Direct zincation of functionalized aromatics and heterocycles by using a magnesium base in the presence of ZnCl2

Article abstract of DOI:10.1002/chem.200801558

A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by using (TMP)₂:Mg·2LiCl (TMP = 2,2,6,6-tetramethylpiperamidyl) in the presence of ZnCl₂. The possible pathways of this metalation proc

Full text of DOI:10.1002/chem.200801558

FULL PAPER
DOI: 10.1002/chem.200801558
Direct Zincation of Functionalized Aromatics and Heterocycles by Using a
Magnesium Base in the Presence of ZnCl2
Zhibing Dong,[a, b] Giuliano C. Clososki,[c] Stefan H. Wunderlich,[a] Andreas Unsinn,[a]
Jinshan Li,[b] and Paul Knochel*[a]
Dedicated to Professor Wolfgang Steglich on the occasion of his 75th birthday
Abstract: A wide range of polyfunctional aryl and heteroaryl zinc reagents were
efficiently prepared in THF by using (TMP)2Mg·2LiCl (TMP=2,2,6,6-tetramethyl-
piperamidyl) in the presence of ZnCl2. The possible pathways of this metalation
Keywords: cross-coupling · hetero-
procedure as well as possible reactive intermediates are discussed. This experimen-
cycles · metalation · organometal-
tal protocol expands the tolerance of functional groups and allows an efficient zinc-
lics · zincation
ation of sensitive heterocycles such as quinoxaline or pyrazine. The zincated
arenes and heteroarenes react with various electrophiles providing the expected
products in 60–95% yield.
Introduction
reactivity of the intermediate magnesium species
(Scheme 1). It is already known that the metalation of dia-
zines is challenging due to very facile competitive nucleo-
philic addition reactions.[5] However, in the course of our
studies, we have found that the addition of ZnCl2 to the sub-
strate, prior to the addition of the base (1), leads to excel-
lent results. Eaton and co-workers have already performed
Directed lithiations are important reactions for the function-
alization of aromatics and heterocycles.[1] In contrast, direct-
ed metalations using magnesium bases have been much less
used.[2] Recently, we have shown that the mixed lithium–
magnesium bases (TMP)MgCl·LiCl[3] and especially
(TMP)2Mg·2LiCl (1; TMP=2,2,6,6-tetramethylpiperamid-
yl)[4] are highly active and soluble magnesium bases allowing
smooth metalations of various aromatics and heterocycles
with an excellent functional group compatibility. However,
deprotonation of some heterocyclic aromatic rings such as
quinoxaline (2a) gave unsatisfactory results due to the high
direct lithiations with LiACTHNURGTNE(UNG TMP) in the presence of mercury
salts.[6] The in situ generated organomercurials can be fur-
ther converted to corresponding halides or transmetalated
with organomagnesium or organolithium reagents in a pro-
cess called reverse transmetalation.[7,8] Herein, we wish to
report a direct method for the deprotonation and functional-
ization of some sensitive aromatic and heteroaromatic sub-
strates by using (TMP)2Mg·2LiCl in the presence of ZnCl2.
The methodology allows many sensitive aromatics and het-
erocycles to be metalated at 258C, which gives the expected
[a] Z. Dong, S. H. Wunderlich, A. Unsinn, Prof. Dr. P. Knochel
Department Chemie und Biochemie
Ludwig-Maximilians-Universitꢀt Mꢁnchen
Butenandtstrasse 5–13 Haus F
81377 Mꢁnchen (Germany)
Fax : (+49)89-2180-77680
E-mail: paul.knochel@cup.uni-muenchen.de
[b] Z. Dong, Prof. Dr. J. Li
State Key Laboratory of Elemento-Organic Chemistry
Nankai University
Tianjin 300071 (P.R. China)
[c] Prof. Dr. G. C. Clososki
Faculdade de CiÞncias FarmacÞuticas de Ribeir¼o Preto
Universidade de S¼o Paulo
Av. do Cafꢂ s/n
14040-903 Ribeir¼o Preto-SP (Brazil)
Scheme 1. Functionalization of quinoxaline (2a) with (TMP)2Mg·2LiCl
(1) in THF in the presence and absence of ZnCl2.
Chem. Eur. J. 2009, 15, 457 – 468
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457

functionalized products in good yields after reaction with
electrophiles.
played an even lower metalation ability. Furthermore, a
third pathway has to be considered (Scheme 2, pathway c):
the heterocycle 2a coordinates ZnCl2 affording the tentative
Zn complex 8,[10] which reacts with 1 leading to the zinc de-
rivative 6 after fast transmetalation. This last pathway is the
preferred one, since we noticed that 1 reacts very rapidly
with ZnCl2 to afford the zinc reagent 7.[11] Therefore, the
order of addition of all the reaction partners (first ZnCl2,
then base 1) is essential for achieving the reported metala-
tion times. To obtain more information about the possible
intermediates, additional kinetic studies were performed by
changing the ratio between 1 and ZnCl2 (more details are
given below).
Results and Discussion
We first investigated the metalation of quinoxaline (2a).
The treatment of 2a with (TMP)2Mg·2LiCl (1; 0.55 equiv)
at 258C for 2 h in THF gave only traces of the desired quin-
ACHTUNGTRENNUNGoxalyl iodide (3) after iodolysis, while the major product,
the dimeric heterocycle 4, was isolated in 34% yield
(Scheme 1). Attempts to perform the same reaction at lower
temperature (0 to À788C) also gave unsatisfactory yields
due to the formation of dimer 4. In contrast, treatment of
2a with ZnCl2 (0.5 equiv) in THF followed by the slow addi-
tion of 1 (0.55 equiv) gave a metalated intermediate within
2 h at 258C. After iodolysis we observed traces of dimer 4,
and quinoxalyl iodide (3) was isolated in 94% yield
(Scheme 1).
This metalation procedure, for example, the magnesiation
of organic substrates by 1 in THF in the presence of ZnCl2
proves to be quite general. Thus, a number of sensitive
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Several reaction pathways leading to this result are con-
ceivable (Scheme 2). In pathway a, base 1 reacts first with
quinoxaline (2a) affording the magnesiated heterocycle 5.
After a fast transmetalation with ZnCl2 (0.5 equiv) the quin-
N
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
ACHTUNGTRENNUNGoxalylzinc reagent 6 is formed (Scheme 2, pathway a). Alter-
natively in pathway b, base 1 reacts rapidly with ZnCl2 to
provide (TMP)2Zn·MgCl2·2LiCl (7; Scheme 2, pathway b),
which subsequently reacts with quinoxaline (2a) leading to
the zinc reagent 6. This second pathway can be excluded
since the reaction times of the in situ procedure are consid-
erably shorter (258C, 2 h) than the metalation using
(TMP)2Zn·2MgCl2·2LiCl (9) generated separately (258C,
5 h; Table 2, entry 1, see below).[9] Also, a freshly prepared
solution of 7 in THF obtained by mixing ZnCl2 with 1 dis-
the corresponding alcohol 14e
in 60% yield (entry 5). This
protocol was also used to per-
form metalations on bromo-
substituted pyACTHNUTRGENUGNrimidines. Thus,
2-bromopyrimidine (10a) and
5-bromopyrimidine (10b) were
quantitatively zincated within
12 and 0.5 h, respectively. Palla-
dium-catalyzed cross-couplings
and copper-mediated allylations
gave the corresponding func-
tionalized pyrimidines 15a–f in
66–91% yield (entries 6–11).
Similarly,
3-bromoquinoline
(11) was exclusively zincated at
position 2 providing, after the
reactions with electrophiles, the
corresponding derivatives 16a
and 16b in 70–82% yield (en-
tries 12 and 13). The direct zin-
cation of aromatic esters bear-
Scheme 2. Postulated intermediates of the metalation of 2a with (TMP)2Mg·2LiCl (1) in the presence of
ZnCl2.
ing
a
halogen group using
458
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Chem. Eur. J. 2009, 15, 457 – 468

Direct Zincation of Functionalized Aromatics
FULL PAPER
Table 1. Products of type 14–18 obtained by direct metalation of the substrates 2–13 with (TMP)2Mg·2LiCl
(1) at 258C in the presence of ZnCl2 (0.5 equiv) followed by the reaction with electrophiles.
was also accomplished at 258C
leading to the zincated inter-
mediates within 12 h reaction
time. After quenching with var-
ious electrophiles, the corre-
sponding functionalized ethyl
benzoates 17a–d were isolated
in 76–90% yields (entries 14–
17). In contrast, full metalation
Yield [%][a]
À
E X
Entry
Substrate
t [h]
Product
1
2
2a
2a
2
2
p-IC6H4O
c-C6H9Br
(TIPS)
14a: E=p-C6H4O
14b: E=c-C6H9
G
71[c]
65[b]
of ethyl ACHTNUTRGNEUNG3-fluorobenzoate (12c)
3
4
2b
2b
0.1
0.1
tBuCOCl
PhCOCl
14c: E=COtBu
14d: E=COPh
81[b]
86[b]
was completed after 3 h by
using only 0.55 equiv of base 1.
Further bromolysis or benzoyla-
tion in the presence of CuCN·2
LiCl gave the derivatives 17e
and 17 f in 74–80% yield (en-
tries 18 and 19). Although the
lithiation of 1,3-difluoroben-
zene (13a) was achieved with
sec-butyllithium at À758C,[16]
the metalation of this substrate
can be successfully performed
at 258C by using the ZnCl2–
5
2c
0.5
PhCHO
14e: E=PhC(OH)
60
6
7
8
9
10a
10a
10a
10a
12
12
12
12
p-IC6H4CN
p-IC6H4CO2Et
c-C6H9Br
15a: E=p-C6H4CN
15b: E=p-C6H4CO2Et
15c: E=c-C6H9
91[c]
72[c]
70[b]
72[b]
CH2=C
A
15d: E=CH2=C
ACHTUGNRTNE(NUNG CH3)CH2
(TMP)2Mg·2LiCl
protocol.
10
11
10b
10b
0.5
0.5
c-C6H9Br
CH2=C(CH3)CH2Br
15e: E=c-C6H9
15 f: E=CH2=CACHTUGNTERNNU(G CH3)CH2
70[b]
66[b]
After palladium-catalyzed
a
N
cross-coupling with ethyl 4-io-
dobenzoate or a copper-mediat-
ed benzoylation, the functional-
ized 1,3-difluorobenzenes 18a
and 18b were isolated in 82–
90% yield (entries 20 and 21).
Moreover, this methodology
also allows multiple functionali-
zation of heterocyclic sub-
strates. For example, quinoxa-
line (2a) was sequentially func-
tionalized at positions 2 and 3.
The zincated quinoxaline 6 was
reacted with ethyl 4-iodoben-
12
13
11
11
2.5
2.5
p-IC6H4CO2Et
CH2=C(CH3)CH2Br
16a: p-IC6H4CO2Et
16b: E=CH2=C(CH3)CH2
82[c]
70[b]
G
ACHTUNGTRENNUNG
14
15
12a
12a
12
12
p-IC6H4CO2Et
CH2=C(CH3)CH2Br
17a: E=p-C6H4CO2Et
17b: E=CH2=CACHTUGNTERNNU(G CH3)CH2
90[c]
76[b]
T
16
17
12b
12b
12
12
A
17c: E=Br
17d: E=COPh
76
PhCOCl
76[b]
zoate
(2 mol%)
using
and
[Pd
PACHTUNGTRENNUNG(o-furyl)3
ACHTUNGTRENNUNG(dba)2]
(4 mol%) as a catalytic system
to provide the functionalized
quinoxaline 14 f in 82% yield.
A subsequent zincation of 14 f
followed by the reaction with
iodine afforded iodide 19 in
73% overall yield (Scheme 3).
