The transition-metal-catalyst-free oxidative homocoupling of organomanganese reagents prepared by the insertion of magnesium into organic halides in the presence of MnCl2·2LiCl

Article abstract of DOI:10.1039/c4ob01235f

Organomanganese reagents were prepared by the insertion of magnesium into aryl halides in the presence of MnCl₂·2LiCl. These organomanganese reagents smoothly undergo 1,2-addition, acylation, and Pd-catalyzed cross-coupling with various electrophiles. Especially, the oxidative homocoupling of organomanganese reagents was completed in one pot without an additional transition-metal catalyst.

Full text of DOI:10.1039/c4ob01235f

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The transition-metal-catalyst-free oxidative
homocoupling of organomanganese reagents
prepared by the insertion of magnesium into
organic halides in the presence of MnCl2·2LiCl†
Cite this: Org. Biomol. Chem., 2014,
12, 7800
Zhihua Peng,* Na Li, Xinyang Sun, Fang Wang, Lanjian Xu, Cuiyu Jiang, Linhua Song
and Zi-Feng Yan
Received 14th June 2014,
Accepted 8th August 2014
Organomanganese reagents were prepared by the insertion of magnesium into aryl halides in the pres-
ence of MnCl2·2LiCl. These organomanganese reagents smoothly undergo 1,2-addition, acylation, and
Pd-catalyzed cross-coupling with various electrophiles. Especially, the oxidative homocoupling of
organomanganese reagents was completed in one pot without an additional transition-metal catalyst.
DOI: 10.1039/c4ob01235f
www.rsc.org/obc
At present, a common method for the preparation of orga-
nomanganese(II) reagents is still the transmetallation from
Introduction
The traditional transition-metal-catalyzed coupling reaction of corresponding organomagnesium or organolithium com-
organometallics with organic halides occupied a central posi- pounds by treating with manganese halides.7 Rieke reported
tion in organic synthesis.1 Recently, many efforts have been that an insertion of Rieke manganese into organic halides
focused on the transition-metal-catalyst-free coupling reaction gave a variety of organomanganese(II) reagents.8 A recent paper
because of its economic, low toxic, eco-friendly process.2 published by Knochel’s group showed that organomanganese(II)
Especially, the transition-metal-catalyst-free coupling reactions reagents could be formed by the insertion of commercial
of organometallics have attracted increasing attention.3 For manganese powder into aromatic and benzylic halides in the
instance, arylzinc reagents or arylmagnesium reagents could presence of LiCl, InCl3 and PbCl2.9 Although organomanga-
couple with aryl iodides in the absence of a transition-metal nese reagents could be prepared using the above-mentioned
catalyst via a single electron transfer mechanism.4 Among methods, many drawbacks such as low functional group toler-
organometallics, organomanganese(II) reagents can behave not ance, a hard to handle procedure, harsh conditions and so on
only like soft Grignard reagents but also like transition metal still existed. Recently, Knochel’s group reported that organo-
derivatives.5 Mechanically, an organomanganese(II) reagent zinc reagents could be readily prepared by the reaction of
has great potential to undergo coupling reaction directly in the organic halides with magnesium in the presence of ZnCl2.10
absence of an additional transition-metal catalyst. In 2004, Similarly, organoindium reagents could be obtained by the
Cahiez reported that organomanganese reagents readily insertion of magnesium into organic halides in the presence
reacted with ortho-acylated aryl chlorides without any tran- of InCl3.11 Compared with other methods, this kind of prepa-
sition-metal catalyst, affording the expected coupling pro- ration method is more convenient, efficient, easy to handle
ducts.6 However, the scarcity of convenient methods for the and highly functional group tolerant.
preparation of organomanganese(II) reagents possibly limited
further investigation on this direct coupling reaction. In this
paper, we wish to report a simple, operational, economical
method for the preparation of organomanganese reagents and
Results and discussion
the possibility of transition-metal-catalyst-free coupling of
organomanganese reagents.
Herein, we report a convenient method for the preparation of
organomanganese(II) reagents. In the presence of MnCl2·2LiCl
(1.1 equiv.), the initially obtained aryl magnesium species by
the reaction of aromatic halides with magnesium (2.5 equiv.)
in THF was transmetallated in situ to give the corresponding
organomanganese(II) reagents in moderate yields. These orga-
nomanganese(II) reagents can readily react with various elec-
trophiles, providing the expected products (eqn (1), Scheme 1).
