Strain‐Release Pentafluorosulfanylation and Tetrafluoro(aryl)sulfanylation of [1.1.1]Propellane: Reactivity and Structural Insight**

Abstract

We leveraged the recent increase in synthetic accessibility of SF 5 Cl and ArÀ SF 4 Cl compounds to combine chemistry of the SF 5 and SF 4 Ar groups with strain-release functionalization. By effectively adding SF 5 and SF 4 Ar radicals across [1.1.1]propellane, we accessed structurally unique bicyclopentanes, bearing two distinct elements of bioisosterism. Upon evaluating these "hybrid isostere" motifs in the solid state, we measured exceptionally short transannular distances; in one case, the distance rivals the shortest nonbonding C•••C contact reported to date. This prompted SC-XRD and DFT analyses that support the notion that a donoracceptor interaction involving the "wing" CÀ C bonds is playing an important role in stabilization. Thus, these heretofore unknown structures expand the palette for highly coveted three-dimensional fluorinated building blocks and provide insight to a more general effect observed in bicyclopentanes.

Straightforward Pentafluorosulfanylation for Molecular Design

“…The oxidative fluorination is achieved either with chlorine gas as the stoichiometric oxidant in the presence of KF, introduced by Umemoto et al (9,10) or with solid chlorinating reagent TCICA, as reported by Togni and Shibata. (11,12) Due to these advances, the interest of the synthetic organic community in pentafluorosulfanylation and its related chemistry has been re-ignited recently (13)(14)(15)(16)(17)(18)(19)(20)(21) and novel SF5-pharmaceuticals have appeared in clinical trials and patents. (22)(23)(24) However, the total efficiency of the current synthetic route toward Ar-SF5 compounds remains unsatisfactory due to several associated problems: a multi-step synthetic sequence; overall low to moderate yields; difficulty in handling of intermediates due to strong smell and/or moisture sensitivity; limitations in substrate scope (e.g.…”

Rapid and Scalable Halosulfonylation of Strain‐Release Reagents**

“…[6] Thioether‐ and selenoether‐substituted BCP sulfones have been prepared in a similar manner through mild heating or irradiation of dichalcogenides, [7] as well as penta‐ and tetra‐fluoro(aryl)sulfanyl chlorides. [8] S,C‐ disubstituted BCP sulfones bearing β‐carbonyl, allyl or alkynyl substituents are accessible using photocatalysis; however, this method utilizes non‐commercial, tailored substrates such as enol sulfonate esters or alkynyl sulfones. [9]…”

Rapid and Scalable Halosulfonylation of Strain‐Release Reagents**

“…[6] Thioether-and selenoether-substituted BCP sulfones have been prepared in a similar manner through mild heating or irradiation of dichalcogenides, [7] as well as penta-and tetrafluoro(aryl)sulfanyl chlorides. [8] S,C-disubstituted BCP sulfones bearing β-carbonyl, allyl or alkynyl substituents are accessible using photocatalysis; however, this method utilizes non-commercial, tailored substrates such as enol sulfonate esters or alkynyl sulfones. [9] We recently demonstrated the suitability of [1.1.1]propellane and [3.1.1]propellane to engage in atom transfer radical addition (ATRA) reactions with carbon and nitrogen-centred radicals to afford halide-functionalized para- [10] and meta-arene bioisosteres.…”

“…This approach has been explored in the addition of certain sulfonyl chlorides (R=Me, Ph) to 1 , but required harsh UV irradiation, and suffered from poor to average yields and/or uncontrolled reactivity that generated ′staffane′ oligomers [6] . Thioether‐ and selenoether‐substituted BCP sulfones have been prepared in a similar manner through mild heating or irradiation of dichalcogenides, [7] as well as penta‐ and tetra‐fluoro(aryl)sulfanyl chlorides [8] . S,C‐ disubstituted BCP sulfones bearing β‐carbonyl, allyl or alkynyl substituents are accessible using photocatalysis; however, this method utilizes non‐commercial, tailored substrates such as enol sulfonate esters or alkynyl sulfones [9]…”