Hydroxyphosphinates

Yamagishi, T., Yokonatsu, T., Suemune, K., and Shibuya, S., Enantioselective synthesis of a-hydroxyphosphinic acid derivatives through hydrophosphi-nylation of aldehydes catalyzed by Al-Li-BINOL complex, Tetrahedron, 52, 11725, 1996. 

Similar treatment of 1.1-spiro compounds leads to different results depending upon the number of atoms in the iro ring. The fivemiembered compound 207 a yields the cyclic 2-oxyphosphinic acid ester 208 a (60%) and only 8% of the 4-hydroxyphosphinic acid ester 209a (R = H). Acetic acid ist not necessary for these transformations. 207b and c (R = D, CH3) react in a similar manner ... 

Fig. 11.11. Wittig-Horner synthesis of stereouniform alkenes via ketophosphine oxide B. The reaction proceeds via its Felkin-Anh-selective or chelate-controlled reduction to form the syn-configured hydroxyphosphine oxides D and the anti-configured hydroxyphosphine oxides E. D and E continue to react—after deprotonation with KO-tert-Bu—via a syn-elimination to give the trans- and cis-alkene, respectively. R1 in the formula A-C corresponds to a primary (prim-alkyl) or a secondary alkyl residue (sec-altyl).

The corresponding diastereomeric adducts of /J-hydroxyphosphines 9 and 10 were obtained, as unseparable mixtures (Table 3). The diastereomeric excesses observed in this transformation ranged from 20 to 56%. 

Reaction of olefins with P, Oj and H2O yields /3-hydroxyphosphinic acids in a complex reaction ... 

Diastereoselective synthesis of p-substituted a-hydroxyphosphinates (252) and (253) by hydroxyphosphinylation of a-silyloxy aldehydes (254) and a-amino aldehydes (255) with ethyl allylphosphinate (256), catalysed with lithium phenoxide, has been reported (Figure 47). ... 

New y-ethoxycarbonyl- and ot-amino-alkyl-hydroxyphosphinic acid derivatives (366) and (367) were conveniently prepared by Michael addition or Kabachnik-Fields reaction of a new precursor, benzyloxymethyl hydrogen-phosphinate (368), with a,p-unsaturated esters or imines (Scheme 94). " Phosphinic acid inhibitors (369) of Cathepsin C were synthesized by addition of methyl acrylate to the appropriate a-amino phosphinic acid and by... 

In Homer s original work, phosphine oxides (202) were treated with potassium r-butoxide or sodamide and allowed to react with an aldehyde or ketone to form the alkene (203) directly (Scheme 28). Homer observed that the use of a lithium anion resulted in the isolation of Ae p-hydroxyphosphine oxide (204). In addition, he found that the intermediate hydroxyphosphine oxide could be obtained by LAH reduction of the ketophosphine oxide. Warren and coworkers t ve utilized and expanded upon these techniques by isolating and separating the diastereomeric, frequently crystalline, p-hydroxyphosphine... 

The intermediate p-hydroxyphosphine oxide is isolated only if lithium is used to deprotonate the phosphine oxide. Sodium or potassium anions eliminate in situ to form the alkene direedy. Eliminations of... 

Trans-tSksaes can be synthesized by the Homer reaction from the ketophosphine oxide, which is reduced selectively to the threo adduct. This inteimediate is typically foimed by reaction of the phosphine oxide widi an ester or acid chloride. Alternatively, the keto intermediate may be obtained by oxidation of -hydroxyphosphine oxides. This sequence was applied to the synthesis of the pure ( )-triene (237) by Warren (equation 57). ... 

In analogy to the Peterson alkenation, the intermediate hydroxyphosphine oxidn (269) cm be prepared by addition to epoxide derivatives (268 Scheme 36). Overall yields are high for this process, and this sequence can be applied to the synthesis of phosphonate intermediates as well. Warren has studied hydroxy-directed epoxidation. Provided the allylic phosphine oxide is trisubstituted, as is (270) in equation (6S), these oxidations proceed with good selectivity. Ring opening can then be undertaken to generate the hyth-oxyphosphine oxide. 

Another variation of the Wittig reaction is the Wittig-Horner reaction, in which the anion generated ot- to phosphine oxide is used as a nucleophile to react with carbonyl compounds. The intermediate formed in this reaction, -hydroxyphosphine oxide, is isolable particularly when bases with lithium counterion are used for deprotonation. Since the j6-hydroxyphosphine oxides are diastereomers, they can be separated and subjected to elimination to form the corresponding alkenes. Since the elimination of phosphonate moiety is syn, stereospecific alkenes are obtained from the elimination step. As expected, the generation of erythro and threo isomers is dependent on the solvent and the reaction conditions. 

Excellent activities in the coupling of all kinds of aryl chlorides were achieved by use of catalyst 13 containing the bulky bis(adamantyl)( -butyl)phosphane. TONS of 10 to 2 X 10 were recorded even for non-activated aryl chlorides [23]. Quite recently, phosphine oxides according to the equilibrium in eq. (4) were used with Pd2(dba)3 in the Suzuki coupling of aryl chlorides, while a hydroxyphosphine complex/Ni(COD)2 catalyzes the Kumada coupling of the same substrates [26],... 

The polarographic reduction of triphenylphosphine oxide and trioctyl-phosphine oxide at low concentration in nitroethane has been studied. The estimation of phosphate insecticides by polarography has been reported, and the rearrangement of a-hydroxyphosphinates has been followed by conductance. ... 

An additional access to chiral sulfonated phosphines was also described [13a,b]. The method is based on the acylation of chiral hydroxyphosphines with commercial o-sulfobenzoic anhydride and was demonstrated on a number of diphosphines based on the DIOP skeleton (Eq. 1). The chelating properties of the diphosphines were studied by preparation of cationic rhodium complexes. The presence of the o-sulfobenzoate group is thought not to influence the catalytic properties. Chiral phosphines containing a sulfonate group (e.g., 8) were also obtained from BPPM by acylation with trimellitic anhydride followed by treatment with sodium tauri-nate [13 c],... 

Simple hydroxyphosphines can be prepared conveniently by the ring-opening reaction of cyclic ethers with phosphides (Eq. 1) [4],... 

Phosphine and hydroxy groups emerge simultaneously and therefore subsequent reaction with the air-sensitive hydroxyphosphine can be avoided. The structure of the cyclic ether determines in each case the distance separating functional groups in the product this means epoxides form 1,2-hydroxyphosphines, 1,3-prod-ucts can be produced by the employment of oxetanes [5], etc. Problems may be caused by the formation of regio- and stereoisomeric byproducts during the ringopening step by application of internal nonsymmetric cyclic ethers [6],... 

On the way to water-soluble polyether phosphines Mayer and co-workers synthesized a tripodal polyhydroxyalkylphosphine ligand in a three-step synthesis starting from the relevant hydroxyphosphine (Eq. 2) [13]. The most interesting feature of this approach is the protection of the phosphine groups as a Mo(CO)3 complex during the synthesis. 

It should be finally noted that hydroxyphosphines can be converted under very smooth conditions into sulfonated phosphines by acylation with o-sulfobenzoic anhydride, as shown by Borner et al. (Eq. 5) [26]. With this methodology in hand the severe conditions commonly used for the incorporation of sulphonate groups in phosphines can be avoided. Acid-labile functional groups like acetals survive under these conditions. In comparison to the parent hydroxyphosphines the water solubility of the relevant Rh catalysts was strongly enhanced [27]. In the asymmetric hydrogenation of prochiral olefins, moderate enantioselectivities were achieved. 

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