Diastereoselective cyclization of lactones via Brønsted acid catalysis

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Symone Alexander (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Kimberly Petersen

Abstract: Chiral molecules play a vital role in supporting biologically effective drugs. Consequently, a majority of pharmaceutical companies seek to isolate the enantiomers of molecules in drug design. Enantioselective synthesis can be a valuable tool for creating single enantiomers. A particular technique for synthesizing enantiomers is desymmetrization, where a prochiral molecule loses its symmetry elements through a reaction. In this work, desymmetrization will be done utilizing a diester with a Brønsted acid catalyst, to achieve mild reaction conditions for cyclization. Providing these mild conditions decreases the chances of side reactions which can happen in harsher reaction conditions hindering enantioselectivity. This approach of using organocatalysts to perform these cyclizations is novel given cyclizations of this nature typically utilize transition metal catalysts. This thesis describes the expansion of previous work in the Petersen Group in the synthesis of six-membered lactones with multiple stereocenters. Previous work utilized prochiral nitrile compounds to synthesize ?-lactones, and this work provides the results of diastereo- and enantioselective desymmetrizations with malonic esters. Once cyclization was achieved the reaction was optimized by varying the achiral Brønsted acid catalyst used, the temperature, and solvents. After optimization of our first substrate containing a bulky phenyl group, a second less bulky alkylating agent was used to examine the diastereoselectivity of this new multicentered compound.

Additional Information

Publication
Thesis
Language: English
Date: 2020
Keywords
Brønsted acid catalysts, Cyclization, Diesters, Lactones
Subjects
Lactones $x Synthesis
Ring formation (Chemistry)
Diastereoisomers

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