Part 1. Lewis Base-Catalyzed Cross-Aldol Reactions of Aldehydes: Preparative and Mechanistic Studies. Part 2. Initial Studies on Lewis Base-Catalyzed Reactions of Silyl Ynol Ethers With Aldehydes

257 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006.Chiral phosphoramide-catalyzed, enantioselective aldol additions of isobutyraldehyde-derived trichlorosilyl enol ether to aldehydes have been investigated. These aldol additions are general and provide beta-hydroxy aldehydes protected as dimethyl acetals in high yields albeit moderate selectivities. Enantioselectivities are highly dependent on the electronic nature of aldehyde substituent. Two linear but divergent trends in selectivity observed for electron-rich and electron-poor aromatic aldehydes exist. Studies of Arrhenius activation parameters and 12C/13C kinetic isotope effects at natural abundance indicated that no significant change in mechanism occurs up on changing the electronic nature of aldehydes. The divergent trends in selectivity were interpreted according to the Hammond postulate and the Curtin-Hammett principle. Also, chiral phosphoramide-catalyzed, enantioselective Mukaiyama-type aldol reactions of acetaldehyde with other aldehydes have been achieved. Aldol products from aromatic aldehydes were obtained in high yields and selectivities. Intermediates in these aldol additions have been spectroscopically identified as chlorohydrins, and they can be trapped in situ with tert-butyl isocyanide to afford an alpha-hydroxy lactone and alpha-hydroxy amide in good overall yield. Last, proof of principle for Lewis base activation of acids in reactions of silyl ynol ethers with aldehydes has successfully demonstrated. Particularly, the phosphoramide/SiCl4 system has been shown to function as a catalyst in these reactions. More importantly, experimental results have revealed that a new stereogenic center can be created and preserved in these processes.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD