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. 2017 Mar 6;56(11):2903-2908.
doi: 10.1002/anie.201611048. Epub 2017 Feb 6.

Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF 4 Hub

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Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF 4 Hub

Suhua Li et al. Angew Chem Int Ed Engl. .
Free PMC article

Abstract

Sulfur(VI) fluoride exchange (SuFEx) is a new family of click chemistry based transformations that enable the synthesis of covalently linked modules via SVI hubs. Here we report thionyl tetrafluoride (SOF4 ) as the first multidimensional SuFEx connector. SOF4 sits between the commercially mass-produced gases SF6 and SO2 F2 , and like them, is readily synthesized on scale. Under SuFEx catalysis conditions, SOF4 reliably seeks out primary amino groups [R-NH2 ] and becomes permanently anchored via a tetrahedral iminosulfur(VI) link: R-N=(O=)S(F)2 . The pendant, prochiral difluoride groups R-N=(O=)SF2 , in turn, offer two further SuFExable handles, which can be sequentially exchanged to create 3-dimensional covalent departure vectors from the tetrahedral sulfur(VI) hub.

Keywords: SuFEx reaction; amines; click chemistry; phenols; thionyl tetrafluoride.

Figures

Figure 1
Figure 1
A) Structure and boiling point of SF6, SOF4 and SO2F2; B) Early examples of fluoride substitution reactions of SOF4; C) Comparing the trajectories of the Click connections derived from: CuAAC-triazole, SO2F2 and SOF4.
Figure 2
Figure 2
The reactions of primary amines with SOF4 in the presence of Et3N. [a] The yield in parenthesis is for the reaction without Et3N. [b]The amine was generated in situ by reducing the azide under Staudinger conditions with PMe3 and 1 to 3 equiv of H2O, see supporting information.
Figure 3
Figure 3
The selectivity of SO2F2 and SOF4 towards aromatic hydroxyl and amino groups.
Figure 4
Figure 4
The reaction of iminosulfur oxydifluorides with secondary amines. [a] 1.2 equiv of proline methyl ester and 2 equiv of Et3N in MeCN. [b] 1 equiv of amoxapine and 2 equiv of Et3N in DMSO.
Figure 5
Figure 5
The reaction of iminosulfur oxydifluorides with amino acids.
Figure 6
Figure 6
Connecting amines with phenols.
Figure 7
Figure 7
Comparison of the reactivity of iminosulfur oxydifluoride with sulfonyl fluoride and fluorosulfate.
Figure 8
Figure 8
The connections of primary amines with two phenols or one phenol and one secondary amine.
Figure 9
Figure 9
The reaction of iminosulfur oxydifluorides with catechols and the activity of the product towards amines.

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