Surprisingly, 6-bromoquinoxa-
line (2b) was first metalated at
position 5 to give dibromide
14g by the reaction with
(BrCl2C)2 in 70% yield. The
18
19
12c
12c
3
3
PhCOCl
AHCTUNTGREG(NNUN BrCl2C)2
17e: E=COPh
17 f: E=Br
80[b]
74
20
21
13a
13a
12
12
p-IC6H4CO2Et
PhCOCl
18a: E=p-C6H4CO2Et
18b: E=COPh
90[c]
82[b]
[a] Isolated yield of analytically pure product. [b] A transmetalation using CuCN·2LiCl (1.1 equiv) was per-
formed. [c] Obtained by a palladium-catalyzed cross-coupling.
(TMP)Zn
(tBu)2Li as the metalation reagent usually requires
presence of the extra bromine atom in position 6 changes
the regioselectivity, due to the inductive effect of the bro-
mine atom, to an exclusive proton abstraction in position 5.
Furthermore, the second metalation occurs only at position
Chem. Eur. J. 2009, 15, 457 – 468
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459

P. Knochel et al.
using
freshly
prepared
(9).
(TMP)2Zn·2MgCl2·2LiCl
Moreover, the full conversion
of the halo esters 12a and 12b
into the corresponding zinc re-
agents with 9 was only achieved
after 110 h (Table 2, entries 5–
7). The same reaction can be
completed within 12 h by using
the
ZnCl2–(TMP)2Mg·2LiCl
protocol (Table 1, entries 14–
17). These results suggest that
Scheme 3. Double functionalization of the quinoxalines 2a and 2b.
the formation of a zinc bis-
amide intermediate (pathway b,
8 giving the corresponding ketone 20 by means of a copper-
mediated benzoylation in 82% yield (Scheme 3). Therefore,
the use of a bromine substituent in position 6 reveals a
route to functionalization of the aromatic ring of quinoxa-
lines and may be of general synthetic value.
Additional experiments were performed to obtain more
information about the reaction mechanism. Thus, the metal-
ation and functionalization of some of the aromatics and
heterocycles listed in Table 1 using directly the zinc bis-
amide (TMP)2Zn·2MgCl2·2LiCl (9)[9] were studied and the
metalation rates were compared with those of the ZnCl2–
(TMP)2Mg·2LiCl protocol. In general, the metalation time
dramatically increased when 9 was used (Table 2). A re-
markable example is the metalation of 5-bromopyrimidine
(10b; Table 2, entry 3). In this case, the metalation using the
ZnCl2–(TMP)2Mg·2LiCl protocol occurs 10 times faster than
Scheme 1) does not occur, and that the more reactive base 1
performs the metalation rapidly on the precomplexed aro-
matic or heterocyclic system, which is immediately convert-
ed into the corresponding zinc reagent. Kinetic studies were
also performed by changing the ratio between base 1 and
ZnCl2. Interestingly, when 1.1 equiv of 1 and 0.5 equiv of
ZnCl2 were used, full metalation of ethyl 4-chlorobenzoate
(12a) was achieved within 1 h, thus showing that this reac-
tion can be accelerated by increasing the amount of
(TMP)2Mg·2LiCl (1; Figure 1).
We also investigated the preparation and application of
other mixed bases[17] derived from (TMP)2Mg·2LiCl and
ZnCl2. Thus, mixed-metal bases like (TMP)3ZnMgCl·
0.5MgCl2·3LiCl and (TMP)4ZnACTHUNRTGNEUNG(MgCl)2·4LiCl were pre-
pared by stirring 1 equiv of ZnCl2 with 1.5 and 2 equiv of
(TMP)2Mg·2LiCl, respectively (30 min at 258C), and their
activities were investigated for
the metalation of ethyl 4-
Table 2. Products of type 14–17 obtained by direct metalation of the substrates 2–12 with
(TMP)2Zn·2MgCl2·2LiCl (9) at 258C followed by the reaction with electrophiles.
chloro
Remarkably,
(TMP)4Zn(MgCl)2·4LiCl
ACHTUNGTRENNUNG
Entry
Substrate
t [h][a]
E X
Product
Yield [%][b]
À
AHCTUNGTRENNUNG
(0.55 equiv) showed high activi-
ty leading to the complete met-
alation of 12a within 1 h. After
transmetalation with CuCN·2
LiCl, the reaction with benzoyl
chloride provided ketone 17g
in 76% yield (Scheme 4). This
result is comparable to the
yield of 17g obtained by using
(TMP)2Mg·2LiCl (1.1 equiv) in
1
2
2a
2a
5 (2)
p-IC6H4CO2Et
m-IC6H4CF3
14 f: E=p-C6H4CO2Et
14h: E=m-C6H4CF3
82[c]
88[d]
5 (2)
5 (0.5)
2 (0.5)
110 (12)
3
4
5
10b
11
p-IC6H4CN
p-IC6H4CN
PhCOCl
15g: E=p-C6H4CN
16c: E=p-C6H4CN
17g: E=COPh
75[d]
95[d]
85[c]
the
(0.55 equiv).
(TMP)4Zn(MgCl)2·4LiCl could
presence
of
ZnCl2
Therefore,
AHCTUNGTRENNUNG
be one of the active intermedi-
ates in this reaction (Figure 2
and Scheme 4). When 1.1 equiv
12a
of (TMP)4ZnACTHNUGTRNE(UNG MgCl)2·4LiCl was
used the metalation of 12a ap-
peared to be even faster, but
after the subsequent reaction
with benzoyl chloride in the
presence of CuCN·2LiCl only
6
7
12b
12b
110 (12)
110 (12)
m-IC6H4CF3
p-IC6H4CO2Et
17h: E=m-C6H4CF3
17i: E=p-C6H4CO2Et
83[d]
78[d]
[a] Metalation times using (TMP)2Zn·2MgCl2·2LiCl (9); in parentheses are the metalation times using
(TMP)2Mg·2LiCl (1) in the presence of ZnCl2. [b] Isolated yield of analytically pure product. [c] A transmeta-
lation CuCN·2LiCl (1.1 equiv) was performed. [d] Obtained by a palladium-catalyzed cross-coupling.
460
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Chem. Eur. J. 2009, 15, 457 – 468

Direct Zincation of Functionalized Aromatics
FULL PAPER
the formation of 1-benzoyl-2,2,6,6-tetramethylpiperidine was
observed. Similarly, the base (TMP)3ZnMgCl·0.5MgCl2
·3LiCl (1.1 equiv) displayed a good kinetic basicity, but after
a copper-mediated benzoylACTHNURGTNEaUNG tion ketone 17g was isolated in
only 13% yield (Scheme 4). Attempts to improve these re-
actions by using less than 0.5 equiv of the mixed-metal bases
(TMP)3ZnMgCl·0.5MgCl2·3LiCl and (TMP)4ZnACHTUNGTRENNUNG(MgCl)2
·4LiCl led to lower metalation rates but not to improved
yields of 17g.
We have also investigated the preparation of other or-
ACHUTNGERNgNUG anoAHCTUNGTRNENmUGN etallics by performing selective deprotonations with
(TMP)2Mg·2LiCl (1) in the presence of various other or-
ganometallic compounds. Thus, 1 (1.1 equiv) was added
dropwise to a mixture of quinoxaline (2a) and nBu3SnCl
(1.1 equiv) in THF at À788C. After stirring for 30 min, stan-
nane 21 was isolated in 73% yield (Scheme 5). Similarly,
ethyl 4-chlorobenzoate (12a) is smoothly deprotonated with
1 in the presence of CuCN·2LiCl (1.1 equiv), giving the
functionalized ketone 17g in 71% yield after a subsequent
reaction with benzoyl chloride.
Figure 1. Influence of the (TMP)2Mg·2LiCl/ZnCl2 ratio on the metalation
&
rate of the ethyl 4-chlorobenzoate (12a) at 258C:
=1.10 equiv
=0.55 equiv
*
(TMP)2Mg·2LiCl+0.5 equiv
ZnCl2
in
situ;
(TMP)2Mg·2LiCl+0.5 equiv ZnCl2 in situ.
Scheme 5. Metalation of 2a and 12a with (TMP)2Mg·2LiCl (1) in the
presence of other salts.
Conclusion
In summary, we have reported a simple method to deproto-
nate and functionalize a broad range of reactive aromatics
and
heterocycles
by
using
the
powerful
base
(TMP)2Mg·2LiCl in the presence of ZnCl2. The deprotona-
tion reaction can be drastically accelerated by increasing the
(TMP)2Mg·2LiCl-to-ZnCl2 ratio. Mechanistic studies indi-
cate that a precomplexation of the aromatic or heteroaro-
matic substrate facilitates the deprotonation with
(TMP)2Mg·2LiCl. Finally, the methodology proved to be
also efficient for preparing other reactive organometallics
such as copper or tin derivatives through an in situ trapping
by other salts. Applications toward the synthesis of biologi-
cally active molecules are currently being investigated in
our laboratories.
&
Figure 2. Metalation of substrate 12a using different mixed bases:
=
*
1.1 equiv (TMP)2Mg·2LiCl+0.5 equiv ZnCl2 in situ;
=1.1 equiv
(MgCl)2·4LiCl;
~
(TMP)3ZnMgCl·0.5MgCl2·3LiCl; =1.1 equiv (TMP)4Zn
U
!
=0.55 equiv (TMP)4ZnACHTUNRTGNEUNG(MgCl)2·4LiCl.
Experimental Section
Scheme 4. Metalation of substrate 12a using different mixed bases fol-
General: All reactions were carried out under an argon atmosphere in
lowed by a copper-mediated reaction with benzoyl chloride.
flame-dried glassware. Syringes that were used to transfer anhydrous sol-
Chem. Eur. J. 2009, 15, 457 – 468
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461

P. Knochel et al.
vents or reagents were purged with argon prior to use. THF was freshly
distilled from sodium benzophenone ketyl under nitrogen. Yields refer to
isolated yields of compounds estimated to be >95% pure as determined
by 1H NMR spectroscopy (258C) and capillary GC. Column chromatog-
raphy was performed by using silica gel (0.040–0.063 mm, 230–400 mesh
ASTM) from Merck if not indicated. (TMP)H and liquid acid chlorides
were distilled prior to use.
4-iodobenzene (564 mg, 1.5 mmol). The reaction mixture was stirred at
258C for 1 h and was quenched with aqueous saturated NH4Cl solution
(10 mL). After extraction with diethyl ether (3ꢄ20 mL), the combined
organic layers were washed with brine, dried over MgSO4, filtered, and
concentrated under vacuum. Purification by using flash chromatography
on silica gel (pentane/diethyl ether 4:1) furnished 14a as a pale yellow oil
1
(265 mg, 71%). H NMR (600 MHz, CDCl3): d=9.30 (d, J=9.6 Hz, 1H),
8.14–8.11 (m, 4H), 7.79–7.70 (m, 2H), 7.09–7.06 (m, 2H), 1.35–1.03 ppm
(m, 21H); 13C NMR (150 MHz, CDCl3): d=158.41, 151.55, 143.09,
142.26, 141.09, 130.17, 129.50, 129.35, 129.04, 129.01, 128.94, 120.62, 17.91,
17.71, 12.71, 12.30 ppm; IR (ATR): n˜ =2942, 2864, 1602, 1544, 1513, 1487,
1462, 1422, 1313, 1269, 1229, 1169, 1134, 1047, 1011, 996, 956, 906, 881,
840, 759, 737, 729, 682 cmÀ1; MS (70 eV, EI): m/z (%): 379 (17), 378 (51)
[M]+, 336 (30), 335 (100), 308 (14), 307 (53), 293 (15), 280 (21), 279 (84),
266 (11), 265 (49), 249 (11), 205 (15), 140 (34), 133 (10); HRMS (EI):
Typical
procedure
1
(TP 1)—Preparation
of
the
reagent
(TMP)2Mg·2LiCl: In an argon-flushed Schlenk flask, 2,2,6,6-tetramethyl-
piperidine ((TMP)H) (5.07 mL, 30 mmol) was dissolved in THF (30 mL).
