Unnatural synthons nucleophilic

Allyl (7) and propargyl (22) haiides can act as latent unnatural synthons (24) and (2S) respectively by electrophilic addition to the double bond in (21) or hydration of the triple bond in (23). If the nucleophile is an enolate ion, a... 

To a first approximation, the chiral discrimination should be independent of the nucleophile. The palladium-catalyzed desymmetrization protocol utilizing a heterocyclic nucleophile provides enantio- and diastereoselective entries to diverse carbo-nucleosides. As shown in Scheme 8E.9, introduction of purine bases rather than the hydroxymethyl synthon also affords high enantioselectivities [61]. A variety of natural and unnatural nucleosides can be flexibly prepared because the simple change of ligand chirality or, alternatively, switching the alkylation sequence leads to opposite enantiomers. The palladium-catalyzed approach sharply contrasts with the chiral-pool method, whose enantiodivergency is limited by the availability of the starting material. 

In chapters 19 (1,3-diCO) and 21 (1,5-diCO) we were able to use an enol(ate) as the carbon nucleophile when we made our disconnection of a bond between the two carbonyl groups. Now we have moved to the even-numbered relationship 1,2-diCO this is not possible. In the simple cases of a 1,2-diketone 1 or an a-hydroxy-ketone 4, there is only one C-C bond between the functionalised carbons so, while we can use an acid derivative 3 or an aldehyde 5 for one half of the molecule, we are forced to use a synthon of unnatural polarity, the acyl anion 2 for the other half. We shall start this chapter with a look at acyl anion equivalents (d1 reagents) and progress to alternative strategies that avoid rather than solve the problem. 

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