Date of Award
Bachelor of Arts (BA)
The Diels-Alder reaction has become a prominent synthetic tool due to the effectiveness for which it facilitates the construction of new carbon-carbon bonds to form six-membered rings. Since first reported in 1952, Intramolecular Diels-Alder (IMDA) reactions have been widely employed for complex synthesis, especially for natural products. Our lab was the first to report a Tandem Intramolecular Diels-Alder (TIMDA) reaction, and TIMDA reactions have similarly proved powerful in the synthesis of natural products. Predicting the absolute stereochemistry of the major products of such intramolecular reactions is complicated by the competition between steric factors imposed by the necessary distortion of the tether between diene and dienophile. This logic competes with the prediction established by the “endo addition rule,” which suggests the thermodynamically favored product is that yielded by an endo approach where secondary orbital interactions between the electron withdrawing group and the diene can stabilize the transition state. Herein a step-wise approach is engaged, enabling an isolated study of the first intramolecular Diels-Alder product. The seven-step synthesis was optimized, and NMR experiments as well as derivatization strategies were explored in attempts to absolutely assign the stereochemistry of the TIMDA major product. Additionally, a computational approach was applied to evaluate the thermodynamic stability of the possible TIMDA products. All work supported the working hypothesis that the major product is the result of an endo approach, meaning thermodynamic drivers outcompete any steric limitations imposed by the tandem intramolecular reaction. Further work, however, is required to confirm this conclusion.
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Pelham, Katie, "Stereochemical Investigation of a Novel Tandem Intramolecular Diels-Alder Reaction" (2020). Chemistry Senior Theses. 14.