Imides and sulfonimides in noncovalent organocatalysis

Although amides are present in many biological compounds (eg. peptides, drugs,…) and many methods for their synthesis have been widely developed to date, the methods of synthesis of the related imides, which are also present in many biological compounds are not so well-stablished. There are scarce methodologies for their synthesis and harsh conditions are often required. On the other hand, the imides have interesting properties: they dimerise less strongly than structurally related amides because of the lower basicity of their carbonyl fragments, due to this property they could be employed as H-bond donors in organocatalysis. During the course of this project, an array of acyclic imides was synthesized in order to study their application as organocatalysts. The methods for the synthesis of the imides were either the oxidation of the related amides, or the direct synthesis from the corresponding amides and carboxylic acids. The benzylic positions of an amide are very reactive toward oxidation, and therefore it was possible to develop a suitable method for the synthesis of monoimides in this way. The array of imide derivatives was next tested as organocatalysts in the model reaction of acetylation of alcohols, and its catalytic activity was measured by comparison with the stablished Schreiner thiourea catalyst. These synthesized mono and bisimides derivatives are not acidic enough to work as organocatalysts. Therefore, in order to increase the acidity of the imidic proton, a sulfonamide derivative 4 was synthesized, and tested in the acetylation reaction of alcohols. The reaction proceeded with full conversion with only 1 mol% catalyst loading. Next, an imide camphor derivative was synthesized and used in the Mukaiyama aldol reaction. Unfortunately, this catalyst couldn’t provide any enantiomeric excess in the reaction. On the other hand, α-carboxysulfonamides are interesting H-bond donors candidates so they were employed in the aldol reaction between cyclohexanone and p-nitrobenzaldehyde. This reaction was carried out in different solvents: water, DMSO, DMF and triethylamine. However, the first attempts were not successful. To sum up, different imide derivatives were synthesized and tested as organocatalysts in the acetylation of alcohols, observing that only a sulfonimide derivative worked as catalyst with a very low catalyst loading (1 mol%). Next, different chiral sulfonimides and α-carboxysulfonamides were synthesized in order to use them in enantioselective aldol reactions. However, the first attempts did not afford any product and further optimization is required in order to observe reactivity