Stereoselective Wittig-Horner reaction

Wittig-Horner reaction. The reagent reacts with a wide range of aldehydes, aliphatic, aromatic, and a,P-unsaturated, in the presence of a base to form (E)-a-methyl-a, -unsaturated esters stereoselectively. The reaction can be carried out either with potassium t-butoxide in DMF or with K,COj in QH /HjO and Aliquat 336 as phase-transfer agent. 

Etemad-Moghadam, G., and Seyden-Penne, J., Stereoselective synthesis of -a-fluoro a,P-unsaturated esters by Wittig-Horner reaction from methyl a-((9,(9-diethylphosphono)-a-fluoroacetate. Comparison with methyl a-(diphenylphosphinyl)-a-fluoroacetate. Bull. Soc. Chim. Fr, 448, 1985. 

A series of Af-(alk-l-enyl) nucleobase compounds has been prepared by Wittig-Horner reaction of phosphine oxides (165)-(167) or the Horner-Wadswor-th-Emmons reaction of the analogous phosphonates (168) and (169). Hor-ner-Wittig reactions have been utilised for the stereoselective synthesis of single... 

The other half was made from 172 by formation of the protected keto-aldehyde 183 followed by successive stereoselective Wittig-Horner and Wittig reactions to put in the two alkenes with control over stereochemistry. The Wittig-Horner is under thermodynamic control giving the trisubstituted E-alkene 185 while the Wittig is under kinetic control giving the Z-iodoalkene 175 R = Ac (chapter 15). 

Isocyanoacrylic acid esters are useful as precursors of heterocyclic and unsaturated amino-acids. These compounds are prepared in a stereoselective manner and in good yield using the Wittig-Horner reaction of t-butyl(diphenylphosphinyl)isocyanoacetate with aldehydes. cw-Enoates have been prepared by the reaction of a-diazoesters with Rh(OAc)2. An interesting one-pot synthesis of a-fluoro-a,/3-unsaturated esters from ethyl chloromalonate and carbonyl compounds works well using spray dried potassium fluoride but not with other forms of this salt (Scheme 47) the E-ester was the major product with a stereoselectivity of 86—96%. 

The cyclopropylphosphonate anion undergoes the stereoselective addition reaction with aldehydes [106]. Although the Wittig-Horner elimination is not observed at this stage, the olefinic compounds are produced by treatment of the adduct alcohols 201 with NaH in the presence of 18-crown-6 as illustrated in Scheme 76. 

Fig. 11.10. Wittig-Horner synthesis of alkenes with stereogenic C=C double bond via condensation of lithiated phosphine oxides B <-> B with aldehydes. In the two-step reaction the initially formed addition products syn- and anti-D are protonated and the resulting alcohols syn- and anti-C are isolated and separated the suitable diastere-omer is then stereoselectively converted into the desired alkene isomer. The one-step reaction leads to the same alkene in a cis,trans mixture.

Warren and co-workers continue to develop the use of phosphine oxides, and the Horner-Wittig elimination, to control the stereoselectivity of organic reactions ... 

Matsuura, N., Yashiki, Y, Nakashima, S., Maeda, M., and Sasaki, S., A shortcut and stereoselective synthesis of l-P-alkyl-2-deoxy-D-ribose derivatives via Wittig-Horner-Emmons reaction. Heterocycles, 51, 975, 1999. 

A.iu. Phosphine Oxides and Phosphonate Esters. Many extensions of the Wittig reaction have been introduced that improve or modify the reactivity and/or stereoselectivity of the ylid. Horner et al. showed that a-lithiophosphine oxides such as that derived from 552 react with aldehydes or ketones to give a p-hydroxy phosphine oxide (553) as an isolable species. Subsequent treatment with base liberates the alkene, (554). Wadsworth and Emmons modified the Horner reaction to use phosphonate ester derivatives such as... 

The Wittig-Horner olefination of the aldehyde 28 provided alkenes 29 which were subjected to radical cyclization leading to benzofused tricyclic j6-lactams 30, obtained as single diastereomers (Scheme 8) [36]. A convenient, direct regio- and stereoselective route to optically pure unusually fused or bridged tricyclic /3-lactams has been developed by the use of intramolecular nitrone-alkene cycloaddition reactions. For example, the aldehyde 21 can be transformed into nitrone 31 which subsequently was used for a variety... 

The Horner-Wittig reaction of a-phosphoryl sulphoxides 442, which are chemically stable, results in the formation of a, -unsaturated sulphoxides 443 in high yields (equation 264). The reaction has been found to be non-stereoselective, mixtures of E and Z isomers being formed from aldehydes and unsymmetrical ketones . In the case of aromatic aldehydes this reaction can also be advantageously performed in a two-phase catalytic system even without the usual PTC catalysts (Table 24). Intramolecular Horner-Wittig reaction of a-phosphoryl-5-oxosulphoxides 444 leads to a, -unsaturated cyclic sulphoxides 445 (equation 265). Starting from optically active 0,0-... 

Armstrong, D. R., Barr, D., Davidson, M. G., Hutton, G., O Brien, P., Snaith, R., Warren, S. Experimental and molecular orbital calculational study of the stereoselective Horner-Wittig reaction with phosphine oxides control of stereoselectivity by lithium. J. Organomet. Chem. 1997, 529, 29-33. 

The Horner-Wadsworth-Emmons modification of the Wittig reaction continues to find wide application in contemporary organic synthesis. Two reviews, looking at different aspects of the stereoselectivity of this procedure, have been published. One considers approaches to improve the Z-selectivity of the Horner-Wadsworth-Emmons reaction, and the other the use of heteroatoms to improve the stereoselectivity of the Horner-Wadsworth-Emmons reaction. A combined experimental and computational study of the selectivity of the Horner-Wadsworth-Emmons reaction of a series of phosphonoacetates (172) has... 

---