A facile one-pot preparation of organoselanyltrifluoroborates from dihalobenzenes and their cross-coupling reaction

Article abstract of DOI:10.1021/ol8025999

(Chemical Equation Presented) Potassium organoselanyltrifluoroborates have been prepared from the corresponding dihalobenzene compounds in 56-92% yields through a facile one-pot, multicomponent reaction. The microwave-promoted Suzuki-Miyaura cross-couplin

Full text of DOI:10.1021/ol8025999

ORGANIC
LETTERS
2009
Vol. 11, No. 2
361-364
A Facile One-Pot Preparation of
Organoselanyltrifluoroborates from
Dihalobenzenes and Their
Cross-Coupling Reaction
Hong Ryul Ahn,† Young Ae Cho,†,‡ Dong-Su Kim,†,‡ Jungwook Chin,§
Young-Soo Gyoung,‡ Seokjoon Lee, Heonjoong Kang,*,§ and Jungyeob Ham*,†
Korea Institute of Science and Technology, 290 Daejeon-dong, Gangneung 210-340,
Korea, Center for Marine Natural Products and Drug DiscoVery, School of Earth and
EnVironmental Sciences, Seoul National UniVersity, NS-80, Seoul 151-747, Korea,
Department of Chemistry, Kangnung National UniVersity, Gangneung 210-702, Korea, and
Department of Basic Science, Kwandong UniVersity College of Medicine,
Gangneung 210-701, Korea
ham0606@kist.re.kr; hjkang@snu.ac.kr
Received November 11, 2008
ABSTRACT
Potassium organoselanyltrifluoroborates have been prepared from the corresponding dihalobenzene compounds in 56-92% yields through
a facile one-pot, multicomponent reaction. The microwave-promoted Suzuki-Miyaura cross-coupling reaction of these substrates with various
aryl and alkenyl bromides in the presence of 3.0 mol % of Pd(PPh3)4 and 3.0 equiv of K2CO3 in aqueous 1,4-dioxane at 130 °C provided the
desired compounds in 54-91% yields.
Organoselenium compounds have attracted considerable
attention owing to their utility as synthetic intermediates1
and their potential biological activities, serving as antioxi-
dants, antimicrobials, antitumor, antiviral, and antihyperten-
sive agents.2 Generally, most organoselenium compounds
have been prepared from the condensation of activated
electrophiles with alkali metal selenolates as synthetic
intermediates, which are generated from the corresponding
organoselenol and diorganoyl diselenide compounds in the
presence of strong base.1 Alternatively, the metal selenolates
may be prepared from aryl halides and BuLi in the presence
of selenium. However, these synthetic methods have been
limited by lengthy synthetic sequences and harsh reaction
conditions. Thus, a facile and efficient protocol for the
preparation of highly functionalized organoselenium com-
pounds remains a high priority in various fields of chemistry.
† Korea Institute of Science and Technology (Gangneung Institute).
‡ Kangnung National University.
§ Seoul National University.
Kwandong University.
(2) (a) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem. ReV. 2001, 101,
2125. (b) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. ReV. 2004,
104, 6255. (c) Grange, R. L.; Ziogas, J.; Angus, J. A.; Schiesser, C. H.
Tetrahedron Lett. 2007, 48, 6301. (d) Garud, D. R.; Koketsu, M. Org. Lett.
2008, 10, 3319. (e) Okoronkwo, A. E.; Rosa´rio, A. R.; Alves, D.; Savegnago,
L.; Nogueira, C. W.; Zeni, G. Tetrahedron Lett. 2008, 49, 3252. (f) Sharma,
A.; Schwab, R. S.; Braga, A.; Barcellos, T.; Paixa˜o, M. W. Tetrahedron
Lett. 2008, 49, 5172.
(1) (a) Patai, S.; Rappoport, Z. In The Chemistry of Organic Selenium
and Tellurium Compounds; Wiley & Sons: New York, 1986 and 1987;
Vols. 1 and 2. (b) Liotta, D.; Monahan, R., III Science 1986, 231, 356. (c)
Krief, A.; Hevesi, L. In Organoselenium Chemistry; Springer-Verlag: Berlin,
1988; Vol. 1. (d) Back, T. G. In Organoselenium Chemistry: A Practical
Approach; Oxford University Press: New York, 1999. (e) Wirth, T. Angew.
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10.1021/ol8025999 CCC: $40.75
Published on Web 12/12/2008
2009 American Chemical Society

