HARNESSING ALCOHOLS AS ALKYLATING REAGENTS USING NONPRECIOUS METAL-CATALYSIS: SYNTHESIS OF N-HETEROARENES, SECONDARY AMINES, GEM-ß,ß’-BIS SUBSTITUTED ALCOHOLS AND OLEFINS

Abstract

The work accomplished during the research period has been collated in the form of a thesis with the title “Harnessing Alcohols as Alkylating Reagents using Non-precious Metal- Catalysis: Synthesis of N-Heteroarenes, Secondary Amines, Gem- , ’-bis Substituted Alcohols and Olefins”. The thesis has been divided into five chapters. Chapter 1 : Metal-catalyzed application of alcohols for the construction of C-C and C-N Bonds Chapter 2A : Nickel-catalyzed dehydrogenative coupling of aromatics diamines with alcohols: selective synthesis of substituted benzimidazoles and quinolines Chapter 2B : Nickel-catalyzed N-alkylation of amines with secondary alcohols Chapter 3 : Nickel-catalyzed alkylation of oxindoles with secondary alcohols Chapter 4 : A simple nickel-catalyst for double deoxygenative coupling of primary alcohols: Selective synthesis of internal olefins, dienes and alkanes Chapter 5 : Fe-catalyzed -alkylation of ketones with alcohols: Access to gem-,’- bis substituted secondary alcohols and substituted pyrrolesCHAPTER 1. Metal-catalyzed application of alcohols for the construction of C-C and C-N Bonds This chapter demonstrates brief literature summary on the sustainable constructions of C-C and C-N bonds. Transition metal catalysis has immensely contributed to the field of borrowing hydrogen via activation of alcohols to the corresponding carbonyl compounds, which act as versatile intermediates in a number of synthetic transformations. A wide variety of functionally and pharmaceutically significant compounds have been synthesized using transition metal catalyzed Borrowing Hydrogen strategy. However, majority of the previous studies depended on precious metal catalysis and expensive ligand systems. On the contrary, earth abundant metal catalysis opens up a wider scope for chemists owing to cost effectiveness and accessibility. This chapter summarised the comparative literature survey of precious and nonprecious transition metal catalysis for the constructions of C-C and C-N bonds.CHAPTER 2A. Nickel-catalysed dehydrogenative coupling of aromatic diamines with alcohols: selective synthesis of substituted benzimidazoles and quinoxalines. (Chem. Commun., 2019, 55, 5958-5961) The first nickel-catalysed dehydrogenative coupling of primary alcohols and ethylene glycol with aromatic diamines for selective synthesis of mono- and di-substituted benzimidazoles and quinoxalines is reported. The earth-abundant, non-precious and simple NiCl2/L1 system enables the synthesis of N-heterocycles releasing water and hydrogen gas as byproducts. Mechanistic studies involving deuterium labelling experiments and quantitative determination of hydrogen gas evaluation were performed.CHAPTER 3. Nickel-Catalyzed Alkylation of Oxindoles with Secondary Alcohols (J. Org. Chem. 2023, 88, 7162−7171) Herein, we have demonstrated a simple nickel-catalyzed C-3-selective alkylation of 2- oxindoles using a wide variety of secondary alkyl alcohols. As a special highlight, functionalization of cholesterol derivative was reported. Control experiments, initial mechanistic studies and deuterium-labelling experiments were performed for the alkylation process.CHAPTER 4. A simple nickel-catalyst for double deoxygenative coupling of primary alcohols: Selective synthesis of internal olefins, dienes and alkanes (manuscript submitted 2024) Substituted alkenes and dienes are one of the most valuable building blocks widely used in natural product synthesis, pharmaceutical and in chemical industries. Herein, we report the first nickel catalyzed double deoxygenative coupling of primary alcohols to furnish olefines, dienes and alkanes. Both cross-coupling and homo-coupling of primary alcohols proceed smoothly under the catalytic condition with acceptable yields. Additionally, we have explored the homocoupling of substituted allylic alcohols to 1,5-dienes. A series of mechanistic studies were performed to understand the catalytic double deoxygenative coupling.CHAPTER 5. Fe-catalyzed -alkylation of ketones with alcohols: Access to gem- , ’-bis substituted secondary alcohols and substituted pyrroles (manuscript submitted 2024) Herein, we have reported Fe2(CO)9 catalytic system for α-alkylation of methylene ketones with primary alcohols and amino alcohols to ,’-di-substituted branched alcohols and pyrroles. A series of aryl, and alkyl primary alcohols were tolerated including methanol to yield the desired product in good to high yield. Initial mechanistic studies, deuterium labelling experiments, and EPR analysis indicate the hydrogen borrowing mechanism through HAT process.