10.1002/anie.201812356
Angewandte Chemie International Edition
COMMUNICATION
notable departure from six-membered ring-based substrates and
interestingly favors the cis isomer over the trans (2.9:1 cis:trans).
In addition, compound 28 is a rare example of a benzo-fused
heteroaryl-SF4Cl compound, highlighting the potential to install
SF5 on more complex heteroaromatics that are only accessible
otherwise using building block approaches.20
arenes containing nitro substituents.26-27 The TCICA/KF method
offers alternative access, for example, to compounds 33 and 34
in similar or slightly lower yields than this approach (Figure 2,
bottom panel). Additionally, if one considers the number of
steps involved in converting traditional starting materials to
compounds 33 and 34, it is clear that the TCICA/KF approach
could save time, resources, cost, etc. with its increased
substrate scope, even when compared alongside known
applications of the Cl2/KF method in the literature to date. The
bottom panel of Figure 2 puts things in perspective – it is no
wonder that the SF5 group has not appeared more frequently in
the chemical literature, as it often took 4-5 steps or use of gas
reagents to make basic benzene derivatives.
Despite ample evidence in the scientific literature that the
SF5 group can impart advantageous properties on parent
molecules,1,28 it is clear that the reason it is not of immense
general interest at the moment is because of the synthetic
bottleneck that has existed. With this TCICA/KF approach, the
first gas-reagent-free synthesis of aryl-SF5 compounds (via key
aryl-SF4Cl intermediates) is now possible, carrying the benefits
of added functional group tolerance, and thus, "step savings"
over previous strategies. In addition, since aryl-SF3 and aryl-
SeF3 compounds (potential fluorinating reagents) are equally
accessible, the TCICA/KF approach opens up opportunities
beyond the field of aryl-SF5 synthesis with respect to
fluorofunctionalization and reagent design. By side-stepping Cl2
and dangerous fluorine sources, we offer a simple solution to a
complex oxidative fluorination problem and believe this is a
timely leap toward accessible chemistry with the SF5 group and
its kin.
As previously mentioned, aryl-SF4Cl formation is inhibited by
the presence of ortho substituents larger than hydrogen or
fluorine atoms. In such cases, we noted that instead of reaching
the SVI oxidation state, we observed excellent yields of
compounds in the SIV oxidation state, i.e. aryl-SF3 compounds
29 and 30. Although these specific compounds have not been
evaluated as such, other aryl-SF3 compounds, such as
mesitylsulfur trifluoride,21 have applications as fluorinating
reagents, and still rely on the Cl2/KF method of preparation.
When using diphenyl diselenide as a substrate, we observed
nearly quantitative conversion to the product in the SeIV
oxidation state (31), as opposed to PhSeF4Cl. Interestingly,
these aryl-SeF3 compounds are reported to act as difluorinating
reagents,22 but studies on this topic have not resurfaced in the
literature for the past 20 years. This is likely, in part, due to the
fact that the only known synthesis of aryl-SeF3 compounds
requires stoichiometric and prohibitively expensive XeF2.
At this juncture, we have established the ability of the
TCICA/KF approach to make several novel aryl-SF4Cl
compounds, but, accordingly, it is important to comment on
whether such new compounds are viable intermediates in the
syntheses of aryl-SF5 products. As there are many methods for
this Cl-F exchange in the literature, we chose a generic protocol
(AgF, neat, elevated temperatures15) to illustrate the "proof-of-
concept" for their conversion (Figure 2, top panel). We obtained
ester- (32, 34, and 35), amide- (36), azide- (37),
More detailed studies regarding the roles of putative electron
transfer processes and of 'acid activation' in the reaction
mechanism will be a topic for future work.
trifluoromethoxy-
(38),
and
ketone-containing
(39)
pentafluorosulfanyl arenes in good yields with relative ease (and
virtually no optimization) from their novel aryl-SF4Cl precursors.
We also noted that the workup procedure can be modified, for
instance, to transform compound 14 directly to phenol derivative
33 without adding another step to the sequence. On the other
hand, initial attempts to convert compounds 26-28 to
pentafluorosulfanyl arenes using the AgF protocol were
unsuccessful, resulting in aryl-SO2F formation alongside other
decomposition products.
Furthermore, beyond applications in SF5 chemistry, the
Welch23 and Shibata24 laboratories have shown that these aryl-
SF4Cl intermediates can be used to make more unusual aryl-
SF4R (R = alkyl, alkenyl, alkynyl) compounds that are stable to
column chromatography and subsequent modification if they
bear strong electron-withdrawing substituents. Accordingly, we
can also show that some aryl- and heteroaryl-SF4Cl compounds
in Table 1 can be converted to isolable aryl-SF4-containing
derivatives bearing alkyl (40) and alkenyl (41) groups using
catalytic triethylborane/O2 (Figure 2, top panel), as well as
complex molecules bearing alkynyl groups (42).25
Acknowledgements
The authors thank Dr. Thomas C. Fessard (SpiroChem AG,
Basel) for providing select starting materials and valuable
discussions, as well as the ETH transfer office for support in
filing a patent application on this work, where C.R.P., N.S., and
A.T. are listed as inventors. MoBiAS (ETH) and University of
Zürich are acknowledged for assistance with HRMS analyses.
Support was provided by ETH Zürich and the ETH Postdoctoral
Fellowship Program (C.R.P.).
Keywords: oxidative fluorination • pentafluorosulfanyl group •
trichloroisocyanuric acid • gas reagent-free • inorganic fluorine
chemistry
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Pitts, Cody Ross
