Hydroxyphosphonates oxidation

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... 

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... 

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 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... 

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. 

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. 

A procedure for the transformation of a formyl moiety into p-ketophosphonate has been described. It involves the selective addition of dimethyl l-Uthiomethylphosphonate to the formyl group followed by oxidation with CrO,-Py of the intermediate P-hydroxyphosphonate. ... 

The phosphonamide route has some advantages over the Wittig reaction. The reagents are readily prepared and potentially cheaper. The products are readily isolated (separation from triphenylphosphine oxide is sometimes troublesome). The intermediate /3-hydroxyphosphonic acid amides are readily purified. There is more opportunity to control the geometry and position of the double bond. 

A recent paper reports the oxidation of benzylic a-hydroxyphosphonates to aroylphos-phonates in good yields, by refluxing them with 10 equiv. of Mn02 in toluene The same paper reports that other oxidizing agents, including pyridinum chlorochromate and dichlorodicyanobenzoquinone (DDQ),or the Swem method are also applicable for the oxidation of benzylic a-hydroxyphosphonates to benzoylphosphonates. This approach to acylphosphonates was found, however, to be limited to tert-huty esters. ... 

Investigation of the oxidation reaction of electron-rich, alkoxy-sub-stituted S-aryl S-hydroxyphosphonates (368-370) to corresponding jS-ketophosphonates (371-373) as key substrates in syntheses of lignans, with various oxidizing agents, has been described by Balczewski and co-workers (Scheme 85). ... 

Optically active a-substituted phenyloxyacyloxy and aryloxy phosphonates have been synthesized via catalytic asymmetric hydrogenation of the corresponding prochiral a,P-unsaturated phosphonates using Rh(i)/(7, i )-Me-DuPhos as the catalyst. The reactions exhibit excellent enantioselectivity with ee up to 96%. A new kinetic resolution process for a-hydroxyphosphonates with the assistance of N-salicylidene-L-tert-leucine-based vanadyl(v) methoxide complexes (209), achieving highly enantioselective and chemoselective aerobic oxidation at ambient temperature (Scheme 78). ... 

Phenylethynyl-alkyl-ketones reacted selectively with secondary phosphine oxides to afford the corresponding a-hydroxyphosphonates (Scheme 23). ... 

It has been also found that chiral phosphine oxides (5)-BINAPO catalyzed silicon tetrachloride-mediated, enantioselective phosphonylation of aldehydes with trialkyl phosphites, led to formation of optically active a-hydroxyphosphonates with low to moderate enantioselectivities (ee 22-52%)7 This reaction constituted the first example of asymmetric Abra-mov-type phosphonylation of aldehydes with trialkyl phosphites catalyzed by chiral Lewis bases. 

SCHEME 4.137 Calcium oxide-promoted synthesis of a-hydroxyphosphonates [122]. 

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