Silver-catalyzed radical fluorination of alkylboronates in aqueous solution

Article abstract of DOI:10.1021/ja509548z

We report herein an efficient and general method for the deboronofluorination of alkylboronates. Thus, with the catalysis of AgNO₃, the reactions of various alkylboronic acids or their pinacol esters with Selectfluor reagent in acidic aqueous solution afforded the corresponding alkyl fluorides under mild conditions. A broad substrate scope and wide functional group compatibility were observed. A radical mechanism is proposed for this site-specific fluorination.

Full text of DOI:10.1021/ja509548z

Subscriber access provided by UNIVERSITY OF LEEDS
Article
Silver-Catalyzed Radical Fluorination of Alkylboronates in Aqueous Solution
Zhaodong Li, Zhentao Wang, Lin Zhu, Xinqiang Tan, and Chaozhong Li
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja509548z • Publication Date (Web): 28 Oct 2014
Downloaded from http://pubs.acs.org on November 2, 2014
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Silver-Catalyzed Radical Fluorination of Alkylboronates in
Aqueous Solution
Zhaodong Li, Zhentao Wang, Lin Zhu, Xinqiang Tan, and Chaozhong Li*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P.
R. China
Supporting Information Placeholder
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
RESULTS AND DISCUSSION
ABSTRACT: We report herein an efficient and general
method for the deboronofluorination of alkylboronates.
Thus with the catalysis of AgNO3, the reactions of various
alkylboronic acids or their pinacol esters with Selectfluor
reagent in acidic aqueous solution afforded the correꢀ
sponding alkyl fluorides under mild conditions. A broad
substrate scope and wide functional group compatibility
were observed. A radical mechanism is proposed for this
siteꢀspecific fluorination.
We recently reported the AgNO3ꢀcatalyzed decarboxyꢀ
lative fluorination of aliphatic carboxylic acids with Seꢀ
lectfluor.7a We wondered whether the fluorination of alꢀ
kylboronic acids could also be implemented with Agꢀ
NO3/Selectfluor.
Thus,
(5ꢀ(1,3ꢀdioxoisoindolinꢀ2ꢀ
yl)pentyl)boronic acid (A-1a) was used as the model subꢀ
strate. With AgNO3 (20 mol %) as the catalyst, the reacꢀ
tion of A-1a with Selectfluor (2 equiv) in CH2Cl2–H2O
(1:1, v:v) mixed solvent at reflux for 24 h led to the forꢀ
mation of the expected fluorination product 1a in 56%
yield. The addition of acetic acid (4 equiv)7c lowered the
product yield to 34%. However, switching the additive
from acetic acid to trifluoroacetic acid (TFA)6g or H3PO4
resulted in the increase of product yield (65% and 74%,
respectively). By further adjusting the ratio of CH2Cl2 to
H2O, we were delighted to find that, with four equivaꢀ
lents of H3PO4 as the additive and CH2Cl2–H2O (2:1, v:v)
as the solvent, the reaction proceeded smoothly at reflux
INTRODUCTION
The increasing importance of fluorine in agrochemiꢀ
cals and pharmaceuticals1 as well as the use of 18Fꢀlabeled
organic compounds as contrast agents for positron emisꢀ
sion tomography (PET)2 has spurred a vigorous research
for the development of new methods for C–F bond forꢀ
mations under mild conditions. As a consequence, signifꢀ
icant progresses have been achieved in this area.3 In parꢀ
ticular, radical fluorination is emerging as a versatile tool
in C(sp3)–F bond formations.4–7 For example, Sammis
and coworkers6a reported the alkyl fluorination of perestꢀ
ers with Nꢀfluorobis(benzenesulfonyl)imide (NFSI)8.
