Research Projects

Exploiting the reactivity of a functional group within a molecule to induce the desired transformation at a distal position is a challenging task in organic synthesis. Remote functionalization strategies have the potential to provide access to substitutions at otherwise inaccessible positions. These strategies entail the modification of the distal position via a relay process, either (i) by spatial means or (ii) through the molecular architecture. The former approach involves construction, incorporation, and subsequent removal of complex directing templates to enable functionalization at a remote site. The latter approach is typically achieved through alkene migration along a hydrocarbon chain, driven by a thermodynamically favorable termination process or by vinylogous reactions of conjugated π-systems. The design and development of selective C-H activation reactions at remote positions from a leading functional group have evolved into an exciting research topic for synthetic chemists. However, the inert nature of distal C-H bonds and the complexity of guiding functionalization to those sites present significant difficulties. The strategies of coupling vinylogous systems (enolizable π-extended carbonyl system) with electrophilic coupling partners like aryl halides (or pseudohalides) is another powerful tool to functionalize remote positions in a molecule. In such vinylogous systems, the electronic properties of the functional group propagate along the carbon chain to remote positions through a conjugated π-system. Several challenges associated with the development of an effective method to modify a distal position selectively in vinylogous systems include: (i) potential for the generation of other regioisomeric products, (ii) multiple functionalizations, (iii) di- & tri-enolates are more prone to self-condensation through Michael reactions, (iv) lower nucleophilicity of di- & tri-enolates compared to simple enolates. Despite these challenges, seminal works have been reported in this area by many research groups. In this context, γ-aryl-α,β-unsaturated enones, in particular, cyclic ones, are the core building blocks in numerous alkaloids and several diterpenoids having promising bioactivity. Only a limited number of methods have been reported for the enantioselective construction of γ-aryl-α,β-unsaturated ketones, most of which proceed via an intramolecular pathway and require a multi-step synthetic sequence for starting material preparation. To the best of our knowledge, the only report on the enantioselective γ-arylation of β,γ-unsaturated cyclohexenones in an intermolecular fashion to construct a γ-quaternary center is by Buchwald and co-workers in 2007. However, the method involved a limited range of substrates and provided low yields. Taking into consideration the undeniable significance of these motifs, we aim to develop an efficient and general catalytic platform to synthesize enantioenriched cyclohexenones bearing γ-aryl all-carbon quaternary chiral center. The core objective of our proposal is to apply the hereby developed methodology to construct the unified chiral core framework, thereby enabling streamlined access to a broad array of structurally and stereochemically complex natural products (of the alkaloid and terpenoid class) from a common intermediate, while drawing inspiration from nature’s strategy of collective natural product synthesis. This will provide access to a newly conceptualized disconnection of complex molecular architectures through a methodology-driven approach, significantly expanding the current retrosynthetic toolbox and enabling the efficient preparation of medicinally relevant compounds. The newly developed methodology can show promising potential in organic materials chemistry such as cyclohexane-bridged bis-spirofluorenes, which may exhibit noteworthy chiroptical properties and hold potential applications as OLED materials.