Efficient synthesis of substituted selenophenes based on the first palladium(0)-catalyzed cross-coupling reactions of tetrabromoselenophene

Article abstract of DOI:10.1002/adsc.200800316

Regioselective Suzuki cross-coupling reactions of tetrabromoselenophene allow a convenient synthesis of aryl-substituted selenophenes. High yields were obtained using a novel biarylmonophosphine ligand. The first tetra(1-alkynyl)selenophene was prepared in one step by a Sonogashira reaction of tetrabromoselenophene.

Full text of DOI:10.1002/adsc.200800316

UPDATES
DOI: 10.1002/adsc.200800316
Efficient Synthesis of Substituted Selenophenes Based on the
First Palladium(0)-Catalyzed Cross-Coupling Reactions of
Tetrabromoselenophene
a
a
a,b,
ˇ
Dang Thanh Tœng, Alexander Villinger, and Peter Langer *
¯
.
a
Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax : (+49)-381-498-6412; e-mail: peter.langer@uni-rostock.de
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
b
Received: May 21, 2008; Published online: August 25, 2008
Abstract: Regioselective Suzuki cross-coupling re-
actions of tetrabromoselenophene allow a conven-
ient synthesis of aryl-substituted selenophenes.
High yields were obtained using a novel biaryl-
monophosphine ligand. The first tetra(1-alkynyl)se-
lenophene was prepared in one step by a Sonoga-
shira reaction of tetrabromoselenophene.
able for the synthesis of organosulfur compounds can
often not be applied to selenium. Therefore, the de-
velopment of new methods for the synthesis of orga-
noselenium compounds is of considerable current in-
terest. Substituted selenophenes[14] have been mostly
prepared so far based on cyclocondensation reactions.
For example, 2,5-diarylselenophenes and tetraarylse-
lenophenes are available by cyclocondensation of al-
kynes (2 equiv.) with selenium in the presence of lithi-
um metal.[15] However, these reactions often suffer
from the harsh reaction conditions. Kirsch and co-
workers reported[16] the synthesis of 2,5-diarylseleno-
phenes in which b-aryl-b-chloro acroleins, easily pre-
pared from substituted acetophenones and Vilsmaier-
Keywords: cross-coupling; heterocycles; P ligands;
palladium; selenium
Selenium represents an essential element for higher Haack reagent, are condensed with appropriate
organisms.[1] In this context, the selenium-containing benzyl bromide derivatives to give the title com-
enzymes glutathione peroxidase and 5’-deiodase type pounds. Heterocycles have been widely functionalized
1 play an important role. In fact, a number of diseases by palladium(0)-catalyzed cross-coupling reactions.[17]
can result from selenium deficiency.[2,3] In addition, se- However, syntheses of functionalized selenophenes by
lenium-containing molecules are of considerable phar- such reactions are relatively rare. 2,5-Diarylseleno-
macological relevance.[4] A prominent example is the phenes were prepared by Suzuki reactions of 2,5-diha-
antitumor and antiviral active C-glycosylselenazole loselenophenes.[18] The Sonogashira reaction of 2-
selenazofurin.[5] Selenophenes have also been report- bromo- and 2-iodoselenophene with alkynes has been
ed to be of considerable pharmacological relevance. reported to give (1-alynyl)selenophenes.[19] The reac-
For example, they act as muscarinic antagonists,[6] tion of 2,5-diiodoselenophene with two equivalents of
show antiviral activity,[7] exert inhibitory activity an alkyne has been reported to give 2,5-bis(1-alkyn-
against human myelogenous leukemia K562 cells, cy-
A
totoxicity against HT-29, HeLa, ACHN and 5637 alkynyl)selenophenes has, to the best of our knowl-
cells,[8] and in vitro antiproliferative activity against edge, not been reported to date.
human acute B-lymphoblastic leukemia and human
In recent years, it has been shown that polyhalo-
acute T-lymphoblastic leukemia.[9] In addition, seleno- genated heterocycles can be regioselectively function-
phenes promote the polymerization of tubulin and alized in palladium(0)-catalyzed cross-coupling reac-
stabilize microtubules.[10] Selenophene-containing por- tions by selective activation of a single halogen atom.
phyrins have been shown to possess activity against The regioselectivity is controlled by electronic and
murine colon carcinoma Colo-26 cells.[11] Seleno- steric parameters.[20] Recently, we reported the syn-
phenes also exhibit antifungal activity[12] and are cyto- thesis of tetraarylthiophenes[21] and -pyrroles[22] based
toxic against human cervical cancer KB cells and on regioselective Suzuki reactions of tetrabromothio-
human hepatocellular carcinoma HepG2 cells.[13]
phene and tetrabromo-N-methylpyrrole, respectively.
Unfortunately, selenium compounds are in most Herein, we disclose our preliminary results related to
cases less stable than their corresponding sulfur ana- Suzuki reactions of tetrabromoselenophene. These re-
logues. In addition, the methods and conditions avail- actions allow a convenient and regioselective ap-
Adv. Synth. Catal. 2008, 350, 2109 – 2117
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2109

ˇ
Dang Thanh Tœng et al.
¯
UPDATES
.
Scheme 1. Synthesis of tetrabromoselenophene (1); condi-
tions: i, 1) Br2 (7.0 equiv.), 08C, CH2Cl2; 2) reflux, 3 d; 3)
NaOH, H2O (2M), reflux, 6 h.
proach to aryl-substituted selenophenes which are not
readily available by other methods. In addition, we
report the synthesis of what is, to the best of our
knowledge, the first tetrakis(1-alkynyl)selenophene
Scheme 2. Synthesis of 5-aryl-2,3,4-tribromoselenophenes
by a Sonogashira reaction of tetrabromoselenophene. 2a–d and of 2,5-diaryl-3,4-dibromoselenophenes 3a, b; con-
ditions: i, procedure A:
(1.3 equiv.), Pd(PPh3)4 (5 mol%), K3PO4 (4.0 equiv.), diox-
ane/toluene/H2O (2:2:1), reflux, 8 h; procedure B:
(1.0 equiv.), Ar1B(OH)2 (1.1 equiv.), Pd
(OAc)2 (5 mol%), L
(see Figure 1, 10 mol%), K3PO4 (4.0 equiv.), dioxane/toluene
(1:1), reflux, 8 h; ii, 2a, b (1.0 equiv.), (4-MeC6H4)B(OH)2
1
(1.0 equiv.), Ar1B(OH)2
Helmholdt and co-workers have recently reported
the synthesis of tetrabromoselenophene (1) in 39%
yield by reflux of a CHCl3 solution of selenophene
with an excess of bromine.[23] We have been able to
improve the yield to 84% by some modifications
(Scheme 1). The solvent CHCl3 was replaced by
CH2Cl2. Due to the lower boiling point of CH2Cl2, the
amount of bromine present in solution (and not in the
gas phase) could be increased. The reaction time had
to be extended from 12 to 72 h in order to make sure
that the bromination is complete. Considerable
amounts of di- and tribrominated selenophenes were
formed when the reaction time was too short. Tetra-
bromoselenophene was isolated as a crystalline solid
which can be stored under argon at À188C for several
weeks.
AHCTREUNG
1
AHCTREUNG
(1.1 equiv.), Pd(OAc)2 (5 mol%), L (see Figure 1, 10 mol%),
G
K3PO4 (4.0 equiv.), dioxane/toluene (1:1), reflux, 8 h.
Table 1. Products and yields.
