Construction of C-C bonds by C-H Activation: Rh(III)-Catalyzed reactions of Arenes and Heteroarenes with Maleimides and Allylic Alcohols

Abstract

The thesis presents a few Rh-catalyzed C-H activations for the construction of C-C bonds. The difficulty of substitution or the arylation at the maleimide's double bond under C-H activation conditions prompted a detailed study on the reaction of maleimides with 3-trifluoromethyl ketone of indole. In this study, it was realized that switching the reactions between the Heck-type reaction and hydroarylation can be achieved by using basic or acid additives. A weakly coordinating carboxylate directing group assisted C-H activation with maleimides leading to a novel and switchable decarboxylative Heck-type and [4+1] annulation products catalyzed by Rh(III)-catalyst is investigated. In these reactions, solvents play a vital role in switching the selectivity. An aprotic solvent, THF, leads to the decarboxylative Heck-type product while the protic solvent, TFE, paves [4+1] annulation product. Allyl alcohol is chemically equivalent to α,β-unsaturated ketones, and aldehydes. A weakly coordinating carbonyl-directed coupling of allyl alcohols at the C-4 position of indole derivatives under the C-H activation conditions using an Rh(III)-catalyst has been explored. The product was transformed into a tricyclic derivative, which can serve as a potential precursor for synthesizing a few alkaloid molecules such as ergot, hapalindole alkaloids, and related heterocyclic compounds. A novel strategy, catalyzed by Rh(III), for synthesizing benzazepinone and azepinone derivatives by using allyl alcohol as a coupling partner has been studied. In this reaction, Rh(III) acts as a catalyst and oxidant. Under the reaction conditions, the allyl alcohol is in-situ converted to its carbonyl compound. The alkylated product obtained in the reaction further undergoes oxidative cyclization in the presence of Lewis acidic AgSbF6. The benzolactum obtained is a valuable intermediate to synthesize berberine-like analog dopamine D3 receptor ligand, which is a potential target in the treatment of neurological disorders.