New and convenient method for incorporation of pentafluorosulfanyl (SF5) substituents into aliphatic organic compounds

Article abstract of DOI:10.1021/ol026483o

(figure presented) Use of Et₃B as a catalytic initiator allows the convenient, regiospecific, and highly stereoselective addition of SF₅Cl in high yield to a variety of alkenes and alkynes.

Full text of DOI:10.1021/ol026483o

ORGANIC
LETTERS
2002
Vol. 4, No. 17
3013-3015
New and Convenient Method for
Incorporation of Pentafluorosulfanyl
(SF5) Substituents Into Aliphatic Organic
Compounds
Samia A1ıt-Mohand and William R. Dolbier, Jr.*
Department of Chemistry, UniVersity of Florida, GainesVille, Florida 32611-7200
wrd@chem.ufl.edu
Received July 9, 2002
ABSTRACT
Use of Et3B as a catalytic initiator allows the convenient, regiospecific, and highly stereoselective addition of SF5Cl in high yield to a variety
of alkenes and alkynes.
There is currently great interest in methods for the preparation
of selectively fluorinated organic compounds, in no small
part because of the profound influence that fluorine incor-
poration can have on the physical and chemical properties
and biological activity of molecules. Thus, for example,
methods for putting the bulky, highly electronegative, and
generally inert trifluoromethyl group into organic compounds
have received much research attention during recent years.
Another fluorinated substituent that could attract at least as
much interest among synthetic organic chemists in the future
is the pentafluorosulfanyl (SF5) group,1-3 which bears much
similarity to the trifluoromethyl group but is more electrone-
gative (σp ) +0.68 versus +0.54 for CF3)4 and more
sterically demanding. The SF5 substituent should emulate
the CF3 group in altering molecular properties such as
density, refractive index, dipole moment, lipophilicity, and
thermal and chemical stability, and it should have a similar
but intriguingly distinct impact on biological activity, as
foreshadowed by its demonstrated effect on insecticidal
properties.5,6
However, until now the methods required to put an SF5
substituent onto a benzene ring (elemental F2 or oxidative
fluorination by AgF2)7-10 or to incorporate an SF5 group into
aliphatic compounds (high-pressure autoclave or specialized
photochemical procedures)11-14 have not encouraged utility
by synthetic organic chemists.
SF5Cl is presently the only commercially available “re-
agent” that can be used to introduce the SF5 substituent into
aliphatic compounds. As a gaseous pseudo-halogen, this
reagent cannot be used as an electrophilic source of SF5,
but ever since Roberts’ pioneering work in 1961,11 it has
(5) Salmon, R. Preparation of N-(4-pentafluorosulfenylphenyl)-pyrazoles
as insecticides and acaricides. Patent WO 9306089, 1993.
(6) Howard, M. H., Jr.; Stevenson, T. M. Arthropodicidal pentafluo-
rothiosubstituted anilides. Patent WO 9516676, 1995.
(7) Sheppard, W. A. J. Am. Chem. Soc. 1962, 84, 3064-3072.
(8) Chambers, R. D.; Spink, R. C. H. Chem. Commun. 1999, 883-884.
(9) Bowden, R. D.; Comina, P. J.; Greenhall, M. P.; Kariuki, B. M.;
Loveday, A.; Philp, D. Tetrahedron 2000, 56, 3399-3408.
(10) Sipyagin, A. M.; Bateman, C. P.; Tan, Y.-T.; Thrasher, J. S. J.
Fluorine Chem. 2001, 112, 287-295.
(11) Case, J. R.; Ray, N. H.; Roberts, H. L. J. Chem. Soc. 1961, 2066-
2070.
(12) Wessel, J.; Kleemann, G.; Seppelt, K. Chem. Ber. 1983, 116, 2399-
2407.
(13) Winter, R.; Gard, G. L. J. Fluorine Chem. 1994, 66, 109-116.
(14) Fokin, A. V.; Studnev, Y. N.; Stolyarov, V. P.; Chilikin, V. G.;
Prigorelov, G. A. Russ. Chem. Bull. 1996, 45, 2804-2806.
(1) Winter, R.; Gard, G. L. In Inorganic Fluorine ChemistrysToward
the 21st Century; Thrasher, J. S., Strauss, S. H., Eds.; American Chemical
Society: Washington, DC, 1994; Vol. 555, pp 128-147.
(2) Lentz, D.; Seppelt, K. In Chemistry of HyperValent Compounds;
Akiba, K., Ed.; Wiley-VCH: New York, 1999; pp 295-326.
(3) Verma, R. D.; Kirchmeier, R. L.; Shreeve, J. M. In AdVances in
Inorganic Chemistry; Sykes, A. G., Ed.; Academic Press: San Diego, 1994;
Vol. 41, pp 125-169.
(4) Sheppard, W. A. J. Am. Chem. Soc. 1962, 84, 3072-3076.
10.1021/ol026483o CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/30/2002

