Still-Gennari reactions

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,... 

The Still-Gennari reaction proceeded with very high selectivity for the cis isomer, 30 1 to 40 1 to give 47. The geometrical isomers were separated by chromatography. This is advantageous as the trans isomer... 

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... 

Fig. 11.14. Preparation of tmns- or f-configured a,/3-unsaturated esters by the Horner-Wadsworth-Em mons reaction (left) or preparation of their cis- or Z-isomers by the Still-Gennari variant of it (right). 18-Crown-6 is a so-called crown ether containing a saturated 18-membered ring that is made up from six successive —CH2—0—CH2-units. 18-Crown-6 dissociates the K ions of the Horner-Wadsworth-Emmons reagent by way of complexation.

The stereostructure of the alkoxide intermediate of a Horner-Wadsworth-Emmons reaction which finally leads to the trans-o cim was recorded in Figure 9.14 (as formula A). The Still-Gennari variant of this reaction (Figure 9.15) must proceed via an alkoxide with the inverse stereostructure because an olefin with the opposite configuration is produced. According to Figure 9.16, this alkoxide is a 50 50 mixture of the enantiomers C and ent-C. Each of these enantiomers contributes equally to the formation of the finally obtained cw-configured acrylic ester D. 

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... 

In the Horner-Wadsworth-Emmons (HWE) reaction, a lithium, sodium or potassium salt of a P-keto-phosphoric acid dialkyl ester or an a-(alcoxycarbonyl) phosphoric acid dialkyl ester is reacted with an aldehyde to form an a,p-unsaturated ketone or an a,p-unsaturated ester as product and a phosphoric acid dialkyl ester as byproduct. The product of a Horner-Wadsworth-Emmons reaction possesses a new -configured C=C double bond. To obtain products with Z-confi-guration of the C=C double bond the Still-Gennari variant or the Ando variant can be employed. The Still-Gennari variant uses two partly fluorinated F3C-CH2-O groups at the phosphorus and the Ando variant uses two aryloxy residues and the transferable alcoxycarbonyl group at the phosphorus. 

This is the Still-Gennari variant of the Horner-Wadsworth-Emmons reaction. 

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