2
Ar1
Yield [%] of 2[a]
a
b
c
4-EtC6H4
50 (A)
85 (B)
68 (A)
47 (A)
3,5-Me2C6H3
4-(MeO)C6H4
3-PhC6H4
d
[a]
The Suzuki reaction of 1 with various boronic acids
(1.1 equiv.) afforded the 5-aryl-2,3,4-tribromoseleno-
phenes 2a–d in good yields and with very good regio-
selectivity (Scheme 2, Table 1). During the optimiza-
tion, it was important to suppress the formation of
Isolated yields; in brackets: procedure (see legend of
Scheme 1).
The Suzuki reaction of 1 with 2.5 equiv. of various
2,5-diaryl-3,4-dibromoselenophenes, as their separa- arylboronic acids afforded the symmetrical 2,5-diaryl-
tion from the desired products proved to be difficult. 3,4-dibromoselenophenes 4a–h in good yields and
Therefore, the stoichiometry was an important para- with very good regioselectivity (Scheme 3, Table 2).
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
(2:2:1) (procedure A). For the reaction of 1 with ster- yields for halogenated arylboronic acids (products 4f,
ically encumbered 3,5-dimethylphenylboronic acid (to g). This can be explained by the assumption that
give product 2b) the application of procedure A gave
N
N
unsatisfactory results (formation of a complex mix- genated arylboronic acid which competes with the de-
ture). The problem was solved by employment of the sired cross-coupling reaction.
new ligand L (Figure 1) which has been recently in-
The reaction of 4b with (4-methoxyphenyl)boronic
troduced by Buchwald and co-workers.[24] The reac- acid (3.0 equiv.) gave tetraarylselenophene 6 contain-
tion of a dioxane/toluene solution (1:1) of 1 with 3,5-
dimethylphenylboronic acid, in the presence of
A
N
85% yield (procedure B). The reaction of 2a, b with
1.2 equiv. of (4-tolyl)boronic acid, following proce-
dure B, resulted in the regioselective formation of the
unsymmetrical
2,5-diaryl-3,4-dibromoselenophenes
3a, b (Scheme 2).
Figure 1. Biaryl-monophosphine ligand developed by Buch-
wald and co-workers (ref.[24]).
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Efficient Synthesis of Substituted Selenophenes
UPDATES
Table 3. Synthesis of 5a–e.
5
Ar1
Yield [%] of 5[a]
a
b
c
d
e
Ph
55 (A), 79 (B)
89 (B)
98 (B)
74 (A)
89 (B)
4-MeC6H4
4-EtC6H4
3,5-Me2C6H3
4-(MeO)C6H4
[a]
Isolated yields; in brackets: procedure (see legend of
Scheme 2).
formed when the amounts of boronic acid and cata-
lyst were too low.
All products were characterized by spectroscopic
methods. The structures of 4d and 5d were independ-
ently confirmed by X-ray crystal structure analyses
(Figure 2 and Figure 3).[25]
Scheme 3. Synthesis of 2,5-diaryl-3,4-dibromoselenophenes
4a–h and tetraarylselenophenes 5a–e and 6; conditions: i,
procedure A: 1 (1.0 equiv.), Ar1B(OH)2 (2.5 equiv.), Pd-
ACHTREUNG
ACHTREUNG
AHCTREUNG
mol%), L (see Figure 1, 10 mol%), K3PO4 (4.0 equiv.), diox-
ane/toluene (1:1), reflux, 8 h; iii, procedure A: 1 (1.0 equiv.),
Ar1B(OH)2 (5.0 equiv.), Pd
ACHTREUNG
AHCTREUNG
Figure 2. ORTEP plot of 4d (50% probability level).
(10 mol%), L (see Figure 1, 20 mol%), K3PO4 (4.0 equiv.),
dioxane/toluene (1:1), reflux, 8 h.
Table 2. Synthesis of 4a–h.
4
Ar1
Yield [%] of 4[a]
a
b
c
d
e
f
4-MeC6H4
4-EtC6H4
3,5-Me2C6H3
4-(MeO)C6H4
2-(MeO)C6H4
3-ClC6H4
83 (A)
69 (A), 83 (B)
65 (A), 79 (B)
82 (B)
42 (A), 68 (B)
45 (A), 15 (B)
55 (A)
g
h
4-BrC6H4
3-PhC6H4
48 (A)
[a]
Isolated yields; in brackets: procedure (see legend of
Scheme 2).
ing two different types of aryl groups (Scheme 2). Tet-
raarylselenophene 5, containing four identical aryl
groups, was prepared by reaction of 1 with various ar-
ylboronic acid (5.0 equiv.) (Table 3). The sterically en-
cumbered tetraarylselenophenes 5a–e and 6 were iso-
lated in very good yields when a) procedure B was
employed, b) an excess of the respective boronic acid
was employed and c) the amount of catalyst was in-
creased (10 rather than 5 mol%). Considerable
amounts of 2,3,5-triaryl-4-bromoselenophenes were Figure 3. ORTEP plot of 5d (50% probability level).
Adv. Synth. Catal. 2008, 350, 2109 – 2117
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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ˇ
Dang Thanh Tœng et al.
¯
UPDATES
.
crystals) was washed with very cold ethyl acetate for several
times to give the product as slightly yellow crystals; yield:
84%; mp 97–988C. 13C NMR (75 MHz: CDCl3): d=112.2,
117.9 (CBr).
General Procedure A for the Synthesis of Aryl-
Substituted Selenophenes 2a, c, d, 4a–h, and 5a, d
ꢀ
Scheme 4. Synthesis of 7; conditions: i, 1 (1.0 equiv.), PhC
To a toluene/dioxane solution (1:1, 4 mL) of tetrabromosele-
CH (6.0 equiv.), Pd(PPh3)4 (10 mol%), CuI (4.0 equiv.), i-
G
nophene (0.134 g, 0.3 mmol) was added Pd(PPh3)4 at 208C.
G
Pr2NH, 1008C, 14 h.
After stirring for 30 min, the arylboronic acid, K3PO4 and
water (1 mL) were added. The mixture was stirred and
heated under reflux for 8 h. After cooling to ambient tem-
perature, the mixture was diluted with EtOAc, dried
(Na2SO4), and filtered through a short Celite pad. The solu-
tion was concentrated under vacuum and the residue was
purified by flash column chromatography (fine flash silica
gel, heptanes).
The Sonogashira coupling of 1 with phenylacety-
lene afforded tetrakis(1-alkynyl)selenophene 7 in
77% yield (Scheme 4). During the optimization, the
employment of an excess of alkyne (6.0 equiv.), a rel-
atively high temperature (1008C) and a long reaction
time (14 h) proved to be important. The best results
were obtained when Pd(PPh3)4 (10 mol%) was used
A
Synthesis of 5-(4-Ethylphenyl)-2,3,4-tribromo-
selenophene (2a)
as the catalyst. The use of an excess of CuI allowed us
to significantly improve the yield compared to the use
of only 10 mol%. Diisopropylamine was used as the
solvent. To the best of our knowledge, the synthesis
of a tetrakis(1-alkynyl)selenophene has not been re-
ported to date.
In conclusion, we have reported a new strategy for
the synthesis of 5-aryl-2,3,4-tribromoselenophenes,
2,5-diaryl-3,4-dibromoselenophenes, and tetraarylsele-
General procedure A was employed (reflux, 8 h). Starting
with 1 (0.134 g, 0.3 mmol), 4-ethylphenylboronic acid (1.0
equiv., 0.33 mmol, 0.050 g), Pd(PPh3)4 (5 mol%, 17 mg),
G
powdered, anhydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g),
and water (1 mL), 2a was isolated as a slightly yellow solid;
yield: 0.07 g (50%); mp 60–628C. 1H NMR (250 MHz,
CDCl3): d=1.27 (t, 3H, CH3), 2.70 (q, 2H, CH2), 7.25, 7.44
3
(d, J=8.2 Hz, 2H, 2 CH, Ar); 13C NMR (75 MHz, CDCl3):
nophenes based on regioselective Suzuki reactions of d=15.3 (CH3), 28.7 (CH2), 128.2, 129.0 (CH, Ar), 110.2,
111.3, 119.5 (C, CBr), 131.7, 144.8, 145.5 (C, Ar); IR (KBr,):
tetrabromoselenophene. The first tetrakis(1-alkynyl)-
selenophene was prepared by Sonogashira reaction of
tetrabromoselenophene with phenylacetylene.
