CATSO · New Catalytic Reactions using Sulfur Dioxide

New Catalytic Reactions using Sulfur Dioxide

Sulfur (IV & VI) functional groups containing molecules were neglected in medicinal chemistry and agrochemical industries until the last two decades. These molecules gained interest largely in developing inhibitors, anti-viral, anti-bacterial, anti-fungal, anti-inflammatory, anti-cancer, and anti-tumour compounds. There are more than 150 drugs available in the market approved by FDA. The fast growth of these molecules in the drug industry is because of their bioisosteric properties with carboxylic acids and amide compounds with better nucleophilicity, solubility, and stability. For example, amide bioisosteres sulfonamide containing compounds have better stability in the gut. Acyl sulfonamides are using as the bioisosteres of carboxylic acids with better permeability. The synthesis of these molecules is achieved starting from the thiols and sulphides. However, these methods involve a lengthy process and more number of steps to synthesize the desired sulfur pharmacophores. To address these problems, pioneers in the synthetic chemistry have been developing sulfur reagents and reactions. In the Willis group, DABSO regent was prepared from the sulfur dioxide and DABCO, used in the palladium and copper catalysis reactions for the synthesis of sulfonamide and sulfone synthesis. Sharpless SuFEx chemistry and Shi DAST-type reagents which are using sulfur, fluorine exchange chemistry to synthesize the sulfur (VI) compounds. Hydroxylamine-derived reagent as dual oxidant and amino group donor was used for the direct synthesis of primary sulfinamides from the corresponding thiols. Other than these methods, many other methodologies have been developed by Bull, Maruoka, and Zhang groups for the synthesis of the sulfur functional groups. However, the importance of these compounds in the drug industry makes them attractive towards the discovery of new reagents and novel methodologies. In 2017, we rediscovered the importance of the sulfinylamine reagents in our group, synthesized them in very stable forms TrNSO, t-OctNSO, t-BuONSO, and BiPhONSO (known sulfinyl amine reagents are moisture sensitive). By using these compounds, we have synthesized sulfones, sulphonamides, and sulfinimidmides. Most of these sulfinylamine reactions and sulfur dioxide capture reactions with DABSO were employed aliphatic Grignard reagents to attach the first carbon atom to the sulfur group. However, these reactions have very limited scope for the aliphatic groups due to the uncommon availability of the aliphatic Grignard reagents. To overcome the problem of introducing the aliphatic functional groups, in the proposal, we come up with an idea of using the photoredox catalysed decarboxylative generation of alkyl radicals to synthesise the sulfur (IV, VI) compounds. The planned route enables a convenient way to modify the carboxylic compounds to the corresponding bioisosteric sulfur compounds and test them in biological studies. However, the main challenge in the reaction could be finding the compatible photocatalyst under the reactions. We also want to expand the method to check the reactivity of the other sulfinylamine reagents in obtaining the sulfur compounds.

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