The 1,6-difunctionalized compounds preferably use the reconnection strategy for their respective synthesis; This strategy can very well be combined with the Diels-Alder reaction, which generally produces six-membered olefinic adducts, or the Birch reduction of benzene rings, which likewise generates six-membered olefinic products.

1.       1,6-dioxygenated compounds

The reaction that generates dicarbonyl compounds, of different possible combinations: diketones, ketoacids, ketoaldehydes, diacids, etc. and at different distances from one another, is undoubtedly the reaction of   ozonolysis of olefinic compounds.

Depending on the structure of the substrate and the reaction conditions on the ozonide intermediate formed, an enormous diversity of compounds will be achieved as a result of the cleavage of the olefinic double bond. Of these, those that are in a 1, 6 – dioxygenated ratio are of special interest, as can be inferred from the following synthetic “reconnection” operation:  


The best way to understand the operation of this "synthetic reconnection operation" is   will be achieved through the solution of the synthesis of the following organic molecules:

MOb 50


MOb 51


MOb 52


MOb 53


MOb 54


MOb 55


MOb 50 . Retrosynthetic analysis : In the first instance it is disconnected by the lactone function of the molecule. On the generated precursor molecule, in turn, it can be argued that its formation may have occurred from the diacarboxylic acid in position 1-6. Which are reconnected to give rise to the alkene that produced them by oxidative ozonolysis reaction. The alkene formed is a typical Diels-Alder adduct between cyclopentadiene and crotonaldehyde.


Synthesis: The Diels-Alder reaction between   cyplopentadiene and   the α,β-unsaturated aldehyde provides the alkene adduct, for its corresponding opening by oxidative ozonolysis, prior to a protection reaction of the aldehyde group, which is subsequently deprotected, to be reduced to the alcohol function. This alcohol reacts with the ester group in an acid medium to form the desired lactone, MOb 50

MOb 51 , Retrosynthetic analysis : Se   projects the precursor molecule of the mob 51, towards a diacid, which could have been obtained by oxidative ozonolysis from a six-membered olefinic molecule. The ether by successive IGFs is functionalized to a carboxylic compound, the result of the acid hydrolysis of an anhydride function. The latter is a   typical adduct of the Diels-Alder cyclization.


Synthesis.   With the Diels-Alder reaction, the cyclic anhydride adduct is formed, which after being hydrolyzed is reduced to the respective alcohol, which by Williamson is transformed into   ethers. The cyclohexene is opened by oxidative ozonolysis and the acid groups react in an acid medium with the methyl alcohol to transform into the mob 51.


MOb 52 . Retrosynthetic analysis: Initially disconnected   the mob , following the α,β-insat.CO model, thus originating a precursor molecule with a 1,6-diCO ratio, which can be reconnected to a disubstituted hexacycloalkene, which is functionalized to another α,β-insat CO molecule for its subsequent disconnection and generation of a synthetic equivalent with 1,5-diCO ratio. From this precursor molecule, one continues to disconnect and apply relatively simple IGFs until arriving at simple and affordable starting materials such as ketone and ethyl alcohol.


Synthesis : Acetone allows the formation of the intermediate t-Butylformaldehyde, which in a basic medium and ethanol condenses with ethanal. To the product, α, β-insat CO formed, the butanone enolate is added, the same basic medium allows intramolecular cyclization. Then the C=O is transformed into –CH2, by reduction. The cycloalkene produced is opened by ozonolysis in Me 2 S. And it is again cyclized in a basic medium to obtain the mob 52.


MOb 53 . Retrosynthetic analysis: It begins with the simultaneous disconnection of the lactones from the MOb. He The generated precursor presents several dioxygenated ratios, the 1,6-dicarboxylic reconnection is taken and the groups of this molecule are stabilized, as ketone and ester respectively. Next, a retro Diels-Alder disconnection is carried out. In the dienophile it is disconnected by the double bond.

On the other hand, butanone is prepared from a terminal acetylene and the latter from an ethyl halide and sodium acetylene.


Synthesis.   After the opening of the cyclohexene, by oxidative ozonolysis,   The acid hydrolysis of the remaining ester group and the corresponding formation of the ketone hydrate is sufficient for the formation of the lactones and the respective closing of the cycle, to produce the mob 53.


MOb 54 . Retrosynthetic analysis : The disconnection by the double bond of the mob , makes it possible to generate a precursor with a 1,6-diCO ratio, which can be reconnected to   form a cyclohexene, a typical adduct in Diels-Alder reactions, for which a retro-DA is exercised, to reach the simple starting materials.


Synthesis: The Diels-Alder reaction between two molecules of 2-methyl butadiene forms an adduct that with HMCPBA forms an epoxide with the most reactive center.

·          On acid hydrolysis of the epoxide a diol is formed which is oxidized by acid. periodic, towards a 1,6-diCO compound. The CHO group is protected with an enamine, while activating its C alpha, for a condensation in an acid medium, the system is heated and we obtain the mob 54


MOb 55. Retrosynthetic analysis : The synthesis of the mob 53, allows you to propose the disconnections that are detailed, to the mob 55.


Synthesis.   The reactions indicated have already been studied in the synthesis of the mob 53.