Functional groups difunctionalized compounds

Notice that the acceptor synthons have odd numbers the donor synthon has an even number donor and acceptor properties alternate along the chain as we move away from a carbonyl group. This natural reactivity5 of carbonyl compounds explains why we find it easy to discuss ways of making 1,3- and 1,5-difunctionalized compounds, because they arise from a1 + d2 and from a3 + d2. Reagents corresponding to synthons like d1 or a2 are rarer, and therefore compounds with 1,2- or 1,4- related functional groups require special consideration retrosynthetically,... 

When X and Y are polar functions, they are made essentially from functional groups such as alcohols, amines, acids, amides, amidines, or guanidines (Figure 14.4). A classical representative of a difunctionalized, symmetrical compound is decamethonium. 

In this chapter, we have seen many reactions that form C—C bonds. Three of those reactions are worth special attention, because of their abiUty to produce compounds with two functional groups. The aldol addition, the Claisen condensation, and the Stork enamine synthesis all produce difunctionahzed compounds, yet they differ from each other in the ultimate positioning of the functional groups. The Stork enamine synthesis produces 1,5 difunctionalized compounds. 

This compound is 1,3-difunctionalized, so we should focus our attention on either an aldol or a Claisen. To decide which reaction to use, look at the oxidation states of the two functional groups (a carbonyl group and a carboxylic acid moiety). In this case, a Claisen condensation seems like the likely candidate. The product of a Claisen condensation is always a (3-keto ester, so if we use a Claisen condensation to form the carbon skeleton, then the last step of our synthesis will be hydrolysis of the ester to give a carboxylic acid. 

Using a functional Y lads to the telechelic compound but generally one of both end groups of XY is not functional and in this case, it does not produce the difunctionality of the oligomer. 

An elegant approach to the diastereoselective synthesis of densely functionalized 1,2,5,6-tetrahydropyridines 31 based on the a,Y-difunctionalization of 1,3-dicarbonyl compounds was pioneered in 2007 by Clarke [23], and then followed up by other groups [24-26], It generates five new eovalent bonds and proceeds via a domino pseudo five-component reaction from anilines, aromatic aldehydes (2 equiv. of each). 

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