Harnessing the Reactivity of Sulfamate Esters and Sulfamides in Photoredox-Mediated Bond-Forming Reactions

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Gant Kanegusuku, Anastasia L


Roizen, Jennifer L

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Advancements in photocatalysis have enabled access to previously inaccessible intermediates, and have allowed for the development of innovative strategies for bond-formation. By employing a series of metal polypyridyl complexes, chemists have been able to tune reaction conditions to favor productive methodologies for the synthesis of challenging molecular targets. In recent years, photochemically-mediated strategies utilizing this series of privileged metal polypyridal complexes, have overcome significant hurdles when applied to C–H functionalization reactions. C–H functionalization processes take inspiration from the precision of enzymatic reactions in Nature, which are able to transform otherwise indistinguishable and unreactive C(sp3)–H bonds into high value functional groups. A typical strategy employed by chemists for selectively engaging strong C(sp3)–H bonds (BDE = 90 – 105 kcal/mol) involves the use of directing groups that are geometrically disposed to guide reactions at one C–H bond in preference to others. Photoredox-catalyzed platforms have enabled the controlled access to reactive radical intermediates capable of acting as directing groups for the transformation of unreactive C–H bonds under mild conditions.

In addition to allowing access to unprecedented radical intermediates, photosensitizers can also overcome longstanding challenges associated with metal catalyzed cross-coupling reactions. The use of photocatalysts in nickel-catalyzed cross-coupling reactions enables more efficient reductive elimination, and has revolutionized the types of nucleophiles capable of engaging in C–C, C–O, C–S, and C–N coupling reactions. As a result, these photochemically-driven strategies potentiate access to diverse chemical structures, including many underexplored classes of small molecules.

Through this research, we apply photocatalysis to the generation of sulfamyl and sulfamidyl radicals for site-selective carbon–carbon bond formation. These guided alkylation reactions are the first of their kind to generate sulfamyl and sulfamidyl radicals from non-preoxidized or activated sulfamate esters and sulfamides. As directing groups, both sulfamate esters and sulfamides offer modified Hofmann-Löffler Freytag (HLF) position selectivity for late-stage C–H functionalization processes. Additionally, we have applied a dual photochemically driven, nickel-catalyzed reaction manifold to the N-(hetero)arylation of sulfamate esters and sulfamides. We demonstrate that both sulfamates and sulfamides are competent nucleophiles in these dual photochemical and nickel-catalyzed processes. Furthermore, these user-friendly methods improve access to underexplored arylated sulfamate ester and sulfamide small molecules.





Organic chemistry



Gant Kanegusuku, Anastasia L (2020). Harnessing the Reactivity of Sulfamate Esters and Sulfamides in Photoredox-Mediated Bond-Forming Reactions. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/21032.


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