Lewis Base-Catalyzed Modification of Ortho-Substituted Phenols

Lewis base catalysis in chemical transformations has received tremendous recognition in both academic and industrial applications over the years as it offers a convenient alternative to the use of expensive/toxic metal or large enzyme catalysts under mild reaction conditions. In light of this, efforts towards the development of synthetic strategies that employ Lewis base catalysts in mild and selective organic transformations are highly desirable. In this thesis, we present an efficient Lewis base promoted hydrosilylation protocol with a novel cyclic 5-membered pinacol-derived chlorohydrosilane (PCS). This study provides information on the reactivity of this chlorohydrosilane as a hydride donor in the reduction of carbonyl and C=N moieties. Screening of various Lewis bases led to identification of DMPU as an effective catalyst for the hydrosilylation of salicylaldehydes. The role of the base as a catalyst in the reaction mechanism is further supported by computational studies. Hydroquinone serves as a starting material for the synthesis of formyl-hydroquinone, which was used to test the efficiency of our hydrosilylation protocol. The synthesis of hydroquinone from naturally available quinic acid was also studied. The hydrosilylation method was further developed for the preparation of novel tertiary alkylphenolmethyl amines employing pyridine as an effective Lewis base catalyst. During the course of the study, the unprecedented preparation of 6, 12disubstituted methanodibenzo[b,f][1,5]dioxocins from pyrrolidine-catalyzed selfcondensation of 2’-hydroxyacetophenones was discovered and improved. This fascinating highly bridged polycyclic core is present in numerous biologically active natural products and pharmaceuticals. The findings presented in this thesis exemplifies the high reactivity of PCS as a new reagent for Lewis base-catalyzed hydrosilylation. It is nevertheless envisioned that this silane finds usefulness in the hydrosilylation of other functional groups besides those employed in this work. In addition, the study provides mild and selective synthetic strategies to access diverse phenolic compounds of potential use by the pharmaceutical industry in the development of new bioactive molecules