancement of the ( )-selectivity in alkene formation by increasing the steric requirements of the phosphonate. This selectivity may be derived by increasing the selective formation of the rAreo- -hydroxyphosphonate. 

Condensations. Alumina promotes the formation of a-hydroxyphosphonate esters from aromatic aldehydes and dialkyl phosphonates, and the adducts are converted to a-aminophosphonate esters on reaction with ammonia. A solvent-free synthesis of a-nitro ketones comprises mixing nitroalkanes, aldehydes, and neutral alumina and oxidizing the adducts with wet, alumina-supported CrOj (15 examples, 68-86%). The Knoevenagel reaction, the Michael addition of nitromethane to gcm-diactivated alkenes, and the formation of iminothiazolines from thioureas and a-halo ketones are readily effected with alumina under microwave irradiation. 

Nucleoside Pyrophosphonates. Rosenberg et al. have reported that treatment of the geminal hydroxyphosphonate moiety of 2 -thymidine-3 -C-phosphonate with acetic anhydride yielded the phosphonate anhydride derivative (85a), the cyclic dinucleoside diphosphonate (85b) and the tetranucleoside diphosphonate (85c). ... 

Alkenyl, Alkynyl, Aryl, Heteroaryl and Related Acids. - Alkenyl-phosphonates have been prepared by the dehydration of P-hydroxyphosphonates with DCC and CuCh, by dehydrohalogenation of P-bromoalkylphosphonates with triethyl orthoformate, and from alk-l-ynylphosphonates 116 by hydrogenation using Lindlar s catalyst (to give the m-isomer 118) and by stereoselective addition of alkylcuprates to give 117 (Scheme 7). A convenient... 

When performed in ether at —70 °C containing HCl, the reaction between triethyl phosphite and either chloral or bromoacetone affords higher yields of the a-hydroxyphosphonates (34), relative to vinyl phosphate, than are normally obtained. The rate-determining step in the formation of the phosphonate (35) from chloroacetone and dimethyl hydrogen phosphonate appears to be the tautomerism of dialkyl phosphonate to phosphite. ... 

Dialkyl phosphites react slowly with epoxy ketones at room temperature in the presence of a catalytic amount of sodium metal to form dialkyl l-hydroxy-2,3-epoxypropylphosphonates in 41-99% yields.Similarly, dialkyl phosphites react with f7.v-]-fonnyl-l-trimethylsilyl-l,2-cpoxy-alkanes in the presence of DBU in THF to give dialkyl ] -hydroxy-2-trirnethylsilyl-2,3-epoxy ilkyl-phosphonate in high yields (84%, Scheme 4.16).By contrast, DBU or EtjN in C,H, at reflux was found inefficient for the addition of dimethyl phosphite to the epoxide derived from chalcone. The reaction is best carried out in the presence of KF2H2O to produce a diastereomeric mixture of hydroxyphosphonates free from other organophosphorus compounds. 

Ohler. E.. and Kanzler, S., (2//-A/.irin-2-yl)mcthy I Iphosphonates. Synthesis from allylic a- and y-hydroxyphosphonates and application to diastereoselective formation of substituted [(azirin-2-yl)methyl]phosphonates, Liebigs Ann. Chem., 867, 1994. 

Low-temperature reduction of P-phthalimido-a-ketophosphonates with catecholborane in toluene in the presence of a catalytic amount of oxazaborolidine affords P-phthaUmido-a-hydoxy-phosphonates in high yields and high diastereoselectivity. Deprotection of the amino group produces the P-amino-oc-hydroxyphosphonates.5" ... 

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. 

Firouzabadi, H., Iranpoor, N., Sobhani, S., and Sardarian, A.R., High yield preparation of a-keto-phosphonates by oxidation of a-hydroxyphosphonates with zinc dichromate trihydrate (ZnCr2O7 SHjO) under solvent-free conditions. Tetrahedron Lett., 42, 4369, 2001. 

Pudovik, A.N., Konovalova, I.V, and Dedova, L.V., Reanangement of a-hydroxyphosphonic and a-hydroxyphosphonothioic esters into phosphonates and phosphorothioates, Dokl. Akad. Nauk SSSR, 153, 616, 1963 Chem. Abstr, 60, 8060a, 1964. 

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