been used in free radical chain alkene/alkyne addition
processes,15 generally done thermally, in an autoclave, with
or without an initiator, or using room-temperature gas-phase
or low-temperature solution-phase photochemical processes.
For example:11
Table 1. Yields for Addition of SF5Cl to Alkenesa
SF5Cl
90 °C, 10 h
autoclave 8
SF CH CHClCH
5
2
3
+
78%
CH2)CHCH3
R1
R2
R3
product, % yield
In order for SF5 derivatives to become incorporated into
the day-to-day strategic planning of working synthetic
organic chemists, a convenient, benchtop procedure needs
to be developed for introduction of SF5 substituents into
organic substrates. In this Letter, we provide such a method,
one that will allow convenient addition of SF5Cl to a large
variety of alkenes and alkynes in excellent yield. The method
is based upon our discovery that Et3B could readily initiate
the free radical chain addition of SF5Cl to unsaturated
compounds at the low temperatures required for convenient
use of SF5Cl in solution at atmospheric pressure. Triethyl-
borane has been recognized for more than a decade to be a
unique low-temperature initiator of free radical reactions.16
Although other potential initiators were examined, thus far
Et3B is the only one that has been found to successfully
initiate the SF5Cl addition reactions.
H
H
H
H
n-C6H13
n-C4H9
t-C4H9
C2H5
H
H
H
1, 95
2, 9819
3, 96
4, 89
C2H5
n-C3H7
n-C3H7
H
5, 95b
6, 98b,11
7, 79
(CH2)4
H
H
H
H
H
p-tolyl
OAc
8, 9820
a In hexane, at -30 °C, 0.1 equiv of Et3B, 30 min. b One major
diastereomer (>90% by NMR).
is obviously competing with the chain transfer step. Using a
larger excess of SF5Cl in the reaction can minimize this 2:1
product.
With a boiling point of -21 °C, SF5Cl is readily condensed
into hexane, which contains the alkene or alkyne substrate,
at -40 °C. When the Et3B initiator is added by syringe at
ca. -30 °C, an immediate reaction is evident, and for most
substrates, the reaction is effectively complete after 30 min.17
The reaction can be worked up by simple evaporation of
the hexane to give, in most cases, essentially pure product.
1
(No significant impurities are observed by H, 19F, or 13C
NMR, but passage through a short column is recommended
before further use, to eliminate possible traces of Et3B.) Table
1 gives the yields for addition of SF5Cl to a variety of
alkenes, whereas Table 2 gives the results for addition to
three typical alkynes.18
In the reaction with phenyl acetylene, a 2:1 adduct was
also obtained in 27% yield. In this case, addition of the
propagating radical intermediate to a second phenyl acetylene
The addition reactions are regiospecific and highly dia-
stereoselective, with essentially one product being formed
from the additions to cyclohexene, trans-4-octene, and the
alkynes. Although confirmation of the specific stereochem-
istries of products 5, 6, 9, 10, and 11 is not possible at this
time, one can be almost certain that the stereochemical
outcomes of these reactions are sterically controlled, that the
(15) Sidebottom, H. W.; Tedder, J. M.; Walton, J. C. Trans. Faraday
Soc. 1969, 65, 2103-2109.
(16) Takeyama, Y.; Ichinose, Y.; Oshima, K.; Utimoto, K. Tetrahedron
Lett. 1989, 30, 3159-3162.
Table 2. Addition of SF5Cl to Alkynesa
(17) Typical Procedure. Into a three-necked flask equipped with a dry
ice reflux condenser and a nitrogen inlet were added at -40 °C 15 mL of
anhydrous hexane, alkene (3-4 mmol), and SF5Cl (1.2 equiv). The solution
was stirred at this temperature for 5 min, and then Et3B (0.1 equiv, 1 M in
hexane) was added slowly using a syringe. The solution was vigorously
stirred for 1 h at -30 to -20 °C, and then the mixture was allowed to
warm to room temperature. The mixture was hydrolyzed with aqueous
NaHCO3 (10%), and the organic layer was dried over MgSO4. The solvent
was removed, and the crude product was passed through a short column of
silica gel, eluting with CH2Cl2. Removal of solvent in most cases provided
the products in essentially pure form without the need for additional
purification.
(18) Products containing the SF5 substituent are readily confirmed by
the presence of the characteristic AB4 pair of pentuplet and doublet signals
in their 19F NMR spectra, which along with their 1H and 13C spectra allowed
unambiguous characterization of all of the products (see Supporting
Information).
R1
R2
product,b % yield
n-C3H7
n-C3H7
n-C6H13
Ph
9, 93
10, 94
11, 94 + 12, 27
H
H
a In hexane, at -30 °C, 0.1 equiv of Et3B, 30 min. b Single diastereomer
in each case.
3014
Org. Lett., Vol. 4, No. 17, 2002