Department of Chemistry, China University of Petroleum, Qingdao, 266580,
P. R. China. E-mail: zpech@upc.edu.cn; Fax: +86532 8698 3374;
Tel: +86532 8698 3374
†Electronic supplementary information (ESI) available: Experimental procedure
and spectral data. See DOI: 10.1039/c4ob01235f
7800 | Org. Biomol. Chem., 2014, 12, 7800–7809
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in moderate to good yields (Table 1). Thus, bromobenzene (1a)
reacted with magnesium (2.5 equiv.) in the presence of
MnCl2·2LiCl (1.1 equiv.) within 3.5 h at 10 °C, affording phe-
nylmanganese(II) chloride 1a in a yield of 63%. 1-Bromo-3-
methoxybenzene (1b), which bears an electron donating group
(–OMe), smoothly underwent the insertion reaction of mag-
nesium in the presence of MnCl2·2LiCl (1.1 equiv.) within 3 h
at 10 °C, giving (3-methoxyphenyl)manganese(II) chloride 2b
in a 52% yield. Similarly, (4-methoxyphenyl)manganese(II)
chloride (2c) could be obtained from 1-iodo-4-methoxyben-
zene. It has to be noted that the yield of organomanganese
reagent 2c determined by GC after iodolysis was 42%.
However, the yield of 2c was 80% when determined by GC
after allylation with allyl bromide. A possible reason is that
more side products were formed when organomanganese
reagent 2c was quenched with iodine. 1-Bromo-4-(trifluoro-
methoxy)benzene (1d) can also convert to corresponding orga-
nomanganese(II) reagent 2d in a 53% yield. The compounds
containing the fluorine group has widespread application in
many fields. Several aromatic manganese reagents 2e–i having
the fluorine or trifluoromethyl group were produced in
40–87% yield in a similar manner starting from the corres-
ponding aryl halides. To our delight, magnesium smoothly
inserted 2-bromobenzonitrile (1j) in the presence of
MnCl2·2LiCl, leading to corresponding organomanganese(II)
reagent 2j in a 54% yield. In addition, heterocyclic halides as
substrates have been screened. Under similar conditions, thio-
phen-3-ylmanganese(II) chloride (2k) and thiophen-2-ylmanga-
nese(II) chloride (2l) were prepared in 30% and 50% yield
respectively. The reaction of 3-chloropyridine (1m) with mag-
nesium in the presence of MnCl2·2LiCl within 15 h at 15 °C
performed well, affording the expected organomanganese(II)
reagent 2m in a yield of 80%. In addition, the treatment of
2-bromopyridine (1n) with magnesium in the presence of
MnCl2·2LiCl produced pyridin-2-ylmanganese(II) chloride 2n
in a low yield of 39%, which was accompanied by an amount
(31%) of the reduction product (pyridine). When 5-bromo-
1,2,3-trichlorobenzene (1o) and 4-bromo-3-fluorobenzonitrile
(1p) were employed as starting materials, the corresponding
organomanganese reagents 2o–p were synthesized in a low
yield of 33% and 26% (Table 1).
Scheme 1 Preparation of organomanganese(II) reagents by the reaction
of aromatic halides with magnesium (2.5 equiv.) in the presence of
MnCl2·2LiCl (1.1 equiv.) in THF and their subsequent reactions. aCom-
plexed LiCl and magnesium halides are omitted for clarity.
Moreover, in the absence of an additional transition-metal
catalyst such as Pd (Ni et al.), organomanganese reagents can
be directly oxidized by the oxidant 3,3′,5,5′-tetra-tert-butyl-
[1,1′-bi(cyclohexylidene)]-2,2′,5,5′-tetraene-4,4′-dione (6), leading
to homocoupling products in one pot (eqn (2), Scheme 1).