˜
n=3068 (w), 3037 (w), 3019 (w), 2966 (w), 2925 (w), 2847
(w), 1905 (w), 1885 (w), 1660 (w), 1607 (w), 828 cmÀ1 (w);
MS (EI, 70 eV): m/z (%)=475 (M+,[81Br, 81Br, 81Br], 11),
473 (M+,[81Br, 81Br, 79Br], 16), 472 (100), 471 (M+,[81Br, 79Br,
79Br], 19), 469 (M+,[79Br, 79Br, 79Br], 13); HRMS (EI,
70 eV): calcd. for C12H9Br3Se (M+,[81Br, 81Br, 79Br]):
473.73732; found: 473.73826, (M+,[81Br, 79Br, 79Br]):
471.73936, found: 471.73943, (M+,[79Br, 79Br, 79Br]):
469.74141, found: 469.74065.
Experimental Section
General Comments
All solvents were dried by standard methods and all reac-
1
tions were carried out under an inert atmosphere. For H
and 13C NMR spectra the deuterated solvents indicated
were used. Mass spectrometric data (MS) were obtained by
electron ionization (EI, 70 eV), chemical ionization (CI,
H2O) or electrospray ionization (ESI). For preparative scale
chromatography, silica gel (60–200 mesh) was used. Melting
points are uncorrected.
Synthesis of 5-(3,5-Dimethylphenyl)-2,3,4-tribromo-
selenophene (2b)
An oven-dried Schlenk flask was charged with Pd(OAc)2,
E
ligand L, tetrabromoselenophene, boronic acid and pow-
dered, anhydrous K3PO4. The Schlenk flask was capped with
a rubber septum and then evacuated and filled with argon.
A toluene/dioxane mixture (1:1, 4 mL) was added by syringe
through a septum. The septum was replaced by a condenser
in an argon stream. The reaction mixture was stirred at
1008C for 6 h under argon. The solution was allowed to cool
to ambient temperature and water (5 mL) was added. The
aqueous and the organic layer were separated and the latter
was dried (Na2SO4). The solution was filtered and the fil-
trate was concentrated under vacuum. The residue was puri-
fied by flash column chromatography (fine flash silica gel,
heptanes). Starting with 1 (0.134 g, 0.3 mmol) and 3,5-dime-
thylphenylboronic acid (1.1 equiv., 0.33 mmol, 0.050 g),
Synthesis of Tetrabromoselenophene, C4Br4Se
Selenophene (2.50 g, 0.019 mol) was dissloved in CH2Cl2
(10 mL). This solution was cooled to 08C in an ice bath and
subsequently an excess of bromine (13.00 g, 0.13 mol) was
added dropwise during 2 h. The solution was stirred under
reflux for 3 days. To the residue was added a saturated aque-
ous solution of NaOH and the solution was heated under
reflux for 6 h. The aqueous layer and the organic layer were
separated. The organic layer was dried (Na2SO4), filtered,
and the filtrate was concentrated under vacuum. The prod-
uct was recrystallized from a 1:1-solution of chloroform and
methanol at À188C. The product (in the form of yellow
A
N
was isolated as a white solid; yield: 1.2 g (85%); mp 130–
1
1328C. H NMR (250 MHz, CDCl3): d=2.36 (s, 6H, 2CH3),
2112
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Adv. Synth. Catal. 2008, 350, 2109 – 2117

Efficient Synthesis of Substituted Selenophenes
UPDATES
7.04 (s, 1H, CH, Ar), 7.12 (s, 2H, 2 CH, Ar); 13C NMR
(75 MHz, CDCl3): d=21.3 (CH3), 126.8, 130.8 (CH, Ar),
110.2, 111.4, 119.4 (C, CBr), 134.1, 138.4, 145.1 (C, Ar); IR
the boronic acid (1.1 equiv., 0.33 mmol) and powdered, an-
hydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g). The Schlenk
flask was evacuated and subsequently flushed with argon. A
mixture of toluene and dioxane (1:1, 4 mL) was added by
syringe. The reaction mixture was heated under reflux for
6 h. The mixture was allowed to cool to ambient tempera-
ture and water (5 mL) was added. The aqueous and the or-
ganic layer were separated. The latter was dried (Na2SO4),
filtered, and the filtrate was concentrated under vacuum.
The residue was purified by flash column chromatography
(fine silica gel, heptanes).
˜
(KBr): n=2909 (w), 2851 (w), 2721 (w), 1796 (w), 1769 (w),
1746 (w), 1722 (w), 1592 (w), 1453 (w), 1229 (w), 848 (w),
722 (w), 690 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=475
(M+,[81Br, 81Br, 81Br], 10), 473 (M+,[81Br, 81Br, 79Br], 17), 472
(100), 471 (M+,[81Br, 79Br, 79Br], 19), 469 (M+,[79Br, 79Br,
79Br], 13); HR-MS (EI, 70 eV): calcd. for C12H9Br3Se
(M+,[81Br, 81Br, 79Br]): 473.73732; found: 473.73824,
(M+,[81Br, 79Br, 79Br]): 471.73936, found: 471.73962,
(M+,[79Br, 79Br, 79Br]): 469.74141, found: 469.74110.
Synthesis of 2-Ethylphenyl-5-(p-tolyl)-3,4-dibromo-
selenophene (3a)
Synthesis of 5-(4-Methoxyphenyl)-2,3,4-tribromo-
selenophene (2c)
Starting with 2a (0.141 g, 0.3 mmol), Pd(OAc)2 (3.4 mg, 5
G
General procedure A was employed (reflux, 8 h). Starting
with 1 (0.134 g, 0.3 mmol), 4-methoxyphenylboronic acid
mol%), L (12.3 mg, 10 mol%), powdered, anhydrous K3PO4
(1.2 mmol, 4.0 equiv., 0.254 g) and 4-methylphenylboronic
acid (1.0 equiv., 0.33 mmol, 0.041 g, 3a was isolated as an
orange highly viscous oil after reflux for 8 h; yield: 0.11 g
(1.1 equiv., 0.33 mmol, 0.051 g), Pd(PPh3)4 (5 mol%, 17 mg),
A
powdered, anhydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g),
1
and water (1 mL), 2c was isolated as a yellow solid; yield:
(76%). H NMR (250 MHz, CDCl3): d=1.25 (t, 3H, CH3),
1
0.96 g (68%); mp 125–1278C. H NMR (250 MHz, CDCl3):
2.35 (s, 3H, CH3), 2.67 (q, 2H, CH2), 7.19, 7.25, 7.42, 7.47
d=3.84 (s, 3H, CH3), 6.94, 7.44 (d, 2H, CH, Ar); 13C NMR
(75 MHz, CDCl3): d=55.4 (CH3), 114.1, 130.4 (d, 3J=
8.2 Hz, CH, Ar), 110.0, 110.9, 119.4 (C, CBr), 126.7, 144.6,
3
(d, J=8.2 Hz, 2H, 2 CH, Ar); 13C NMR (75 MHz, CDCl3):
d=15.6, 21.1 (CH3), 28.5 (CH2), 126.79, 126.90, 128.2, 129.4
(CH, Ar), 132.06, 132.28, 136.7, 138.6, 143.0, 145.0 (C, Ar),
˜
160.2 (C, Ar); IR (KBr): n=3026 (w), 2953 (w), 2895 (w),
˜
112.0 (overlap of two CBr, Ar); IR (KBr): n=3020 (w),
2830 (w), 2546 (w), 2090 (w), 1884 (w), 1601 (w), 1492 (w),
1245 (w), 1029 (w), 826 (w), 690 cmÀ1 (m); MS (EI, 70 eV):
m/z (%)=477 (M+,[81Br, 81Br, 81Br], 7), 475 (M+,[81Br, 81Br,
79Br], 14), 474 (100), 473 (M+,[81Br, 79Br, 79Br], 18), 471
(M+,[79Br, 79Br, 79Br], 12); HR-MS (EI, 70 eV): calcd. for
C11H7Br3OSe (M+,[81Br, 79Br, 79Br]): 473.71863, found:
473.72001, (M+,[79Br, 79Br, 79Br]): 471.72068, found:
471.72235.
