Bronsted Acid Catalyzed Asymmetric Allylation and Propargylation of Aldehydes

Carbonyl allylation and propargylation reactions have been an important tool for the stereocontrolled formation of carbon-carbon bonds for synthetic chemists. The chiral homoallylic and homopropargylic alcohols obtained from these reactions serve as versatile intermediates for the synthesis of natural and pharmaceutical products. Over the past three decades and continuing on, various synthetic groups around the globe have directed their research towards the efficient synthesis of these chiral moieties. In spite extensive research, asymmetric allylation and propargylation reactions remain an enduring challenge in organic chemistry.;Chapter 1 of this thesis describes the first phosphoric acid catalyzed asymmetric allylboration of aldehydes. We found that the BINOL-derived phosphoric acids can efficiently catalyze the allylation reaction under specific conditions. Homoallylic alcohols were obtained in high yields and enantioselectivities from a wide variety of substrates. The optimized conditions were also found to be effective towards crotylboration of aldehydes.;Chapter 2 describes the extension of the Bronsted acid catalyzed allylboration methodology to the propargylation of aldehydes. Homopropargylic alcohols were obtained with high selectivities with TRIP-PA as the catalyst. Synthesis of various important synthetic scaffolds from these chiral alcohols is also presented.;The mechanistic insights studied by research groups of Kendall Houk and Jonathan Goodman have been outlined in chapter 3. These studies show that the major isomer is formed via a transition state involving the hydrogen bonding interaction between the hydroxyl group of the catalyst and the pseudoaxial oxygen of the boronate, with a stabilizing interaction of the phosphoryl oxygen to the formyl hydrogen. These insights helped us in developing new and highly efficient boronates that are described in the next chapter.;Chapter 4 illustrates the impact of the phosphoric acid catalyzed allylboration on the synthetic community and the reports emerging consequently. As the Computational studies suggests the clash of the methyl groups on the pinacol boronate with the bulky aromatic substituents on the catalyst plays an important role in controlling the absolute stereochemistry, new boronates were synthesized and utilized in allylation and propargylation reactions. These boronates gave much better selectivities for both allylboration and allenylboration of aldehydes compared to the previously reported methodologies with pinacol boronates. The extension of the methodology to utilize substituted allyl boronates as substrates in presence of chiral phosphoric acid is also presented in this chapter.