Solving Molecular Complexities with Oxidative Dearomatisation and Transition Metal Catalysis

Abstract

Controlled generation of multifunctionalized and biologically important compounds from simple starting materials is one of the sincere challenges for any organic chemist.With the continuation to the recent trends, the proposed research work was designed to synthesize biologically active core molecules employing oxidative dearomatisation and transition metal catalysis. Dearomatisation of aromatics has been considered to be the best and most powerful approach towards the synthesis of complex molecules. Many groups have been putting serious efforts on dearomatisation from years albeit, spiro-oxacycle synthesis has been a less explored direction. The thesis chapter highlights the transformation of planar phenols, naphthol and pyridine derivatives into multifunctionalised spiro and pyridone molecules employing Phenyl Trimethylammonium Tribromides (PTAB) and ruthenium catalysis. Heterocyclic motifs have been important point of attraction due to their demanded biological activity and pharmaceutical importance. The thesis is divided into the following five chapters


Chapter-I describes a new methodology for spirocyclisation of planar phenols and naphthols employing Phenyl Selenium Bromide (PhSeBr) and Phenyl Trimethyl Ammonium Tribromide (PTAB) into 3D framework. The work recognizes PTAB and PhSeBr as an effective reagent for dearomatisation. A generalised economical route for the synthesis of a wide variety of spiro-oxacycles from planar naphthols and phenols is achieved. Diastereoselective generation of oxa-spirodieneones, overall fantastic yields, a rich substrate scope, and mild conditions along with the economy involved makeing this a sustainable methodology. Importantly this work also reveals no side reactions like polymerization which are commonly observed in dearomatisation reactions and thus makes it a reliable solution.

Chapter-II describes the metal-free synthesis of benzofurans and naphthofurans employing Phenyl Trimethyl Ammonium Tribromides. Benzoaxacycles like benzofurans and naphthofurans are an important scaffolds present in many biologically and medicinally important natural products.

Chapter-III describes a lucrative Ru (VIII) catalyzed spiro-etherification and spiro-amidation of phenols. An open air ruthenium (VIII) catalysed oxidative spiro-etherification as well as spiro-amidation of phenols has been accomplished. The transformation works satisfactorily with both phenols and naphthols and thus exhibit a wide range of flexibility. The catalysis is executed in open air and room temperature condition with an improved yield achieved upto 95%.

Chapter-IV describes an extension of the feasible methodology described in chapter (III) and describes the Ru (VIII) catalyzed dearomatisation of pyridines. The synthesis is carried out in open air condition, and the products obtained are N-protected pyridones, which have been immensely useful synthetic motifs.

Chapter-V describes the synthesis of trisubstituted nicitonitriles. A de novo palladium carboncatalyzed
synthesis of trisubstituted nicotinonitriles from easily synthesized homopropagylic or homoallylic aromatic alcohols in the presence of nitriles has been explored.The mechanism
proceeds with an interesting generation of a Pd (II)-C palladacycle followed by an oxidative aromatization to generate the pyridine core. The pyridine core is generated with a noteworthy C−C bond cleavage in the case of the substituted nitriles.The moderate yields and easy separation of the products lend a unique importance to this one-pot methodology.