2961 (w), 2927 (w), 2968 (w), 1901 (w), 1605 (w), 1490 (m),
940 (w), 817 (m), 799 (m), 718 cmÀ1 (w); MS (EI, 70 eV):
m/
A
z (%)=485 (M+,[81Br, 81Br], 11), 484 (100), 483 (M+,[81Br,
79Br], 19), 481 (M+,[79Br, 79Br], 22); HR-MS (EI, 70 eV):
calcd. for C19H16Br2Se (M+,[81Br, 81Br]): 485.87425; found:
485.87411, (M+,[81Br, 79Br]): 483.87635, found: 483.87642,
(M+,[79Br, 79Br]): 481.87840, found: 481.87849.
Synthesis of 2-(3,5-Dimethylphenyl)-5-(p-tolyl)-3,4-
dibromoselenophene (3b)
Synthesis of 5-(3-Biphenyl)-2,3,4-tribromo-
selenophene (2d)
Starting with 2b (0.141 g, 0.3 mmol), Pd(OAc)2 (3.4 mg, 5
R
General procedure A was employed (reflux, 8 h). Starting
with 1 (0.134 g, 0.3 mmol), 4-methoxyphenylboronic acid
mol%), L (12,3 mg, 10 mol%), powdered, anhydrous K3PO4
(1.2 mmol, 4.0 equiv., 0.254 g) and 4-methylphenylboronic
acid (1.1 equiv., 0.33 mmol, 0.041 g), 3b was isolated as an
orange highly viscous oil after reflux for 8 h; yield: 0.116 g
(1.1 equiv., 0.33 mmol, 0.065 g), Pd(PPh3)4 (5 mol%, 17 mg),
T
powdered, anhydrous K3PO4 (1.2 mmol, 4.0 equiv, 0.254 g),
1
and water (1 mL), 2d was isolated as a yellow solid; yield:
(80%). H NMR (250 MHz, CDCl3): d=1.25 (s, 6H, 2CH3),
1
3
0.73 g (47%); mp 90–938C. H NMR (250 MHz, CDCl3): d=
1.30 (s, 3H, CH3), 7.19, 7.28 (d, J=8.2 Hz, 2H, 2 CH, Ar),
7.38–7.74 (m, 9H, CH, Ar); 13C NMR (75 MHz, CDCl3): d=
127.21, 127.91, 128.93 (CH, 2CH, Ar), 127.79, 127.85, 129.2
(CH, 1 CH, Ar), 110.9, 111.9, 119.7 (C, CBr), 134.8, 140.2,
7.51 (s, 1H, CH, Ar), 7.59 (s, 2H, 2 CH, Ar); 13C NMR
(75 MHz, CDCl3): d=21.1, 21.4 (CH3), 125.1 (C, 1 CH, Ar),
126.8, 129.1, 129.4 (C, 2 CH, Ar), 132.1, 136.7, 138.1, 138.8,
141.4, 142.9 (C, Ar), 112.1 (overlap of two CBr, Ar); IR
˜
141.8, 144.5 (C, Ar); IR (KBr): n=3057 (w), 3024 (w), 1926
(w), 1874 (w), 1798 (w), 1693 (w), 1568 (w), 1468 (w), 1233
(w), 745 (w), 689 (w), 619 (w), 588 cmÀ1 (m); MS (EI,
70 eV): m/z (%)=523 (M+,[81Br, 81Br, 81Br], 6), 521
(M+,[81Br, 81Br, 79Br], 10), 519 (M+,[81Br, 79Br, 79Br], 9), 517
(M+,[79Br, 79Br, 79Br], 7); HR-MS (EI, 70 eV): calcd. for
C16H9Br3Se (M+,[81Br, 81Br, 79Br]): 521.73732; found:
521.73765, (M+,[81Br, 79Br, 79Br]): 519.73936, found:
519.73924, (M+,[79Br, 79Br, 79Br]): 517.74141, found:
517.74031.
˜
(KBr): n=3019 (w), 2914 (w), 2857 (w), 2729 (w), 1666 (w),
1597 (m), 1490 (m), 1239 (m), 840 (m), 799 (m), 693 cmÀ1
(w); MS (EI, 70 eV): m/z (%)=485 (M+,[81Br, 81Br], 12),
484 (100), 483 (M+,[81Br, 79Br], 21), 481 (M+,[79Br, 79Br], 22).
HR-MS (EI, 70 eV): calcd for C19H16Br2Se (M+,[81Br, 81Br]):
485.87425; found: 485.87431, (M+,[81Br, 79Br]): 483.87635,
found: 483.87649, (M+,[79Br, 79Br]): 481.87840, found:
481.87836.
Synthesis of 2,5-Ditolyl-3,4-dibromoselenophene (4a)
General Procedure for the Synthesis of Unsym-
metrical 2,5-Diaryl-3,4-dibromoselenophenes 3a, b
General procedure A was employed (reflux, 8 h). Starting
with 1 (0.134 g, 0.3 mmol), p-tolylboronic acid (2.2 equiv.,
An oven-dried Schenk flask was charged with Pd
G
0.66 mmol, 0.09 g), Pd
G
(3.4 mg, 5 mol%), L (12,3 mg, 10 mol%), 3a, b (0.3 mmol),
anhydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water
Adv. Synth. Catal. 2008, 350, 2109 – 2117
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2113

ˇ
Dang Thanh Tœng et al.
¯
UPDATES
.
(1 mL), 4a was isolated as a yellow solid; yield: 0.117 g
(M+,[81Br, 79Br], 25), 495 (M+,[79Br, 79Br], 20); HR-MS (EI,
70 eV): calcd. for C20H18Br2Se (M+,[81Br, 81Br]): 499.88941;
found: 499.89033 (M+,[81Br, 79Br]): 497.89145, found:
497.89246, (M+,[79Br, 79Br]): 495.89350, found: 495.89365.
