| In chapter 1, we described the development of a (BINOLate)Ti-based catalyst for the asymmetric allylation of ketones. The catalyst exhibits good to excellent levels of enantioselectivity across a broad range of substrates. The products, homoallylic alcohols, are versatile materials in organic synthesis and can be transformed into other useful chiral intermediates. It is noteworthy that high enantioselectivities were obtained with a variety of cyclic enone substrates, providing access to tertiary alcohols possessing both allylic and homoallylic double bonds.; In chapter 2, we discussed the first catalyst for the asymmetric methallylation of ketones. The (H8-BINOLate)Ti complex showed better performance in methallyation than the (BINOLate)Ti catalyst, which is an excellent catalyst for the allylation of ketones. The larger dihedral angle of H8-BINOL may be responsible for the increased enantioselectivity over the BINOL-based catalyst. In addition, acetonitrile solvent was crucial for higher enantioselectivity in the methallylation. Acetonitrile may coordinate to the titanium catalyst and alter the structure of the catalyst. Under the optimized conditions, good to high levels of enantioselectivity were observed across a broad range of ketone substrates. These previously inaccessible tertiary homoallylic alcohols can be converted to various chiral building blocks as demonstrated by their conversion to tertiary beta-hydroxy ketones.; The synthetic utility of cyclic enone with our allylation was explored in chapter 3. The asymmetric allylation products of cyclic enones, cyclic 1,5-dien-3-ols, underwent the asymmetric allylation and diastereoselective epoxidation in one-pot using Ti-BINOLate. Beginning from achiral precursors, this one-pot sequence affects the generation of three contiguous stereocenters with excellent enantio- and diastereoselectivity and with high yields. We also demonstrated that the oxy-Cope rearrangement proceeded well on the cyclic 1,5-dien-3-ols. The resulting beta-allyl cyclic ketones are the net result of an asymmetric conjugate addition of an allyl group to a cyclic enone, a reaction that remains challenging in asymmetric catalysis.; In chapter 4, the catalytic arylation of aldehydes was developed beginning from readily available aryl halide. Key to the success of this methods is the introduction of a diamine, such as TEEDA. In the absence of TEEDA, the addition reaction is promoted by the LiCl byproduct, resulting in low enantioselectivity (2%). TEEDA inhibits the LiCl byproduct and allows the addition to proceed through the chiral zinc catalyst. Importantly, in the presence of the diamine it is not necessary to filter, centrifuge, or isolate the arylzinc reagents, minimizing decomposition of these pyrophoric and moisture sensitive materials. Also noteworthy is the fact that addition of functionalized aryl zinc reagents can be accomplished, enabling the synthesis of a variety of benzylic alcohols that were previously difficult to access in enantioenriched form. |