alkyne and cyclohexene products are E-isomers, and that the
product (5) from trans-4-octene is erythro. All of the alkyne
adducts are new, although the SF5Cl adduct of propyne has
been reported.11 Although many of the alkene adducts have
been reported previously,11,19 styrenes, 2,2-disubstituted
alkenes, and nonterminal alkenes had not previously proved
to be good substrates for SF5Cl addition. The mildness of
the Et3B-catalyzed reaction conditions obviously contributes
to the apparent broad applicability of this new method.
Regarding the scope of the present procedure, at least one
limitation has already been observed. Although additions to
enol ethers or enol esters should be fine, as exemplified by
the almost quantitative addition to vinyl acetate, attempted
additions to R,â-unsaturated carbonyl compounds, such as
ethyl acrylate or ethyl methacrylate, were not successful,
presumably because of a combination of reduced chain
transfer rate to the electrophilic propagating radical and the
problem of the ester tying up the Et3B catalyst,21 thus
inhibiting free radical initiation and allowing polymerizing
chain propagation to dominate the reaction.
We believe that the simplicity of our new method,
combined with the generally excellent yields that are
obtained, constitutes a breakthrough in SF5 synthetic meth-
odology that should open the door to the convenient,
benchtop preparation of a multitude of SF5-containing
aliphatics by synthetic organic chemists. Future work will
provide insight regarding the reaction’s tolerance of func-
tional groups, which appears to be good.
Acknowledgment. Support of this research in part by the
National Science Foundation is gratefully acknowledged.
Supporting Information Available: 1H, 19F, and 13C
NMR spectra for all products are provided. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL026483O
(20) E. I. duPont de Nemours & Co., U.S. Patent 3102903, 1961.
(21) Beraud, V.; Gnanou, Y.; Walton, J. C.; Maillard, B. Tetrahedron
Lett. 2000, 41, 1195-1198.
(19) Winter, R.; Nixon, P. G.; Gard, G. L.; Radford, D. H.; Holcomb,
N. R.; Grainger, D. W. J. Fluorine Chem. 2001, 107, 23-30.
Org. Lett., Vol. 4, No. 17, 2002
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