Groves et al.5a successfully developed the manganeseꢀ
catalyzed oxidative aliphatic C–H fluorination with fluoꢀ
ride ion. Boger and Barker6b nicely introduced the
Fe(III)/NaBH4ꢀmediated free radical hydrofluorination
of unactivated alkenes. Lectka and coworkers5b accomꢀ
plished the copperꢀcatalyzed aliphatic C–H fluorination
o
(~ 50 C), providing 1a in 90% yield. Control experiꢀ
ments indicated that no fluorination could be observed
without the catalysis of AgNO3. Under the optimized
conditions, the pinacol ester (B-1a) and trifluoroborate
of A-1a also underwent deboronofluorination, but in
lower yields (25% and 49%, respectively).
Scheme 1. Fluorination of Alkylboronic Acids
with
1ꢀchloromethylꢀ4ꢀ
fluorodiazoniabicyclo[2,2,2]octane bisꢀ(tetrafluoroborate)
(Selectfluor)9. Nevertheless, siteꢀspecific radical fluorinaꢀ
tion of complex molecules, especially in late stages, is
still challenging.
Organoborane compounds are among the most comꢀ
monly employed intermediates in organic synthesis.10
The deboronative fluorination of aryl or alkylboronates is
certainly an ideal method for siteꢀspecific C–F bond forꢀ
mation. As a consequence, the fluorination of arylꢀ
boronic acids and derivatives has been extensively studꢀ
ied.11 However to our surprise, the fluorination of alkylꢀ
boronates remains virtually unexplored.12 Herein we reꢀ
port an efficient and general method for siteꢀspecific
C(sp3)–F bond formation by radical deboronofluorinaꢀ
tion of alkylboronic acids or their pinacol esters.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 6
a
AgNO3 (cat)
SelectFluor, TFA
Conditions: A-1 (0.2 mmol), AgNO3 (0.04 mmol), Seꢀ
O
O
1
2
3
4
5
6
7
8
lectfluor (0.4 mmol), H3PO4 (0.8 mmol), CH2Cl2 (1 mL),
H2O (0.5 mL), 50 C, 8 h. Isolated yield based on A-1.
R
B
R
F
o
b
c
CH2Cl2/H2O, 50 oC, 8 h
2, yielda, b
H3PO4 (0.1 mL), CH2Cl2 (0.6 mL), H2O (0.9 mL) and TFA
(0.4 mL) were used.
B-2
O
F
F
O
F
A number of primary alkylboronic acids were then
subjected to the above optimized conditions and the corꢀ
responding alkyl fluorides 1b–1i were obtained in high
yields (Scheme 1). Functional groups such as nitrile, carꢀ
bonyl, ether and ester were well tolerated. In particular,
free alkyl carboxylic acid group in 1i remained intact raꢀ
ther than undergoing decarboxylation, indicating the
mildness of reaction conditions. The fluorination of a
secondary alkylboronic acid, cyclododecylboronic acid,
also proceeded nicely to give 1j in 82% yield under slightꢀ
ly altered conditions (vide infra). On the other hand, arꢀ
ylboronic acids such as 1k were inert under the above
conditions.
PhthN
2a, 93%
N
Ph
Ph
H
2c, 87%
F
2b, 60%
F
9
O
F
F
EtO2C
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
O
NC
Ph
O
Br
2f, 92%
2e, 88%
2d, 78%
F
O
F
F
N
Ph
CO2Et
Bz
Br
2i, 71%c
2h, 80%
2g, 88%
Our attempt to test more secondary or tertiary alkylꢀ
boronic acids, especially functionalized ones, was hamꢀ
pered by their difficult purification due to their instabilꢀ
ity.13 In view of the fact that alkylboronic acids are generꢀ
ally prepared from the hydrolysis of their esters and that
the corresponding pinacol esters are much more stable
and easier to purify, it should be of more synthetic value
to use directly pinacol esters for the fluorination. With
this idea in mind, we first tested secondary and tertiary
alkylboronic esters B-2. The pinacol ester of (5ꢀ(1,3ꢀ
dioxoisoindolinꢀ2ꢀyl)pentanꢀ2ꢀyl)boronic acid (B-2a)
was then chosen as the model substrate. The reaction of
B-2a under the above optimized conditions gave the exꢀ
pected alkyl fluoride 2a in only 30% yield while ~70% B-
2a was recovered. Switching the additive from H3PO4 to
TFA speeded up the reaction and 2a was obtained in 77%
yield within 24 h. Furthermore, increasing the amount of
Selectfluor to three equivalents resulted in the formation
of 2a in 86% yield within 12 h. Finally, by adjusting the
ratio of CH2Cl2/H2O to 1:1, a clean reaction was observed,
furnishing the product 2a in almost quantitative yield
(93% isolated yield). Control experiments indicated that
no reaction occurred without the presence of AgNO3.
