Semester
Summer
Date of Graduation
2022
Document Type
Dissertation
Degree Type
PhD
College
Eberly College of Arts and Sciences
Department
Chemistry
Committee Chair
Gregory B. Dudley
Committee Co-Chair
Brian V. Popp
Committee Member
Bjorn Soderberg
Committee Member
Carsten Milsmann
Committee Member
Lori Hazelhurst
Abstract
The synthesis of complex, polysubstituted aromatic rings from simple, non-aromatic building blocks is a consistent challenge to the synthetic community. Neopentylene ring fusions are found in several natural products but are largely absent from synthetic compound libraries. This discrepancy reflects the limitations in modern chemical synthesis. Utilizing, in part, a thoroughly developed fragmentation/olefination methodology from the Dudley Lab, a library of novel 1-sulfonyl-1,6-enynes have been developed. In this methodology, they are prepared in three steps from dimedone (5,5-dimethyl-1,3-cyclohexanedione), an inexpensive starting material. A total of 14 novel 1-sulfonyl-1,6-enynes were synthesized. These substrates were subjected to a novel benzannulation reaction based on metal-catalyzed [2 + 2 + 2] cyclotrimerization methodology. The nickel-catalyzed reaction of sulfonyl enyne with an exogenous alkyne partners and in situ elimination of phenylsulfinic acid provides neopentylene-fused indane cores. The novel methodologies presented herein were used to shorten the synthesis of neoprofen, a synthetic analogue of ibuprofen, from ten steps to seven. Improved access to neopentylene-tethered 1,6-enynes advances target- and diversity-oriented synthesis, expanding synthetic libraries.
Recommended Citation
Martin, Alexa C., "Synthesis and Cyclotrimerization of Sulfonyl Enynes" (2022). Graduate Theses, Dissertations, and Problem Reports. 11418.
https://researchrepository.wvu.edu/etd/11418