Other synthesis strategies that use “illogical” syntons

1.       triple bond addition

The strategy of "adding" a triple bond, between two oxygenated functions in position 1,4, allows working later with a disconnection based on the chemistry of acetylides. In order to exemplify this strategy, let us see the elaboration of a synthesis plan for the   MOb 40:

MOb. 40. Retrosynthetic Analysis .   A first IGF in the mob , allows us to understand the necessary addition of unsaturations, to form an internal acetylene, which had to be combined with two carbonyl precursor molecules, as can be seen below:


Synthesis. The diacetylide or acetylide in stages, combines with molecules of   different aldehydes, the intermediate molecule formed is hydrogenated and then its alcohols are oxidized to the diketonic compound Mob 40.


The γ-lactones can also be prepared in an analogous way, as shown below:


2.       Adding the COOR group as an activating group

The addition of the COOR group, in addition to activating the anion synthon, facilitates the disconnection of a 1,4 diX molecule.

synthesize the mob 41, to from simple materials :


MOb 41. Retrosynthetic analysis. the MOb 41, is transformed into a γ-hydroxycarbonyl and an ester group is added to the C α of the precursor molecule, to later disconnect as 1,4-diO. The next steps are already known.


synthesis . Ethyl acetoacetate is a nucleophile that opens the epoxide in a basic medium.

The ester group is hydrolyzed and decarboxylated to arrive at the Mob 41.


Propose a synthesis plan for the following molecules:

MOb 42


MOb 43


MOb 44


MOb 45


MOb 46


MOb 47


MOb 42 . Retrosynthetic analysis . The 1,3-diO disconnection of the Mob 42, leads to a 1,4-diCO precursor, which can be disconnected conventionally or after an IGF from it, transforming it into a precursor structure, which by Wacker oxidation, forms the dicarbonyl compound.

Wacker oxidation:



Synthesis.   The allyl bromide alkylates the aldehyde, the product is oxidized and then cyclized in a basic medium, to form the Mob 42


MOb 43, Retrosynthetic Analysis . The lactone, MOb 43, is opened, to originate a γ-hydroxy acid, which by IGFs, reaches a 1,4-ketoester, which is disconnected according to the model.

Cyclohexenone is formed by the Robinson annelation and 1,5-diCO is prepared from the Michael reaction.


Synthesis. The secondary carbon enamine is obtained using a bulky secondary amine. The 1,5-diCO compound is cyclized by Robinson annelation and then reacted with the α bromo ester in a basic medium. The resulting diketone compound is reduced with LiAlH 4 and then, in an acidic medium, the lactone MOb 43 is formed.


MOb 44 . Retrosynthetic analysis.   The first IGF of the Mob 44, transforms it into the precursor 1,3-diCO, the disconnection of this   The last molecule generates a precursor with two 1,4-diCO ratios, continuing with the indicated disconnection, which will require the use of an allyl bromide.


Synthesis.   It is a sequence of condensations of the aldol or Claisen type. In order to synthesize the Mob 44.


MOb 45 . Retrosynthetic analysis : The disconnection of the lactone function of the mob 45, begins the series of disconnections. The functionalization of the hydroxyl group to the carbonyl, then allows the Michael reaction and the Robinson ringing to proceed.


Synthesis: All the reactions used are linked to the Michael condensation, Robinson annelation and the Fischer ester formation reaction, it allows to obtain the lactone, that is to say the mob Four. Five.


MOb 46. Retrosynthetic analysis. . It follows the   1,4-diCO disconnection, because it allows splitting into two parts the mob 46. Continue with the 1,3-diCO disconnection, followed by the α,β-unsaturated CO disconnection, ending with the retroNef disconnection


synthesis . According to Michael, the nitroarene nucleophile adds to α,β-unsaturated cyclopentanone. The nitro group is transformed into C=O, by the Nef reaction. The dicarbonyl compound is reacted with the ethyl propanoate enolate, followed by the Dieckmann reaction,   and the reactions necessary to arrive at the MOb. 46.


MOb 47. Retrosynthetic analysis. the MOb 47, is a polyalcohol, which by an IGF, is transformed into suitable oxygenated groups, to show that there are 2 relationships, 1,4-diCO and one 1,5-diCO, which cannot be applied due to the impossibility of locating a double bond. conjugated with a C=O. It is disconnected by both 1,4-diCO and continues with the necessary IGFs until reaching simple starting materials, such as benzene and malonic anhydride.


synthesis .   The synthesis of the mob 47, does not require any extraordinary strategy, as can   See, the reactions involved in it are those known and for which the mechanisms and performance in the laboratory are positively manageable. This is how you can start from benzene and malonic anhydride.