Date of Completion
Honors College Thesis
Honors College, College of Arts and Science Honors
Guanidine, Claisen Rearrangement, [3, 3] sigmatropic rearrangement, More O'Ferrall Jencks, Catalysis, Optimization
Guanidines are a class of compounds with many uses ranging from reagents in organic synthesis to medicinal uses. They can be found in nature through several natural product scaffolds and biological systems, but their synthesis still poses as a challenge to chemists. A method to synthesize complex guanidine compounds was developed by the Madalengoitia group in 2004 through a zwitterionic 1,3-diaza-Claisen rearrangement. The rearrangement has undergone many expansions over the years to encompass more linear precursors, facile methodologies, and increase generality. This thesis will focus on expanding the scope and reaction rate of the allyl cyanamide 1,3-diaza-Claisen rearrangement.
Historical precedent like the transition of allyl thiocyanate to allyl isothiocyanate and allylic [3,3] sigmatropic cyanate-isocyanate rearrangement gave inspiration for our allyl cyanamide 1,3-diaza-Claisen rearrangement. However, unlike those rearrangements, ours is much higher in activation energy, thus modifications to reduce activation energy for the rearrangement is a necessity. Using molecular modelling and calculations we were able to visualize how different electron withdrawing groups and R group substituents would affect the activation energy and test those synthetically. The work herein focuses on the exploration of scope expansion of the tosyl allyl cyanamide 1,3-diaza-Claisen and its catalysis. Attempts at catalysis failed, however, as part of the catalysis search, we expanded from the use of a sulfonyl group as an electron withdrawing source for the first time to 2,3,4,5,6-pentafluorobenzoyl. Unexpected results found towards the end of the process by another member suggested that perhaps the reaction mechanism might differ from what we have known, which might give a reason as to why none of the catalysts tried worked.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Le, Wen P., "Optimization and Catalysis of the Allyl-Cyanamide 1,3-Diaza Claisen Rearrangement" (2023). UVM Honors College Senior Theses. 565.
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