Fluorination of alkenylstannanes,16 -silanes,17 and -boronic
acid derivatives18 have been described in the literature. For
example, treatment of potassium alkenyltrifluoroborates with
F-TEDA-BF4 can afford alkenylfluorides, typically as 1:1
E/Z mixtures.18 The Ag-mediated fluorination presented
herein has been extended to alkenylboronic acids and
proceeds with complete control of stereochemistry, which
indicates a change in mechanism compared with fluorination
in the absence of transition metal due to the redox activity
of silver (eq 2). Control of stereochemistry is consistent with
stereospecific transmetalation from boron to silver, subse-
quent silver fluorination, and stereospecific reductive elimi-
nation to form the C-F bond.
elimination from high-valent Ag complexes is general beyond
C-F bond formation.
A variety of boronic acids is commercially available.
However, many C-B bond forming reactions that afford
more valuable, complex molecules afford boronic esters
instead of boronic acids.12 Boronic acids can typically be
prepared by hydrolysis of the corresponding esters;
however, hydrolysis is an additional synthetic step and
can be low yielding for hindered esters such as pinaco-
lates.12 Arylboronic esters such as neopentylglycolate 28b
and pinacolate 28c can participate in fluorination without
prior hydrolysis, albeit in lower yield than the boronic
acid 28a (eq 3). A single set of reaction conditions (1.2
equiv of NaOH, 3.0 equiv of AgOTf, 1.05 equiv of 3)
could be used for all three substrates 28a-c.
The transmetalation-fluorination procedure for both aryl-
boronic acids and alkenylboronic acids was executed in one
pot; methanol was evaporated after transmetalation, and
acetone was used for fluorination. Fluorination proceeded
best in acetone, which was not a suitable solvent for
transmetalation. Methanol was required for efficient trans-
metalation but cannot be used as solvent for fluorination due
to the formation of aryl methyl ethers instead of fluoroarenes.
Similarly, the presence of water resulted in phenol formation,
which could be suppressed to less than 2% by addition of 3
Å molecular sieves. The formation of the observed byprod-
ucts may be explained by ligand exchange of a fluoro ligand
of a postulated bimetallic Ag(II) complex11 with hydroxide
or methoxide and subsequent C-O reductive elimination.
Intriguingly, C-O bond formation suggests that reductive
Another advantage of the presented fluorination reaction
is its potential for combination with reported C-B bond
forming reactions. For example, Smith and Maleczka as well
as Ishiyama and Hartwig have developed Ir- and Rh-
catalyzed borylation reactions of unactivated aromatic C-H
bonds.19 Fluorination of boronic acids obtained by C-H
borylation can afford 3,5-disubstituted fluoroarenes (Scheme
2). The 1,3,5-substitution pattern in arenes is difficult to
Scheme 2. Applications of Boronic Acid and Ester Fluorination
(10) (a) Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2008, 130, 10060–
10061. For other electrophilic fluorination reactions from arylpalladium
complexes, see: (b) Kaspi, A. W.; Yahav-Levi, A.; Goldberg, I.; Vigalok,
A. Inorg. Chem. 2008, 47, 5–7. (c) Ball, N. D.; Sanford, M. S. J. Am. Chem.
Soc. 2009, 131, 3796–3797.
(11) Furuya, T.; Strom, A. E.; Ritter, T. J. Am. Chem. Soc. 2009, 131,
1662–1663.
(12) Hall, D. G. Boronic acids. Preparation and applications in organic
synthesis and medicine; Wiley-VCH: Weinheim, 2005.
(13) (a) For examples, see: Manickam, G.; Schlu¨ter, A. D. Eur. J. Org.
Chem. 2000, 3475–3481. (b) Yamamoto, Y.; Seko, T; Nemoto, H. J. Org.
Chem. 1989, 54, 4734–4736.
1
(14) (a) Silver complex 2 was characterized by H and 19F NMR, but
its instability and low solubility prevented further characterization. To
establish transmetalation and the purity of the resulting arylsilver complex,
we also prepared previously characterized 2,4,6-trimethylphenylsilver
tetramer, which participated in fluorination under the same reaction
conditions as 2 (see Supporting Information for details). For characterization
of 2,4,6-trimethylphenysilver tetramer, see: (b) Meyer, E. M.; Gambarotta,
S.; Floriani, C.; Chiesi-Villa, A.; Guastini, C. Organometallics 1989, 8,
1067–1079.
obtain,19b especially for arylfluorides such as previously
unknown 29. C-H borylation followed by fluorination gives
access to a C-H to C-F bond transformation without the
use of coordinating directing groups. The C-H to C-F bond
transformation shown in Scheme 2 cannot be readily ac-
complished by any other available reaction chemistry.
Fluorination could further be extended to a one-pot hydrof-
luorination of an alkyne, as shown in Scheme 2. Hydrobo-
ration of phenylacetylene (30) followed by fluorination of
the intermediate alkenylboronate ester 31 afforded ꢀ-fluo-
rostyrene (25) in 76% yield from 30.
(15) Byproducts resulting from C-H instead of C-F bond formation,
as found for the Ag-mediated fluorination of arylstannanes, were not
observed in the fluorination of boronic acids reported here. C-H bond
formation in the Ag-mediated fluorination of arylstannanes is not due to
the presence of water and cannot be suppressed by the addition of molecular
sieves. We have determined that Bu3SnOTf is involved in C-H bond
formation. Transmetalation from arylboronic acids to Ag in methanol
produces B(OMe)3, which does not provoke C-H bond formation.
(16) (a) Tius, M. A.; Kawakami, J. K. Synth. Commun. 1992, 22, 1461–
1471. (b) Tius, M. A.; Kawakami, J. K. Synlett. 1993, 207–208. (c) Tius,
M. A.; Kawakami, J. K. Tetrahedron 1995, 51, 3997–4010.
In conclusion, we report a regiospecific Ag-mediated
fluorination of aryl- and alkenylboronic acids and esters. The
fluorination reaction is practical because it uses commercially
(17) Greedy, B.; Gourverneur, V. Chem. Commun. 2001, 233–234.
(18) Petasis, N. A.; Yudin, A. K.; Zavialov, I. A.; Prakash, G. K. S.;
Olah, G. A. Synlett. 1997, 606–608.
2862
Org. Lett., Vol. 11, No. 13, 2009