Date of Completion
College of Arts and Science Honors
José S. Madalengoitia
Chemistry, Organic Synthesis
The 1,3 diaza-Claisen rearrangement is a variant of the classical Claisen rearrangement discovered by the Madalengoitia group in 2004 that provides efficient access to guanidines- a functional group commonly present in bioactive molecules of interest. In recent studies, the Madalengoitia group has been developing a new variant of the 1,3 diaza-Claisen rearrangement known as the allyl cyanamide rearrangement.
This thesis work was focused on investigating the reaction design of this allyl cyanamide 1, 3 diaza-Claisen rearrangement with respect to the allylic functionality of the allyl cyanamide, as well as the nucleophile which adds in this transformation. Specifically, novel electron-deficient allyl cyanamides were synthesized and attempts were made to expand the product scope of this reaction beyond guanidines to include amidines and aminals by 1,3 diaza-Claisen rearrangement.
After unsuccessful attempts to synthesize amidines and aminals via this allyl cyanamide 1,3 diaza-Claisen rearrangement, focus was shifted back to the synthesis of guanidines where surprisingly, the introduction of secondary amines into the reaction’s design led to an unprecedented rate acceleration and suggested that the current hypothesis for this reaction’s mechanism is not complete. In which case, attempts were made to study the effect of the adding nucleophile as well as the presence of acid which is potentially assisting in the rate-determining step of the rearrangement. In effect, these findings provide a foundation for further research into the allyl cyanamide rearrangement and the unusual rate acceleration observed, potentially affording greater access to novel guanidines via this strategy.
Higgins, Seamus, "Investigation Into The Scope Of The Allyl Cyanamide 1,3 Diaza-Claisen Rearrangement" (2023). UVM College of Arts and Sciences College Honors Theses. 123.
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