Harnessing the Reactivity of N-Sulfonyl Hydrazones to Access Intermediates for Small and Medium Ring Syntheses
Public Deposited- Creator
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Ritchie, Nina
- College of Arts and Sciences, Department of Chemistry
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Ritchie, Nina
- Abstract
- I. Divergent Reactivity of ,-Disubstituted Alkenyl Hydrazones: Bench Stable Cyclopropylcarbinyl EquivalentsWe have developed a bioinspired approach to access cyclopropylcarbinyl intermediates from the palladium-catalyzed cross-coupling of ,-disubstituted alkenyl hydrazones and aryl bromides via a 3-exo-trig cyclization. These intermediates undergo divergent reactivity to form Z-1,4-“skipped”-dienes in up to 85% yield and vinyl cyclopropanes in up to 69% yield. The selectivity between the skipped diene and vinyl cyclopropane products is dependent on both the substituents on the hydrazone reagent and the substituents on the aryl bromide. Sulfonyl hydrazones with terminal phenyl substitution serve as mechanistic probes and reveal a competing alkenyl migration pathway. II. Experimental and Computational Studies on the Generation and Fate of Cyclopropylcarbinyl Palladium IntermediatesWe disclose mechanistic studies on the reactivity of cyclopropylcarbinyl palladium intermediates and elucidate the factors that control the selectivity for 1,4-“skipped”-diene and vinyl cyclopropane products. By changing the electronics on the aryl ring we show a pronounced impact on the product selectivity. The ability of both palladium hydride intermediates and anionic palladium(0) to isomerize vinyl cyclopropanes to skipped dienes is investigated. Through substituent effects on the hydrazone reagent and the aryl bromide a library of vinyl cyclopropanes is selectively synthesized in up to 91% yield. DFT calculations reveal that steric parameters on the ligand have a drastic effect on the ability of CPC intermediates to undergo -carbon elimination by influencing the preceding C-C bond rotation. Clustering methods identify ligands that are selective for either skipped diene or vinyl cyclopropane products. III. Studies on the Synthesis of Benzannulated Medium Rings by N2 Deletion from 3H-PyrazolesWe report the synthesis of benzannulated medium rings from a light-induced N2 deletion of 3H-pyrazole adducts. 3H-Pyrazoles are appended onto aromatic rings through a [3+2]-cycloaddition reaction of sulfonyl hydrazones and pyridazinones. These stable 1,3-diradical precursors can be synthesized and isolated in up to 51% yield. Exposing the cycloadducts to 390 nm light reveals the aryl 1,3-diradical which can undergo a [4+3]-cycloaddition with butadiene derivatives to access benzannulated medium rings.
- Date of publication
- 2024
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright - Educational Use Permitted
- Advisor
- Wilkerson-Hill, Sidney M
- Johnson, Jeffrey S
- Meek, Simon J
- Alexanian, Erik
- Gagné, Michel R
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2024
- Language
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