Organotrifluoroborates3 are becoming very useful reagents
in the Suzuki-Miyaura cross-coupling reaction, which is
among the most powerful yet mild protocols currently
available for the formation of carbon-carbon bonds. The
organotrifluoroborates provide numerous advantages over the
corresponding boronic acids and boronate esters. For ex-
ample, they are easily prepared by the addition of inexpensive
KHF2 to commercially available organoboron compounds
and can be stored indefinitely without special precaution as
a result of the air- and moisture-stable nature of the
crystalline solids. Moreover, the organotrifluoroborates are
inert to many nucleophilic reagents such as cyanide, azide,
amines, enolates, alkoxides, and organometallic reagents
because the boron atom in organotrifluoroborates does not
have an empty p-orbital to interact with the incoming
nucleophile. Therefore, direct functionalization of potassium
organotrifluoroborates is successfully performed without loss
of the valuable trifluoroborate group.
Scheme 1. One-Pot Syntheses of Potassium
Organoselanyltrifluoroborate
During the course of our synthetic studies on the develop-
ment of potassium organotrifluoroborates as new coupling
partners in the Suzuki-Miyaura cross-coupling reaction, we
discovered a facile one-pot synthesis for the preparation of
various potassium organoselanyltrifluoroborates from the
corresponding dihalobenzenes. Although a selenium-contain-
ing organoboron compound, methylselenyl phenylboronic
acid, was first reported in 1996 by Jones et al.,4 its detailed
method of preparation was not mentioned in this paper.
nated with side products such as BuSeSeBu or BuSeCH2R.
The results are summarized in Table 1.
In a test of reactivity between o-, m-, and p-dihalobenzenes
(Table 1, entries 1 and 2), when using dibromobenzene as a
starting material, similar yields of organoselanyltrifluorobo-
rates were obtained. However, when using diiodobenzene,
higher yields were achieved for the para isomers. 1,3-
Disubstituted trifluoroborates could not be isolated from the
corresponding o-dihalobenzenes (data not shown).
Herein we report initial results toward developing a
convenient preparation of potassium organoselanyltrifluo-
roborates in good yields via a simple one-pot, multicompo-
nent reaction involving dihalobenzenes, electrophiles, and
selenium powder. Suzuki-Miyaura cross-coupling of the
organotrifluoroborates thus obtained with various aryl and
alkenyl bromides under microwave irradiation is also de-
scribed.
A wide range of functional groups could be tolerated, and
the presence of an electron-donating or -withdrawing group
on the benzyl bromide electrophiles did not affect the yields
of products (Table 1, entries 3-8).
When 4-cyano- and 4-nitrobenzyl bromides were used
(Table 1, entries 7 and 8), the corresponding organotrifluo-
roborates were not obtained by way of our one-pot, muti-
component procedure because the sensitive -CN and -NO2
groups interfered in the reaction. Therefore, these substrates
were utilized in the sequential one-pot method to obtain the
desired products in 56% and 77% yields, respectively. By
contrast, saturated alkyl halides gave good yields (Table 1,
entries 11-15).
In our initial studies, we attempted the one-pot, sequential
preparation of organoselanyltrifluoroborates from the cor-
responding dihalobenzenes (I f II f III f IV in Scheme
1), in which the electrophile was added to a solution of
intermediate III at the end of the reaction. The resulting
organoboron intermediate was treated with 1 N KHF2.
Although the desired organoselanyltrifluoroborates were
obtained in good yields, reaction times were too long and
the products were contaminated with potassium tert-butyl-
trifluoroborate as a side product during large-scale prepara-
tion. Thus, we developed a simple method for the preparation
of organoselanyltrifluoroborates through a one-pot, multi-
component process (I f V f VI f IV in Scheme 1). In
this reaction, intermediate V was generated in situ by addition
of n-BuLi to a solution of equimolar amounts of dihaloben-
zene, selenium, and electrophile at -78 °C. After the reaction
mixture became homogeneous, B(-OiPr)3 and n-BuLi were
continuously added at -78 °C. Without isolation of the
generated intermediate VI, the reaction mixture was quenched
with 1 N KHF2 and then purified according to the previous
literature procedure.3 These one-pot, multicomponent reac-
tions proceeded readily to give the desired organoselanyl-
trifluoroborates in satisfactory yields without being contami-
Next, we turned our attention to the Suzuki-Miyaura
cross-coupling reaction of the organoselanyltrifluoroborates
with aryl or alkenyl bromides using microwave irradiation
(Table 2).
(3) (a) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005, 38, 49.
(b) Stefani, H. A.; Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623. (c)
Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275. (d) Darses, S.;
Genet, J.-P. Chem. ReV. 2008, 108, 288. (e) Doucet, H. Eur. J. Org. Chem.
2008, 2013. (f) Park, Y. H.; Ahn, H. R.; Canturk, B.; Jeon, S. I.; Lee, S.;
Kang, H.; Molander, G. A.; Ham, J. Org. Lett. 2008, 10, 1215. (g) Molander,
G. A.; Febo-Ayala, W.; Ortega-Guerra, M. J. Org. Chem. 2008, 73, 6000.
(h) Molander, G. A.; Ellis, N. M. J. Org. Chem. 2008, 73, 6841. (i) Ge, H.;
Niphakis, M. J.; Georg, G. I. J. Am. Chem. Soc. 2008, 130, 3708. (j) Dreher,
S. D.; Dormer, P. G.; Sandrock, D. L.; Molander, G. A. J. Am. Chem. Soc.
2008, 130, 9257. (k) Molander, G. A.; Canturk, B. Org. Lett. 2008, 10,
2135.
(4) Bahl, A.; Grahn, W.; Jones, P. G. Acta Crystallogr., Sect. C: Cryst.
Struct. Commun. 1996, 2017.
362
Org. Lett., Vol. 11, No. 2, 2009