This solution was cooled to À408C and nBuLi (2.4m in hexane, 12.5 mL,
30 mmol) was added dropwise. After the addition was complete, the reac-
tion mixture was warmed to 08C and was stirred at this temperature for
30 min. Freshly titrated (TMP)MgCl·LiCl (1.0m in THF, 30 mL,
30 mmol) was then added dropwise to the LiACTHNUTRGNE(NUG TMP) solution and the re-
AHCNUTTGERGmNUNN /z calcd for C23H30ON2Si: 378.2127; found: 378.2132.
action mixture was stirred at 08C for 30 min, warmed to 258C, and stirred
for 1 h. The solvents were then removed under vacuum to afford a yel-
lowish solid. Freshly distilled THF was then slowly added under vigorous
stirring until the complete dissolution of the salts. The freshly prepared
solution of (TMP)2Mg·2LiCl (1) in THF was titrated prior to use at 08C
with benzoic acid using 4-(phenylazo)diphenylamine as indicator. A con-
centration of 0.6m in THF was obtained.
Synthesis of 2-cyclohex-2-enylquinoxaline (14b):[18] By following TP 2,
the metalation of quinoxaline (2b; 130 mg, 1 mmol) was completed
within 2 h at 258C. The reaction mixture was cooled to À408C, then
CuCN·2LiCl (1m in THF, 1.1 mL, 1.1 mmol) and 3-bromocyclohexene
(242 mg, 1.5 mmol) were added. The mixture was allowed to warm to
258C overnight. The reaction mixture was quenched with saturated
NH4Cl solution (10 mL) and extracted with diethyl ether (3ꢄ20 mL).
The combined organic layers were washed with brine, dried over MgSO4,
and concentrated under vacuum. The residue was purified by using flash
chromatography on silica gel (pentane/diethyl ether 5:1) to give 14b as a
colorless oil (137 mg, 65%). 1H NMR (300 MHz, CDCl3): d=8.82 (s,
1H), 8.11–8.07 (m, 2H), 7.76–7.71 (m, 2H), 6.10–6.03 (m, 1H), 5.94–5.90
(m, 1H), 3.90–3.83 (m, 1H), 2.23–2.17 (m, 3H), 1.94–1.72 ppm (m, 3H);
13C NMR (75 MHz, CDCl3): d=160.11, 145.14, 142.05, 141.38, 130.08,
129.89, 129.10, 129.03, 129.01, 127.01, 42.94, 30.31, 24.85, 21.29 ppm; IR
(ATR): n˜ =3176, 3020, 2929, 2859, 2835, 1558, 1491, 1446, 1366, 1294,
1204, 1176, 1126, 1016, 969, 918, 882, 758, 723 cmÀ1; MS (70 eV, EI): m/z
(%): 210 (82) [M],+ 209 (40), 196 (10), 195 (37), 183 (14), 182 (28), 181
(100), 169 (24), 168 (15), 154 (15), 145 (12), 144 (97), 130 (15), 129 (22),
103 (13), 102 (30), 77 (28), 76 (33), 75 (16), 63 (13), 53 (10), 52 (10), 51
(23), 50 (15); HRMS (EI): m/z calcd for C14H14N2: 210.1157; found:
210.1145.
Typical procedure 2 (TP 2)—Zincation of polyfunctionalized aromatics
and heterocycles with (TMP)2Mg·2LiCl: In a dry, argon-flushed 25 mL
Schlenk flask, equipped with a magnetic stirring bar and a septum, the
given starting material (1 mmol) was dissolved in THF (2 mL), and
ZnCl2 (1m solution in THF, 0.5 mL, 0.5 mmol) was added.
(TMP)2Mg·2LiCl (0.6m in THF, 0.92 mL, 0.55 mmol) was added drop-
wise and the reaction mixture was stirred at 258C for the indicated time.
Complete metalation was detected by using GC analysis of reaction ali-
quots, which were quenched with I2 in dry THF.
Typical
procedure
3
(TP 3)—Preparation
of
the
reagent
(TMP)2Zn·2MgCl2·2LiCl (9): In an argon-flushed Schlenk flask, ZnCl2
(53.0 mmol, 7.22 g) was dried under vacuum at 1408C for 4 h. After cool-
ing to 258C, dry THF (25 mL) and freshly titrated (TMP)MgCl·LiCl
(100 mmol, 1.00m, 100 mL) were added slowly. The resulting mixture was
stirred for 15 h at 258C. The freshly prepared (TMP)2Zn·2MgCl2·2LiCl
(9) solution was titrated prior to use at 08C with benzoic acid using
4-(phenylazo)diphenylamine as indicator. A concentration of 0.4m in
THF was obtained.
Synthesis of 1-(6-bromoquinoxalin-5-yl)-2,2-dimethylpropan-1-one (14c):
By following TP 2, the metalation of 6-bromoquinoxaline (2b; 208 mg,
1.0 mmol) was completed within 5 min at 258C. The reaction mixture was
cooled to À408C, then CuCN·2LiCl (1m in THF, 1.1 mL, 1.1 mmol) and
pivaloyl chloride (0.19 mL, 1.5 mmol) were added. The mixture was al-
lowed to warm to 258C and was stirred overnight. The reaction mixture
was quenched with saturated NH4Cl solution (10 mL) and extracted with
diethyl ether (3ꢄ20 mL). The combined organic layers were washed with
brine, dried over MgSO4, and concentrated under vacuum. The crude
product was purified by means of column chromatography (pentane/di-
ethyl ether 4:1) to give 14c as a colorless solid (238 mg, 81%). M.p.
108.7–110.08C; 1H NMR (300 MHz, CDCl3): d=8.90 (s, 1H), 8.84 (s,
1H), 8.00 (d, J=9 Hz, 1H), 7.92 (d, J=9 Hz, 1H), 1.38 ppm (s, 9H);
13C NMR (75 MHz, CDCl3): d=213.25, 145.16, 143.01, 141.42, 134.35,
130.49, 119.11, 44.79, 27.88 ppm; IR (ATR): n˜ =2969, 2930, 1694, 1587,
1566, 1475, 1464, 1363, 1356, 1216, 1209, 1154, 1116, 1082, 1022, 946, 889,
870, 835, 805, 788, 738, 688 cmÀ1; MS (70 eV, EI): m/z (%): 292 (3) [M]+,
228 (17), 237 (97), 236 (18), 235 (100), 213 (11), 210 (11), 209 (20), 208
(11), 207 (19), 129 (10), 128 (11); HRMS (EI): m/z calcd for
C13H13ON2Br: 292.0211; found: 292.0195.
Typical procedure 4 (TP 4)—Zincation of polyfunctionalized aromatics
and heterocycles with (TMP)2Zn·2MgCl2·2LiCl: A dry, argon-flushed
25 mL Schlenk flask, equipped with a magnetic stirring bar and a septum,
was charged with a solution of the corresponding arene (1.0 mmol) in dry
THF (1 mL). After setting the desired temperature (Table 1), the zinc
base (0.55 mmol) was added dropwise and was stirred at the same tem-
perature. The completion of the metalation was checked by using GC
analysis of reaction aliquots quenched with a solution of I2 in dry THF.
Synthesis of 2-iodoquinoxaline[5e] (3): By following TP 2, the metalation
of quinoxaline (2b; 130 mg, 1 mmol) was completed within 2 h at 258C.
Iodine (506 mg, 2 mmol) dissolved in THF (2 mL) was added to the reac-
tion and the reaction mixture was stirred at 258C for 1 h and was
quenched with aqueous saturated NH4Cl solution (10 mL). After extrac-
tion with diethyl ether (3ꢄ20 mL), the combined organic layers were
washed with saturated Na2S2O3 solution and brine, dried over MgSO4, fil-
tered, and concentrated under vacuum. The crude product was purified
by means of column chromatography (pentane/diethyl ether 10:1) to give
3 as a pale yellow solid (230 mg, 94%). M.p. 107.5–108.88C; 1H NMR
(600 MHz, CDCl3): d=8.99 (s, 1H), 8.08–8.03 (m, 2H), 7.80–7.76 ppm
(m, 2H); 13C NMR (150 MHz, CDCl3): d=152.06, 144.79, 140.97, 130.86,
130.42, 129.50, 128.80, 118.08 ppm; IR (ATR): n˜ =3057, 3039, 1562, 1527,
1486, 1459, 1318, 1235, 1131, 1064, 947, 898, 849, 758 cmÀ1; MS (70 eV,
EI): m/z (%): 256 (77) [M]+, 130 (10), 129 (100), 102 (43), 75 (15);
HRMS (EI): m/z calcd for C8H5N2I: 255.9497; found: 255.9485.
Synthesis of (6-bromoquinoxalin-5-yl)phenylmethanone (14d): By follow-
ing TP 2, the metalation of 6-bromoquinoxaline (2b; 208 mg, 1.0 mmol)
was completed within 5 min at 258C. The reaction mixture was cooled to
À408C, then CuCN·2LiCl (1m in THF, 1.1 mL, 1.1 mmol) and benzoyl
chloride (0.18 mL, 1.5 mmol) were added. The mixture was allowed to
warm to 258C overnight. The reaction mixture was quenched with
AHCTUNGTREsGNNNU aturated NH4Cl solution (10 mL) and was extracted with diethyl ether
Synthesis of 2-(4-triisopropylsilanyloxyphenyl)quinoxaline (14a): By fol-
lowing TP 2, the metalation of quinoxaline (2b; 130 mg, 1 mmol) was
(3ꢄ20 mL). The combined organic layers were washed with brine, dried
over MgSO4, and concentrated under vacuum. The crude product was pu-
rified by means of column chromatography (pentane/diethyl ether 1:1) to
completed within 2 h at 258C. A solution of [Pd
ACHUTGTNRNE(UNG dba)2] (15 mg) and PACHTUGNTREN(NUGN o-
furyl)3 (12.5 mg) in THF (2 mL) was added, followed by triisopropylsilyl-
462
www.chemeurj.org
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 457 – 468

Direct Zincation of Functionalized Aromatics
FULL PAPER
give 14d as
a
colorless solid (532 mg, 86%). M.p. 169.6–172.48C
ACTHUNGRTENNUNGPAHCTUNGTRENN(NUG o-furyl)3 (25 mg) in THF (2 mL) was added, followed by 4-iodobenzo-
(decomp); 1H NMR (600 MHz, CDCl3): d=8.86 (d, J=0.6 Hz, 1H), 8.74
(d, J=0.6 Hz, 1H), 8.10 (d, J=9 Hz, 1H), 7.97 (d, J=9 Hz, 1H), 7.81 (d,
J=7.2 Hz, 2H), 7.59 (t, J=7.2 Hz, 1H), 7.44 ppm (t, J=7.8 Hz, 2H);
13C NMR (150 MHz, CDCl3): d=194.79, 145.75, 145.53, 142.04, 141.45,
140.03, 136.05, 134.18, 134.07, 131.29, 130.09, 129.78, 128.85, 128.43,
120.97 ppm; IR (ATR): n˜ =3065, 3026, 3002, 1669, 1594, 1579, 1479, 1468,
1446, 1372, 1352, 1316, 1290, 1268, 1258, 1216, 1198, 1179, 1150, 1112,
1018, 928, 868, 845, 835, 794, 781, 711, 690 cmÀ1; MS (70 eV, EI): m/z
(%): 314 (29), 312 (30) [M]+, 286 (13), 285 (60), 284 (13), 283 (61), 206
(17), 205 (100), 105 (13), 77 (32); HRMS (EI): m/z calcd for
C15H9ON2Br: 311.9898; found: 311.9877.
