Still-Gennari phosphonate reaction

A variant of the Homer-Emmons reaction using bis(trif QJ.pg JJ n Jjqs honate to give Z-olefins.  

Name Reactions, 4th ed., DOI10.1007/978-3-642-01053-8 245, Springer-Verlag Berlin Heidelberg 2009 

Gemiari, C. Tetrahedron Lett. 1983, 24, 4405-4408. W. Claik Still (1946-) was bom in Augusta, Georgia. He was a professor at Columbia University. 

Yokoyama, K. Shiro, M. Nagao, Y. Chem. Pharm. Bull. 2002, 50, 706-709. 

Homer-Wadsworth-Emmons reaction. In Name Reactions for Homologa-tions-Part I Li, J. J., Corey, E. J. Eds. Wdey Sons Hoboken, NJ, 2009, pp 420-466. (Review). 

Homer-Emmons reaction using bis(trifluoroethyl)phosphonate to give Z-olefms. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4J63, Springer International Publishing Switzerland 2014 

Example 5, An ejqjedient access to Still-Gennari phosphonates  

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Homer-Wadsworth-Emmons reaction/Still-Gennari phosphonate reaction... 

As outlined in Scheme 28, the synthesis of the P-ketophosphonate 131 began with a one-pot anh -aldol/reduction step between ethyl ketone 101 and aldehyde 133, giving the 1,3-syn diol 134 (>30 ldr) [130, 132-136, 145, 146], The diol 134 was then converted into the carboxylic acid 135 in six steps. Completion of the subunit 131 required conversion into the acid chloride and reaction with the lithium anion of methyl-(di-l,l,l-trifluoroethyl)-phosphonate. The C9-C24 aldehyde 132 was prepared in two steps from 136, an intermediate from previous routes [55-58], The Still-Gennari-type coupling of 131 and 132 was readily achieved via treatment with... 

The Ando variant is an alternative to the Still-Gennari variant of the Horner-Wadsworth-Emmons reaction. Here, phosphonates are employed that contain two aryloxy residues, for example, the ortho-tolyloxy residues of the phosphonate A. The Ar-O groups in this reaction... 

We now analyze the Still-Gennari reaction of Figure 11.17. The reagents there are the enantiomerically pure chiral phosphonate A, with which you are familiar from Figure 11.16,... 

Still-Gennari modification of the HWE reaction Z-isomers are predominantly formed under conditions of kinetic control, e.g. at low temperatures, in weak polar solvents and under the action of strong bases. The use of phosphonates with an electron-withdrawing... 

The stereochemical outcome of the Homer-Wadsworth-Emmons reaction is primarily dependent on the nature of the phosphonate used. In general, bulky substituents at both the phosphoms and the carbon adjacent to the carbanion favor formation of the -alkene. This selectivity has been rationalized in terms of a lowering of steric strain in intermediate SB as compared to intermediate SA. Z-Selectivity in HWE reactions can, however, be achieved using the Still-Gennari modification [20]. Here, the use of a (2,2,2-trifluoroethyl) phosphonate enhances the rate of elimination of the originally formed adduct SA (Scheme 1.6) relative to equilibration of the intermediates 4 and S. An example of the Still-Gennari modification is illustrated in Scheme 1.7. 

In the effort of total synthesis of discodemolide, the Still-Gennari type HWE reaction was also used by Paterson and Lyothier to form the Cg-C9 olefin. Phosphonate 94 was treated with NaH in THE at 0 °C for 30 min prior to the addition of aldehyde 93. The crude product showed a mixture of (Z)- and ( )-olefins, 95 and 96, in a 5 1 ratio. The desired (Z)-isomer 96 could be isolated by flash chromatography in 73% yield. The (Z)-enone 96 was further treated with K-Selectride at 25 C for 24 h. A single diastereomeric alcohol 97 was formed selectively and isolated in 59% yield. This alcohol processing (7/ )-configuration was leading to 1-epi-discodermolide 98 as final product by four additional reactions. 

Modifications directly to the alkoxy phosphonate were examined. The Still-Gennari modification of the HWE reaction provided access to (Z)-selective alkenes. In this example, the substituents on the phosphonate were modified as in 51. Executing the standard reaction conditions with aldehyde 52 now resulted in 53. It was postulated that this modification accelerates the elimination of the initial adduct, thus preventing equilibration to the more stable threo intermediate vide supra). 

This reaction has been modified to occur under mild conditions such as those of Masamune and Roush, Still, and Ando. In addition, chiral phosphonates (or phospho-namides) have been used for this reaction. In particular, the method developed by Still and Gennari using [bis(trifiuoroethyl)phosphono] esters, generally known as Gennari-Still phosphonates, is very useful in the preparation of Z-olefins. Illustrated is the HWE reaction using Gennari-Still phosphonates to give c/ -olefins, and its mechanism. 

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