C-C Cross Coupling Catalysis: A Transition Metal-Free Approach using Phenalenyl Radicals

Ahmed, Jasimuddin (2020) C-C Cross Coupling Catalysis: A Transition Metal-Free Approach using Phenalenyl Radicals. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Jasimuddin Ahmed (13IP002)) 13IP002.pdf - Submitted Version Restricted to Repository staff only Download (15MB)

Abstract

C-C cross-coupling reaction is one of the most important organic synthetic methodologies due to its wide application towards the preparation of different structural motifs, which are attractive in pharmaceuticals, natural products, agrochemicals, materials, etc. Thus, there is an interest in academia as well as in industry for the development of the C-C cross-coupling methodology. Since the first discovery in 1900, using organomagensium compounds (R-Mg-X; Grignard reaction) as coupling reagents, there are a large number of methodologies based on transition metal catalysts for C-C cross coupling reactions. But most of these methodologies suffer from the use of special functionalization of the coupling partner, use of expensive palladium catalysts, which technically, economically and environmentally compromise the industrial outcome. To resolve this issue, a new C-C cross-coupling methodology appeared in literature by introducing the concept of direct C-H arylation of the heteroarene partners, which could avoid the use of special functionalization of the coupling partners. Still, this process suffers from the use of expensive Pd-metal or other transition metal based catalysts. From 2008, base promoted homolytic aromatic substitution reaction (BHAS) was introduced as a transition metal-free C-C cross-coupling methodology by direct C-H arylation of heteroarenes/arenes with aryl halides in presence of equivalent amount of strong base and semi stoichiometric ligand loading under elevated temperature. This process also suffers from several drawbacks associated with high temperature (~100-130 ⁰C) reaction condition, high ligand loading (20-30 mol%) and limited substrate scopes. In this regards, to resolve this problem, we took advantage of the easily accessible low-lying non-bonding molecular orbitals (NBMO) of the phenalenyl molecule which is an odd alternant hydrocarbon (OAH). This phenalenyl molecule is known from the last 60 years from a completely different aspect of material science. The phenalenyl molecules are built with 13 carbon atoms, as a result, it offers a NBMO in the FMOs. As the electron occupation in the NBMO does not affect the stability of a molecule and this fact introduces a major advantage of phenalenyl based neutral radical as a SET agent. In this work, the major objective is to develop transition metal-free C-C cross-coupling catalysis at room temperature under low-catalyst loading conditions. At first transition metal-free direct C-H arylation of heteroarenes was performed using aryldiazonium salt coupling partner by K-phenalenyl based redox catalyst. Later on, to achieve the direct C-H arylation of unactivated arenes organic phenalenyl cation was introduced. The dual role (Lewis acidity and redox activity) of the phenalenyl cation was utilized in this direct C-H arylation of simple arenes. Next, three component carboalkoxylation reaction was developed under transition metal-free condition in catalytic fashion using K-phenalenyl based redox catalysts. These transition metal-free developments utilized aryldiazonium salt coupling partner, which makes these reaction protocols costly and atom uneconomic. To overcome this issue, aryl halide activation and catalytic functionalization was carried out under transition metal-free condition utilizing a new concept of double chemical reduction to a neutral phenalenyl backbone. All the methodologies could afford satisfactory yields of the biarylated products at room temperature without using any external stimuli such as light or heat. Full mechanistic understanding by various spectroscopic tools and crystallizing the active catalysts help to figure out the role of phenalenyl catalysts in this C-C cross coupling catalytic methodologies. This work could establish that the use of redox non-innocence phenalenyl molecule can replace the transition metal based catalysts in C-C cross coupling reactions. In future, the phenalenyl molecules can be chemically tuned to achieve the appropriate redox potential to activate other challenging substrates such as unactivated aryl chlorides, CO₂ etc.

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