This method could be applied to prepare various organo-
manganese reagents bearing many sensitive functional groups
Table 1 Organomanganese reagents prepared by the insertion of mag-
nesium into aromatic halides in the presence of MnCl2·2LiCla
With these organomanganese(II) reagents in hand, the reac-
tions of organomanganese(II) reagents were investigated. Phe-
nylmanganese(II) chloride (2a) and (3-methoxyphenyl)-
manganese(II) chloride (2b) readily underwent 1,2-addition to
2-bromobenzaldehyde (3a), providing the functionalized
alcohol 4a and 4b in 73% and 72% yield respectively (entries
1–2, Table 2). Note that the reaction of bromobenzene (1a)
with magnesium (2.5 equiv.), 2-bromobenzaldehyde (3a, 0.6
equiv.) and MnCl2·2LiCl (1.1 equiv.) in one pot within 12 h at
10 °C did not give the expected alcohol 4a. A smooth acylation
of the aromatic manganese reagents 2d–e with 4-chlorobenzoyl
a Reaction was performed using 1.5–3 mmol of the starting aromatic
halides. b Yields were determined by GC after iodolysis using
n-dodecane as an internal standard unless otherwise noted. Each
reaction was monitored by GC-analysis of the hydrolyzed reaction chloride (3b, 0.6 equiv.) generated the functionalized ketone
aliquots and the reaction mixture was stirred until the conversion of
derivatives 4d–e in a 69–91% yield (entries 3–4, Table 2). Simi-
larly, the organomanganese reagents 2f–g underwent 1,2-
addition to 2-bromobenzaldehyde (3a), giving the functiona-
the organic halide reached >95%. c Complexed LiCl and magnesium
halides are omitted for clarity. d Yield was determined by GC after
allylation with allyl bromide.
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Table 2 Reactions of organomanganese reagents with various
Table 2 (Contd.)
electrophiles
Aromatic manganese
chloridea
Entry
11
Electrophileb
Product (yieldc)
Aromatic manganese
Entry
1
chloridea
Electrophileb
Product (yieldc)
2l
3b
4l (90%)
2a
2b
3a
3a
4a (73%)
4b (72%)
a Complexed LiCl and magnesium halides are omitted for clarity. b 0.6
equivalent of electrophile was used. c Yield of the isolated, analytically
pure products. d Obtained after cross-coupling in the presence of 5%
PdCl2 and 10% PPh3.
2
3
lized alcohol derivatives 4f–g in a 68–89% yield (entries 5 and
6, Table 2). A Pd-catalyzed cross-coupling of organomanganese
reagents 2h–j with ethyl 4-iodobenzoate (1q, 0.6 equiv.) or
1-iodo-4-methoxybenzene (1c, 0.6 equiv.) in the presence of
PdCl2 (5 mol%) and PPh3 (10 mol%) generated the expected
products 4h–j in a 40–89% yield (entries 7–9, Table 2). The
treatment of heterocyclic reagents 2k–l with 4-chlorobenzoyl
chloride (3b, 0.6 equiv.) afforded the desired ketone derivative
4k–l in a 65–90% yield (entries 10 and 11, Table 2).
Usually, aryl magnesium reagents bearing a sensitive ester
group could not be prepared by the insertion of magnesium
into aryl halides in the presence of LiCl because they decom-
posed rapidly.10b To our satisfaction, starting from ethyl
4-iodobenzoate (1q), (4-(ethoxycarbonyl)phenyl)manganese(II)
chloride (2q) was obtained in a 44% yield by treating with
magnesium in the presence of MnCl2·2LiCl. The acylation of
2q with 4-chlorobenzoyl chloride (3b, 0.6 equiv.) led to the
expected ketone 4q in a yield of 58%. Similarly, the subsequent
allylation with allyl bromide gave the corresponding product
4r in a 53% yield (Scheme 2).
2d
3b
4d (91%)
4
2e
2f
3b
3a
3a
4e (69%)
4f (68%)
4g (89%)
5
6
7
2g
The oxidative coupling reaction between two organometal-
lics is a new field.12 Up to now, only a few examples of tran-
sition metal catalyzed oxidative coupling reactions between
two organometallics have been demonstrated.13 Interestingly,
2h
2i
1q
1q
4h (90%d)
4i (52%d)
8
9
2j
1c
4j (40%d)
4k (65%)
10
Scheme 2 (4-(Ethoxycarbonyl)phenyl)manganese(II) chloride (2q) pre-
pared by the insertion of magnesium into ethyl 4-iodobenzoate (1q) in
the presence of MnCl2·2LiCl and subsequent reactions. aComplexed LiCl
and magnesium halides are omitted for clarity. bYield was determined by
GC after allylation with allyl bromide.
2k
3b
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Table 3 The transition-metal-catalyst-free oxidative homocoupling of
organomanganese reagents
Scheme 3 The transition-metal-catalyst-free oxidative heterocoupling
between organomanganese reagent and Grignard reagent. aYields were
determined by GC after using n-dodecane as an internal standard.
