Hydroxyphosphine oxides

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).

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). ... 

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. 

In analogy to the Peterson alkenation, the intermediate hydroxyphosphine oxides (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 interm iates as well. Warren has studied hydroxy-directed epoxidation. Provided the allylic phosphine oxide is trisubstituted, as is (270) in equation (65), these oxidations proceed with good selectivity. Ring opening can then be undertaken to generate the hydroxyphosphine oxide. 

The stereospecific olefination method involving synthesis, separation, and base-catalysed, decomposition of diastereomeric P-hydroxyalkylphosphine oxides has been used for the preparation of pure isomers of y,S-unsaturated acetals (Scheme 11). The same principle has been extended to trisubstituted alkenes. The yields are generally still good, but the diastereomeric hydroxyphosphine oxides involved are less stable in some cases and the routes to them are less stereoselective. However, the method works reasonably well for the synthesis of ( )-and (Z)-allylic amines (Scheme 12). Unfortunately, (2-substituted-2-amino)-... 

Warren showed that olefination of ketones and aldehydes, or even esters, with phosphine oxide carbanions allows some control of stereochemistry in the alkene products. Reaction with an aldehyde or ketone generates diastereomeric P-hydroxyphosphine oxide products, which can be isolated and then chromatographically separated. Reaction of 573 with n-butyllithium was followed by addition of 3,4-methylenedioxy-benzaldehyde (574, known as piperonal) to give a 9 1 mixture of 575/576, the syn and anti alcohol, respectively.514 7i,e pyre syn alcohol 575 was isolated in 75% yield by chromatography on silica gel. 

A soln. of startg. phosphine imine in THF added dropwise to /-PrjNLi in the same solvent at —30° under argon, the mixture stirred for 1 h, cooled to —70°, treated dropwise with benzaldehyde in THF, then allowed to warm to room temp. - erythro-product. Y 86%. F.e., electrophiles, and conversion to p-hydroxyphosphine oxides, s. J. Barluenga et al.. Synthesis 1988, 562-4. 

Trofimov et al. accomplished the addition of bis(phenylethyl)phosphine-oxide and -sulfide to aldehydes and ketones to afford the corresponding a-hydroxyphosphine oxides/sulfides (Scheme 27). ... 

Potassium tert-butoxide Cyclopropanes from oxido compounds via >hydroxyphosphine oxides... 

Probably the presence of a second ligating group in the ligand enhances the stability of phosphine oxide-rhodium complexes [177]. Thus, the group of Alper utilized successfully a-hydroxyphosphine oxides, which work, for example, in the reaction of HPPh2 with benzaldehyde (Scheme 2.53) [178], as promoting ligands in the rhodium-catalyzed hydroformylation [179]. 

Scheme 2.53 Preparation of a-hydroxyphosphine oxides (in the paper no information is given as to where the oxygen for the oxidation of the phosphine group comes from).

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