Two-Group Disconnections IV 1,2-Difunctionalised Compounds

Background Needed for this Chapter References to Clayden, Organic Chemistry  

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. 

The simplest reagent for an acyl anion is cyanide ion, one of the few genuine carbanions. After addition to an aldehyde, say, the resulting cyanohydrin 7 can be converted into a range of compounds 6 and 8-10. The cyanide ion represents the synthons shown in frames next to each product. 

Organic Synthesis The Disconnection Approach. Second Edition Stuart Warren and Paul Wyatt 2008 John Wiley Sons, Ltd 

Despite this versatility, cyanide adds only one carbon atom of course and we need other more general acyl anion equivalents. In chapter 16 we saw how acetylenes can give rise to ketones by hydration. A very simple example is the hydroxy-ketone 11 that could come from the acetylenic alcohol 12 by hydration and hence from acetone with the anion of acetylene acting as the acyl anion equivalent. 

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