1
(83%); mp 98–1028C. H NMR (250 MHz, CDCl3): d=2.25
(s, 6H, 2CH3), 7.22, 7.39 (d, 3J=8.2 Hz, 4H, 4 CH, Ar);
13C NMR (75 MHz, CDCl3): d=21.3 (CH3), 129.5, 129.8
(CH, Ar), 132.1, 138.8, 142.9 (C, Ar), 112.1 (CBr, Ar); IR
˜
(KBr): n=3019 (w), 2914 (w), 2725 (w), 1894 (w), 1565 (w),
Synthesis of 2,5-Bis(p-methoxyphenyl)-3,4-dibromo-
1488 (m), 1246 (w), 1178 (w), 1021 (w), 957 (w), 809 (m),
719 (m), 637 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=471
(M+,[81Br, 81Br], 20), 469 (M+,[81Br, 79Br], 23), 470 (100), 467
(M+,[79Br, 79Br], 19); HR-MS (EI, 70 eV): calcd. for
C18H14Br2Se (M+,[81Br, 81Br]): 471.85811; found: 471.85951,
(M+,[81Br, 79Br]): 469.86015, found: 469.86074, (M+,[79Br,
79Br]): 467.86220, found: 467.86196.
selenophene (4d)
General procedure A was employed (reflux, 8 h). Starting
with 1 (0.134 g, 0.3 mmol), p-methoxyphenylboronic acid
(2.2 equiv., 0.66 mmol, 0.09 g), Pd(OAc)2 (3.4 mg, 5 mol%),
L (12,3 mg, 10 mol%), and powdered, anhydrous K3PO4
(1.2 mmol, 4.0 equiv., 0.254 g), 4d was isolated as a yellow
G
solid; yield: 0.123
g
(82%); mp 157–1618C. 1H NMR
(250 MHz, CDCl3): d=3.75 (s, 6H, 2OCH3), 6.84, 7.45 (d,
3J=8.2 Hz, 4H, 4 CH, Ar); 13C NMR (75 MHz, CDCl3): d=
55.3 (OCH3), 114.0, 130.4 (CH, Ar), 127.3, 142.3, 159.9 (C,
Synthesis of 2-(2,5-Diethylphenyl)-3,4-dibromo-
selenophene (4b)
˜
Ar), 111.7 (CBr, Ar); IR (KBr): n=2983 (w), 2965 (w),
General procedure A (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), p-ethylphenylboronic acid (2.2 equiv., 0.66 mmol,
2832 (w), 1605 (m), 1491 (m), 1242 (m), 1174 (m), 1028 (m),
827 (m), 783 (w), 728 (w), 685 (w), 656 (w), 631 cmÀ1 (m);
MS (EI, 70 eV): m/z (%)=503 (M+,[81Br, 81Br], 11), 502
(100), 501 (M+,[81Br, 79Br], 21), 500 (100), 499 (M+,[79Br,
79Br], 17); HR-MS (EI, 70 eV): calcd. for C18H14Br2O2Se
(M+,[81Br, 81Br]): 503.84794; found: 503.84884, (M+,[81Br,
79Br]): 501.84998, found: 501.84986, (M+,[79Br, 79Br]):
499.85203, found: 499.85235.
0.099 g), Pd(PPh3)4 (5 mol%, 17 mg), powdered, anhydrous
G
K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water (1 mL), 4b
was isolated as a yellow solid; yield: 0.103 g (69%).
General procedure
(0.134 g, 0.3 mmol), p-ethylphenylboronic acid (2.2 equiv.,
0.66 mmol, 0.099 g), Pd(OAc)2 (3.4 mg, mol%),
B (reflux, 8 h): Starting with 1
A
5
L
(12,3 mg, 10 mol%), and powdered, anhydrous K3PO4
(1.2 mmol, 4.0 equiv., 0.254 g), 4b was isolated as a yellow
solid; yield: 0.124 g (83%); mp 68–728C. 1H NMR
(250 MHz, CDCl3): d=1.19 (t, 6H, 2CH3), 2.56 (q, 4H,
Synthesis of 2,5-Bis(o-methoxyphenyl)-3,4-dibromo-
selenophene (4e)
3
2CH2), 7.12, 7.41 (d, J=8.2 Hz, 4H, 4 CH, Ar); 13C NMR
General procedure A (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), o-methoxyphenylboronic acid (2.2 equiv.,
0.66 mmol, 0.09 g), Pd(PPh3)4 (5 mol%, 17 mg), powdered,
anhydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water
(1 mL), 4e was isolated as a yellow solid; yield: 0.063 g
(42%).
(75 MHz, CDCl3): d=15.3 (CH3), 28.6 (CH2), 128.2, 129.1
(CH, Ar), 132.2, 143.0, 145.0 (C, Ar), 112.1 (CBr, Ar); IR
A
˜
(KBr): n=2959 (w), 2926 (w), 2867 (w), 1906 (w), 1668 (w),
1607 (w), 1522 (w), 1490 (m), 1453 (w), 834 (m), 796 (m),
769 (m), 688 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=499
(M+,[81Br, 81Br], 21), 498 (100), 497 (M+,[81Br, 79Br], 23), 495
(M+,[79Br, 79Br], 19); HRMS (EI, 70 eV): calcd for
C20H18Br2Se (M+,[81Br, 81Br]): 499.88941; found: 499.88998,
(M+,[81Br, 79Br]): 497.89145, found: 497.89169, (M+,[79Br,
79Br]): 495.89350, found: 495.89277.
General procedure
(0.134 g, 0.3 mmol), o-methoxyphenylboronic acid (2.2
equiv., 0.66 mmol, 0.09 g), Pd(OAc)2 (3.4 mg, 5 mol%), L
B (reflux, 8 h): Starting with 1
AHCTREUNG
(12,3 mg, 10 mol%) and powdered, anhydrous K3PO4
(1.2 mmol, 4.0 equiv., 0.254 g), 4e was isolated as a yellow
solid; yield: 0.102 g (68%); mp 85–878C. 1H NMR
(250 MHz, CDCl3): d=3.76 (s, 6H, 2OCH3), 6.89, 6.98 (t,
Synthesis of 2,5-Bis(3,5-dimethylphenyl)-3,4-dibromo-
selenophene (4c)
3J=8.2 Hz, 2H, 2 CH, Ar), 7.29, 7.35 (d, J=8.2 Hz, 2H, 2
3
CH, Ar); 13C NMR (75 MHz, CDCl3): d=55.6 (OCH3),
General procedure A (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), 3,5-dimethylboronic acid (2.2 equiv., 0.66 mmol,
111.2, 120.3, 130.3, 131.8 (CH, Ar), 123.8, 139.2, 156.5 (C,
˜
Ar), 113.6 (CBr, Ar); IR (KBr): n=3011 (w), 2936 (w),
0.099 g), Pd(PPh3)4 (5 mol%, 17 mg), powdered, anhydrous
G
2833 (w), 1472 (m), 1428 (m), 1256 (m), 1237 (m), 1113 (m),
1017 (m), 805 (w), 747 (w), 681 (w), 565 (w), 537 cmÀ1 (m);
MS (EI, 70 eV): m/z (%)=503 (M+,[81Br, 81Br], 14), 502
(100), 501 (M+,[81Br, 79Br], 23), 500 (100), 499 (M+,[79Br,
79Br], 19); HR-MS (EI, 70 eV): calcd. for C18H14Br2O2Se
(M+,[81Br, 81Br]): 503.84794; found: 503.84889, (M+,[81Br,
79Br]): 501.84998, found: 501.84990, (M+,[79Br, 79Br]):
499.85203, found: 499.85213.
K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water (1 mL), 4c
was isolated as a yellow solid; yield: 0.097 g (65%).
