Master of Science
Dr. Michael Kerr
Previous work done by the Kerr group has shown that tetrahydro-1,2-oxazines can be efficiently synthesized using a three component coupling reaction between a hydroxylamine, aldehyde and cyclopropane diester. This affords the desired heterocycle efficiently with a wide variety of substitution. When one esters bears an allyl group a Tsuji dehydrocarbonylation reaction may take place resulting in the formation of a 4,5-dihydro-1,2-oxazine. This motif contains a vinylogously acidic proton which is extremely labile and easily deprotonated. Under basic conditions this proton is removed and consequently the N-O bond is cleaved and subsequent condensation occurs forming a pyrrole. Using a sequence of chemical transformations specific pyrroles generated from the above methodology could be transformed into either BM 212 an anti-tuberculosis drug or Atorvastatin Calcium an anti-cholesterol drug. Each pharmaceutical will be derived using a three component coupling reaction and then conversion to a pyrrole followed by manipulations of the resulting functional groups.
Humenny, William J., "The Multicomponent Synthesis of Pyrroles from Cylcopropane S Using a One Pot Pd(0) Catalyzed Dehydrocarbonylation Protocol" (2012). Electronic Thesis and Dissertation Repository. 695.