Synthesis of phenylpyrazin-2-ylmethanol (14e):[19] By following TP 2, the
metalation of pyrazine (2c; 160 mg, 2.0 mmol) was completed within
30 min at 258C. Benzaldehyde (0.303 mL, 3 mmol) was added at 258C
and the reaction mixture was stirred for 1 h. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. Purification by
using flash chromatography (pentane/diethyl ether 80:1; then diethyl
ether) furnished 14e as a pale yellow oil (221 mg, 60%). 1H NMR
(300 MHz, CDCl3): d=8.61 (s, 2H), 8.52–8.48 (m, 2H), 7.42–7.32 (m,
5H), 5.88 (s, 1H), 4.23 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=
156.94, 143.44, 143.32, 142.87, 141.86, 128.83, 128.29, 126.88, 74.19 ppm;
IR (ATR): n˜ =3254, 3058, 1493, 1452, 1400, 1301, 1226, 1190, 1146, 1060,
1016, 857, 810, 752, 698 cmÀ1; MS (70 eV, EI): m/z (%): 186 (100) [M]+,
185 (16), 169 (15), 168 (11), 107 (36), 105 (20), 81 (37), 80 (66), 79 (60),
78 (11), 77 (50), 53 (14), 52 (12), 51 (14); HRMS (EI): m/z calcd for
C11H10ON2: 186.0793; found: 186.0781.
nitrile (687 mg, 3.0 mmol), and the reaction mixture was stirred overnight
at 258C. The reaction mixture was quenched with saturated aqueous
NH4Cl solution (10 mL), extracted with diethyl ether (3ꢄ20 mL), and
dried over anhydrous MgSO4. After filtration, the solvent was evaporated
under vacuum. The crude product was purified by means of column chro-
matography (pentane/ethyl acetate 1:1) to give 15a as a pale yellow solid
(479 mg, 91%). M.p. 229.5–231.18C; 1H NMR (300 MHz, CDCl3): d=
8.69 (d, J=5.1 Hz, 1H), 8.25–8.21 (m, 2H), 7.86–7.83 (m, 2H), 7.74 ppm
(d, J=5.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=164.69, 160.24,
153.91, 138.99, 132.85, 127.98, 115.92, 115.35 ppm; IR (ATR): n˜ =3079,
3049, 2229, 1562, 1532, 1498, 1429, 1341, 1314, 1184, 1170, 1099, 1061,
983, 836, 830, 821, 767, 753, 673 cmÀ1; MS (70 eV, EI): m/z (%): 261 (36),
259 (37) [M]+, 181 (15), 180 (100), 199 (100), 128 (30), 127 (12), 102 (15),
101 (10), 76 (10), 75 (14), 53 (12); MS (70 eV, EI): m/z calcd for
C11H6N3Br: 258.9745; found: 258.9746.
Synthesis of 4-(2-bromopyrimidin-4-yl)benzoic acid ethyl ester (15b):[20]
By following TP 2, the metalation of 2-bromopyrimidine (10a; 318 mg,
2.0 mmol) was completed within 12 h at 258C. A solution of [Pd
ACHTUNGTRENNUNG(dba)2]
(30 mg) and P(o-furyl)3 (25 mg) in THF (2 mL) was added, followed by
AHCTUNGTRENNUNG
ethyl 4-iodobenzoate (828 mg, 3.0 mmol), and the reaction mixture was
stirred at 258C for 10 h. The reaction mixture was quenched with saturat-
ed aqueous NH4Cl solution (10 mL), extracted with diethyl ether (3ꢄ
20 mL), and dried over anhydrous MgSO4. After filtration, the solvent
was evaporated under vacuum. The crude product was purified by means
of column chromatography (pentane/diethyl ether 2:1) to give 15b as a
colorless solid (444 mg, 72%). M.p. 129.2–130.98C; 1H NMR (300 MHz,
CDCl3): d=8.65 (d, J=5.1 Hz, 1H), 8.22–8.15 (m, 4H), 7.75 (d, J=
5.1 Hz, 1H), 4.44 (q, J=7.2 Hz, 2H), 1.45 ppm (t, J=7.2 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=165.82, 165.80, 159.91, 153.77, 138.81,
133.38, 130.22, 127.38, 115.98, 61.43, 14.31 ppm; IR (ATR): n˜ =3081,
2991, 2902, 1712, 1563, 1531, 1429, 1347, 1277, 1164, 1129, 1117, 1102,
1062, 1021, 983, 848, 801, 780, 754, 712, 694, 653, 632 cmÀ1; MS (70 eV,
EI): m/z (%): 308 (31), 307 (17), 306 (32) [M]+, 305 (12), 280 (55), 278
(54), 264 (17), 263 (97), 262 (18), 261 (100), 235 (23), 233 (24), 199 (43),
181 (10), 154 (34), 129 (11), 128 (15), 127 (43), 102 (14), 101 (28), 100
(11), 91 (12), 77 (13), 76 (19), 75 (24), 74 (11), 51 (12); HRMS (EI): m/z
calcd for C13H11O2N2Br: 306.0000; found: 305.9989.
Synthesis of 4-quinoxalin-2-ylbenzoic acid ethyl ester (14 f): By following
TP 2, the metalation of quinoxaline (2a; 260 mg, 2.0 mmol) was complet-
ed within 2 h at 258C. A solution of [PdACHTNUTRGENN(GU dba)2] (30 mg) and PAHCUTGNTREN(NUGN o-furyl)3
(25 mg) in THF (2 mL) was added, followed by ethyl 4-iodobenzoate
(828 mg, 3.0 mmol). The reaction mixture was stirred at 258C for 6 h.
The reaction mixture was quenched with saturated aqueous NH4Cl solu-
tion (10 mL), extracted with diethyl ether (3ꢄ20 mL), and dried over an-
hydrous MgSO4. After filtration, the solvent was evaporated under
vacuum. The crude product was purified by means of column chromatog-
raphy (pentane/diethyl ether 3:1) to give 14 f as a colorless solid (455 mg,
82%). M.p. 88.8–90.98C; 1H NMR (300 MHz, CDCl3): d=9.39 (s, 1H),
8.33–8.16 (m, 6H), 7.85–7.80 (m, 2H), 4.46 (q, J=7.2 Hz, 2H), 1.47 ppm
(t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=166.15, 150.70,
143.12, 142.30, 141.81, 131.84, 130.57, 130.30, 130.12, 129.78, 129.17,
127.43, 61.27, 14.35 ppm; IR (ATR): n˜ =2923, 1713, 1607, 1363, 1271,
Synthesis of 2-bromo-4-cyclohex-2-enylpyrimidine (15c): By following
TP 2, the metalation of 2-bromopyrimidine (10a; 318 mg, 2 mmol) was
completed within 12 h at 258C. The reaction mixture was cooled to
À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and 3-bromo-
cyclohexene (484 mg, 3.0 mmol) were added. The mixture was allowed to
warm to 258C and was stirred overnight. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
3:1) to give 15c as a colorless oil (333 mg, 70%). 1H NMR (300 MHz,
CDCl3): d=8.46 (d, J=5.1 Hz, 1H), 7.22 (d, J=5.1 Hz, 1H), 6.03–5.98
(m, 1H), 5.75–5.71 (m, 1H), 3.57–3.52 (m, 1H), 2.13–2.09 (m, 3H), 1.75–
1.65 ppm (m, 3H); 13C NMR (75 MHz, CDCl3): d=177.57, 159.06,
153.02, 130.84, 125.87, 118.03, 43.24, 29.65, 24.78, 20.53 ppm; IR (ATR):
n˜ =3022, 2928, 2859, 1562, 1528, 1420, 1335, 1162, 908, 889, 838, 802, 776,
732, 723, 686, 673, 645 cmÀ1; MS (70 eV, EI): m/z (%): 240 (14), 239 (21),
238 (14) [M]+, 237 (21), 225 (20), 223 (21), 212 (12), 211 (59), 210 (12),
209 (57), 199 (11), 174 (31), 172 (33), 160 (12), 159 (100), 157 (13), 130
(13), 79 (22), 78 (11), 77 (21), 53 (14), 52 (14), 51 (14); HRMS (EI): m/z
calcd for C10H11N2Br: 238.0106; found: 238.0097.
1183, 1126, 1099, 1048, 1017, 958, 861, 772, 758, 752, 698, 668, 615 cmÀ1
;
MS (70 eV, EI): m/z (%): 279 (15), 278 (74) [M]+, 250 (32), 233 (100),
206 (12), 205 (32), 102 (12), 76 (14); HRMS (EI): m/z calcd for
C17H14O2N2: 278.1055; found: 278.1030.
Synthesis of 5,6-dibromoquinoxaline (14g): By following TP 2, the metal-
ation of 6-bromoquinoxaline (2b; 208 mg, 1 mmol) was completed within
5 min at 258C. BrCl2CCCl2Br (487 mg, 1.5 mmol) was added at 258C and
the resulting mixture was stirred for 1 h. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
5:1) to give 14g as a colorless solid (202 mg, 70%). M.p. 182.0–184.38C
(decomp); 1H NMR (300 MHz, CDCl3): d=8.99 (d, J=1.8 Hz, 1H), 8.91
(d, J=1.8 Hz, 1H), 8.03 (d, J=9 Hz, 1H), 8.00 ppm (d, J=9 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=145.96, 145.41, 142.55, 141.96, 134.51,
129.67, 128.05, 127.11 ppm; IR (ATR): n˜ =3076, 3044, 1591, 1548, 1469,
Synthesis of 2-bromo-4-(2-methylallyl)pyrimidine (15d): By following
TP 2, the metalation of 2-bromopyrimidine (10a; 318 mg, 2 mmol) was
completed within 12 h at 258C The reaction mixture was cooled to
À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and 3-bromo-
2-methylpropene (406 mg, 3.0 mmol) were added. The mixture was al-
lowed to warm to 258C and was stirred overnight. The reaction mixture
was quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
1430, 1352, 1338, 1188, 1112, 1030, 965, 880, 865, 830, 776, 640, 616 cmÀ1
;
MS (70 eV, EI): m/z (%): 290 (50), 289 (10), 288 (100) [M]+, 286 (53),
261 (18), 236 (12), 234 (24), 232 (12); HRMS (EI): m/z calcd for
C8H6N2Br2: 287.8721; found: 287.8677.
Synthesis of 4-(2-bromopyrimidin-4-yl)benzonitrile (15a): By following
TP 2, the metalation of 2-bromopyrimidine (10a; 318 mg, 2.0 mmol) was
completed within 12 h at 258C. A solution of [PdACTHNURGTNEUNG(dba)2] (30 mg) and
Chem. Eur. J. 2009, 15, 457 – 468
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
463

P. Knochel et al.
was purified by means of column chromatography (pentane/diethyl ether
5:1) to give 15d as a colorless oil (303 mg, 72%). 1H NMR (300 MHz,
CDCl3): d=8.39 (d, J=5.1 Hz, 1H), 7.17 (d, J=5.1 Hz, 1H), 4.88 (m,
1H), 4.74 (m, 1H), 3.40 (d, J=0.6 Hz, 2H), 1.66 ppm (t, J=1.2 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=172.07, 158.94, 152.93, 140.92, 119.21,
114.82, 46.05, 22.24 ppm; IR (ATR): n˜ =3080, 2974, 2938, 1652, 1566,
1530, 1427, 1334, 1205, 1164, 1095, 1021, 985, 894, 852, 817, 771, 732, 717,
692 cmÀ1; MS (70 eV, EI): m/z (%): 214 (15), 213 (100), 212 (17) [M]+,
211 (100), 200 (14), 199 (100), 198 (28), 197 (100), 196 (13), 174 (46), 172
(48), 132 (13), 131 (12), 118 (16), 106 (15), 92 (37), 65 (11); HRMS (EI):
m/z calcd for C8H9N2Br: 211.9949; found: 211.9915.