General procedure
(0.134 g, 0.3 mmol), 3,5-dimethylboronic acid (2.2 equiv.,
0.66 mmol, 0.099 g), Pd(OAc)2 (3.4 mg, mol%),
B (reflux, 8 h): Starting with 1
A
5
L
(12,3 mg, 10 mol%), and powdered, anhydrous K3PO4
(1.2 mmol, 4.0 equiv., 0.254 g), 4c was isolated as a yellow
solid; yield: 0.118 g (79%); mp 162–1648C. 1H NMR
(250 MHz, CDCl3): d=2.29 (s, 12H, 4CH3), 6.97 (s, 2H, 2
CH, Ar), 7.12 (s, 4H, 4 CH, Ar); 13C NMR (75 MHz,
CDCl3): d=31.3 (CH3), 126.9, 130.4 (CH, Ar), 134.8, 138.2,
Synthesis of 2,5-Bis(m-chlorophenyl)-3,4-dibromo-
selenophene (4f)
˜
143.1 (C, Ar), 112.0 (CBr, Ar); IR (KBr): n=2995 (w), 2911
General procedure A (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), m-chlorophenylboronic acid (2.2 equiv.,
(w), 2857 (w), 2725 (w), 1737 (w), 1595 (w), 1444 (w), 1228
(m), 888 (w), 843 (m), 784 (m), 691 cmÀ1 (m); MS (EI,
70 eV): m/z (%)=499 (M+,[81Br, 81Br], 21), 498 (100), 497
0.66 mmol, 0.103 g), Pd
A
anhydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water
2114
asc.wiley-vch.de
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 2109 – 2117

Efficient Synthesis of Substituted Selenophenes
UPDATES
(1 mL), 4f was isolated as a white solid; yield: 0.069 g
(45%).
70 eV): calcd. for C28H18Br2Se (M+,[81Br, 81Br]): 595.88941;
found: 595.89002, (M+,[81Br, 79Br]): 593.8914, found:
593.89108, (M+,[79Br, 79Br]): 591.89350, found : 591.89212.
General procedure
(0.134 g, 0.3 mmol), m-chlorophenylboronic acid (2.2 equiv.,
0.66 mmol, 0.103 g), Pd(OAc)2 (3.4 mg, mol%),
B (reflux, 8 h): Starting with 1
A
5
L
General Procedure C for the Synthesis of Tetraaryl-
selenophenes 5a–e
(12,3 mg, 10 mol%) and powdered, anhydrous K3PO4
(1.2 mmol, 4.0 equiv., 0.254 g), 4f was isolated as a white
solid; yield: 0.023 g (15%); mp 170–1718C. 1H NMR
An oven-dried Schenk flask was charged with Pd(OAc)2
G
3
(6.8 mg, 10 mol%), L (24.6 mg, 20 mol%), 1 (0.3 mmol), the
boronic acid (5 equiv., 1. 5 mmol) and powdered, anhydrous
K3PO4 (2.4 mmol, 8.0 equiv., 0.508 g). The Schlenk flask was
evacuated and subsequently flushed with argon. A 1:1-mix-
ture (4 mL) of toluene and dioxane was added by syringe.
The reaction mixture was heated under reflux for 8 h. The
mixture was allowed to cool to ambient temperature and
water (5 mL) was added. The aqueous and the organic layer
were separated. The latter was dried (Na2SO4), filtered, and
the filtrate was concentrated under vacuum. The residue
was purified by flash column chromatography (fine silica
gel, heptanes).
(250 MHz, CDCl3): d=7.37, 7.39 (d, J=8.2 Hz, 4H, 4 CH,
3
Ar), 7.46 (t, J=8.2 Hz, 2H, 2 CH, Ar), 7.58 (s, 2H, 2CH,
Ar); 13C NMR (75 MHz, CDCl3): d=127.4, 129.0, 129.2,
129.9 (CH, Ar), 134.6, 136.3, 141.8 (C, Ar), 113.4 (CBr, Ar);
˜
IR (KBr): n=3154 (w), 3097 (w), 3045 (w), 1942 (w), 1874
(w), 1802 (w), 1757 (w), 1693 (w), 1590 (m), 1557 (m), 1545
(m), 878 (m), 767 (m), 688 cmÀ1 (m); MS (EI, 70 eV): m/z
(%)=515 (M+,[81Br, 81Br, 37Cl, 37Cl], 6), 513 (M+,[81Br, 79Br,
37Cl, 37Cl], 32), 511 (M+,[79Br, 79Br, 37Cl, 37Cl], 77), 509
(M+,[79Br, 79Br, 35Cl, 37Cl], 100), 507 (M+,[79Br, 79Br, 35Cl,
35Cl], 65); HR-MS (EI, 70 eV): calcd. for C16H8Br2Cl2Se
(M+,[81Br, 81Br, 35Cl, 35Cl]): 511.74886; found: 511.74944,
(M+,[81Br, 79Br, 37Cl, 37Cl]): 509.75091, found: 509.75133,
(M+,[79Br, 79Br, 35Cl, 35Cl]): 507.75295, found: 507.75284.
Synthesis of Tetraphenylselenophene (5a)
General procedure A (reflux, 14 h): Starting with 1 (0.134 g,
0.3 mmol), phenylboronic acid (5.0 equiv., 1.5 mmol,
Synthesis of 2,5-Bis(p-bromophenyl)-3,4-dibromo-
selenophene (4g)
0.183 g), Pd(PPh3)4 (10 mol%, 34 mg), powdered, anhydrous
A
K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water (1 mL), 5a
was isolated as a yellow solid; yield: 0.072 g (55%).
General procedure A (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), p-bromophenylboronic acid (2.2 equiv.,
General procedure
(0.134 g, 0.3 mmol), phenylboronic acid (5.0 equiv, 1.5 mmol,
0.183 g), Pd(OAc)2 (6.8 mg, 10 mol%), L (24.6 mg, 20
C (reflux, 8 h): Starting with 1
0.66 mmol, 0.185 g), Pd(PPh3)4 (5 mol%, 17 mg), powdered,
R
anhydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water
(1 mL), 4g was isolated as a white solid; yield: 0.099 g
(55%); mp 207–2098C. 1H NMR (250 MHz, CDCl3): d=
AHCTREUNG
mol%) and powdered, anhydrous K3PO4 (2.4 mmol,
8.0 equiv., 0.508 g), 5a was isolated as a yellow solid; yield:
7.47, 7.56 (d, 3J=8.2 Hz, 4H,
4
CH, Ar); 13C NMR
1
0.103 g (79%); mp 158–1628C. H NMR (250 MHz, CDCl3):
d=6.94–7.21 (m, 20H, 12 CH, Ar); 13C NMR (75 MHz,
CDCl3): d=124.4, 125.0, 125.7, 126.2, 127.4, 128.9 (CH, Ar),
(75 MHz, CDCl3): d=130.71, 131.89, (CH, Ar), 123.2, 133.6,
˜
142.0 (C, Ar), 113.2 (CBr, Ar); IR (KBr): n=3083 (w), 3044
(w), 3017 (w), 2923 (w), 2295 (w), 1895 (w), 1584 (w), 1472
(m), 1391 (m), 1071 (m), 1008 (m), 820 (m), 733 cmÀ1 (m);
MS (EI, 70 eV): m/z (%)=603 (M+,[81Br, 81Br, 81Br, 81Br],
10), 601 (M+,[79Br, 81Br, 81Br, 81Br], 17), 599 (M+,[79Br, 79Br,
81Br, 81Br], 19), 597 (M+,[79Br, 79Br, 79Br, 81Br], 16), 595
(M+,[79Br, 79Br, 79Br, 79Br], 9); HR-MS (EI, 70 eV): calcd.
for C16H8Br4Se (M+,[79Br, 81Br, 81Br, 81Br]): 601.64578;
found: 601.64663, (M+,[79Br, 79Br, 81Br, 81Br]): 599.64783,
found: 599.64887, (M+,[79Br, 79Br, 79Br, 79Br]): 595.65192,
found: 595.65151.
˜
124.2, 135.9, 139.7, 142.6 (C, Ar); IR (KBr): n=3056 (w),
3020 (w), 2962 (w), 1948 (w), 1876 (w), 1806 (w), 1596 (m),
1440 (m), 1068 (m), 1025 (m), 789 (m), 758 (m), 690 cmÀ1
(m); MS (EI, 70 eV): m/z (%)=435 (M+, 11), 434 (52), 434
(19), 433 (15), 150 (12); HR-MS (EI, 70 eV): calcd. for
C28H20Se (M+): 436.07302; found: 436.07311.