Moreover, no reaction was observed between boronate
B-2a and AgNO3 in the above aqueous CH2Cl2 solution
(without the presence of Selectfluor), implying that the
deboronofluorination is unlikely to proceed via the
transmetallation from boron to silver(I) followed by the
oxidation of the organosilver(I) intermediate.
a
Conditions: B-2 (0.2 mmol), AgNO3 (0.04 mmol), Seꢀ
lectfluor (0.6 mmol), TFA (0.8 mmol), CH2Cl2 (1 mL), H2O
(1 mL), 50 oC, 12 h. Isolated yield based on B-2. See
b
c
Scheme 1.
We then moved on to test primary alkylboronic esters.
As mentioned above, the reaction of boronate B-1a gave
product 1a in 25% yield under the conditions for the
fluorination of boronic acids depicted in Scheme 1. When
B-1a was subjected to the conditions for the fluorination
of boronic esters shown in Scheme 2, the reaction proꢀ
ceeded sluggishly, producing 1a in ~20% yield after 24 h.
However, it accelerated when the amount of TFA was
increased. A brief screening on the solvent ratios reꢀ
vealed that, with CH2Cl2/TFA/H2O (6:4:9, v:v:v) as the
solvent system, 1a was obtained in 89% yield within 8 h.
Furthermore, with the combination of TFA and H3PO4 in
~4:1 (v:v) ratio, we were pleased to find that 1a was isoꢀ
lated in 95% yield. These conditions were applicable to
various primary alkylboronic esters (B-3) and the correꢀ
sponding primary alkyl fluorides 3a–3j were obtained in
satisfactory yields (Scheme 3). While the role of TFA as a
coꢀsolvent is unclear, it might help increasing the solubilꢀ
ity of substrate boronates in the aqueous phase. This was
evidenced by the synthesis of 1j and 2i from the correꢀ
sponding boronates of lower solubility in water.
Scheme 3. Fluorination of Primary Alkyl-
boronates
A number of secondary and tertiary alkylboronic esters
B-2 were then subjected to the above reꢀoptimized conꢀ
ditions to examine the scope of application of this deꢀ
boronofluorination. The results are summarized in
Scheme 2. The corresponding alkyl fluorides 2a–2i were
achieved in excellent yields. Again, a broad substrate
scope and wide functional group compatibility were obꢀ
served.
Scheme 2. Fluorination of Secondary and Ter-
tiary Alkylboronates
2
ACS Paragon Plus Environment

Page 3 of 6
Journal of the American Chemical Society
gemꢀdifluorides (such as 6 and 7) from the correspondꢀ
1
2
ing geminal bis(boronates) (Equations 3 and 4).
As an extension of the above deboronofluorination, the
antiꢀMarkovnikov hydrofluorination of unactivated alꢀ
kenes was then successfully implemented (Scheme 4).
Thus, the Rh(PPh3)3Clꢀcatalyzed hydroborylation14, 15 of
alkenes with pinacolborane (HBpin) followed by Agꢀ
catalyzed fluorination afforded the alkyl fluorides 9a–9d
in a twoꢀstage, oneꢀpot procedure. With the use of more
reactive cobalt pincer complex (iPrPNN)CoCl2 recently
developed by the Huang group15b as the catalyst for hyꢀ
droborylation, the hydrofluorination of 6ꢀchlorohexꢀ1ꢀ
ene furnished 9e in 75% yield. Note that the regioselecꢀ
tivity is opposite to that of literature methods, which gave
Markovnikov hydrofluorination products only.6b, 6e, 16 In
another case, the copperꢀcatalyzed15c hydroborylation of
activated alkene 10 followed by fluorination yielded the
fluoride 11 also in oneꢀpot procedure (Equation 5).
