Executive Summary : | The main goal of this proposal is the synthesis of bioactive natural products, agriculture drugs containing tetra substituted chiral alcohols, and halogenated (F, Cl, Br, I, CF3, SCF3) chiral molecules with challenging functional groups for the application of biomedical treatments, healthcare, and agriculture. Furthermore, the novel design and synthesis of Covid-19 drugs are followed by late-stage functionalization and modifications. The initial plan is to design and synthesize novel thiourea-based-organocatalyst having hydroxyl and acid groups. And also design and synthesis of a new core of aminoindane-based NHC-OH which can further be converted to a new generation of NHOs organocatalyst families having hydroxyl and acid groups and its applications for the synthesis of chiral building blocks, drugs, and its heterocyclic derivatives. To introduce our novel approach of in situ modification of NHC-and NHO-mediated organocatalysts to improve the enantioselectivity and reactivity of various asymmetric reactions via secondary-sphere interaction towards sustainable organic chemistry. This proposal will establish a highly sensitive platform to uncover reactivity and selectivity profiles to demonstrate aminoindane-based N-heterocyclic carbenes, N-heterocyclic olefins, and thiourea organocatalysts containing hydroxyl groups with the addition of aryl and heteroaryl boroxine and halogenated amino acids (F, CF3). Its significant role in the synthesis of highly challenging chiral alcohols, natural products, halogenated and non-halogenated natural products, fluoro-compounds, and bioactive drugs are enabled by in situ modification of the organocatalysts approach. We expect newly designed organocatalyst under drives in situ systematic modification catalytic approach via secondary-sphere interaction which will enhance the reactivity and regio-and enantioselectivity of chiral products with the support of physical organic chemistry analyses, theoretical studies, and DFT calculation. This protocol enables the making of tetra-substituted chiral alcohols that are of essential motifs in natural products and drugs. The design and novel optimization of the catalytic reaction is an effective method which combines experimental results, DFT calculation, computational data, and statistical modeling approaches to identify, design a chemical reaction, principles behind molecular functionality, substrate and catalyst reactivity, and regio-and enantioselectivity to improve the bioactivity with fewer side effects to make it a suitable coronavirus medicine. |