Homer phosphines

Behrens and Wilke (77) have described a method for resolving enantiomeric Homer phosphines (PR Rs) by complexation with tj3-(+)-(l/ ,5/ )-pinenyl nickel bromide dimer a 1 1 adduct is formed, purified by recrystallization, and the optically pure phosphine released by reaction with excess trimethylphosphine. The geometry of the adduct 32 formed by methyl-ferf-butylphenyl phosphine is shown here. The, 3C-NMR spectrum... 

An even more complicated example is to be found in complexes of the type (i73-allyl)Ni(X)L where L is a Homer phosphine having a (1R, 3R, 45)-menthyl substituent (79). The optically pure (R)-phosphine gives rise to a... 

The phosphorus ylides of the Wittig reaction can be replaced by trimethylsilylmethyl-carbanions (Peterson reaction). These silylated carbanions add to carbonyl groups and can easily be eliminated with base to give olefins. The only by-products are volatile silanols. They are more easily removed than the phosphine oxides or phosphates of the more conventional Wittig or Homer reactions (D.J. Peterson, 1968). 

Triphenyl phosphine dibromide [1034-39-5] M 422.1, m 23.5 , 245-255 (dec). Recrystd from MeCN-Et20. Although it has been recrystd from EtOH, this is not recommended as it converts alcohols to alkyl bromides. It deteriorates on keeping and it is best to prepare it afresh. [Anderson and Freenor J Am Chem Soc 86 5037 1964 Homer et al. Justus Liebigs Ann Chem 626 26 1959.]... 

During the late 1960s, Homer et al. [13] and Knowles and Sabacky [14] independently found that a chiral monodentate tertiary phosphine, in the presence of a rhodium complex, could provide enantioselective induction for a hydrogenation, although the amount of induction was small [15-20]. The chiral phosphine ligand replaced the triphenylphosphine in a Wilkinson-type catalyst [10, 21, 22]. At about this time, it was also found that [Rh(COD)2]+ or [Rh(NBD)2]+ could be used as catalyst precursors, without the need to perform ligand exchange reactions [23]. 

According to a method described by Homer et al, phosphine was obtained in 70% yield from the reaction of PCI3 with finely divided sodium in toluene, followed by hydrolysis of the reaction products... 

Optically active (+)-(R) methylpropylphenyl phosphine oxide 39 was reduced using the Homer method, and then the produced phosphine was oxidized by adding 1.2 molar equivalent of BTSP at room temperature. (—)-(S) methylpropylphenyl phosphine oxide 40 was obtained with 95% stereospecificity. Since the reduction step is known to proceed with inversion of the configuration at the phosphorus center , oxidation occurs with retention (equation 63). 

In 1968, the first homogeneous asymmetric hydrogenation was reported independently by Homer and Knowles (8). The Wilkinson complex and related complexes modified by the incorporation of a chiral tertiary phosphine, such as P(C6H5)(n-C3H7)(CH3), catalyzed the hydrogenation of certain hydrocarbon olefins in optical yields of 3-15%. 

When the substituent becomes very anion-stabilising, as in 42, the ylid may not react with ketones and anions of phosphonate esters are usually preferred in the Homer-Wadsworth-Emmons (HWE) variant.11 The reagent triethyl phosphonoacetate 46 is made by combining a phosphite (EtO)3P instead of a phosphine, with ethyl bromoacetate. Displacement of bromide 44 gives a phosphonium ion that is dealkylated by bromide 45. 

J. Seyden-Penne, Lithium Ccoordination by Wittig-Homer Reagents Formed by a-Carbonyl Substituted Phosphonates and Phosphine Oxide, Bull. Soc. Chim. Fr. 1988, 238. 

Unlike the carbanions derived from phosphonate esters, the carbanions of dimethyl methylphosphonate18 and, in some instances phosphine oxides (Homer-Wittig reaction), do not react directly with aldehydes and ketones to give the corresponding alkene.2,3 Rather, the reaction yields an intermediate P-hydroxy derivative that can be isolated and purified to high diastereoisomeric purity. Subsequent reaction then gives the desired alkene with control of stereochemistry (see Schemes 3, 5 and Protocols 7, 8). 

Geometrically pure alkenes were generated by Homer-Wittig elimination of stereochemically pure p-hydroxy diphenylphosphine oxides available from reduction of the corresponding P-keto phosphine ox-... 

The use of anions derived from a phosphine oxide (132) or a diethyl phosphonate (133) to form al-kenes was originally described by Homer.Although these papers laid the foundations for the use of phosphoryl-stabiliz carbanions for alkene synthesis, it was not until Wadsworth and Emmons published a more detailed account of the general applicability of the reaction that phosphonates bet e widely used. Since the work of Wadsworth and Emmons was significant and crucial to the acceptance of this methodology, the reaction of a phosphonate caibanion with a carbonyl derivative to form an alkene is referred to as a Homer-Wadsworth-Emmons reaction (abbreviated HWE). The phosphine oxide variation of the Wittig alkenation is called the Homer reaction. 

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... 

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). ... 

The Wittig and Homer processes can be combined in a cyclic process to form ( -dienes (249 Scheme 35). The initial Wittig process proceeded in 63% yield with 68 32 to (Z)-selectivity. Deprotonation of the phosphine oxide (248) and reaction with benzddehyde gave exclusively the erythro isomer in 82% yield. The phosphine oxide was eliminated with NaH in DMF to give the ( .Z)-1,6-diene in an isomer ratio of 92 8 with the ( , )-diene. 

The Homer-Wittig process has been utilized in the synthesis of vitamin D and its metabolites. Recently, a process was developed for the synthesis of hydrindanols by the 1,4-addition of the phosphine oxide to cyclopentenone. After further elaboration, the phosphine oxide formed (250) can be utilized to incorporate side chains (251 equation 58). 

Recently, the Homer coupling was utilized by Smith and coworkers in the total synthesis of milbe-mycin (equation 59). In an excellent example of the sensitivity of the alkene stereochemistry to the base utilized, when the phosphine oxide anion (253) was generated with NaH as the base the ( ) (Z) ratio was 7 1, but epimerization occurred at the aldehyde methine (252) and the yield was only 15%. Switching to KHMDS, the yield improved to 74% but virtually a 1 1 ratio of alkenes formed. Use of sodium hexamethyldisilazide solved these difficulties, forming the desired ( )-diene (254) in a 7 1 ratio with the (Z)- in 85-95% yield. Additional examples of the use of phosphine oxides in the synthesis of milbemy-cins and FK-506 are presented in Section 3.1.11.4. 

The Homer reaction can be applied to the synthesis of trisubstituted alkenes. As in the case of HWE reactions, the yield obtained by adding a disubstituted phosphine oxide to an aldehyde is frequently higher than that obtained by adding an anion to a ketone. This methodology was applied to the synthesis... 

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