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
By taking advantage of the endꢀgroup C–H borylaton
developed by Hartwig and others,17, 18 a twoꢀstep terminal
C–H fluorination could be implemented, as shown in
Equation 6. Although a number of C(sp3)–H fluorination
methods5 have recently been developed, none deals with
terminal C–H bonds. Therefore, our example provides a
nice complement to the literature methods.
a
Conditions: B-3 (0.2 mmol), AgNO3 (0.04 mmol), Seꢀ
Scheme 4. Anti-Markovnikov Hydrofluorination
of Unactivated Alkenes
lectfluor (0.6 mmol), H3PO4 (0.1 mL), CH2Cl2 (0.6 mL), H2O
(0.9 mL), TFA (0.4 mL), 50 oC, 8 h. b Isolated yield based on
B-3.
1. catalyst, HBpin
F
R
R
The above results clearly demonstrated the generality
of deboronofluorination. Furthermore, the fluorination
could also be stereoselective, as exemplified by the synꢀ
thesis of 4 as a single stereoisomer (Equation 1). In the
meantime, the mild reaction conditions allowed the
fluorination of more complex molecules, as shown in the
synthesis of fluorinated steroid 5 (Equation 2). The reacꢀ
tion could be further extended to the synthesis of
2. AgNO3 (20 mol %)
Seletfluor, H3PO4
CH2Cl2/H2O/TFA
9
8
F
F
Ph
O
F
F
PhthN
NC
EtO2C CO2Et
9c, 62%a, b
O
9a, 67%a, b
9b, 56%a, b
O
F
Cl
9e, 75%c, d
9d, 53%a, b
O
a
b
c
catalyst: Rh(PPh3)3Cl (2 mol %). Isolated yield. cataꢀ
lyst: (iPrPNN)CoCl2 (0.05 mol %)/NaBHEt3 (0.1 mol %). d 19
NMR yield.
F
A radical fluorination mechanism can be inferred from
the above results. The oxidative generation of alkyl radiꢀ
cals from alkylboronates is also known.19, 20 To provide
direct evidence, cyclopropylmethylboronate 14 was deꢀ
signed as the radical probe. The reaction of 14 under the
optimized conditions afforded the ringꢀopening product
15 in 52% yield (Eq. 7). This clearly demonstrated that
alkyl radicals are generated from alkylboronates.
3
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 6
gent access of alkylboronates, the deboronofluorination
should find important application in organic synthesis.
1
2
3
4
EXPERIMENTAL SECTION
Typical Procedure for Silver-Catalyzed De-
boronative Fluorination of Alkylboronates. 2ꢀ(4ꢀ
(4,4,5,5ꢀTetramethylꢀ1,3,2ꢀdioxaborolanꢀ2ꢀyl)pentyl)ꢀ
isoindolineꢀ1,3ꢀdione (B-2a, 68.6 mg, 0.2 mmol), AgNO3
(6.8 mg, 0.04 mmol) and Selectfluor (212 mg, 0.6 mmol)
were placed in a Schlenk tube under nitrogen atmosꢀ
phere. Dichloromethane (1 mL), water (1 mL) and triꢀ
fluoroacetic acid (58 ꢁL, 0.8 mmol) were then added
successively at rt. The reaction mixture was stirred at
reflux for 24 h. The resulting mixture was cooled down to
rt and then extracted with CH2Cl2 (15 mL × 3). The comꢀ
bined organic phase was dried over anhydrous Na2SO4.
After removal of solvent under reduced pressure, the
crude product was purified by column chromatography
on silica gel with hexane/ethyl acetate (5:1, v:v) as the
eluent to give pure 2ꢀ(4ꢀfluoropentyl)isoindolineꢀ1,3ꢀ
dione (2a) as a yellow oil. Yield: 44 mg (93%).
