Retrosynthetic process

An example which illustrates that the retrosynthetic process may sometimes find a parallel in the laboratory is provided by the preparation of ( )-(+)-3-methylcyclohexanone from (+)-pulegone (24). described by Wallach in 1896, [28] in which the experimental conditions are such that the equilibrium is displaced to "reagents". 

Here, in contrast with the above examples, the retrosynthetic process is purely "mental", since the mesylate, as a good leaving group, is a poor nucleophile and the "reaction" will never take place whatever the reaction conditions. 

As shown in Scheme 4.16, the retrosynthetic process proceeds as follows i) FGI (substitution of the unconjugated aldehyde by an acetal group and the conjugated double bond by an OH group) ii) retro-aldol disconnection of the 1,3-C system iii) "reconnection" of the resulting 1,6-D system to a 6-membered ring iv) FGI (substitution of the double bond by an OH group and the acetal by a carbonyl... 

The retrosynthetic process (Scheme 6.2) involves the following operations i) substitution of the conjugated double bond by an OH group ii) retro-aldol disconnection of the 1,3-C system, and iii) disconnection at the a-position of the resulting 1,4-D system which leads to 2-methylcyclopentane-l,3-dione and an umpoled three-carbon atom fragment. This retrosynthetic process offers, however, only a theoretical scheme which, in practice, presents some difficulties. For example. Table 5.1 gives 2-nitropropene (3) as a possible equivalent of the umpoled C3 fragment, in which case the process in the synthetic direction would be as... 

In practice, whatever the methodology used, the retrosynthetic process always leads to sequences of intermediate precursors which go from the target to commercially available starting materials, but they do not say anything about the "control elements" which it may be necessary to introduce in order to carry out the synthesis in the laboratory so that the reactions proceed as required. 

The 1,4-dihydropyridine 148 (as well as the 3,4-dihydropyridine 147 which is retrosynthetically equivalent) can be linked with the retrosynthetic process a. As a double enamine, it could be derived from the enaminone 149 (via h), which in turn should be accessible (via i) from the 1,5-dicarbonyl system 150 and NH3 by cyclocondensation. The systems 149 and 150 are retroanalytically interlinked, not only by dehydrogenation of 145 and 146 respectively, but also by a retro-MiCHAEL addition involving enamines or enolates with a, p-unsaturated carbonyl systems as starting materials for the synthesis of 1,4-dihydropyridines. 

Remember The open arrow is a symbol used to show a retrosynthetic process that relates the target molecule to its precursors ... 

---