1398, 1366, 1290, 1275, 1243, 1181, 1122, 1107, 1072, 1024, 954, 913, 878,
850, 767, 748, 714, 696 cmÀ1; MS (70 eV, EI): m/z (%): 357 (31), 355 (33)
[M]+, 312 (33), 310 (35), 284 (22), 282 (22), 277 (21), 276 (100), 248 (36),
204 (13), 203 (48), 202 (33), 201 (12), 176 (13), 101 (20), 75 (13); HRMS
(EI): m/z calcd for C18H14O2NBr: 355.0208; found: 355.0200.
Synthesis of 3-bromo-2-(2-methylallyl)quinoline (16b): By following
TP 2, the metalation of 3-bromoquinoline (11; 416 mg, 2 mmol) was com-
pleted within 0.5 h at 258C. The reaction mixture was cooled to À408C,
then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and 3-bromo-2-methyl-
propene (406 mg, 3.0 mmol) were added. The mixture was allowed to
warm to 258C and was stirred overnight. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
10:1) to give 16b as a colorless oil (366 mg, 70%). 1H NMR (300 MHz,
CDCl3): d=8.36 (s, 1H), 8.09 (d, J=9.0 Hz, 1H), 7.75–7.70 (m, 2H),
7.57–7.52 (m, 1H), 4.92–4.91 (m, 1H), 4.56–4.54 (m, 1H), 3.90 (s, 2H),
1.90 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=158.12, 146.47, 142.45,
139.09, 129.70, 129.07, 128.05, 126.93, 126.44, 119.03, 112.52, 46.10,
23.15 ppm; IR (ATR): n˜ =3078, 3059, 2970, 2913, 1650, 1586, 1486, 1442,
1424, 1401, 1373, 1306, 1221, 1195, 1140, 1125, 984, 887, 858, 802, 780,
745, 679 cmÀ1; MS (70 eV, EI): m/z (%): 263 (25), 262 (80), 261 (25) [M]+,
260 (79), 249 (14), 248 (96), 247 (33), 246 (100), 245 (19), 223 (30), 221
(34), 182 (11), 181 (14), 180 (29), 167 (55), 166 (17), 142 (10), 141 (13),
140 (38), 139 (10), 127 (14), 115 (29), 114 (14), 113 (11), 101 (11), 91 (10),
90 (10), 89 (12), 84 (10), 75 (16), 63 (12), 51 (10); HRMS (EI): m/z calcd
for C13H12NBr: 261.0153; found: 261.0156.
Synthesis of 5-bromo-4-cyclohex-2-enylpyrimidine (15e): By following
TP 2, the metalation of 5-bromopyrimidine (10b, 318 mg, 2 mmol) was
completed within 0.5 h at 258C. The reaction mixture was cooled to
À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and 3-bromo-
cyclohexene (484 mg, 3.0 mmol) were added. The mixture was allowed to
warm to 258C and was stirred overnight. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
8:1) to give 15e as a colorless oil (333 mg, 70%). 1H NMR (300 MHz,
CDCl3): d=9.04 (s, 1H), 8.71 (s, 1H), 6.02–5.97 (m, 1H), 5.71–5.66 (m,
1H), 4.02–3.96 (m, 1H), 2.15–2.04 (m, 3H), 1.90–1.85 (m, 1H), 1.72–
1.62 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=171.14, 158.59,
157.06, 129.61, 126.24, 121.05, 41.88, 28.00, 24.60, 21.34 ppm; IR (ATR):
n˜ =3027, 2932, 1557, 1516, 1436, 1387, 1272, 1154, 1015, 891, 770, 720,
676, 658, 614, 569 cmÀ1; MS (70 eV, EI): m/z (%): 240 (27), 239 (26), 238
(28) [M]+, 237 (25), 225 (15), 223 (15), 212 (27), 211 (100), 210 (28), 209
(100), 199 (11), 198 (11), 197 (12), 196 (10), 174 (32), 172 (32), 159 (23),
131 (13), 130 (11), 118 (10), 79 (11), 77 (13), 51 (10); HRMS (EI): m/z
calcd for C10H11N2Br: 238.0106; found: 238.0105.
Synthesis of 5-chlorobiphenyl-2,4’-dicarboxylic acid diethyl ester (17a):
By following TP 2, the metalation of ethyl 4-chlorobenzoate (12a;
369 mg, 2.0 mmol) was completed within 12 h at 258C. A solution of
AHCTUNGRTEG[NNUN PdAHCUTNRTGEG(NNUN dba)2] (30 mg) and PACHTNUGERTN(NUGN o-furyl)3 (25 mg) in THF (2 mL) was added,
Synthesis of 5-bromo-4-(2-methylallyl)pyrimidine (15 f): By following
TP 2, the metalation of 5-bromopyrimidine (10b; 318 mg, 2 mmol) was
completed within 0.5 h at 258C. The reaction mixture was cooled to
À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and 3-bromo-
2-methylpropene (406 mg, 3.0 mmol) were added. The mixture was al-
lowed to warm to 258C and was stirred overnight. The reaction mixture
was quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
4:1) to give 15 f as a colorless oil (279 mg, 66%). 1H NMR (300 MHz,
CDCl3): d=9.06 (s, 1H), 8.77 (s, 1H), 4.95 (m, 1H), 4.70 (m, 1H), 3.66
(s, 2H), 1.82 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=166.54, 158.72,
158.71, 156.79, 156.78, 140.56, 121.84, 113.97, 44.97, 22.70 ppm; IR
(ATR): n˜ =2973, 2916, 1650, 1556, 1522, 1439, 1386, 1276, 1142, 1022,
892, 758, 720 cmÀ1; MS (70 eV, EI): m/z (%): 214 (10), 213 (79), 212 (10)
[M]+, 211 (78), 199 (99), 198 (19), 197 (100), 196 (11), 174 (41), 172 (43),
133 (11), 132 (20), 131 (19), 118 (28), 117 (10), 106 (10), 104 (11), 77 (14),
52 (15), 51 (22); HRMS (EI): m/z calcd for C8H10N2Br: 211.9949; found:
211.9855.
followed by ethyl 4-iodobenzoate (828 mg, 3.0 mmol), and the reaction
mixture was stirred at 258C overnight. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
6:1) to give 17a as a pale yellow oil (598 mg, 90%). 1H NMR (300 MHz,
CDCl3): d=8.12–8.09 (m, 2H), 7.87 (d, J=8.4 Hz, 1H), 7.46–7.36 (m,
4H), 4.43 (q, J=7.2 Hz, 2H), 4.11 (q, J=7.2 Hz, 2H), 1.44 (t, J=7.2 Hz,
3H), 1.04 ppm (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=
167.15, 166.32, 144.92, 143.48, 137.48, 131.62, 130.52, 129.70, 129.32,
129.22, 128.32, 127.90, 61.23, 61.06, 14.35, 13.71 ppm; IR (ATR): n˜ =3069,
2980, 2904, 1710, 1610, 1591, 1556, 1465, 1386, 1365, 1266, 1241, 1177,
1099, 1032, 1015, 858, 770, 670 cmÀ1; MS (70 eV, EI): m/z (%): 334 (22),
333 (14), 332 (63) [M]+, 289 (35), 288 (19), 287 (100), 276 (12), 261 (13),
260 (13), 259 (36), 217 (16), 215 (48), 186 (11), 152 (28), 151 (21), 150
(19); HRMS (EI): m/z calcd for C18H17O4Cl: 332.0815; found: 332.0823.
Synthesis of 4-chloro-2-(2-methylallyl)benzoic acid ethyl ester (17b): By
following TP 2, the metalation of ethyl 4-chlorobenzoate (10a; 369 mg,
2.0 mmol) was completed within 12 h at 258C. The reaction mixture was
cooled to À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and
3-bromo-2-methylpropene (406 mg, 3.0 mmol) were added. The mixture
was allowed to warm to 258C and was stirred overnight. The reaction
mixture was quenched with saturated aqueous NH4Cl solution (10 mL),
extracted with diethyl ether (3ꢄ20 mL), and dried over anhydrous
MgSO4. After filtration, the solvent was evaporated under vacuum. The
crude product was purified by means of column chromatography (pen-
tane/diethyl ether 160:1) to give 17b as a colorless oil (365 mg, 76%).
1H NMR (300 MHz, CDCl3): d=7.85–7.82 (m, 1H), 7.29–7.25 (m, 1H),
4.84–4.83 (m, 1H), 4.51–4.50 (m, 1H), 4.35 (q, J=7.2 Hz, 2H), 3.71 (s,
2H), 1.76 (s, 3H), 1.39 ppm (t, J=7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=166.87, 144.54, 143.02, 137.76, 131.92, 131.16, 129.03, 126.39,
112.08, 61.02, 41.46, 22.77, 14.23 ppm; IR (ATR): n˜ =3080, 2981, 2937,
2907, 1719, 1592, 1566, 1478, 1446, 1366, 1252, 1128, 1102, 1074, 1020,
887, 868, 836, 772, 692 cmÀ1; MS (70 eV, EI): m/z (%): 240 (16), 238 (46)
[M]+, 225 (22), 223 (66), 197 (25), 196 (12), 195 (100), 194 (23), 193 (79),
Synthesis of 4-(3-bromoquinolin-2-yl)benzoic acid ethyl ester (16a): By
following TP 2, the metalation of 3-bromoquinoline (11; 416 mg,
2.0 mmol) was completed within 0.5 h at 258C. A solution of [Pd
ACHTUNGERTN(NUNG dba)2]
(30 mg) and P(o-furyl)3 (25 mg) in THF (2 mL) was added, followed by
ACHTUNGTRENNUNG
ethyl 4-iodobenzoate (828 mg, 3.0 mmol), and the reaction mixture was
stirred at 258C for 12 h. The reaction mixture was quenched with saturat-
ed aqueous NH4Cl solution (10 mL), extracted with diethyl ether (3ꢄ
20 mL), and dried over anhydrous MgSO4. After filtration, the solvent
was evaporated under vacuum. The crude product was purified by means
of column chromatography (pentane/diethyl ether 5:1) to give 16a as a
colorless solid (582 mg, 82%). M.p. 132.2–133.38C; 1H NMR (300 MHz,
CDCl3): d=8.54 (s, 1H), 8.22–8.14 (m, 3H), 7.86–7.76 (m, 4H), 7.65–7.60
(m, 1H), 4.45 (q, J=7.2 Hz, 2H), 1.45 ppm (t, J=7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=166.31, 157.18, 146.54, 144.03, 140.14, 130.72,
130.31, 129.58, 129.56, 129.29, 128.39, 127.82, 126.52, 116.45, 61.12,
14.36 ppm; IR (ATR): n˜ =3066, 2974, 1713, 1612, 1571, 1546, 1484, 1476,
464
www.chemeurj.org
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 457 – 468

Direct Zincation of Functionalized Aromatics
FULL PAPER
192 (39), 191 (10), 176 (10), 167 (11), 165 (25), 158 (15), 157 (38), 130
(32), 129 (71), 128 (42), 127 (23), 125 (13), 115 (23), 89 (13); HRMS (EI):
m/z calcd for C13H15O2Cl1: 238.0760; found: 238.0740.
was completed within 3 h at 258C. BrCl2CCCl2Br (974 mg, 3.0 mmol) was
added at 258C and the resulting mixture stirred for 1 h. The reaction mix-
ture was quenched with saturated aqueous NH4Cl solution (10 mL), ex-
tracted with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4.