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The deboronofluorination is no doubt triggered by the
interaction of Ag(I) with Selectfluor. This interaction was
evidenced by 19F NMR monitoring with the use of
equimolar amounts of Selectfluor and AgNO3 in water at
room temperature, which showed that the N–F signal at
+47.1 ppm decreased slowly and disappeared completely
after 10 h. However, no new signal could be observed.
Instead, a gray precipitate was formed at the bottom of
the NMR tube, which unfortunately exhibited no reactiviꢀ
ty towards boronic acids such as A-1a. The redox potenꢀ
tial of the Ag(I)/Ag(II) couple is +1.98 V vs SCE,21 while
the reported reduction potential of Selectfluor is ꢀ0.296
V vs AgRE.22 These data suggest that an outerꢀsphere
single electron transfer from Ag(I) to Selectfluor is unꢀ
likely.23 Based on the above results and our previous
findings,7 we propose the following mechanism depicted
in Figure 1. The interaction of Ag(I) with Selectfluor genꢀ
erates the Ag(III)–F intermediate presumably via oxidaꢀ
tive addition. The single electron oxidation of alkylꢀ
boronates by Ag(III)–F gives alkyl radicals and Ag(II)–F.
The subsequent fluorine atom transfer between alkyl
radicals and Ag(II)–F affords alkyl fluorides as the final
products and regenerates Ag(I) as the catalyst. Further
mechanistic investigations are certainly required to reꢀ
veal the nature of the above transformation.
ASSOCIATED CONTENT
Supporting Information
Full experimental details, characterizations of new comꢀ
1
pounds, copies of H, 13C, 11B and 19F NMR spectra (PDF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
clig@mail.sioc.ac.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Dedicated to Professor LiꢀXin Dai on the occasion of his 90th
birthday. This project was supported by the National Natuꢀ
ral Science Foundation of China (Grants 21228202,
21272259, 21290180, 21472220 and 21361140377) and by
the National Basic Research Program of China (973 Proꢀ
gram) (Grants 2015CB931900 and 2011CB710805). We
thank Prof. Zheng Huang of SIOC for his generous help in
providing the cobalt catalyst.
REFERENCES
(1) (a) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317,
1881–1886. (b) O’Hagan, D. Chem. Soc. Rev. 2008, 37,
308–319. (c) Purser, S.; Moore, P. R.; Swallow, S.; Gouꢀ
verneur, V. Chem. Soc. Rev. 2008, 37, 320–330. (d) Kirk,
K. L. Org. Process Res. Dev. 2008, 12, 305–321.
(2) (a) Miller, P. W.; Long, N. J.; Vilar, R.; Gee, A. D. Angew.
Chem., Int. Ed. 2008, 47, 8998–9033. (b) Ametamey, S.
M.; Horner, M.; Schubiger, P. A. Chem. Rev. 2008, 108,
1501–1516.
(3) For the latest selected reviews, see: (a) Grushin, V. V. Acc.
Chem. Res. 2010, 43, 160–171. (b) Furuya, T.; Klein, J. E.
M. N.; Ritter, T. Synthesis 2010, 42, 1804–1821. (c)
Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473,
470–477. (d) Liang, T.; Neumann, C. N.; Ritter, T. Angew.
Chem., Int. Ed. 2013, 52, 8214–8264.
Figure 1. Proposed mechanism for deboronofluorination.
CONCLUSION
In conclusion, we have successfully developed a cataꢀ
lytic, efficient and general method for the fluorination of
alkylboronates in acidic aqueous solution with wide funcꢀ
tional group compatibility. AntiꢀMarkovnikov hydroꢀ
fluorination of unactivated alkenes and terminal C–H
fluorination have also been realized based on the deꢀ
boronofluorination. In view of the convenient and diverꢀ
4
ACS Paragon Plus Environment

Page 5 of 6
Journal of the American Chemical Society
(4) For highlights, see: (a) Sibi, M. P.; Landais, Y. Angew.
135, 2552–2559. (e) Furuya, T.; Ritter, T. Org. Lett. 2009,
11, 2860–2863. (f) Furuya, T.; Ritter, T. J. Am. Chem. Soc.
