Master of Science
Kerr, Michael A.
The efficient synthesis of heterocyclic compounds is of great importance to organic chemistry. One method for achieving efficiency is through the use and development of one-pot reactions. This thesis describes the planning and development of an extension to the tandem cyclopropane opening Conia-ene reactivity previously reported. A search for a substrate capable of undergoing the reaction was undertaken and the reaction was optimized. The highest yielding conditions tested used catalytic Sc(OTf)3 and superstoichiometric ZnBr2, but other catalyst systems also worked. The optimized reaction conditions tolerated 6-membered rings well in addition to 7-membered rings in some rotationally restricted cases. Heteroatom linkers such as oxygen and protected amines were also well tolerated. This protocol provides efficient access to bicyclic piperidines that can be mapped onto natural products.
Summary for Lay Audience
Man-made pharmaceuticals need to be synthesized efficiently for the compounds to be commercially or medicinally relevant. These pharmaceuticals are nearly universally made through multistep processes. One way to make the synthesis of these compounds more efficient is by reducing the number of isolation and cleaning steps. Nearly every distinct reaction step necessitates purification of the product and inevitably some loss of material occurs. Therefore, a reaction method that involves more than one chemical change in a single vessel without isolation is desirable. This thesis describes the development of an efficient synthesis of a complicated chemical structure.
Stephens, David G., "One-Pot Synthesis of Bicyclic Piperidines from Donor Acceptor Cyclopropanes" (2020). Electronic Thesis and Dissertation Repository. 7568.