Synthesis of Tetra(p-tolyl)selenophene (5b)
A
General procedure C (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol) and tolylboronic acid (5.0 equiv., 1.5 mmol,
0.205 g), Pd(OAc)2 (6.8 mg, 10 mol%), L (24.6 mg, 20
mol%) and powdered, anhydrous K3PO4 (2.4 mmol,
A
Synthesis of 2,5-Bis(3-biphenyl)-3,4-dibromo-
selenophene (4h)
8.0 equiv., 0.508 g), 5b was isolated as a yellow solid; yield:
1
0.131 g (89%); mp 240–2448C. H NMR (250 MHz, CDCl3):
General procedure A (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), 3-biphenylboronic acid (2.2 equiv., 0.66 mmol,
d=2.26, 2.31 (s, 6H, 2CH3), 6.86, 6.90, 7.03, 7.10 (d, 3J=
8.2 Hz, 4H, 4 CH, Ar); 13C NMR (75 MHz, CDCl3): d=
21.13, 21.22 (CH3), 128.4, 128.9, 129.3, 130.7 (CH, Ar),
0.131 g), Pd(PPh3)4 (5 mol%, 17 mg), powdered, anhydrous
C
K3PO4 (1.2 mmol, 4.0 equiv, 0.254 g), and water (1 mL), 4h
˜
133.6, 135.2, 135.7, 136.6, 141.4, 144.0 (C, Ar); IR (KBr): n=
was isolated as a yellow solid; yield: 0.085 g (48%); mp 90–
1
3021 (w), 2917 (w), 2860 (w), 1907 (w), 1738 (w), 1511 (m),
1495 (m), 1181 (m), 1110 (m), 857 (m), 831 (m), 813 (m),
731 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=491 (M+, 15), 490
(47), 489 (17), 488 (15), 206 (9); HR-MS (EI, 70 eV): calcd.
for C32H28Se (M+): 492.13507; found: 492.13510.
938C. H NMR (250 MHz, CDCl3): d=7.35–7.87 (m, 18H,
18 CH, Ar); 13C NMR (75 MHz, CDCl3): d=125.2, 125.5,
125.7, 125.0, 126.9, 127.1 (CH, Ar), 133.3, 138.4, 139.7, 141.1
˜
(C, Ar), 110.7 (CBr, Ar); IR (KBr): n=3054 (w), 3027 (w),
2961 (w), 1945 (w), 1878 (w), 1799 (w), 1594 (m), 1467 (m),
1261 (m), 1238 (m), 904 (m), 749 (m), 692 cmÀ1 (m); MS
(EI, 70 eV): m/z (%)=595 (M+,[81Br, 81Br], 24), 593
(M+,[81Br, 79Br], 24), 591 (M+,[79Br, 79Br], 19); HR-MS (EI,
Adv. Synth. Catal. 2008, 350, 2109 – 2117
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2115

ˇ
Dang Thanh Tœng et al.
¯
UPDATES
.
the boronic acid (3 equiv., 0.9 mmol) and powdered, anhy-
drous K3PO4 (2.4 mmol, 8.0 equiv., 0.508 g). The Schlenk
flask was evacuated and subsequently flushed with argon. A
mixture (1:1, 4 mL) of toluene and dioxane was added by
syringe. The reaction mixture was heated under reflux for
8 h. The mixture was allowed to cool to ambient tempera-
ture and water (5 mL) was added. The aqueous and the or-
ganic layers were separated. The latter was dried (Na2SO4),
filtered, and the filtrate was concentrated under vacuum.
The residue was purified by flash column chromatography
(fine silica gel, heptanes).
Synthesis of Tetra(p-ethylphenyl)selenophene (5c)
General procedure C (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), p-ethylphenylboronic acid (5.0 equiv., 1.5 mmol,
0.225 g), Pd(OAc)2 (6.8 mg, 10 mol%), L (24.6 mg, 20
R
mol%) and powdered, anhydrous K3PO4 (2.4 mmol,
8.0 equiv., 0.508 g), 5c was isolated as a yellow solid; yield:
0.161 g (0.98%); mp 101–1038C. 1H NMR (250 MHz,
CDCl3): d=1.20, 1.25 (t, 6H, 2CH3), 2.57, 2.64 (q, 4H,
3
2CH2), 6.90, 6.93, 7.06, 7.14 (d, J=8.2 Hz, 4H, 4 CH, Ar);
13C NMR (75 MHz, CDCl3) d=15.16, 15.27 (CH3), 28.43
(overlap of two carbons) (CH2), 127.0, 127.6, 129.3, 130.8
(CH, Ar), 133.9, 135.5, 141.6, 142.0, 142.8, 144.0 (C, Ar); IR
Synthesis of 2,5-Bis(p-ethylphenyl-3,4-bis(p-methoxy-
phenyl)selenophene (6a)
˜
(KBr): n=2961 (m), 2930 (w), 2871 (w), 1903 (w), 1789 (w),
1510 (m), 1494 (m), 1453 (m), 1019 (m), 830 (m), 800 (m),
680 (m), 546 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=547 (M+,
13), 546 (50), 547 (14), 546 (19), 262 (13); HR-MS (EI,
70 eV): calcd. for C36H36Se (M+): 548.49767; found:
548.19767.
General procedure D (reflux, 8 h): Starting with 4b (0.149 g,
0.3 mmol), p-methoxyboronic acid (3 equiv., 0.9 mmol,
0.137 g), Pd(OAc)2 (6.8 mg, 10 mol%), L (24.6 mg, 20
A
mol%) and powdered, anhydrous K3PO4 (2.4 mmol,
8.0 equiv., 0.508 g), 6a was isolated as a yellow solid; yield:
1
0.13 g (79%); mp 182–1858C. H NMR (250 MHz, CDCl3):
Synthesis of Tetra(3,5-dimethylphenyl)selenophene
(5d)
d=1.22 (t, 6H, 2CH3), 2.60 (q, 4H, 2CH2), 3.73 (s, 6H,
3
OCH3), 6.66, 6.84, 7.04, 7.10 (d, J=8.2 Hz, 4H, 4 CH, Ar);
13C NMR (75 MHz, CDCl3), d=15.2, 55.0 (CH3), 28.4
General procedure A (reflux, 14 h): Starting with 1 (0.134 g,
0.3 mmol), 3,5-dimethylphenylboronic acid (5.0 equiv,
(CH2), 113.1, 127.7, 129.3, 132.0 (CH, Ar), 130.7, 133.9,
141.1, 142.7, 143.9, 157.9 (C, Ar); IR (KBr): n=2962 (w),
1.5 mmol, 0.225 g), Pd(PPh3)4 (10 mol%, 34 mg), powdered,
N
˜
anhydrous K3PO4 (1.2 mmol, 4.0 equiv., 0.254 g), and water
(1 mL), 5d was isolated as a yellow solid; yield: 0.122 g
(74%); mp 158–1608C. 1H NMR (250 MHz, CDCl3): d=
2.11, 2.19 (s, 12H, 4CH3), 6.72, 6.81 (s, 2H, 2 CH, Ar), 6.61,
6.86 (s, 4H, 4 CH, Ar); 13C NMR (75 MHz, CDCl3): d=
21.1, 21.2 (CH3), 127.2, 128.7, 136.6, 137.3 (CH, Ar), 127.7
(overlap of two quaternary carbons), 128.5, 138.1, 142.1,
2930 (w), 2834 (w), 2058 (w), 1894 (w), 1604 (m), 1506 (m),
1493 (m), 1241 (m), 1029 (m), 807 (m), 779 (m), 554 cmÀ1
(m); MS (EI, 70 eV): m/z (%)=551 (M+, 16), 550 (47), 549
(11), 549 (16), 266 (17); HR-MS (EI, 70 eV): calcd. for
C34H32O2Se (M+): 552.15620; found: 552.15502.
