The primary objective of this proposal is to develop powerful methods for the synthesis of complex molecules. The new methods to be specifically addressed during this project period will rely on the catalytic generation and functionalization of nickel metallacycles. A new synthetic strategy employing sequential nickel-catalyzed reactions will be developed that should provide access to a variety of carbocyclic and heterocyclic aromatic substructures. Other new cyclization methods that utilize allene precursors and vinylzirconium precursors will be developed. The efforts in synthetic methodology development should provide fundamentally new solutions to a variety of synthetic problems.
The aims of this proposal also include the total syntheses of biologically interesting natural products utilizing new reactions developed in this program. The target molecules that will be pursued include testudinariols A and B, domoic acid, isodomoic acids G and H, serratezomine A, and pumiliotoxin 341A. These problems in total synthesis will allow us to pursue solutions to numerous substantial synthetic challenges including the generation of densely functionalized five and six membered rings that possess multiple contiguous stereocenters, the stereoselective generation of tri- and tetrasubstituted alkenes, and the stereoselective creation of quaternary carbon centers. Furthermore, the synthesis of preparative quantities of these biologically interesting natural products and closely related late stage intermediates will allow evaluation of their utility as potential pharmaceutical agents and as research tools in pharmacology.
| Walk, Jordan T; Buchan, Zachary A; Montgomery, John (2015) Sugar Silanes: Versatile Reagents for Stereocontrolled Glycosylation via Intramolecular Aglycone Delivery. Chem Sci 6:3448-3453 |
| Wang, Hengbin; Negretti, Solymar; Knauff, Allison R et al. (2015) Exo-selective reductive macrocyclization of ynals. Org Lett 17:1493-6 |
| Jackson, Evan P; Montgomery, John (2015) Regiocontrol in catalytic reductive couplings through alterations of silane rate dependence. J Am Chem Soc 137:958-63 |
| Jackson, Evan P; Malik, Hasnain A; Sormunen, Grant J et al. (2015) Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings. Acc Chem Res 48:1736-45 |
| Haynes 2nd, M Taylor; Liu, Peng; Baxter, Ryan D et al. (2014) Dimer involvement and origin of crossover in nickel-catalyzed aldehyde-alkyne reductive couplings. J Am Chem Soc 136:17495-504 |
| Miller, Zachary D; Montgomery, John (2014) Regioselective allene hydroarylation via one-pot allene hydrosilylation/Pd-catalyzed cross-coupling. Org Lett 16:5486-9 |
| Miller, Zachary D; Li, Wei; Belderrain, Tomás R et al. (2013) Regioselective allene hydrosilylation catalyzed by N-heterocyclic carbene complexes of nickel and palladium. J Am Chem Soc 135:15282-5 |
| Partridge, Katherine M; Bader, Scott J; Buchan, Zachary A et al. (2013) A streamlined strategy for aglycone assembly and glycosylation. Angew Chem Int Ed Engl 52:13647-50 |
| Lage, Marta L; Bader, Scott J; Sa-Ei, Kanicha et al. (2013) Chemoselective hydrosilylation of hydroxyketones. Tetrahedron 69:5609-5613 |
| Shareef, Abdur-Rafay; Sherman, David H; Montgomery, John (2012) Nickel-Catalyzed Regiodivergent Approach to Macrolide Motifs. Chem Sci 3:892-895 |
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