Date of Completion
2023
Document Type
Honors College Thesis
Department
Chemistry
Thesis Type
College of Arts and Science Honors, Honors College
First Advisor
Matthias Brewer
Keywords
Synthetic organic chemistry, conjugate additions, stereocontrol
Abstract
Conjugate additions are powerful chemical reactions in organic synthesis that allow for the formation of new carbon-carbon bonds. The Brewer group developed a diazo-retentive conjugate addition that allows for the addition of carbon nucleophiles to vinyl diazoniums. This reaction produces highly congested carbon centers, while retaining the versatile diazo functional group. The retention of the diazo group allows for further transformations of the products to create complex small molecules. 1,3 – dipolar cycloadditions with the conjugate addition products and a dipolarophile were studied to give highly substituted bi- and tri-cyclic tetrahydrofurans. This work explores OH insertions of the reduced conjugate addition products to give highly substituted monocyclic tetrahydrofurans. Formation of dihydrofurans from the conjugate addition products was also explored; however, these were not obtained in synthetically useful yields.
Additionally, the conjugate addition is not enantioselective, meaning the 3D orientation of these products cannot be controlled. The 3D orientation of molecules affects biological activities, thus, it is imperative to control the orientation of molecules produced in a bond-forming reaction. This work looks at synthesizing and assessing chiral organocatalysts for the conjugate addition to render it enantioselective. Thiourea, squaramide, phosphoric acid, and silanediol catalysts were explored; however, none of these catalysts induced significant enantioselectivity.
This work then looks at achieving the diastereoselective conjugate addition via the incorporation of chiral auxiliaries. This was more successful, and using Oppolzer’s camphorsultam as the chiral auxiliary, a diastereoselective conjugate addition was achieved when the reaction was run at room temperature in methyl-tert-butyl ether to give the product in a 33 : 1 diastereomeric ratio. Future work consists of cleaving the chiral auxiliary group and testing the enantioselectivity of this reaction.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Recommended Citation
Petrucci, Isabelle E., "Achieving Stereoselective Control Over the Conjugate Addition of Carbon Nucleophiles to Vinyl Diazoniums" (2023). UVM Patrick Leahy Honors College Senior Theses. 584.
https://scholarworks.uvm.edu/hcoltheses/584