Graduation Year
2026
Document Type
Campus Only Senior Thesis
Degree Name
Bachelor of Arts
Department
Chemistry
Reader 1
Nicholas Ball
Reader 2
Daniel O'Leary
Terms of Use & License Information
Abstract
The development of modular and predictable chemical transformations is a cornerstone of modern drug discovery and materials sciences. Among these, Sulfur(VI) Fluoride Exchange (SuFEx) has emerged as a leading “click” reaction due to the unique balance of the sulfur-fluoride bond’s high stability and its capacity for selective activation.Despite this, site-selective control in molecules with multiple, competing electrophilic centers remains largely underexplored. Specifically, aryl fluorosulfates possessing both a sulfur(VI) center and an electrophilic aromatic ring offer a unique platform to investigate the competition between SuFEx and nucleophilic aromatic substitution (SNAr).
To address this gap, this thesis work focuses on the synthesis and functionalization of difluoro aryl fluorosulfates. Initial investigations revealed that these dual-reactive scaffolds are difficult to isolate using standard protocols. To circumvent these challenges, a one-pot scheme was developed to generate the species in situ, allowing for immediate functionalization without the need for intermediate isolation steps. Using this optimized protocol, the successful synthesis of various fluorosulfates and subsequent nucleophilic substitution at the SuFEx site has been demonstrated. Furthermore, N-trimethyl (TMS) nucleophiles were employed as a probe, with early results showing SuFEx-pathway preference over SNAr.
While high selectivity for the SuFEx pathway has been achieved, current efforts are focused on activating the remaining electrophilic sites on the aromatic ring. Although SuFEx-substituted derivatives have not yet shown SNAr reactivity, future work aims to identify the conditions necessary to promote substitution at these positions. This thesis aims to establish a reliable methodology for the modification of these complex scaffolds, enabling SNAr functionalization directly after fluorosulfate formation or following SuFEx substitution.
Recommended Citation
Butler, Andrew and Ball, Nicholas, "Orthogonal Reactivity of Aryl Fluorosulfates: A Platform for Selective SNAr and SuFEx Click Chemistry" (2026). Pomona Senior Theses. 381.
https://scholarship.claremont.edu/pomona_theses/381
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.
