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Developing new synthetic methods and strategies is an important area of research in organic chemistry. Especially useful are transformations that rapidly and rationally generate complex molecular architectures, with multiple new bonds and new stereocenters, from simple, achiral and modular precursors. This dissertation discusses the synthetic investigation and exploitation of two such reactions. In PART I, the intramolecular Diels-Alder (IMDA) reaction of aromatic dienes and allene dienophiles, utilized in conjunction with ring-rearrangement metathesis (RRM) to prepare angularly-fused polycyclic lactams, is discussed. The mechanism of the IMDA reaction was investigated with the aid of computational molecular modeling. The reaction was determined to proceed through a concerted mechanism; however, competing radical pathways accounted for stereochemical infidelity and fragmentation observed for some substrates. An improved, modular synthesis of the precursors was developed to directly couple aromatic amines with the allene fragment precursor, which allowed for the preparation of a small library of heterocyclic compounds. This two-step protocol generates topologically interesting structures, containing two or more new rings, and two new sp3 stereocenters. Computational modeling also guided the development of the unknown analogous reaction for allenyl ketone substrates, which yield carbocyclic products. Unexpected stereoselectivity and reactivity observations were made in the alkene metathesis reaction, which could not be readily explained. Computational studies were able to elucidate a subtle yet fundamental relationship between reaction mechanism and length of alkene tether in these types of substrates. In PART II, efforts toward the synthesis of the alkaloid natural product gelsemine are discussed. The synthetic strategy employs a Zincke aldehyde rearrangement/IMDA cascade previously developed by the Vanderwal lab. Using 4-phenylpyridine as a model system, the expecte

Developing new synthetic methods and strategies is an important area of research in organic chemistry. Especially useful are transformations that rapidly and rationally generate complex molecular architectures, with multiple new bonds and new stereocenters, from simple, achiral and modular precursors. This dissertation discusses the synthetic investigation and exploitation of two such reactions. In PART I, the intramolecular Diels-Alder (IMDA) reaction of aromatic dienes and allene dienophiles, utilized in conjunction with ring-rearrangement metathesis (RRM) to prepare angularly-fused polycyclic lactams, is discussed. The mechanism of the IMDA reaction was investigated with the aid of computational molecular modeling. The reaction was determined to proceed through a concerted mechanism; however, competing radical pathways accounted for stereochemical infidelity and fragmentation observed for some substrates. An improved, modular synthesis of the precursors was developed to directly couple aromatic amines with the allene fragment precursor, which allowed for the preparation of a small library of heterocyclic compounds. This two-step protocol generates topologically interesting structures, containing two or more new rings, and two new sp3 stereocenters. Computational modeling also guided the development of the unknown analogous reaction for allenyl ketone substrates, which yield carbocyclic products. Unexpected stereoselectivity and reactivity observations were made in the alkene metathesis reaction, which could not be readily explained. Computational studies were able to elucidate a subtle yet fundamental relationship between reaction mechanism and length of alkene tether in these types of substrates. In PART II, efforts toward the synthesis of the alkaloid natural product gelsemine are discussed. The synthetic strategy employs a Zincke aldehyde rearrangement/IMDA cascade previously developed by the Vanderwal lab. Using 4-phenylpyridine as a model system, the expecte

The nectar of many plant species contains defensive compounds that have been hypothesized to benefit plants through a variety of mechanisms. However, the relationship between nectar defenses and plant fitness has not been established for any species. We experimentally manipulated gelsemine, the principal alkaloid of Carolina jessamine (Gelsemium sempervirens), in nectar to determine its effect on pollinator visitation, nectar robber visitation, and male and female plant reproduction. We found that nectar robbers and most pollinators probed fewer flowers and spent less time per flower on plants with high compared to low nectar alkaloids. High alkaloids decreased the donation of fluorescent dye, an analogue of pollen used to estimate male plant reproduction, to neighboring plants by one-third to one-half. However, nectar alkaloids did not affect female plant reproduction, measured as pollen receipt, fruit set, seed set, and seed mass. The weak effects of nectar alkaloids on female reproduction could represent a balance between the altered behavior of nectar robbers and pollinators, or it could be that neither of these interactions affected plant reproduction. Taken together, these results suggest that secondary compounds in nectar may have more costs than benefits for plants.