Table 1. One-Pot Preparation of Potassium
Table 2. Optimization of Cross-Coupling Reaction Conditions
Organoselanyltrifluoroborates from Dibromobenzenea
by Microwave Irradiationa
Pd catalyst
(3 mol %)
base
(3 equiv)
MW
(°C)b
reaction
time
yield
(%)c
entry
1d
2
Pd(OAc)2
Pd(PPh3)4
Pd(PPh3)4
Pd(OAc)2
Pd(PPh3)4
Pd(OAc)2
PdCl2(dppf)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
80e
12 h
21
47
42
45
87
76
81
80e
12 h
3
100
130
130
130
130
1 h
4
20 min
20 min
30 min
30 min
5
6f
7g
a All reactions were performed on a 0.05 mmol scale. b Initial microwave
irradiation of 80 W was used. c Yields are given for isolated products.
d Reaction solvent was MeOH. e Reactions were performed in an oil bath.
f 6 mol
%
of RuPhos was used as
a % of
ligand. g 10 mol
PdCl2(dppf)·CH2Cl2 was used.
decrease from 12 h to 20 min, but the yield of 16 also
increased from 47% to 87% with use of Pd(PPh3)4 (Table 2,
Table 3. Cross-Coupling Reaction of Various Potassium
Organoselanyltrifluoroborates with 4-Bromobenzonitrilea
a All reactions were performed on a 1.0 mmol scale. b Yields are given
for isolated products. c Reactions were carried out with diiodobenzene (1.0
mmol). d Reaction was performed on a 3.5 mmol scale. e Reactions were
carried out according to a sequential one-pot method. f 1-Bromobutane is
produced as a byproduct of the halogen-lithium exchange step.
Optimization studies were carried out to access 16, which
was formed in yields of 21% and 47% when reactions were
performed at 80 °C in an oil bath for 12 h with the use of
Pd(OAc)2 and Pd(PPh3)4, respectively (Table 2, entries 1 and
2). Changes in reaction temperature with microwave-heating
conditions had a much greater impact on reaction rates and
product yields. When the reaction temperature was increased
from 80 to 130 °C, not only did the reaction time dramatically
a All reactions were carried out on 0.1 mmol scale using the optimized
conditions of 16 for 20 min and an initial microwave irradiation of 80 W.
b Yields are given for isolated products.
Org. Lett., Vol. 11, No. 2, 2009
363

