Unsaturated carbonyl compounds retrosynthetic analysis

In a reaction which is mechanistically related to the Skraup reaction an a,/ -unsaturated carbonyl compound, generated by way of an acid-catalysed aldol condensation, reacts with a primary aromatic amine in the presence of acid to yield a quinoline derivative (Doebner-Miller reaction). For example, when aniline is heated with paraldehyde (which depolymerises to acetaldehyde during the reaction) in the presence of hydrochloric acid the final product is 2-methyl-quinoline (101) (quinaldine, Expt 8.40). Retrosynthetic analysis for the 1,2-dihydroquinoline reveals crotonaldedhyde as the unsaturated carbonyl component which is in turn formed from acetaldehyde (see Section 5.18.2, p. 799). 

The (3-hydroxy carbonyl products of aldol reactions are often very easily dehydrated to give a, 3-unsaturated carbonyl compounds and, if you spot an a,p-unsaturated carbonyl group in the molecule, you should aim to make it by an aldol reaction. You will 6rst need to do an FGI to the P-hydroxy carbonyl compound, then disconnect as before, oxanamide intermediate retrosynthetic analysis... 

In retrosynthetic analysis, we recognize the need for the Claisen rearrangement when we see a y,6-unsaturated carbonyl compound. Compound 8.19 contains unsaturation y, 6 to the bromo-functional carbon. Consider a carbonyl compound as a likely intermediate and then write a retro-Claisen rearrangement (Scheme 8.19). The ketene acetal could come from ethyl orthoacetate. Continue with a disconnection at the alcohol. The actual synthesis is shown in Equation 8.37 [52]. 

A retrosynthetic analysis of an a,/J-unsaturated aldehyde or ketone involves an initial functional group interconversion into a /1-hydroxycarbonyl compound, followed by a disconnection into the carbocation (12) and the carbanion (13) synthons. The reagent equivalents of these two synthons are the corresponding carbonyl compounds. 

The diester has a 1,3-diCO relationship and could be disconnected but we have in mind using malonate so we would rather disconnect the alternative 3-amino carbonyl compound (the MezN group has a 1,3-relationship with both ester groups) by a 1,3-diX disconnection giving an unsaturated ester. This ot,p-unsaturated ester disconnects nicely to a heterocyclic aldehyde and diethyl malonate, doxplcomlne retrosynthetic analysis II... 

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