After filtration, the solvent was evaporated under vacuum. The crude
product was purified by means of column chromatography (pentane/di-
ethyl ether 10:1) to give 17 f as a colorless oil (360 mg, 74%). 1H NMR
(300 MHz, CDCl3): d=7.58–7.54 (m, 1H), 7.37–7.21 (m, 2H), 4.42 (q, J=
7.2 Hz, 2H), 1.41 ppm (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d=165.42 (d, 4JC,F =2.8 Hz), 159.47 (d, 1JC,F =247 Hz), 134.77, 128.41 (d,
3JC,F =8.0 Hz), 126.38 (d, 3JC,F =3.4 Hz), 118.89 (d, 2JC,F =23 Hz), 109.19
Synthesis of 2,4-dibromobenzoic acid ethyl ester (17c):[21] By following
TP 2, the metalation of ethyl 4-bromobenzoate (12b; 369 mg, 2.0 mmol)
was completed within 12 h at 258C. BrCl2CCCl2Br (974 mg, 3.0 mmol)
was added at 258C and the resulting mixture was stirred for 1 h. The re-
action mixture was quenched with saturated aqueous NH4Cl solution
(10 mL), extracted with diethyl ether (3ꢄ20 mL), and dried over anhy-
drous MgSO4. After filtration, the solvent was evaporated under vacuum.
Purification by using flash chromatography (pentane/diethyl ether 160:1)
2
a
semisolid (468 mg, 76%). 1H NMR (600 MHz,
(d, JC,F =22 Hz), 61.92, 14.16 ppm; IR (ATR): n˜ =2984, 2906, 1728, 1572,
furnished 17c as
1462, 1435, 1367, 1289, 1269, 1183, 1142, 1091, 1019, 945, 863, 802, 754,
695 cmÀ1; MS (70 eV, EI): m/z (%): 248 (23), 246 (24) [M]+, 220 (38), 218
(38), 204 (11), 203 (96), 202 (12), 201 (100), 175 (29), 173 (29), 94 (35);
HRMS (EI): m/z calcd for C9H8O2BrF: 245.9692; found: 245.9692.
CDCl3): d=7.76 (d, J=1.8 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.44–7.42
(m, 1H), 4.34 (q, J=7.2 Hz, 2H), 1.34 ppm (t, J=7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3): d=165.19, 136.70, 132.35, 131.03, 130.36, 126.18,
122.53, 61.78, 14.18 ppm; IR (ATR): n˜ =3085, 2980, 1726, 1574, 1549,
1462, 1365, 1281, 1241, 1109, 1083, 1034, 869, 853, 830, 766, 743, 679,
657 cmÀ1; MS (70 eV, EI): m/z (%): 310 (12), 308 (25) [M]+, 306 (13), 282
(21), 280 (42), 278 (22), 265 (51), 264 (12), 263 (100), 261 (54), 237 (11),
235 (22), 233 (11), 156 (10), 154 (10), 75 (18), 74 (13); HRMS (EI): m/z
calcd for C9H10O2Br2: 307.8871; found: 307.8865.
Synthesis of 2-benzoyl-4-chlorobenzoic acid ethyl ester (17g): By follow-
ing TP 2, the metalation of ethyl 4-chlorobenzoate (12a; 369 mg,
2 mmol) was completed within 12 h at 258C. The reaction mixture was
cooled to À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and
benzoyl chloride (0.35 mL, 3.0 mmol) were added. The mixture was al-
lowed to warm to 258C and was stirred overnight. The reaction mixture
was quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
6:1) to give 17g as a yellow solid (500 mg, 86%). M.p. 78.9–80.98C;
1H NMR (400 MHz, CDCl3): d=8.02 (d, J=8.4 Hz, 1H), 7.73–7.77 (m,
2H), 7.52–7.57 (m, 2H), 7.41–7.46 (m, 2H), 7.36 (d, J=8.4 Hz, 1H), 4.07
(q, J=7.1 Hz, 2H), 1.04 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=195.5, 165.2, 143.3, 139.2, 136.7, 133.7, 131.9, 129.9, 129.6,
128.9, 128.0, 127.8, 62.0, 13.8 ppm; IR (ATR): n˜ =2983, 2909, 1712, 1677,
1619, 1590, 1583, 1560, 1490, 1473, 1450, 1445, 1385, 1363, 1319, 1311,
1283, 1267, 1243, 1177, 1153, 1134, 1105, 1089, 1074, 1021, 1001, 979, 966,
954, 942, 899, 875, 860, 843, 815, 808, 780, 770, 712, 698, 690, 643, 619,
609, 591, 585 cmÀ1; MS (70 eV, EI): m/z (%): 288 (24) [M]+, 245 (16), 244
(15), 243 (35), 213 (11), 211 (36), 183 (56), 152 (21), 105 (100), 77 (45), 57
(13); HRMS (EI): m/z calcd for C16H13ClO3: 288.0553; found: 288.0550.
Synthesis of 2-benzoyl-4-bromobenzoic acid ethyl ester (17d): By follow-
ing TP 2, the metalation of ethyl 4-bromobenzoate (12b; 369 mg,
2.0 mmol) was completed within 12 h at 258C. The reaction mixture was
cooled to À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and
benzoyl chloride (0.35 mL, 3.0 mmol) were added. The mixture was al-
lowed to warm to 258C and was stirred overnight. The reaction mixture
was quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
4:1) to give 17d as a colorless solid (501 mg, 76%). M.p. 90.8–92.68C;
1H NMR (600 MHz, CDCl3): d=7.94 (d, J=8.4 Hz, 1H), 7.76–7.74 (m,
2H), 7.70 (dd, J=8.4, 1.8 Hz, 1H), 7.58–7.55 (m, 1H), 7.53 (d, J=1.8 Hz,
1H), 7.46–7.43 (m, 2H), 4.07 (q, J=7.2 Hz, 2H), 1.04 ppm (t, J=7.2 Hz,
3H); 13C NMR (150 MHz, CDCl3): d=195.13, 165.10, 143.22, 136.62,
133.42, 132.66, 131.71, 130.58, 129.37, 128.60, 128.08, 127.40, 61.75,
13.56 ppm; IR (ATR): n˜ =2981, 1711, 1677, 1582, 1554, 1471, 1450, 1362,
1266, 1243, 1135, 1097, 1020, 948, 898, 858, 842, 778, 759, 711, 681, 689,
697 cmÀ1; MS (70 eV, EI): m/z (%): 334 (10), 332 (10) [M]+, 289 (14), 287
(14), 257 (18), 255 (18), 229 (27), 227 (27), 180 (10), 152 (23), 151 (12),
105 (100), 77 (63), 76 (10), 75 (17), 51 (19); HRMS (EI): m/z calcd for
C16H13O3Br: 332.0048; found: 332.0048.
Synthesis of 2’,6’-difluorobiphenyl-4-carboxylic acid ethyl ester (18a):[12c]
By following TP 2, the metalation of 1,3-difluorobenzene (13; 228 mg,
2 mmol) was completed within 12 h at 258C. A solution of [Pd
ACHTUNGTRENNUNG(dba)2]
(30 mg) and P(o-furyl)3 (25 mg) in THF (2 mL) was added, followed by
AHCTUNGTRENNUNG
ethyl 4-iodobenzoate (828 mg, 3.0 mmol) and the reaction mixture was
stirred at 258C overnight. The reaction mixture was quenched with
AHCTUNTGREGNsNNU aturated aqueous NH4Cl solution (10 mL), extracted with diethyl ether
Synthesis of 2-benzoyl-3-fluorobenzoic acid ethyl ester (17e): By follow-
ing TP 2, the metalation of ethyl 3-fluorobenzoate (12c; 336 mg, 2 mmol)
was completed within 3 h at 258C. The reaction mixture was cooled to
À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and benzoyl
chloride (0.35 mL, 3.0 mmol) were added. The mixture was allowed to
warm to 258C and was stirred overnight. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
8:1) to give 17e as a colorless solid (433 mg, 80%). M.p. 103.8–105.58C;
1H NMR (300 MHz, CDCl3): d=7.95 (dd, J=7.8, 1.2 Hz, 1H), 7.85–7.82
(m, 2H), 7.63–7.35 (m, 5H), 4.17 (q, J=7.2 Hz, 2H), 1.10 ppm (t, J=
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=192.53, (d, 3JC,F =1.1 Hz),
164.65 (d, 4JC,F =1.5 Hz), 159.15 (d, 1JC,F =247 Hz), 137.08, 133.53, 130.94
(d, 3JC,F =3.9 Hz), 130.60, 130.49, 129.56 (d, 2JC,F =20 Hz), 129.43, 129.02,
128.65, 126.24 (d, 3JC,F =3.9 Hz), 120.20 (d, 2JC,F =20 Hz), 61.82,
13.59 ppm; IR (ATR): n˜ =3073, 2990, 2944, 2908, 1714, 1673, 1608, 1598,
1581, 1478, 1448, 1366, 1272, 1198, 1151, 1026, 962, 928, 811, 762, 708,
660, 589, 569 cmÀ1; MS (70 eV, EI): m/z (%): 272 (44) [M]+, 228 (18), 227
(38), 199 (14), 195 (49), 170 (16), 168 (10), 167 (100), 151 (12), 105 (60),
77 (31); HRMS (EI): m/z calcd for C16H13O3F: 272.0849; found:
272.0842.
(3ꢄ20 mL), and dried over anhydrous MgSO4. After filtration, the sol-
vent was evaporated under vacuum. The crude product was purified by
means of column chromatography (pentane/diethyl ether 80:1) to give
18a as a colorless solid (471 mg, 90%). M.p. 59.4–61.58C; 1H NMR
(600 MHz, CDCl3): d=8.13–8.11 (m, 2H), 7.54 (dt, J=9, 1.8 Hz, 2H),
7.33–7.28 (m, 1H), 6.70 (t, J=8.4 Hz, 2H), 4.40 (q, J=7.2 Hz, 2H),
1.40 ppm (t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): d=166.24,
159.95 (d, 1JC,F =250 Hz), 159.90 (d, 1JC,F =250 Hz), 133.76, 130.32 (t,
J
C,F =2.1 Hz), 130.15, 129.55 (t, JC,F =10 Hz), 129.37, 117.58 (t, JC,F =
18 Hz), 111.76 (d, JC,F =21 Hz), 111.73 (d, JC,F =21 Hz), 61.04, 14.32 ppm;
IR (ATR): n˜ =2980, 1711, 1624, 1585, 1564, 1464, 1404, 1369, 1266, 1230,
1180, 1107, 1099, 1065, 995, 854, 792, 787, 770, 723, 670 cmÀ1; MS (70 eV,
EI): m/z (%): 263 (10), 262 (57) [M]+, 234 (41), 217 (100), 189 (42), 188
(53), 169 (15); HRMS (EI): m/z calcd for C15H12O2F2: 262.0805; found:
262.0797.
