Reduction keto phosphine oxide

The unique feature of the Horner-Wittig reaction is that the addition intermediate can be isolated and purified. This provides a means for control of the stereochemistry of the reaction. It is possible to separate the two diastereomeric adducts in order to prepare the pure alkenes. The elimination process is syn so that the stereochemistry of the alkene depends on the stereochemistry of the adduct. Usually, the anti adduct is the major product, so it is the Z-alkene which is favored. The syn adduct is most easily obtained by reduction of /i-keto phosphine oxides.160... 

On the synthetic side, single diastereomers of P-keto phosphine oxides have been generated from intermolecular acylation of phosphine oxides using either chiral esters or chiral phosphine oxides. In most cases, reduction of the ketone products was not affected by the presence of extra chiral centres. Addition of metallated phosphine oxides to proline-derived ketoaminals provides a new route to optically active P-hydroxy phosphine oxides. The P-hydroxy phosphine oxide 97 has been prepared by the caesium fluoride mediated reaction of silyl-substituted phosphine oxide 98 and benzaldehyde." The synthesis of two (E)-(6-hydroxy-2-hexen-l-yl)diphenylphosphine oxides (99) has been reported. The Horner-Wittig reactions of these compounds with various carbonyl compounds... 

Subsequent treatment with sodium hydride in DMF gave the (Z)-alkene, a-isosafrole (577). If 573 reacted first with butyllithium and then with the analogous ester (578), the keto-phosphine oxide 579 was produced. Reduction of the ketone with sodium borohydride gave predominantly (>=6 1) the anti isomer 580, which gave the ( )-alkene 581 upon reaction with sodium hydride. An interesting application of this methodology is to extend the chain of an aldehyde by one carbon (R—CHO RCH2CHO). i ... 

Reduction. With TiCl4 to form chelates, P-keto phosphine oxides undergo stereoselective reduction to give the anfi-alcohols as major products. 

Tab. 1.4. Stereoselective reduction of -keto phosphine oxide using different reducing conditions.

The unique feature of the Homer-Wittig reaction is that the phosphine oxide-stabilized carbanion/aldehyde addition intermediates, p-hydroxy phosphine oxides, can be isolated and purified, and the elimination step is stereospecific for the formation of the corresponding alkenes. Usually the reaction gives predominantly erythro adducts that can be converted to Z-alkenes upon being treated with bases (Scheme 43). However, threo p-hydroxy phosphine oxides can be obtained by reduction of the corresponding p-keto phosphine oxides, which are prepared by oxidation of p-hydroxy phosphine oxides, or by acylation of lithio phosphine oxides with esters [206]. 

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-... 

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