Conclusions
In conclusion, we have developed a convenient method for the
preparation of functionalized arylmanganese halides by the
treatment of aromatic halides with magnesium in the presence
of MnCl2·2LiCl. These organomanganese reagents smoothly
underwent 1,2-addition, acylation, allylic substitution, and Pd-
catalyzed cross-coupling with various electrophiles, affording
the desired products in good yields. Especially, in the absence
of a transition-metal catalyst, the oxidation of organomanga-
nese reagents by 3,3′,5,5′-tetra-tert-butyl-[1,1′-bi(cyclohexyli-
dene)]-2,2′,5,5′-tetraene-4,4′-dione led to corresponding biaryl
compounds in good yields. Moreover, a previous study showed
that the organomanganese reagent has the potential to
undergo an oxidative cross-coupling reaction in the absence of
a transition-metal catalyst.
a Complexed LiCl and magnesium halides are omitted for clarity.
b Yield of the isolated, analytically pure products.
Knochel et al.14 showed that a transition-metal-free oxidative
homocoupling of organomagnesium reagents was performed
by means of 3,3′,5,5′-tetra-tert-butyl-[1,1′-bi(cyclohexylidene)]-
2,2′,5,5′-tetraene-4,4′-dione (6) as an oxidant. In the course of
our investigations on transition-metal-catalyst-free reactions of
organomanganese reagents, we found that the oxidative homo-
coupling of organomanganese reagents was completed well
using compound 6 as an oxidant in one pot in the absence of
an additional transition-metal-catalyst, leading to the expected
biaryl derivatives.
Thus, after phenylmanganese(II) chloride was afforded by
the insertion of magnesium turnings into bromobenzene in
the presence of MnCl2·2LiCl (1.1 equiv.) within 3.5 h at 10 °C,
the following addition of the organic oxidant 6 (0.5 equiv.) pro-
vided the expected biphenyl 5a in a 61% yield in one pot in
two steps (Table 3). Under similar conditions, we have pre-
pared various biaryl derivatives 5b–g containing a variety of
functional groups such as –F, –OMe and –OCF3 in a 64–80%
yield. Also, the oxidative procedure was used to synthesize
biheterocyclic compounds. The reaction of thiophen-3-ylman-
ganese(II) chloride (2k) prepared by a previously mentioned
procedure with the oxidant 6 afforded the homocoupling
product 5k in a 45% yield. Similarly, the oxidative homocou-
pling of thiophen-2-ylmanganese(II) chloride (2l) produced the
expected product 5l in a 24% yield (Table 3).
Experimental section
General
All reactions were carried out under a nitrogen atmosphere in
flame-dried glassware. Syringes which were used to transfer
anhydrous solvents or reagents were purged with nitrogen
prior to use. THF was continuously refluxed and freshly dis-
tilled from sodium benzophenone ketyl under nitrogen. Car-
boxylic acid chlorides and allyl bromides were distilled under
nitrogen prior to use. Yields refer to isolated yields of com-
1
pounds estimated to be >95% pure as determined by H NMR
(25 °C) and capillary-GC. NMR spectra were recorded on solu-
tions in deuterated chloroform (CDCl3) with residual chloro-
1
form (δ 7.25 ppm for H NMR and δ 77.0 ppm for 13C NMR).
Abbreviations for signal coupling are as follows: s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet, br, broad. Column
chromatographical purifications were performed using SiO2
(0.040–0.063 mm, 100–200 mesh ASTM) purchased from Branch
of Qingdao Haiyang Chemical Co., Ltd if not indicated otherwise.
Metallic salts
Fantastically, in the presence of the oxidant 6, the treatment
of organomanganese reagent 2b with phenylmagnesium
bromide (7) gave the heterocoupling product 8a in a 44%
yield. This previous study showed that organomanganese
reagent has the potential to undergo the oxidative cross-coup-
ling reaction without a transition-metal catalyst (Scheme 3).
Further studies on the oxidative cross-coupling reaction
between organomanganese reagent and other organometallics
are currently underway.
Manganese dichloride anhydrous (98%) and lithium chloride
(AR) were purchased from Sinopharm Chemical Reagent
Co., Ltd.