Synthesis of 2,6-difluorobenzophenone (18b):[22] By following TP 2, the
metalation of 1,3-difluorobenzene (13; 228 mg, 2 mmol) was completed
within 12 h at 258C. The reaction mixture was cooled to À408C, then
CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and benzoyl chloride
(0.35 mL, 3.0 mmol) were added. The mixture was allowed to warm to
258C and was stirred overnight. The reaction mixture was quenched with
saturated aqueous NH4Cl solution (10 mL), extracted with diethyl ether
(3ꢄ20 mL), and dried over anhydrous MgSO4. After filtration, the sol-
Synthesis of 2-bromo-3-fluorobenzoic acid ethyl ester (17 f): By following
TP 2, the metalation of ethyl 3-fluorobenzoate (12c; 336 mg, 2 mmol)
Chem. Eur. J. 2009, 15, 457 – 468
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
465

P. Knochel et al.
vent was evaporated under vacuum. The crude product was purified by
means of column chromatography (pentane/diethyl ether 80:1) to give
18b as a colorless oil (359 mg, 82%). 1H NMR (300 MHz, CDCl3): d=
(m, 2H), 7.64–7.74 (m, 2H), 1.56–1.67 (m, 6H), 1.33 (m, 6H), 1.2–1.21
(m, 6H), 0.88 ppm (t, 3J=7.2 Hz, 9H); 13C NMR (75 MHz, CDCl3): d=
172.6, 150.0 (t, 2JC,Sn =41.0 Hz), 145.1, 141.5, 129.7, 129.6, 129.2, 129.1,
3
2
1
7.92–7.88 (m, 2H), 7.68–7.62 (m, 1H), 7.54–7.42 (m, 3H), 7.06–6.99 ppm
29.1 (t, JC,Sn =10.3 Hz), 27.3 (t, JC,Sn =28.6 Hz), 13.7, 10.2 ppm (t, JC,Sn =
1
(m, 2H); 13C NMR (75 MHz, CDCl3): d=188.93, 159.86 (d, JC,F
=
170.3 Hz); IR (ATR): n˜ =3080, 3012, 2952, 2870, 2836, 2753, 2683, 1696,
1681, 1638, 1613, 1571, 1546, 1538, 1495, 1473, 1464, 1432, 1422, 1374,
1323, 1263, 1201, 1143, 1127, 1068, 1022, 965, 955, 950, 924, 895, 778, 764,
752, 725, 683, 666 cmÀ1; MS (70 eV, EI): m/z (%): 420 (1) [M]+, 364 (30),
363 (35), 362 (30), 361 (29), 360 (19), 359 (12), 307 (26), 306 (11), 305
(29), 304 (12), 303 (19), 253 (18), 251 (51), 250 (21), 249 (100), 248 (35),
247 (70), 246 (20), 245 (31), 148 (32), 131 (37), 121 (13), 119 (11); HRMS
(EI): m/z calcd for C20H32N2Sn: 420.1587; found: 420.1581.
252 Hz), 159.76 (d, 1JC,F =252 Hz), 136.84, 134.22, 131.91 (t, JC,F
=
9.80 Hz), 129.64, 128.77, 117.05 (t, JC,F =22 Hz), 112.06–111.72 ppm (m);
IR (ATR): n˜ =3064, 1672, 1622, 1583, 1462, 1449, 1316, 1275, 1266, 1233,
1180, 1145, 1004, 925, 783, 732, 696, 686 cmÀ1; MS (70 eV, EI): m/z (%):
219 (14), 218 (93) [M]+, 141 (63), 113 (20), 105 (100), 77 (46), 63 (11), 51
(14); HRMS (EI): m/z calcd for C13H8OF2: 218.0543; found: 218.0527.
Synthesis of 4-(3-iodoquinoxalin-2-yl)benzoic acid ethyl ester (19): By
following TP 2, the metalation of 4-quinoxalin-2-ylbenzoate (12 f;
139 mg, 0.5 mmol) was completed within 15 min at 258C. Iodine (253 mg,
1 mmol) dissolved in THF (2 mL) was added and the reaction mixture
was stirred for 30 min at 258C. Then the reaction mixture was quenched
by the addition of saturated aqueous Na2S2O3 (10 mL) and saturated
aqueous NH4Cl solution (10 mL). The mixture was extracted with diethyl
ether (3ꢄ20 mL) and the combined organic layers were washed with
brine, dried over MgSO4, and the solvent was evaporated under vacuum.
The residue was purified by using flash chromatography on silica gel
(pentane/diethyl ether 4:1) to furnish 19 as a colorless solid (147 mg,
73%). M.p. 159.7–161.88C (decomp); 1H NMR (600 MHz, CDCl3): d=
8.22–8.20 (m, 2H), 8.12–8.10 (m, 2H), 7.82–7.80 (m, 4H), 4.44 (q, J=
7.2 Hz, 2H), 1.44 ppm (t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3):
d=166.05, 156.18, 143.68, 143.12, 140.38, 131.34, 131.00, 130.97, 129.72,
129.41, 129.38, 128.49, 118.63, 61.26, 14.34 ppm; IR (ATR): n˜ =2968,
2921, 2852, 1713, 1605, 1549, 1523, 1506, 1463, 1405, 1364, 1333, 1276,
1181, 1098, 1065, 1022, 959, 882, 854, 762, 718, 699 cmÀ1; MS (70 eV, EI):
m/z (%): 404 (15) [M]+, 278 (25), 277 (100), 250 (12), 249 (56), 233 (12),
204 (11), 102 (22), 76 (12); HRMS (EI): m/z calcd for C17H13O2N2I:
404.0022; found: 404.0016.
Synthesis of 4-quinoxalin-2-ylbenzoic acid ethyl ester (14 f): By following
TP 4, the metalation of quinoxaline (2b; 230 mg, 2 mmol) was completed
within 5 h at 258C. A solution of [PdACHTNUTRGENNUG(dba)2] (56 mg) and PACHTUNGTRENNUNG(o-furyl)3
(46 mg) in THF (2 mL) was added, followed by ethyl 4-iodobenzoate
(615 mg, 2.2 mmol). The reaction mixture was stirred at 258C for 3 h.
The reaction mixture was quenched with saturated aqueous NH4Cl solu-
tion (10 mL), extracted with diethyl ether (3ꢄ20 mL), and dried over an-
hydrous MgSO4. After filtration, the solvent was evaporated under
vacuum. The crude product was purified by means of column chromatog-
raphy (pentane/diethyl ether 3:1) to give 14 f as a colorless solid (455 mg,
82%). M.p. 88.8–90.98C; 1H NMR (300 MHz, CDCl3): d=9.39 (s, 1H),
8.33–8.16 (m, 6H), 7.85–7.80 (m, 2H), 4.46 (q, J=7.2 Hz, 2H), 1.47 ppm
(t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=166.15, 150.70,
143.12, 142.30, 141.81, 131.84, 130.57, 130.30, 130.12, 129.78, 129.17,
127.43, 61.27, 14.35 ppm; IR (ATR): n˜ =2923, 1713, 1607, 1363, 1271,
1183, 1126, 1099, 1048, 1017, 958, 861, 772, 758, 752, 698, 668, 615 cmÀ1
;
MS (70 eV, EI): m/z (%): 279 (15), 278 (74) [M]+, 250 (32), 233 (100),
206 (12), 205 (32), 102 (12), 76 (14); HRMS (EI): m/z calcd for
C17H14O2N2: 278.1055; found: 278.1030.
Synthesis of 2-(3-trifluoromethylphenyl)quinoxaline (14h): By following
TP 4, the metalation of quinoxaline (2b; 230 mg, 2 mmol) was completed
within 5 h at 258C. A solution of [PdACHTNUTRGENNUG(dba)2] (56 mg) and PACHTUNGTRENNUNG(o-furyl)3
Synthesis of (7,8-dibromoquinoxalin-5-yl)phenylmethanone (20): By fol-
lowing TP 2, the metalation of 5,6-dibromoquinoxaline (14g; 144 mg,
0.5 mmol) was completed (treated with 0.5 equiv of ZnCl2 and 0.75 equiv
of 1) within 15 min at 258C. The reaction mixture was cooled to À408C,
then CuCN·2LiCl (1m in THF, 0.55 mL, 0.55 mmol) and benzoyl chloride
(0.09 mL, 0.75 mmol) were added. The mixture was allowed to warm to
258C and was stirred overnight. The reaction mixture was quenched with
saturated aqueous NH4Cl solution (10 mL), extracted with diethyl ether
(3ꢄ20 mL), and dried over anhydrous MgSO4. After filtration, the sol-
vent was evaporated under vacuum. The crude product was purified by
means of column chromatography (pentane/diethyl ether 3:1) to give 20
(46 mg) in THF (2 mL) was added, followed by 1-iodo-3-trifluoromethyl-
benzene (598 mg, 2.2 mmol). The reaction mixture was stirred at 258C
for 3 h. The reaction mixture was quenched with saturated aqueous
NH4Cl solution (10 mL), extracted with diethyl ether (3ꢄ20 mL), and
dried over anhydrous MgSO4. After filtration, the solvent was evaporated
under vacuum. The crude product was purified by means of column chro-
matography (pentane/diethyl ether 3:1) to give 14h as a colorless solid
(482 mg, 88%). M.p. 119.0–121.88C; 1H NMR (600 MHz, CDCl3): d=
9.33 (s, 1H), 8.50 (s, 1H) 8.36 (d, J=7.9 Hz, 1H), 8.18–8.13 (m, 2H),
as
a
colorless solid (160 mg, 82%). M.p. 180.8–182.58C (decomp);
7.82–7.75 (m, 3H), 7.68 ppm (t, J=7.7 Hz, 1H); 13C NMR (150 MHz,
1H NMR (300 MHz, CDCl3): d=8.99 (d, J=1.8 Hz, 1H), 8.81 (d, J=
1.8 Hz, 1H), 8.07 (s, 1H), 7.83–7.80 (m, 2H), 7.66–7.61 (m, 1H),
7.48 ppm (t, J=7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=194.17,
146.42, 145.46, 141.57, 140.62, 139.54, 137.00, 134.01, 132.95, 130.12,
129.13, 128.67, 128.64, 127.51 ppm; IR (ATR): n˜ =3050, 3026, 1655, 1595,
1576, 1548, 1475, 1450, 1428, 1358, 1319, 1297, 1237, 1213, 1198, 1179,
1053, 1027, 1022, 962, 879, 866, 780, 728, 706, 684, 674 cmÀ1; MS (70 eV,
EI): m/z (%): 394 (42), 393 (21), 392 (87) [M]+, 391 (22), 390 (45), 365
(34), 364 (12), 363 (67), 361 (35), 313 (10), 287 (18), 286 (16), 285 (100),
284 (15), 283 (94), 204 (15), 203 (31), 150 (10), 127 (16), 105 (34), 77 (76),
51 (17); HRMS (EI): m/z calcd for C15H10ON2Br2: 391.8983; found:
391.8962.
CDCl3): d=150.13, 142.70, 142.18, 141.81, 137.51, 131.69 (q, JC,F
=
2
32 Hz), 130.61, 130.53 (q, 4JC,F =1 Hz), 130.11, 129.68, 129.61, 129.15,
3
126.68 (q, 3JC,F =3.7 Hz), 124.85 (q, 1JC,F =272 Hz), 124.42 ppm (q, JC,F
=
4.0 Hz); IR (ATR): n˜ =1546, 1487, 1366, 1338, 1327, 1309, 1279, 1263,
1231, 1223, 1209, 1187, 1179, 1160, 1140, 1130, 1110, 1096, 1076, 1048,
1013, 973, 961, 952, 937, 919, 889, 885, 877, 838, 809, 795, 763, 706, 690,
651, 637, 632, 624, 615, 591, 561 cmÀ1; MS (70 eV, EI): m/z (%): 275 (14),
278 (100) [M]+, 247 (30), 178 (5), 76 (19); HRMS (EI): m/z calcd for
C17H14O2N2: 274.0718; found: 274.0703.
Synthesis of 4-(5-bromopyrimidin-4-yl)benzonitrile (15g): By following
TP 4, the metalation of 5-bromopyrimidine (10a; 318 mg, 2.0 mmol) was
completed within 5 h at 258C. A solution of [PdACTHNUGTRNENUG(dba)2] (56 mg) and PACHTUNGTRENNUNG(o-
Synthesis of 2-tributylstannanylquinoxaline (21):[23] In a dry argon-flushed
10 mL Schlenk flask, equipped with a magnetic stirring bar and a septum,
quinoxaline (2a, 230 mg, 2 mmol) was dissolved in THF (2 mL) and tri-
furyl)3 (46 mg) in THF (2 mL) was added, followed by 4-iodobenzonitrile
(504 mg, 2.2 mmol). The reaction mixture was stirred at 258C for 2 h.
