| The enantioselective conjugate addition of nucleophiles to nitroalkenes to furnish chiral nitroalkanes is a valuable strategy that has generated continued interest within the chemistry community. The products of these reactions can be used to access chiral amines along with other important motifs. 1 Despite the large body of literature on additions to nitroalkenes, the enantioselective additions to alpha-substituted nitroalkenes remained sparse and asymmetric additions to alpha, beta,beta-trisubstituted nitroalkenes had never been previously reported. Key to achieving enantioselective additions to alpha-substituted nitroalkenes is setting the a-nitrostereocenter via kinetic protonation. In this thesis, the enantioselective addition of sulfur and carbon nucleophiles to alpha, beta,beta-trisubstituted nitroalkenes is achieved using a conjugate addition-enantioselective protonation strategy.;Chapter 1 reviews the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation. The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of complex structures from simple precursors. The conjugate addition-enantioselective protonation strategy has been successfully achieved using chiral Lewis acids, organocatalysts, and transition metal catalytic systems.;Chapter 2 details the first example of a conjugate-addition enantioselectiveprotonation of a trisubstituted nitroalkene. Using a bifunctional thiourea organocatalyst, thioacids are added in excellent yields and with high enantioselectivity to both activated and unactivated trisubstituted nitroalkenes to access chiral 1,2-nitrothioacetates. The products are then readily converted to biomedically relevant 1,2-aminosulfonic acids without loss of enantiopurity.;Chapter 3 describes the first example of enantioselective nitronate protonation following Michael addition of a carbon nucleophile to an alpha,beta,beta-trisubstituted nitroalkene. An N-sulfinyl urea was employed to catalyze the addition of a variety of 3-substituted pyrazol-5-one nucleophiles to trisubstituted nitroalkenes incorporating an oxetane or azetidine ring at the beta-position. The Michael addition products are then reduced to the corresponding enantioenriched amines with minimal loss of enantiomeric purity.;References (1) For reviews of additions to nitroalkenes, see: (a) Halimehjani, A. Z.; Namboothiri, I. N. N.; Hooshmand, S. E. RSCAdv. 2014, 4, 31261-31299. (b) Dondoni, A.; Massi, A. Angew. Chem. Int. Ed 2008, 47, 4638-4660. (c) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713-5743. (d) Mukherjee, S.; Yang, J. W.; Hoffivann, S.; List, B. Chem. Rev. 2007, 107, 5471-5569. (e) Enders, D.; Grondal, C.; Huttl, M. R. M. Angew. Chem. Int. Ed. 2007, 46, 1570-1581. (f) Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520-1543; (g) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem. 2002, 1877-1894. |
