Alternating polarity disconnections

The chlorine can be disconnected with the alternative polarity via the diazonium salt to amine (19) (guideline 4), The amino group is more powerfully electron-donating than OMe so we can disconnect the NO group. The amino group is itself derived from another nitro group. 

The question of how one chooses appropriate carbon-carbon bond disconnections is related to functional group manipulations since the distribution of formal charges in the carbon skeleton is determined by the functional group(s) present. The presence of a heteroatom in a molecule imparts a pattern of electrophilicity and nucleophilicity to the atoms of the molecule. The concept of alternating polarities or latent polarities... 

Examples of choosing reasonable disconnections of functionally substituted molecules based on the concept of alternating polarity are shown below. 

The same disconnection 41 can be used for carboxylic acids with CO2 as the electrophile for a Grignard reagent 40. Dry ice (solid CO2) is particularly convenient for these reactions. Switching polarity by FGI to the nitrile 42, the same disconnection now uses cyanide ion as the nucleophile but the same alkyl halide 39 that was used to make the Grignard reagent. Mechanistic considerations should decide between these alternatives. 

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. 

You might think you could escape this problem by choosing the alternative disconnection 8, but this is not so. We have more choice here we can use the a3 synthon 7 with natural polarity, in real life an enone, but then we shall have to use the acyl anion equivalents 6 that we met in chapter 23. Reversing the polarity gives us the naturally polarised electrophile, an a1 synthon 9 represented by an acylating agent and the homoenolate, or d3 synthon, 10 with unnatural polarity. 

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