The reaction mixture was quenched with saturated aqueous NH4Cl solu-
tion (10 mL), extracted with diethyl ether (3ꢄ20 mL), and dried over an-
hydrous MgSO4. After filtration, the solvent was evaporated under
vacuum. The crude product was purified by means of column chromatog-
raphy (pentane/diethyl ether 4:1) to give 15g as a colorless solid (390 mg,
ACHTUNGTRENNUNGbutyltin chloride (0.780 g, 0.650 mL, 2.4 mmol) was added. The solution
was cooled to À788C. (TMP)2Mg·2LiCl (1; 0.6m in THF, 1.84 mL,
1.10 mmol) was added dropwise and the reaction mixture was stirred for
0.5 h. The reaction mixture was quenched with saturated aqueous NH4Cl
solution (10 mL), extracted with diethyl ether (3ꢄ20 mL), and dried over
anhydrous MgSO4. After filtration, the solvent was evaporated under
vacuum. The crude product was purified by means of column chromatog-
raphy (pentane/diethyl ether 5:1+1% NEt3) to give 21 as a yellow oil
(675 mg, 74%). 1H NMR (300 MHz, CDCl3): d=8.79 (s, 1H), 8.00–8.15
1
75%). M.p. 158.9–160.98C; H NMR (600 MHz, CDCl3): d=9.19 (s, 1H),
8.97 (s, 1H), 7.93 (d, J=8.8 Hz, 2H), 7.80 ppm (d, J=8.6 Hz, 2H);
13C NMR (150 MHz, CDCl3): d=162.34, 160.55, 157.05, 140.82, 132.06,
130.03, 119.06, 118.15, 114.02 ppm; IR (ATR): n˜ =2231, 1558, 1498, 1438,
1405, 1392, 1283, 1228, 1172, 1152, 1058, 1025, 1017, 926, 842, 815, 774,
466
www.chemeurj.org
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 457 – 468

Direct Zincation of Functionalized Aromatics
FULL PAPER
746, 724, 668, 664, 643, 579, 572, 568, 559 cmÀ1; MS (70 eV, EI): m/z (%):
261 (30), 259 (30) [M+], 181 (14), 180 (100), 153 (25), 126 (10), 74 (11),
59 (15); HRMS (EI): m/z calcd for C17H14O2N2: 258.9745; found:
258.9735.
591, 568, 560, 554 cmÀ1; MS (70 eV, EI): m/z (%): 374 (42), 372 (38)
79
[MÀ Br]+, 346 (26), 345 (11), 344 (25), 330 (17), 329 (94), 328 (16), 327
(100), 248 (38), 221 (11), 220 (68), 219 (28), 201 (18), 170 (10), 43 (12);
HRMS (EI): m/z calcd for C16H12BrF3O2: 371.9973; found: 371.9955.
Synthesis of 5-bromo-3’-trifluoromethylbiphenyl-2-carboxylic acid ethyl
ester (17i): By following TP 4, the metalation of ethyl 4-bromobenzoate
(12b; 458 mg, 2 mmol) was completed within 110 h at 258C. A solution
Synthesis of 4-(3-bromoquinolin-2-yl)benzonitrile (16c): By following
TP 2, the metalation of 3-bromoquinoline (11; 416 mg, 2.0 mmol) was
completed within 2.5 h at 258C. A solution of [Pd
ACHTUNGRTEN(NGNU dba)2] (56 mg) and
of [PdACHTNUGTRENNUG(dba)2] (56 mg) and PAHCUTGNTREN(NGUN o-furyl)3 (46 mg) in THF (2 mL) was added,
ACHTUNGTRENNUNGPACHTUNGTRENNUNG(o-furyl)3 (46 mg) in THF (2 mL) was added, followed by 4-iodobenzo-
followed by ethyl 4-iodobenzoate (615 mg, 2.2 mmol). The reaction mix-
ture was stirred at 258C for 12 h. The reaction mixture was quenched
with saturated aqueous NH4Cl solution (10 mL), extracted with diethyl
ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After filtration, the
solvent was evaporated under vacuum. The crude product was purified
by means of column chromatography (pentane/diethyl ether 20:1) to give
17i as a yellowish oil (586 mg, 78%). 1H NMR (600 MHz, CDCl3): d=
8.08–8.04 (m, 2H), 7.76 (d, J=8.1 Hz, 1H), 7.57 (dd, J=8.2, 2.0 Hz, 1H),
7.50 (d, J=1.9 Hz, 1H), 7.36–7.33 (m, 2H), 4.40 (q, J=7.2 Hz, 2H), 4.07
(q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H), 1.00 ppm (t, J=7.2 Hz, 3H);
13C NMR (150 MHz, CDCl3): d=167.25, 166.29, 144.78, 143.52, 133.37,
131.63, 130.86, 130.12, 129.65, 129.30, 128.30, 127.17, 125.88, 61.23, 61.04,
14.32, 13.67 ppm; IR (ATR): n˜ =2979, 1710, 1609, 1585, 1552, 1464, 1445,
1408, 1385, 1365, 1309, 1266, 1241, 1178, 1132, 1096, 1029, 1013, 887, 858,
835, 798, 771, 760, 700, 649, 642, 635, 623, 614, 608, 602, 583, 576,
nitrile (504 mg, 2.2 mmol). The reaction mixture was stirred at 258C for
4 h. The reaction mixture was quenched with saturated aqueous NH4Cl
solution (10 mL), extracted with diethyl ether (3ꢄ20 mL), and dried over
anhydrous MgSO4. After filtration, the solvent was evaporated under
vacuum. The crude product was purified by means of column chromatog-
raphy (pentane/diethyl ether 5:1) to give 16c as a colorless solid (662 mg,
1
95%). M.p. 130.4–132.08C; H NMR (600 MHz, CDCl3): d=8.51 (s, 1H),
8.19–8.16 (m, 2H), 8.14 (d, J=8.3 Hz, 1H), 7.82–7.74 (m, 4H), 7.60 (td,
J=7.5, 1.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.42 ppm (t, J=7.2 Hz, 3H);
13C NMR (150 MHz, CDCl3): d=166.28, 157.13, 146.42, 143.88, 140.20,
130.71, 130.34, 129.54, 129.48, 129.27, 128.37, 127.83, 126.51, 116.42, 61.11,
14.33 ppm; IR (ATR): n˜ =3064, 2988, 2973, 1712, 1673, 1651, 1612, 1586,
1571, 1546, 1484, 1475, 1457, 1411, 1397, 1387, 1365, 1309, 1289, 1274,
1262, 1242, 1201, 1180, 1153, 1145, 1121, 1106, 1098, 1072, 1023, 971, 954,
913, 884, 878, 857, 850, 824, 791, 780, 767, 748, 714, 697, 636, 630, 622,
613, 606, 597, 581, 576, 570, 565, 560, 552 cmÀ1; MS (70 eV, EI): m/z (%):
357 (38), 356 (12) 355 (40) [M]+, 312 (38), 310 (34), 281 (21), 277 (20),
276 (100) 248 (32), 203 (35), 101 (10); HRMS (EI): m/z calcd for
C17H14O2N2: 355.0208; found: 355.0194.
79
573 cmÀ1; MS (70 eV, EI): m/z (%): 378 (74), 376 (70) [MÀ Br]+, 350
(12), 348 (13), 334 (21), 333 (100), 332 (26), 331 (99), 322 (11), 320 (11),
305 (34), 304 (17), 303 (39), 298 (11), 261 (39), 259 (43), 253 (19), 180
(29), 152 (42), 151 (42), 144 (12), 139 (11), 89 (17) 75 (11); HRMS (EI):
m/z calcd for C16H12BrF3O2: 376.0310; found: 376.0309.
Synthesis of 2-benzoyl-4-chlorobenzoic acid ethyl ester (17g): By follow-
ing TP 4, the metalation of ethyl 4-chlorobenzoate (12a; 369 mg,
2 mmol) was completed within 110 h at 258C. The reaction mixture was
cooled to À408C, then CuCN·2LiCl (1m in THF, 2.2 mL, 2.2 mmol) and
benzoyl chloride (0.35 mL, 3.0 mmol) were added. The mixture was al-
lowed to warm to 258C and was stirred overnight. The reaction mixture
was quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
6:1) to give 17g as a yellow solid (500 mg, 86%). M.p. 78.9–80.98C;
1H NMR (400 MHz, CDCl3): d=8.02 (d, J=8.4 Hz, 1H), 7.77–7.73 (m,
2H), 7.57–7.52 (m, 2H), 7.46–7.41 (m, 2H), 7.36 (d, J=8.4 Hz, 1H), 4.07
(q, J=7.1 Hz, 2H), 1.04 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=195.5, 165.2, 143.3, 139.2, 136.7, 133.7, 131.9, 129.9, 129.6,
128.9, 128.0, 127.8, 62.0, 13.8 ppm; IR (ATR): n˜ =2983, 2909, 1712, 1677,
1619, 1590, 1583, 1560, 1490, 1473, 1450, 1445, 1385, 1363, 1319, 1311,
1283, 1267, 1243, 1177, 1153, 1134, 1105, 1089, 1074, 1021, 1001, 979, 966,
954, 942, 899, 875, 860, 843, 815, 808, 780, 770, 712, 698, 690, 643, 619,
609, 591, 585 cmÀ1; MS (70 eV, EI): m/z (%): 288 (24) [M]+, 245 (16), 244
(15), 243 (35), 213 (11), 211 (36), 183 (56), 152 (21), 105 (100), 77 (45), 57
(13); HRMS (EI): m/z calcd for C16H13ClO3: 288.0553; found: 288.0550.
Acknowledgements
We thank the Fonds der Chemischen Industrie and the Deutsche
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ship Council for a fellowship. We also thank Chemetall GmbH (Frank-
furt), Evonik GmbH (Hanau), and BASF AG (Ludwigshafen) for their
generous gifts of chemicals.
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Synthesis of 5-bromobiphenyl-2,4’-dicarboxylic acid diethyl ester (17h):
By following TP 4, the metalation of ethyl 4-bromobenzoate (12b;
458 mg, 2 mmol) was completed within 110 h at 258C. A solution of
ACHTUNGTRENNUNG[PdACHTUNGTRENNUNG(dba)2] (56 mg) and PACHTNUGERTN(NUGN o-furyl)3 (46 mg) in THF (2 mL) was added,
followed by 1-iodo-3-trifluoromethylbenzene (598 mg, 2.2 mmol). The re-
action mixture was stirred at 258C for 60 h. The reaction mixture was
quenched with saturated aqueous NH4Cl solution (10 mL), extracted
with diethyl ether (3ꢄ20 mL), and dried over anhydrous MgSO4. After
filtration, the solvent was evaporated under vacuum. The crude product
was purified by means of column chromatography (pentane/diethyl ether
15:1) to give 17h as a yellowish oil (619 mg, 83%). 1H NMR (600 MHz,
CDCl3): d=7.79 (d, J=8.3 Hz, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.59 (dd,
J=8.3, 1.9 Hz, 1H) 7.54–7.46 (m, 4H), 4.06 (q, J=7.2 Hz, 2H), 0.98 ppm
(t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): d=167.1, 142.9, 141.0,
133.5, 131.8, 131.6 (q, 4JC,F =1.3 Hz), 131.0, 130.4 (q, 2JC,F =32 Hz), 129.7,
128.5, 126.0, 125.2 (q, 3JC,F =3.9 Hz), 124.3 (q, 3JC,F =3.9 Hz), 123.8 (q,
1JC,F =272 Hz), 61.2, 13.5 ppm; IR (ATR): n˜ =2982, 1715, 1585, 1557,
1492, 1444, 1432, 1384, 1365, 1328, 1272, 1238, 1164, 1122, 1094, 1072,
1035, 1016, 905, 885, 860, 834, 803, 778, 753, 701, 688, 657, 626, 615, 608,
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Received: July 30, 2008
Published online: November 26, 2008
468
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