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COPPER-CATALYZED HYDROXYCYCLOPROPANOL RING OPENING CHEMISTRY AND TOTAL SYNTHESIS OF GA18

thesis
posted on 22.04.2022, 19:57 authored by Weida LiangWeida Liang

  

Tetrahydrofurans (THFs) and tetrahydropyrans (THPs) are important core scaffolds frequently found in many bioactive natural products and important drug molecules. Regardless of the recent advances, achieving high stereoselective disubstituted or polysubstituted THFs and THPs still remains a synthetic challenge especially via metal catalyzed direct intramolecular Csp3-O bond formation for the ring closure. Cyclopropanols are important and useful building blocks in synthetic chemistry, and due to the intrinsic ring strain, they are prone to undergo ring opening process under transition metal catalyst to produce homoenolates. Herein, we have developed a novel Cu(II)-catalyzed hydroxyl tethered cyclopropanol ring-opening cyclization to diastereoselective syntheses of THF and THP rings. The reaction features a broad substrate scope, scalability, and good functional-group tolerability. Further mechanism study has revealed that the 7-membered metallocycle intermediate generated by Cu and hydroxycyclopropanol plays an important role in reaction pathway. It also enabled us to complete the shortest enantioselective total synthesis of hyperione A and B.

The gibberellins contain a family of nearly 130 highly functionalized diterpenoids in the plant world. Gibberellic acids (GAs) are produced by plants and microorganisms to regulate the cell growth and development. We have developed a comprehensive synthesis strategy for the natural product GA18 that includes the ene reaction, one-pot ozonolysis cascade aldol condensation, photocatalyzed [2+2] reaction, and Sm-induced rearrangement to build the critical tetracyclic skeleton.  Additionally, efforts also have been made in functional group interconversion to finalize the end game. 

History

Degree Type

Doctor of Philosophy

Department

Chemistry

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Mingji Dai

Additional Committee Member 2

Jianguo Mei

Additional Committee Member 3

Hilkka Kenttämaa

Additional Committee Member 4

Betsy Parkinson