Perfluorooxosulfate Salts as SOF4-Gas-Free Precursors to Multidimensional SuFEx Electrophiles.

Sulfur(VI) Fluoride Exchange (SuFEx) chemistry stands as a well-established method for swiftly constructing complex molecules in a modular fashion. An especially promising segment of this toolbox is reserved for multidimensional SuFEx hubs: three or more substituents pluggable into a singular SVI centre to make 'beyond-linear' clicked constructions. Sulfurimidoyl difluorides (RNSOF2) stand out as the prime example of this, however their preparation from the scarcely available thionyl tetrafluoride (SOF4) limits this chemistry to only a few laboratories with access to this gas. In this work, we identify silver pentafluorooxosulfate (AgOSF5) as a viable SuFEx hub with reactivity equal to SOF4. The AgF2-mediated oxidation of SOCl2 gives rise to the hexacoordinate AgOSF5 adduct, which in contact with primary amines produces the sulfurimidoyl fluorides in high yields. In addition, we have found this workflow to be fully extendable to the trifluoromethyl homologue, AgOSF4CF3, and we propose the use of AgOSF4X salts as a general route to azasulfur SuFEx electrophiles from commercial starting materials.

De-Risking S-F Bond Formation: A Gas Cylinder-Free Strategy to Access S(IV) and S(VI) Fluorinated Compounds.

The sulfur-fluorine partnership occupies a privileged position in fluorine chemistry given the functional versatility that it imparts to organic structures. Despite this, available methodologies to forge S-F bonds are limited compared to C-F bond formation. Here, we describe a synthetic protocol that selectively enables the oxidative halogenation of aliphatic, aromatic, and heteroaromatic thiols to their corresponding SF4 Cl, SO2 F and SF3 derivatives. Selective oxidation of thiols to either S(IV)-F or S(VI)-F compounds is achieved by employing bench-stable calcium hypochlorite as chlorine surrogate (CLOgen), in the presence of KF as fluoride source. Density functional theory (DFT) calculations provided insight into the mechanistic aspects of the transformation and rationalized the observed isomeric preference towards the SF4 Cl derivatives. Ultimately, this glovebox-free method selectively dispatches three classes of compounds upon reaction condition fine-tuning. Furthermore, first-in-class transformations are reported, including the preparation of aliphatic SF4 Cl intermediates, their transformation into aliphatic sulfur pentafluoride analogs, and post-functionalizations that allow accessing highly complex SF4 -bridged scaffolds.

Chemistry of Pentafluorosulfanyl Derivatives and Related Analogs: From Synthesis to Applications.

Pentafluorosulfanyl (SF5 )-containing compounds and corresponding analogs are a highly valuable class of fluorine-containing building blocks owing to their unique properties. The reason for that is the set of peculiar and tremendously beneficial characteristics they can impart on molecules once introduced onto them. Despite this, their application in distinct scientific fields remains modest, given the extremely harsh reaction conditions needed to access such compounds. The recent synthetic approaches via S-F, and C-SF5 bond formation as well as the use of SF5 -containing building blocks embody a "stairway-to-heaven" loophole in the synthesis of otherwise-inaccessible chemical scaffolds only a few years ago. Herein, we report and evaluate the properties of the SF5 group and analogs, by summarizing synthetic methodologies available to access them as well as following applications in material science and medicinal chemistry since 2015.