Disconnection of 1,2-dioxygenated compounds

The disconnections studied so far have led to the formation of logical synthons, consisting of cations or anions, whose charges have been stabilized by functional groups or completely clear structures. Unfortunately this is not always the case. There is a fairly significant set of organic molecules that present very specific disconnections, so it is difficult to find a general disconnection model, which is why they are studied individually.
1.- Compounds   a -hydroxycarbonyl
α-Hydroxycarbonyl compounds are disconnected at the CC bond that joins the two functions. This operation leads to a natural or logical synthon (the cationic synthon) and to an unnatural or illogical synthon (the anionic synthon). The synthetic equivalents can be aldehydes and acetylide ion respectively.


The terminal acetylene group with mercuric salts in an acid medium forms a methyl ketone. This reaction is also useful if the acetylene group is internal and also symmetric.


A special case of α-hydroxyketones are benzoins or diarylhydroxyketones , where the two R groups are aromatic or heterocycles. Benzoins are the result of the self-condensation of benzaldehyde catalyzed by cyanide ions.


The benzoins may not be symmetrical, for example one of the aldehydes may be a pyridine aldehyde. The cyanide ion does not catalyze aliphatic aldehydes, which undergo the same coupling in the presence of thiazolium salts.


Aliphatic α-hydroxyketones can be formed from the condensation of carboxylic esters with metallic sodium in an inert solvent and under reflux. These hydroxyketones are called acyloins , and condensation reactions can occur intramolecularly and intermolecularly.

The bimolecular reduction of ketones to pinacols is one of the few radical reactions of synthetic utility, due to the ability of these pinacoles to participate in rearrangement reactions, called pinacolinic rearrangement, to produce tert-alkylketones.

The compounds grouped together under the name of oxocarboxylic acids , which include aldehydo acids and ketoacids, are of great importance in the aliphatic series and both because of their biochemical relationship with the oxacids, and because of the synthesis reactions that can take place from them or from them. Its derivatives constitute an important group of organic compounds, on which intense work is being done in recent times. α-Hydroxycarboxylic acids , when disconnected, also generate an illogical synthon, such as the cyanide ion. The cyano or nitrile group, by basic hydrolysis, followed by neutralization, generates the carboxylic group of acids.
2.- Compounds 1,2-Diols .
The 1,2-diols have in the olefins the best precursors for their preparation, it will only depend on the stereochemistry of the diol in question, to resort to one of the specific reactions summarized in the attached table.

In reality, epoxides also allow other 1,2-dioxygenated compounds to be obtained, when opened by a nucleophile such as alkoxides, for example. Aldehydes and ketones also serve as precursor molecules to prepare epoxides when treated with sulfur ylides.

3.- “illogical” electrophiles
1,2-dioxygenated molecules can also be built using illogical electrophiles; The most important reagents of this type are the alpha-halogenated carbonyl compounds obtained by halogenation of the enol form of a carbonyl compound. The halogenation of ketones allows obtaining 1,2-difunctionalized compounds, because the halogen is a good leaving group and can be easily substituted with other nucleophiles. The reaction mechanism involves the formation of a thermodynamic enol.

However, the halogenation of aldehydes and acids is not so simple, due to the low yields,   Therefore, very interesting halogenation alternatives have been devised. Another method to obtain α -hydroxy acids consists of the hydrolysis of α-haloacids (Hell-Volhard-Zelinsky reaction)


4.- Compounds 1,2 difunctionalized by reconnections .
Another method that produces 1,2-difunctionalized compounds consists of the oxidative cleavage of double bonds by ozone to generate two carbonyls, which will vary according to the reaction conditions. Thus, ozonolysis, followed by a treatment with: dimethylsulfide (Me 2 S) generates aldehydes, Hydrogen peroxides produce acids and sodium borohydride, to form alcohols. The strategy consists of the reconnection of the oxygenated carbons (alcohols, aldehydes, ketones or acids), in distance relationships, 1.2 diO,   to form the corresponding alkene from which it is supposed to be derived by the ozonolysis reaction.
Propose a synthesis design for the following molecules: Mob 48:


Retrosynthetic analysis.   the MOb 48 is an unsymmetrical olefinic ether and with the group   aldehyde at one end, which is why it can be assumed that it is the result of the opening of a double bond by ozonolysis followed by the reaction with   Me 2 S. The double bond of the precursor is functionalized to a symmetric ethereal internal alkyne.


The ethers are the result of the application of the Williamson synthesis and the diol of the diacetylide reaction on aldehydes, as starting material.
synthesis . The diacetylide is made with an excess of sodamide, which acts without formaldehyde, to give the alcohol, which is etherified by Williamson. The alkyne is reduced to an alkene which is opened by ozonolysis, followed by reaction with Me 2 S to form the aldehyde.