2008, 130, 10060–10061. (g) Furuya, T.; Kaiser, H. M.;
Ritter, T. Angew. Chem., Int. Ed. 2008, 47, 5993–5996.
(h) Petasis, N. A.; Yudin, A. K.; Zavialov, I. A.; Prakash, G.
K. S.; Olah, G. A. Synlett 1997, 606–608.
Chem., Int. Ed. 2013, 52, 3570–3572. (b) Lin, A.; Huehls,
B.; Yang, J. Org. Chem. Front. 2014, 1, 434–438. (b) Ma,
J.ꢀA.; Li, S. Org. Chem. Front. 2014, 1, 712–715.
1
2
3
4
5
6
7
8
(5) (a) Liu, W.; Huang, X.; Cheng, M.ꢀJ.; Nielsen, R. J.; Godꢀ
dard, W. A., III; Groves, J. T. Science 2012, 337, 1322–
1325. (b) Bloom, S.; Pitts, C. R.; Miller, D. C.; Haselton, N.;
Holl, M. G.; Urheim, E.; Lectka, T. Angew. Chem., Int. Ed.
2012, 51, 10580–10583. (c) Bloom, S.; Pitts, C. R.; Wolꢀ
tornist, R.; Griswold, A.; Holl, M. G.; Lectka, T. Org. Lett.
2013, 15, 1722–1724. (d) Amaoka, Y.; Nagatomo, M.;
Inoue, M. Org. Lett. 2013, 15, 2160–2163. (e) Liu, W.;
Groves, J. T. Angew. Chem., Int. Ed. 2013, 52, 6024–6027.
(f) Xia, J.ꢀB.; Zhu, C.; Chen, C. J. Am. Chem. Soc. 2013,
135, 17494–17500. (g) Xia, J.ꢀB.; Ma, Y.; Chen, C. Org.
Chem. Front. 2014, 1, 468–472. (h) Bloom, S.; Knippel, J.
L.; Lectka, T. Chem. Sci. 2014, 5, 1175–1178. (i) Halperin,
S.; Fan, H.; Chang, S.; Martin, R. E.; Britton, R. Angew.
Chem., Int. Ed. 2014, 53, 4690–4693. (j) Huang, X.; Liu,
W.; Ren, H.; Neelamegam, R.; Hooker, J. M.; Groves, J. T.
J. Am. Chem. Soc. 2014, 136, 6842–6845. (k) Pitts, C. R.;
Bloom, S.; Woltornist, R.; Auvenshine, D. J.; Ryzhkov, L.
R.; Siegler, M. A.; Lectka, T. J. Am. Chem. Soc. 2014, 136,
9780–9791. (l) Xu, P.; Guo, S.; Wang, L.; Tang, P. Angew.
Chem., Int. Ed. 2014, 53, 5955–5958. (m) Kee, C. W.;
Chin, K. F.; Wong, M. W.; Tan, C.ꢀH. Chem. Commun.
2014, 50, 8211–8214.
(6) (a) RuedaꢀBecerril, M.; Sazepin, C. C.; Leung, J. C. T.; Okꢀ
binoglu, T.; Kennepohl, P.; Paquin, J.ꢀF.; Sammis, G. M. J.
Am. Chem. Soc. 2012, 134, 4026–4029. (b) Barker, T. J.;
Boger, D. L. J. Am. Chem. Soc. 2012, 134, 13588–13591. (c)
Leung, J. C. T.; ChatalovaꢀSazepin, C.; West, J. G.; Ruedaꢀ
Becerril, M.; Paquin, J.ꢀF.; Sammis, G. M. Angew. Chem.,
Int. Ed. 2012, 51, 10804–10807. (d) Mizuta, S.; Stenhagen,
I. S. R.; O’Duill, M.; Wolstenhulme, J.; Kirjavainen, A. K.;
Forsback, S. J.; Trewell, M.; Sanford, G.; Moore, P. R.;
Huiban, M.; Luthra, S. K.; Passchier, J.; Solin, O.; Gouverꢀ
neur, V. Org. Lett. 2013, 15, 2648–2651. (e) Shigehisa, H.;
Nishi, E.; Fujisawa, M.; Hiroya, K. Org. Lett. 2013, 15,
5158–5161. (f) RuedaꢀBecerril, M.; Mahe, O.; Drouin, M.;
Majewski, M. B.; West, J. G.; Wolf, M. O.; Sammis, G. M.;
Paquin, J.ꢀF. J. Am. Chem. Soc. 2014, 136, 2637–2641. (g)
Li, Z.; Zhang, C.; Zhu, L.; Liu, C.; Li, C. Org. Chem. Front.
