Wittig reaction with stabilised ylids

The adjustment of the oxidation level is most easily achieved by reducing the protected ester (56) to the alcohol and re-oxidising. The Wittig reaction with a stabilised ylid (55) gives mostly ff-(53). 

The point of this is that the proposed starting material 80 can then be made by a simple Wittig reaction with the stable ylid 81, the equivalent of an enolate of MeCHO, as the extra ylid stabilisation avoids any regioselectivity problems in enolisation. The cyanohydrin derivative 82 can lose the marked proton with strong base and alkylation occurs as planned. The product 83 can be hydrolysed... 

Alkylation of dithian itself 27 with the iodide 32 establishes the 1,4-diO relationship in 34 and this new dithian can be acylated with DMF (IV NCHO). The carbon skeleton of half pyreno-phorin 35 is completed by an -selective Wittig reaction with a stabilised ylid. 

The asymmetric aspects of the syntheses of 169 and 170 appear in the workbook. The other three alkenes were made by E-selective Wittigs with stabilised ylids or HWE reactions. The sulfone 172 for the Julia reaction was prepared from 171, in turn prepared from glucose and gave the corresponding E-alkene (a modified version of 168) in excellent yield and perfect E-selectivity. 

In a Wittig reaction with a non-stabilised ylid, the carbon-carbon bond formation is essentially irreversible and so the product stereochemistry... 

An excellent application of the distinction between stabilised and unstabilised ylids is in the synthesis of leukotriene antagonists.10 The intermediate 39 (R is a saturated alkyl group of 6, 11 or 16 carbon atoms) was needed and disconnection of the Z-alkene with a normal Wittig reaction in mind followed by removal of the epoxide exposed a second alkene with the E configuration that could be made from the aldehyde 43 and the stabilised ylid 42. 

This procedure was used in the synthesis of the upper chain of a prostaglandin 82 (see chapter 6) where the stereochemistry is related to the biological activity.13 Note that the aldehyde is tied up as a hemiacetal in the starting material 81 (see chemoselectivity chapter) and that the salt-free ylid is actually a carboxylate anion made with sodium derivative of DMSO in DMSO. As you will see in the next section, not all Wittig reactions are cis selective - those of stabilised ylids are trans selective. 

Finally the benzyl group was removed, the primary alcohol oxidised to the aldehyde, and an ii-selective Wittig reaction performed with the enantiomerically pure stabilised ylid 137. No racemisation of either partner occurred and the product was almost pure E at the new alkene. Stereoselective reduction gave (+)-pumiliotoxin B 129 identical to the natural product in all respects, including biological effects. 

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