Anionic rearrangement of 2-benzyloxypyridine derivatives and a synthetic approach to aldingenin B

[1,2]-Anionic rearrangements are important tools for altering the complexity of molecules at hand. In Part I of this dissertation, an anionic rearrangement of 2-benzyloxypyridine is described. Pyridine-directed metallation of the benzylic carbon leads to 1,2-migration of pyridine via a postulated associative mechanism (addition / elimination). Several aryl pyridyl carbinols were obtained in high yields. A formal synthesis of carbinoxamine, an antihistamine drug used for the treatment of seasonal allergies and hay fever, emerges from this methodology. As an update, the [1,2]-anionic rearrangement of benzyl 2-pyridyl ethers can also be accessed by a distinct and unusual mechanism: addition of alkyllithium reagents to alpha-(2-pyridyloxy)-styrene triggers anionic rearrangement to teriary pyridyl carbinols. This will be presented in Chapter 4 and the process is explained by invoking contraelectronic, pyridine-directed carbolithiation of the enol ether pi-system.;Part II of this dissertation is focused on a synthetic approach to aldingenin B. The synthesis of the tricyclic core of aldingenin B from a key internal alkyne was completed. Synthesis of alkynes by fragmentation is an on-going interest of the Dudley lab. One current goal is to apply our methodology in conjunction with an innovative oxidative alkyne ketalization to achieve a short and efficient synthesis of aldingenin B. The specific goal for this dissertation was to prepare a model alkyne by conventional methods and establish the feasibility of the oxidative alkyne ketalization. The preparation and selenium-mediated cyclo-ketalization of an alkyne-diol will be described as a model study for the synthesis of aldingenin B in Chapter 8. The oxidative cyclization is a simplifying transformation for aldingenin B, as it provides a convenient method for generating the tricyclic core of the natural product from a functionalized carbocycle. Some preliminary experiments to guide future efforts for completing the synthesis of aldingenin B will be presented in Chapter 9.