and 3.0 equiv of K2CO3 in aqueous 1,4-dioxane at 130 °C
with microwave heating (Table 3).
Table 4. Cross-Coupling Reaction of Potassium
4-(4-Methylbenzylselanyl)phenyltrifluoroborate (3) with Various
Aryl and Alkenyl Bromidesa
As shown in Table 3, all organoselanyltrifluoroborates
gave rise to the corresponding products in satisfactory yields
within a short reaction time. The coupling reaction of
potassium 4- and 3-(benzylselany)phenyltrifluoroborates led
to the corresponding compounds in 87% and 84% yields,
respectively (Table 3, entries 1 and 2). Interestingly, the
cross-coupling yields of alkylselanylphenyltrifluoroborates
(Table 3, entries 4 and 6) were slightly lower than those of
benzylselanylphenyltrifluoroborates.
Finally, we examined the Suzuki-Miyaura cross-coupling
reaction of various aryl and alkenyl bromides with potassium
4-(4-methylbenzylselanyl)phenyltrifluoroborate (3) under the
same conditions, the results of which are summarized in
Table 4. The coupling reaction with aryl and alkenyl
bromides containing an aldehyde functional group gave the
desired products in 80% and 74% yields, respectively (Table
4, entries 1 and 4). Also, a high yield (91%) was obtained
for the coupling reaction with 2-bromopyridine (Table 4,
entry 3). However, when 4-trifluoromethylphenyl bromide
was used, product 22 was obtained in only 54% yield even
in the presence of 6 mol % of catalyst (Table 4, entry 2).
In summary, we have successfully prepared potassium
organoselanyltrifluoroborates from dihalobenzenes through
a one-pot, multicomponent reaction and performed the cross-
coupling reaction with various aryl and alkenyl bromides
with microwave irradiation. The potassium organoselanyl-
trifluoroborates should prove useful for the preparation of a
variety of organoselenium compounds.
a All reactions were carried out on 0.1 mmol scale using the optimized
conditions of 16 for 20 min and an initial microwave irradiation of 80 W.
b Yields are given for isolated products. c Reaction was performed with 6
mol % of Pd(PPh3)4.
Acknowledgment. This research was supported by KIST
Institutional Program (2Z03100) and a grant from Marine
Biotechnology Program funded by Ministry of Land, Trans-
port and Maritime Affairs, Republic of Korea. We are
grateful to Ji Hoon Choi and Professor In Howa Jeong at
Yonsei University for copies of 19F NMR spectra and to
Professor Gary A. Molander and Belgin Canturk (University
of Pennsylvania) for obtaining high resolution mass spectra
and 11B NMR spectra of products reported herein.
entries 2, 3, and 5). In the study of different palladium
catalysts (Table 2, entries 5-7), although the desired
compound 16 was obtained in good yields, Pd(OAc)2
required 6 mol % of RuPhos as a ligand, and PdCl2-
(dppf)·CH2Cl2 required at least 10 mol % of the catalyst to
achieve consistent results.
Using the optimized conditions, the cross-coupling reaction
of various organoselanyltrifluoroborates was performed with
4-bromobenzonitrile in the presence of 3 mol % of Pd(PPh3)4
Supporting Information Available: Experimental pro-
cedures and spectroscopic characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL8025999
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Org. Lett., Vol. 11, No. 2, 2009