Synthesis of 2,5-Bis(3,5-dimethylphenyl)-3,4-bis(p-
methoxyphenyl)selenophene (6b)
˜
143.7 (C, Ar); IR (KBr): n=2997 (w), 2947 (w), 2915 (w),
2858 (w), 1593 (m), 1463 (m), 1375 (m), 847 (m), 810 (m),
693 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=547 (M+, 13), 546
(51), 547 (13), 546 (20), 262 (12); HR-MS (EI, 70 eV): calcd.
for C36H36Se (M+): 548.49767; found: 548.19747.
General procedure D (reflux, 8 h): Starting with 4c (0.149 g,
0.3 mmol), p-methoxyboronic acid (3.0 equiv., 0.9 mmol,
0.137 g), Pd(OAc)2 (6.8 mg, 10 mol%), L (24.6 mg, 20
G
mol%) and powdered, anhydrous K3PO4 (2.4 mmol,
8.0 equiv., 0.508 g), 6b was isolated as a yellow solid; yield:
0.135 g (82%); mp 238–2408C. H NMR (250 MHz, CDCl3):
d=2.19 (s, 12H, 4 CH3), 3.73 (s, 6H, 2 OCH3), 6.66, 6.81 (d,
3J=8.2 Hz, 4H, 4 CH, Ar), 6.83 (s, 4H, 4 CH, Ar), 6.87 (s,
2H, 2 CH, Ar); 13C NMR (75 MHz, CDCl3): d=21.2 (CH3),
Synthesis of Tetra(p-methoxyphenyl)selenophene (5e)
1
General procedure C (reflux, 8 h): Starting with 1 (0.134 g,
0.3 mmol), p-ethylphenylboronic acid (5.0 equiv., 1.5 mmol,
0.228 g), Pd(OAc)2 (6.8 mg, 10 mol%), L (24.6 mg, 20
G
mol%), and powdered, anhydrous K3PO4 (2.4 mmol,
55.1(OCH3), 130.1, 127.7, 128.7, 131.9 (CH, Ar), 130.8,
A
8.0 equiv., 0.508 g), 5e was isolated as a yellow solid; yield:
˜
136.4, 141.2, 144.1, 157.8, 158.0 (C, Ar); IR (KBr): n=2959
(w), 2913 (w), 2836 (w), 2532 (w), 1727 (w), 1599 (m), 1495
(m), 1462 (m), 1242 (m), 1105 (m), 1032 (m), 1011 (m),
800 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=551 (M+, 15), 550
(49), 549 (10), 549 (18), 266 (12); HR-MS (EI, 70 eV): calcd.
for C34H32O2Se (M+): 552.15620; found: 552.15655.
1
0.148 g (89%); mp 188–1938C. H NMR (250 MHz, CDCl3):
3
d=3.72, 3.76 (s, 6H, OCH3), 6.66, 6.75, 6.83, 7.10 (d, J=
8.2 Hz, 4H, 4 CH, Ar); 13C NMR (75 MHz, CDCl3): d=
54.9, 55.1 (CH3), 113.1, 113.6, 130.5, 132.0 (CH, Ar), 129.0,
˜
130.6, 140.7, 143.1, 157.9, 158.4 (C, Ar); IR (KBr): n=3002
(w), 2955 (w), 2838 (w), 1891 (w), 1601 (m), 1494 (m), 1281
(m), 1236 (m), 1110 (m), 1027 (m), 830 (m), 779 (m),
547 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=555 (M+, 18), 554
(51), 553 (21), 542 (16), 539 (10), 223 (15), 195 (15), 152
(11), 44 (20); HR-MS (EI, 70 eV): calcd. for C32H28O4Se
(M+): 556.11339; found: 556.11393.
Procedure for the Synthesis of Tetra(phenylethynyl)-
selenophene (7)
An oven-dried Schenk flask was charged with Pd(Ph3)4
A
(35 mg, 10 mol%), 1 (0.3 mmol), phenyacetylene (5.0 equiv.,
1.5 mmol, 153 mg) and CuI (1.2 mmol, 4.0 equiv., 229 mg).
The Schlenk flask was evacuated and subsequently flushed
with argon. To the mixture was added i-Pr2NH (12 mL) by
syringe. After stirring of the solution at 08C for 4 h, the re-
action mixture was heated under reflux for 8 h. The mixture
was allowed to cool to ambient temperature and the solvent
General Procedure D for the Synthesis of Tetraaryl-
selenophenes (6a, b)
An oven-dried Schlenk flask was charged with Pd
A
(6.8 mg, 10 mol%), L (24.6 mg, 20 mol%), 4b, c (0.3 mmol),
2116
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Adv. Synth. Catal. 2008, 350, 2109 – 2117

Efficient Synthesis of Substituted Selenophenes
UPDATES
was removed under vacuum. The residue was purified by
flash column chromatography (fine silica gel, heptanes).
Product 7 was isolated as a yellow solid; yield: 0.123 g
Gollnick, A. R. Oseroff, S. L. Gibson, J. Med. Chem.
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[14] J. Schatz, Thiophenes, Thiophene 1,1-Dioxides, and
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[15] a) J. Nakayama, R. Yomoda, M. Hoshino, Heterocycles
1987, 26, 2215; b) M. A. Beswick, C. N. Harmer, P. R.
Raithby, A. Steiner, M. Tombul, D. S. Wright, J. Orga-
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1
(77%); mp 80–818C. H NMR (250 MHz, CDCl3): d=7.33,
3
3
7.36 (t, J=8.2 Hz, 4H, 4 CH, Ar), 7.38, 7.39 (t, J=8.2 Hz,
3
2H, 2 CH, Ar), 7.52, 7.55 (d, J=8.2 Hz, 4H, 4 CH, Ar);
13C NMR (75 MHz, CDCl3): d=128.4, 128.5, 129.2, 1231.6,
132.5 (overlap of two CH) (CH, Ar), 73.9, 81.6, 83.3, 100.8
˜
(C, acetylene), 119.6, 122.1, 132.9 (C, Ar); IR (KBr): n=
2959 (w), 2913 (w), 2836 (w), 2532 (w), 1727 (w), 1599 (m),
1495 (m), 1462 (m), 1242 (m), 1105 (m), 1032 (m), 1011 (m),
800 cmÀ1 (m); MS (EI, 70 eV): m/z (%)=531 (M+, 15), 530
(100), 529 (37), 528 (22), 452 (17), 389 (15); HR-MS (EI,
70 eV): calcd. for C36H20Se (M+): 532.07302; found:
532.070312.
[16] D. Prim, D. Joseph, G. Kirsch, Phoshorus, Sulfur, Sili-
con Rel. Elem. 1994, 91,137.
Acknowledgements
[17] Reviews: a) J. J. Li, G. W. Gribble, Palladium in Hetero-
cyclic Chemistry; Pergamon Press, Oxford, 2000;
b) V. N. Kalinin, Synthesis 1992, 413.
Financial support by the State ofVietnam (MOET scholar-
ships for T. T. D.) is gratefully acknowledged.
[18] a) K. Takimiya, N. Niihara, T. Otsubo, Synthesis 2005,
1589; b) P. Prediger, A. V. Moro, C. V. Nogueira, L. Sa-
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2117