Phosphine oxides Homer reaction

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). 

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). 

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. 

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 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... 

Etemad-Moghadam, G., and Seyden-Penne, J., Stereoselective synthesis of or Z a-methyl a,P-ethylenic esters from phosphonates or phosphine oxides by the Wrttig-Homer reaction. Tetrahedron, 40, 5153, 1984. 

Asymmetric Wittig-Homer reactions Wittig-Horncr reactions have usually involved phosphine oxides, phosphonates, or phosphonamidcs. Highly enantioselcctivc ole-finations have now been achieved by use of this chiral phosphonamidatc 1. Thus the anion (t-BuLi) reacts with 4-/-butylcyclohexane to form 2 in >98% de. Elimination with trityl triflate/2,6-lutidine provides the alkylidene 3 with essentially complete stercospccificity. The reaction was shown to be applicable to a variety of 4-alkylcyclohexanones. 

A major review of stereocontrol in organic synthesis using the diphenylphos-phoryl group has appeared and includes coverage of Homer olefination and other reactions of phosphine oxide-stabilised carbanions. ... 

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

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