Mechanism Horner-Wittig reaction

As mentioned above, the use of lithium bases in the HW reaction allows the reaction to be divided into two discrete steps [39] 1) the HW addition of a lithiated phosphine oxide to an aldehyde (or ketone) to produce a j8-hydroxy phosphine oxide, and 2) the HW elimination of a phosphinic acid to afford an alkene (Scheme 1.14). Careful manipulation of each step then allows control of the overall sequence. While the overall mechanism of the Horner-Wittig reaction is similar to that of the HWE reaction (Scheme 1.6), some additional discussion is required to understand its stereochemical outcome. The HW reaction can be carried out without isolation of the intermediate yS-hydroxy phosphine oxides in cases where a nonlithium base is used and is able to stabilize the negative charge of the phosphorus a-carbanion 9. Under these conditions, reaction of an aldehyde with the phosphine oxide to give intermediates 10 and 11 is reversible. The -alkene is then formed preferentially since elimination of intermediate 11 occurs much faster than that of 10. 

Warren and coworkers have reported an interesting synthesis of nonracemic allenes by reaction of vinylphosphine oxides with aldehydes in the presence of chiral lithium [(R)-l-phenylethyl](benzyl)amide to give hydroxyvinylphosphine oxides in 33-87% yields (0-51% ee) [38]. These products underwent a Horner-Wittig elimination reaction to produce nonracemic allenes. A mechanism similar to the Baylis-Hillman reaction was suggested. 

When considering the Horner-Emmons reaction, it is important to recognize that the mechanism and products are similar to those observed during a Wittig reaction. In fact, the Horner-Emmons reaction is a recognized and viable alternative to the Wittig reaction. 

The mechanism of the Horner-Emmons olefination resembles that of the Wittig reaction via betaine intermediates (Scheme 5), and is shown in Scheme 7 for the reaction of a phos-phonate 23 with an aldehyde 27. 

Maercker, A. The Wittig Reaction Organic Reactions 1965, 14, 270-490. Maryanoff, B. E. Reitz, A. B. The Wittig Olefmation Reaction and Modifications Involving Phosphoryl-Stabilized Carbanions. Stereochemistry, Mechanism, and Selected Synthetic Aspects Chemical Reviews 1989, 89, 863-927. Blanchette, M. A. Choy, W. Davis, J. T. Essenfeld, A. P. Masamune, S. Roush, W. R. Sakai, T. Horner-Wadsworth-Emmons Reaction Use of Lithium Chloride and an Amine for Base-Sensitive Compounds Tetrahedron Lett. 1984, 25, 2183-2186. 

On the other hand, high Z-selectivity is seen in the olefination reactions of the carbanion 19 derived from 3,3-diethoxybutylphosphonate with aldehydes (Scheme 2.16) [41, 42]. Similarly, Z-selective Peterson reactions of the in situ generated a-phosphoryl-a-(trimethylsilyl)allyl anion 104 with aldehydes or alkyl formates to afford the 2-dienylphosphonates 105 have been reported (Scheme 2.63) [168, 169]. These methods allow access to (Z)-alkenylphosphonates, whereas Wittig-Horner reactions give the thermodynamic ( )-alkenes almost exclusively. These excellent Z-selectivities can be rationalized in terms of the chelation control mechanism (see Section 2.2.2.3). 

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