Aryl Carbon-Halogen Bond Functionalization: A Transition Metal-Free Approach Using Phenalenyl Based Radicals

Singh, Bhagat (2021) Aryl Carbon-Halogen Bond Functionalization: A Transition Metal-Free Approach Using Phenalenyl Based Radicals. PhD thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

Carbon-halogen bond functionalization is among the most significant approaches in synthetic organic chemistry because of its broad implementation in the construction of various new C-C, C-N, C-O, C-S and C-H bonds. Among all these, the formation of carbon-carbon bond via C-X bond activation is a crucial tool in academia and industry for the synthesis of several valuable natural products, agrochemicals, pharmaceuticals etc. Starting from Ullmann’s work in 1901, there are numerous methodologies reported for carbon-carbon cross-coupling reaction using metal-based catalysts, and most of them utilize palladium-based catalysts. These protocols at an industrial scale face several challenges such as high cost of a palladium catalyst, prefunctionalization of the precursors and presence of trace amount of heavy metal impurities in the products. Later on, a new approach, known as the direct C-H arylation, was established by various scientists such as Dixneuf, Itami, Darcel, Fagnou and many others. This process doesn’t require the participation of specially functionalized coupling partners for C-C cross-coupling reaction. But these modified protocols still needed the costly Pd-based catalyst or other transition meat-based catalysts. In 2008, for the first time, Itami introduced the base promoted C-X bond functionalization for the construction of carbon-carbon bond. The method doesn’t require any transition metal-based catalyst or any special functionalization of the coupling partners. The method became renowned as base promoted homolytic aromatic substitution (BHAS) reaction. Along this direction, several methods were developed, which work under transition metal-free environment utilizing an organic ligand in a semi stoichiometric amount, to construct the new C-C bond between (hetero)aryl halides and (hetero)arenes in the presence of the base. But, these methodologies also suffer from a couple of challenges such as high ligand loading (20-40 mol%) and limited substrate scopes. In this context, to address the aforementioned challenges, the phenalenyl based system was utilized. Phenalenyl is an add alternant hydrocarbon (OAH) known in the literature from more than a half-century and primarily used in material science. Phenalenyl comprises of 13 carbon atoms, and the frontier molecular orbitals (FMOs) possess low-lying nonbonding molecular orbital (NBMO) which is easily accessible. Utilizing its NBMO, phenalenyl can exist in three different redox states; i) closed-shell cation; ii) open-shell radical and iii) closed-shell anion. In the open-shell radical configuration, since electron was introduced to NBMO, it doesn’t affect the aromaticity as well as stability of the molecule. Consequently, the phenalenyl molecule can be used as an electron transporter. In this study, the primary aim has been to develop the carbon-halogen bond functionalization without the assistance of transition metals under homogeneous as well as heterogeneous conditions. In the beginning, the phenalenyl was introduced in C-X bond functionalization towards C-C cross-coupling reaction to construct biaryl motifs from aryl halides and arenes under transition metal-free condition. In this protocol, biaryls were obtained in high yields. The role of the phenalenyl as single-electron transporter in the C-C cross-coupling reaction was established with the help of various control experiments. However, such methodology only works at high temperature. So, to showcase the utility of phenalenyl at ambient conditions, the carbon-halogen bond functionalization toward hydrodehalogenation and dehalogenative deuteration was achieved at room temperature employing the closed-shell anionic (14π e-) configuration of phenalenyl. Also, the deuterated solvent was used to obtain the deuterated arenes in high yields without the aid of transition metal or any external activator such as heat or light. A series of control experiments were performed, which helped in understanding the role of phenalenyl catalyst in hydrodehalogenation and dehalogenative deuteration reactions. Later on, the heterogeneous version of phenalenyl catalyst was synthesized utilizing graphene oxide as solid support. The graphene oxide-phenalenyl composite (GO-PLY) was characterized using various techniques and implemented in the C-X bond functionalization of (hetero) aryl halides, where the GO-PLY exhibits excellent recyclability. This study documents both homogeneous as well as heterogeneous catalyst design for C-X bond functionalization towards catalytic C-C cross-coupling reactions under transition metal-free conditions.

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