ENANTIOSELECTIVE SYNTHESIS OF BIS-HETEROARYL MOLECULES AND STUDIES OF CASCADE C-H BOND INSERTION REACTIONS
|May, Jeremy A.
|Coltart, Don M.
|Czernuszewicz, Roman S.
|Ball, Zachary T.
|Shih, Jiun-le 1985-
|This dissertation presents two major projects. The first is the BINOL-catalyzed 1,4-addition of heteroaryl trifluoroborate salts and its application to the synthesis of the natural product, discoipyrrole D. The second is cascade reactions and their use in the synthesis of azasilacyclopentenes and the natural product, brazilide A. The synthesis of bis-heteroaryl stereocenters with high enantioselectivities via a BINOL-catalyzed conjugate addition of trifluoroborates to heteroaryl-appended enones and enals will be discussed herein. A proposed mechanism of how trifluoroborate salts interacting with the BINOL catalyst was based on control experiments. Importantly, bench, air, and moisture stable trifluoroborate salts are not only very easy to handle, but also completely shut down an unproductive protodeboronation side reaction. The power of the mild organocatalytic reaction was demonstrated in the synthesis of the bioactive natural product, discoipyrrole D. The second half describes use of carbene cascade reactions to construct complex molecules like bridged polycycles, propellanes, and heteropolycycles. The propellane core of brazilide A was synthesized by a Rh(II)-catalyzed carbene/alkyne cascade reaction followed by a rearrangement. The final stage of the synthesis still requires installation of a benzopyran motif and oxidation. Moreover, a transition metal-free nitrene initiated cascade reaction was discovered to obtain azasilacyclopentenes. The mechanism of the reaction was informed by detailed control experiments and the characterization of reaction intermediates. The nitrene initiated cascade reaction has opened several valuable directions for future exploration.
|Chemistry, Department of
|Portions of this document appear in: Shih, Jiun‐Le, Thien S. Nguyen, and Jeremy A. May. "Organocatalyzed asymmetric conjugate addition of heteroaryl and aryl trifluoroborates: a synthetic strategy for discoipyrrole D." Angewandte Chemie International Edition 54, no. 34 (2015): 9931-9935.
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|enantioselective conjugate addition
|C-H bond insertion reaction.
|ENANTIOSELECTIVE SYNTHESIS OF BIS-HETEROARYL MOLECULES AND STUDIES OF CASCADE C-H BOND INSERTION REACTIONS
|College of Natural Sciences and Mathematics
|Chemistry, Department of
|University of Houston
|Doctor of Philosophy