Vicinal Diols as C2 Precursor in N & O- Containing Heteroaryl Synthesis

Abstract

Vicinal diols exhibit a unique combination of properties, including high reactivity, selective oxidation, chiral recognition, hydrophilicity, and biodegradability, making them valuable in various fields. Their versatility in synthesis, biological relevance, pharmaceutical importance, and environmental applications make them useful in multiple industries. Specifically, vicinal diols are employed as anti-corrosion agents, lubricants, surfactants, fragrances and flavors, and agrochemicals. Aliphatic vicinal diols play a crucial role in cellular signaling, metabolism, and antioxidant mechanisms, inhibiting glycosidases and regulating carbohydrate metabolism, while also enhancing adhesive properties and coating durability. Furthermore, aliphatic vicinal diols serve as precursors for polyurethanes, polyesters, and epoxy resins, aid in degrading pollutants like pesticides and heavy metals, and facilitate the synthesis of functionalized nanomaterials. In pharmaceutical applications, aliphatic vicinal diols act as versatile intermediates in organic synthesis, enabling asymmetric synthesis and supporting the design and development of new drugs, including antibiotics, antivirals, and anticancer agents. Oxygen and nitrogen- containing heteroaryl compounds are indispensable in various fields due to their unique properties, including high electron affinity, conductivity, photoluminescence, biocompatibility, and stability. Their biological activity, versatility in synthesis, industrial utility, and pharmaceutical importance make them highly sought after. These compounds play a vital role in pharmaceuticals as antibiotics (quinolones, macrolides), antivirals (HIV, hepatitis), anticancer agents (kinase inhibitors), anti-inflammatory agents, and CNS active compounds (anxiolytics, antidepressants). Additionally, they are utilized in agrochemicals as herbicides (pyridines, quinolines), insecticides (neonicotinoids), and fungicides (azoles). In materials science, heteroaryls are employed as conductive polymers (polythiophenes), organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), and fuel cells. They also find applications in biotechnology such as DNA-binding agents, RNA-targeting compounds, gene delivery systems, and biosensors. Furthermore, heteroaryls participate in asymmetric catalysis, oxidation, and reduction reactions and serve as starting materials in complex molecule synthesis. Some heteroaryl compounds include indole, furan, pyrrole, pyridines, quinolines, isoquinolines, pyrazines, oxazoles, thiazoles, imidazoles, pyrazole and triazoles. In this thesis our objective is to synthesize heteroaryl compounds utilizing vicinal diol as a C2 building block. Chapter 1. Vicinal diols in organic synthesis: A brief review This chapter summarizes the significance and synthetic utility of vicinal diols in heterocyclic chemistry. Vicinal diols possess unique attributes, making them valuable across various disciplines. They serve as anti-corrosion agents, lubricants, and surfactants, and as precursors for polyurethanes and epoxy resins. Vicinal diols find applications in polymer synthesis, as protecting groups, and as a C2 precursor for heterocyclic synthesis, including indoles, pyrroles, imidazolones, pyrazines, piperazines, quinoxalines, and quinolines. Chapter 2. Oxidative coupling of vicinal diols and 2-amino-1,4-naphthoquinone for the synthesis of pyrrolonaphthoquinones An iron-catalyzed oxidative coupling reaction between 1,2-diols and 2- aminonaphthoquinones has been developed, facilitating the regioselective production of benzo[f]indole-4,9-diones under mild conditions. This efficient process involves the oxidation of vicinal diols to α-hydroxy carbonyl compounds, followed by concurrent N-C and C-C bond formation. with 2-amino naphthoquinone. Chapter 3. Access to 2,3-unsubstituted imidazo[2,1-b][1,3]benzothiazole using ethylene glycol as a C2 precursor and subsequent regioselective C3 functionalization Synthesis of imidazo[2,1-b [1,3]benzothiazoles by oxidative coupling of 2- aminobenzothiazoles with vicinal diol was reported. Expectedly, a combination of potassium persulfate and TEMPO oxidized ethylene glycol to α-hydroxy acetaldehyde, which coupled with 2-aminobenzothiazole to afford 2,3- nsubstituted imidazo[2,1- b][1,3]benzothiazoles. The later was exploited as a reliable handle to access 3-substituted imidazo[2,1-b][1,3]benzothiazoles regioselectively Chapter 4. Transition-metal-free access to substituted furans and pyrroles using vicinal diol as C2-precursor A transition metal-free oxidative method to synthesize substituted furans from β- ketoanilides and vicinal diols was reported. This approach accommodates a wide range of functional groups (e.g., halogens, methoxy, methyl, nitro) and enables the regioselective formation of 2,3-disubstituted and 2,3,5-trisubstituted furans via base-promoted oxidative C-C and C-O bond formation. Additionally, substituted pyrroles were synthesized regioselectively using β-ketoenamines, and vicinal diols as C2 precursors. Chapter 5. Vicinal diols as C2 precursor in oxidative ring annulation to form fused Furans This phapter describes a novel synthetic pathway for the metal-free acid-catalyzed oxidative ring annulation of vicinal diols with beta-naphthols, yielding naphtho[2,1- b]furans. Additionally, we successfully applied this catalytic system to achieve a one-pot synthesis of avicequinone B from 2-hydroxy naphthoquinone, resulting in a remarkable yield. The presented methodology offers a convenient and efficient metal-free synthetic pathway for the preparation of diverse biologically active organic compounds.