2014, 1, 100–105. (h) Wang, H.; Guo, L.ꢀN.; Duan, X.ꢀH.
Chem. Commun. 2014, 50, 7382–7384.
(7) (a) Yin, F.; Wang, Z.; Li, Z.; Li, C. J. Am. Chem. Soc. 2012,
134, 10401–10404. (b) Li, Z.; Song, L.; Li, C. J. Am. Chem.
Soc. 2013, 135, 4640–4643. (c) Zhang, C.; Li, Z.; Zhu, L.;
Yu, L.; Wang, Z.; Li, C. J. Am. Chem. Soc. 2013, 135,
14082–14085.
(8) Differding, E.; Ofner, H. Synlett 1991, 187–189.
(9) (a) Banks, R. E.; MohialdinꢀKhaffaf, S. N.; Lal, G. S.; Shaꢀ
rif, I.; Syvret, R. G. J. Chem. Soc., Chem. Commun. 1992,
595–596. (b) Singh, R. P.; Shreeve, J. M. Acc. Chem. Res.
2004, 37, 31–44. (c) Nyffeler, P. T.; Durón, S. G.; Burkart,
M. D.; Vincent, S. P.; Wong, C.ꢀH. Angew. Chem., Int. Ed.
2005, 44, 192–212.
(10) (a) Hall, D. G. Boronic Acids: Preparation and Applica-
tions in Organic Synthesis, Medicine and Materials,
WileyꢀVCH: Weinheim, 2011. (b) Hall, D. G. Boronic Acids:
Preparation and Applications in Organic Synthesis and
Medicine, WileyꢀVCH: Weinheim, 2005. (c) Pelter, A.;
Smith, K.; Brown, H. C. Borane Reagents, Academic Press:
New York, 1988. (d) Brown, H. C. Organic Synthesis via
Boranes, Wiley: New York, 1975.
(12) Lemaire et al. reported the metalꢀfree electrophilic fluoriꢀ
nation of 1ꢀphenylethyltrifluoroborate with Selectfluor in
CH3CN at rt. See: Cazorla, C.; Metay, E.; Andrioletti, B.;
Lemaire, M. Tetrahedron Lett. 2009, 50, 3936–3938.
However, a low yield (15%) was observed and the method
was not applicable to ordinary alkyltrifluoroꢀborates.
Moreover, alkylboronic acids or pinacol esters were unreꢀ
active at all. See SI for details.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(13) Sun, J.; Perfetti, M. T.; Santos, W. L. J. Org. Chem. 2011,
76, 3571–3575.
(14) Burgess, K.; Ohlmeyer, M. Chem. Rev. 1991, 91, 1179–1191.
(15) (a) Pereira, S.; Srebnik, M. J. Am. Chem. Soc. 1996, 118,
909–910. (b) Zhang, L.; Zuo, Z.; Leng, X.; Huang, Z. An-
gew. Chem., Int. Ed. 2014, 53, 2696–2700. (c) Thorpe, S.
B.; Calderone, J. A.; Santos, W. L. Org. Lett. 2012, 14,
1918–1921.
(16) (a) Olah, G. A.; Nojima, M.; Kerekes, I. Synthesis 1973,
779–780.
