This proposal discusses the design and development of a bifunctional chiral organic catalyst that will promote the addition of a variety of nucleophiles into imine substrates. The products of these reactions are functionalized chiral amines, which are important components in natural products and drug candidates. A 50- member catalyst library will be synthesized on solid support and then screened for catalyst efficiency and enantioselectivity in the reaction of allyl- and crotylsilane additions as well as the additions of dialkylzinc reagents to imines. The catalyst will incorporate a Lewis acidic urea group and a Lewis basic group (tertiary amines or phosphine oxides). These electrophiles were chosen due to their susceptibility to Lewis basic activation and the importance of the chiral amine products to drug discovery. With the discovery of an active catalyst, rigorous control experiments will be used to determine if the catalyst is behaving bifunctionally. The overall goal of the project is to elucidate whether the chiral urea functionality is a privileged catalyst structure. Such a catalyst would make a significant contribution to the field of asymmetric catalysis.
