Studies on Sequential Reactions using Alcohols and Peroxides with Naphthols and 1,3-diones Toward the Synthesis of Heterocyclic Compounds

Abstract

Sequential reactions are a class of chemical processes where the product of one reaction serves as the reactant for the next. These reactions are fundamental in both organic processes and are often used in multistep syntheses. Sequential transformations further demonstrated the synthetic potential of this strategy, enabling one-pot access to structurally diverse and complex scaffolds. Peroxides and alcohols serve as versatile precursors for generating electrophiles and utilising them in synthetic transformations, such as alkylation and sequential rearrangement reactions. These precursors can generate reactive intermediates and are suitable for subsequent applications in synthetic transformations involving electron-rich substrates, such as naphthols and 1,3-diones. In this context, we have studied sequential reactions of peroxides and alcohols using naphthols and 1,3-diones. In the first chapter, we have integrated naphthol and alcohol chemistry in a continuous flow system. In this study, β-zeolite mediated alkylation of naphthols using various alcohols in continuous flow has been demonstrated for further functionalization, such as peroxidation, azidation, and halogenation. The recyclability of the catalyst as well as the solvent was also examined to enhance the sustainability profile of the reaction. In the next chapter, Mn(III) catalyzed domino process via in situ formation of ortho quinone methide intermediate (o-QM) for C-3 substituted dihydrocoumarins using 2-hydroxybenzyl alcohols and 4-hydroxy-2H-chromen-2-ones is demonstrated under thermal reaction conditions. This protocol was demonstrated by synthesizing new dihydrocoumarins using various 2-hydroxybenzyl alcohols and 4-hydroxy-2H-chromen-2-ones with 40 examples. Later, FeCl3 mediated sequential oxidative cleavage of proxyoxindole for the synthesis of oxindolo-xanthene derivatives using naphthols, malononitrile, and cyclic 1,3-diones has been discussed. In this study, we have synthesized diverse spiro compounds, and the coupling of unsymmetrical diones has been studied for the first time. Finally, the generation of olefins, such as isobutylene, from tertiary butyl acetate by cleavage of peroxides using TMS-OTf as a catalyst, via sequential rearrangement followed by C-H hydroxylation, has been discussed for the synthesis of new benzoxazine scaffolds. In this study, the product formation varies with the type of substituent on the peroxide substrates. By employing this strategy, we have synthesized a library of benzoxazine derivatives at ambient reaction temperature and further studies are in process.