Experimental procedures
TP1: typical procedure for the preparation of aromatic
manganese reagents (2a–q). LiCl (2.2 equiv.) was placed in an
argon-flushed flask and dried for 5 min at 380 °C (heat gun)
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under high vacuum (1 mbar). After cooling to room tempera-
(4-Chlorophenyl)(4-(trifluoromethoxy)phenyl)methanone (4d).
ture, this flask was charged with manganese chloride (1.1 4-Chlorobenzoyl chloride (3b, 315 mg, 1.8 mmol) and THF
equiv.), and dried for 5 min at 380 °C (heat gun) under high (1 mL) were placed in an argon-flushed flask. To this mixture
vacuum (1 mbar). The flask was evacuated and backfilled with was added (4-(trifluoromethoxy)phenyl)manganese(II) chloride
argon three times and THF (5–10 mL) was added. The mixture (2d, 10 mL) dropwise at 10 °C. The reaction mixture was
was stirred until a clear solution was formed. Magnesium stirred for 12 h followed by quenching with ammonium chlor-
turning (2.5 equiv.) was placed in an argon-flushed flask and ide (5 mL). The aqueous layer was extracted with ethyl acetate
dried for 5 min at 380 °C (heat gun) under high vacuum (3 × 20 mL). The combined organic phases were dried over
(1 mbar). The flask was evacuated and backfilled with argon MgSO4, and the solvent was removed in vacuo. Purification by
three times. The solution of MnCl2·LiCl in THF was transferred flash column chromatography (SiO2, petroleum ether–ethyl
with a syringe at 10 °C. The solution of organic halide acetate = 50 : 1) provided (4-chlorophenyl)(4-(trifluoromethoxy)-
(1 equiv.) was then added at the appropriate temperature phenyl)methanone (4d, 495 mg, 91%) as a white solid. m.p. =
(−5 °C to 15 °C) and the reaction mixture was stirred until the 68.5 °C–70.5 °C; 1H NMR (600 MHz, CDCl3): δ (ppm) = 7.83 (d,
conversion of the organic halide reached >95% (monitored by J = 8.8 Hz, 2 H), 7.73 (d, J = 8.1 Hz, 2 H), 7.47 (d, J = 8.1 Hz,
GC-analysis of the hydrolyzed reaction aliquots). Yields of the 2 H), 7.32 (d, J = 8.1 Hz, 2 H); 13C NMR (150 MHz, CDCl3):
resulting aromatic manganese reagents were determined by δ (ppm) = 193.9, 152.3 (q, J = 3.0 Hz), 139.3, 135.5, 135.4,
iodolysis or allylation with allyl bromide in THF.
131.8, 131.3, 128.8, 120.3 (q, J = 259.7 Hz), 120.3; IR (Diamond-
ATR, neat): ˜ν(cm−1) = 1648.9 (S), 1589.1 (W), 1319.1 (M), 1164.8
(2-Bromophenyl)(phenyl)methanol
(4a). 2-Bromobenzalde-
hyde (3a, 333 mg, 1.8 mmol) and THF (1 mL) were placed in
an argon-flushed flask. To this mixture was added phenylman-
ganese(II) chloride (2a, 10 mL) dropwise at 10 °C. The reaction
(S), 1093.4 (W), 858.2 (M), 759.8 (M); HRMS (C14H8ClF3O2
+
H): Calc.: 301.0243; found: 301.0244 (M+ + H).
(4-Chlorophenyl)(5-fluoro-2-methoxyphenyl)methanone (4e). 4-
mixture was continuously stirred for 12 h followed by quench- Chlorobenzoyl chloride (3b, 315 mg, 1.8 mmol) and THF
ing with ammonium chloride (5 mL). The aqueous layer was (1 mL) were placed in an argon-flushed flask. To this mixture
extracted with ethyl acetate (3 × 20 mL). The combined organic was added (5-fluoro-2-methoxyphenyl)manganese(II) chloride
phases were dried over MgSO4, the solvent was removed (2e, 10 mL) dropwise at 10 °C. The reaction mixture was stirred
in vacuo. Purification by flash column chromatography (SiO2, for 12 h followed by quenching with ammonium chloride
petroleum ether–ethyl acetate = 20 : 1) afforded 4a (347 mg, (5 mL). The aqueous layer was extracted with ethyl acetate (3 ×
73%) as a colorless liquid. 1H NMR (600 MHz, CDCl3): δ (ppm) 20 mL). The combined organic phases were dried over MgSO4,
= 7.41 (dd, J = 22.4 Hz, 7.7 Hz 2 H), 7.28–7.10 (m, 6 H), 6.99 (t, J and the solvent was removed in vacuo. Purification by flash
= 7.7 Hz, 1 H), 6.00 (s, 1 H), 2.73 (br s, 1 H); 13C NMR column chromatography (SiO2, petroleum ether–ethyl acetate =
(150 MHz, CDCl3): δ (ppm) = 142.4, 142.1, 132.7, 128.9, 128.3, 30 : 1) provided the pure compound 4e (326 mg, 69%) as a pale
128.3, 127.6, 127.5, 126.9, 122.6, 74.6; IR (Diamond-ATR, neat): yellow solid. m.p. = 76.5 °C–78.5 °C; 1H NMR (600 MHz,
(cm−1) = 3350.7 (S), 1568.3 (W), 1494.3 (M), 1454.2 (S), 1184.6 CDCl3): δ (ppm) = 7.73 (d, J = 8.1 Hz, 2 H), 7.41 (d, J = 8.8 Hz
(M), 1016.5 (S), 751.4 (S), 698.5 (S), 600.6 (M); HRMS 2 H), 7.19–7.14 (m, 1 H), 7.09 (dd, J = 8.1 Hz, 2.9 Hz, 1 H), 6.93
(C13H11BrO + Na): Calc.: 284.9891; found: 284.9878 (M+ + Na).