(b) Thibaudeau, S.; MartinꢀMingot, A.;
Jouannetaud, M.ꢀP.; Karam, O.; Zunino, F. Chem. Com-
mun. 2007, 3198–3200. (c) Liu, F.; MartinꢀMingot, A.;
Jouannetaud, M.ꢀP.; Karam, O.; Thibaudeau, S. Org. Bio-
mol. Chem. 2009, 7, 4789–4797. (d) Emer, E.; Pfeifer, L.;
Brown, J. M.; Gouverneur, V. Angew. Chem., Int. Ed.
2014, 53, 4181–4185.
(17) (a) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy,
J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890–931. (b)
Hartwig, J. F. Acc. Chem. Res. 2012, 45, 864–873. (c)
Waltz, K. M.; Hartwig, J. F. Science 1997, 277, 211–213.
(18) For recent selected examples, see: (a) Li, Q.; Liskey, C. W.;
Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 8755. (b)
Zhang, L.ꢀS.; Chen, G.; Wang, X.; Guo, Q.ꢀY.; Zhang, X.ꢀS.;
Pan, F.; Chen, K.; Shi, Z.ꢀJ. Angew. Chem., Int. Ed. 2014,
53, 3899–3903. (c) Cho, S. H.; Hartwig, J. F. J. Am. Chem.
Soc. 2013, 135, 8157–8160. (d) Liskey, C. W.; Hartwig, J.
F. J. Am. Chem. Soc. 2013, 135, 3375–3378. (e)
Kawamorita, S.; Murakami, R.; Iwai, T.; Sawamura, M. J.
Am. Chem. Soc. 2013, 135, 2947–2950. (f) Ohmura, T.;
Torigoe, T.; Suginome, M. Organometallics 2013, 32,
6170–6173. (g) Ohmura, T.; Torigoe, T.; Suginome, M. J.
Am. Chem. Soc. 2012, 134, 17416–17419. (h) Liskey, C. W.;
Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 12422–12425.
(i) Wei, C. S.; JimenezꢀHoyos, C. A.; Videa, M. F.; Hartwig,
J. F.; Hall, M. B. J. Am. Chem. Soc. 2010, 132, 3078–3091.
(19) Ollivier, C.; Renaud, P. Chem. Rev. 2001, 101, 3415–3434.
(20) For recent selected examples, see: (a) Sorin, G.;
Mallorquin, R. M.; Contie, Y.; Baralle, A.; Malacria, M.;
Goddard, J.ꢀP.; Fensterbank, L. Angew. Chem., Int. Ed.
2010, 49, 8721–8723. (b) Kapat, A.; König, A.;
Montermini, F.; Renaud, P. J. Am. Chem. Soc. 2011, 133,
13890–13893. (c) Villa, G.; Povie, G.; Renaud, P. J. Am.
Chem. Soc. 2011, 133, 5913–5920. (d) Tobisu, M.; Koh, K.;
Furukawa, T.; Chatani, N. Angew. Chem., Int. Ed. 2012,
51, 11363–11366. (e) Huang, H.; Zhang, G.; Gong, L.;
Zhang, S.; Chen, Y. J. Am. Chem. Soc. 2014, 136, 2280–
2283. (f) Hu, F.; Shao, X.; Zhu, D.; Lu, L.; Shen, Q. Angew.
Chem., Int. Ed. 2014, 53, 6105–6109.
(21) Po, H. N. Coord. Chem. Rev. 1976, 20, 171–195.
(22) Oliver, E. W.; Evans, D. H. J. Electroanal. Chem. 1999,
474, 1–8.
(11) (a) Ye, Y.; Schimler, S. D.; Hanley, P. S.; Sanford, M. S. J.
Am. Chem. Soc. 2013, 135, 16292–16295. (b) Mazzotti, A.
R.; Campbell, M. G.; Tang, P.; Murphy, J. M.; Ritter, T. J.
Am. Chem. Soc. 2013, 135, 14012–14015. (c) Ye, Y.; Sanꢀ
ford, M. S. J. Am. Chem. Soc. 2013, 135, 4648–4651. (d)
Fier, P. S.; Luo, J.; Hartwig, J. F. J. Am. Chem. Soc. 2013,
(23) For a similar discussion, see ref. 5k.
5
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 6
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6
ACS Paragon Plus Environment