(2-Bromophenyl)(3-methoxyphenyl)methanol (4b). 2-Bromo-
(dd, J = 9.2 Hz, 4.0 Hz, 1 H), 3.39 (s, 3 H); 13C NMR (150 MHz,
CDCl3): δ (ppm) = 193.7, 156.6 (d, J = 242.0 Hz), 153.3 (d, J =
2.2 Hz), 139.6, 135.6, 131.7, 129.2 (d, J = 5.5 Hz), 128.7, 118.3
(d, J = 23.1 Hz), 116.2 (d, J = 24.0 Hz), 112.7 (d, J = 7.7 Hz),
55.2; IR (Diamond-ATR, neat): ˜ν(cm−1) = 3070.1 (W), 1656.6 (S),
1585.2 (M), 1494.6 (M), 1421.3 (M), 1284.4 (M), 862.0 (M),
721.3 (W); HRMS (C14H10ClFO2 + Na): Calc.: 287.0251; found:
287.0246 (M+ + Na).
benzaldehyde (3a, 333 mg, 1.8 mmol) and THF (1 mL) were
placed in an argon-flushed flask. To this mixture was added
(3-methoxyphenyl)manganese(II) chloride (2b, 10 mL) dropwise
at 10 °C. The reaction mixture was stirred for 12 h followed by
quenching with ammonium chloride (5 mL). The aqueous
layer was extracted with ethyl acetate (3 × 20 mL). The com-
bined organic phases were dried over MgSO4, and the solvent
(2-Bromophenyl)(2-fluorophenyl)methanol (4f). 2-Bromobenz-
was removed in vacuo. Purification by flash column chromato- aldehyde (3a, 333 mg, 1.8 mmol) and THF (1 mL) were placed
graphy (SiO2, petroleum ether–ethyl acetate = 20 : 1) provided in an argon-flushed flask. To this mixture was added (2-fluoro-
(2-bromophenyl)(3-methoxyphenyl)methanol (4b, 382 mg, phenyl)manganese(II) chloride (2f, 10 mL) dropwise at 10 °C.
72%) as a colorless liquid. 1H NMR (600 MHz, CDCl3): δ (ppm) The reaction mixture was continuously stirred for 12 h fol-
= 7.42 (dd, J = 15.4 Hz, 7.4 Hz, 2 H), 7.19 (t, J = 7.3 Hz, 1 H), lowed by quenching with ammonium chloride (5 mL). The
7.12 (t, J = 7.7 Hz, 1 H), 7.01 (t, J = 7.7 Hz, 1 H), 6.88–6.82 (m, aqueous layer was extracted with ethyl acetate (3 × 20 mL). The
2 H), 6.69 (d, J = 8.1 Hz, 1 H), 6.02 (s, 1 H), 3.64 (s, 3 H), 2.73 combined organic phases were dried over MgSO4, and the
(br s, 1 H); 13C NMR (150 MHz, CDCl3): δ (ppm) = 159.5, 143.8, solvent was removed in vacuo. Purification by flash column
142.4, 132.7, 129.4, 129.0, 128.4, 127.6, 122.7, 119.2, 112.9, chromatography (SiO2, petroleum ether–ethyl acetate
=
112.6, 74.4, 55.1; IR (Diamond-ATR, neat): ˜ν(cm−1) = 3391.8 (S, 20 : 1–10 : 1) provided the pure compound 4f (344 mg, 68%) as
1
br.), 1601.1 (M), 1464.5 (M), 1258.6 (M), 1046.0 (M), 746.5 (W); a colorless liquid. H NMR (600 MHz, CDCl3): δ (ppm) = 7.53
HRMS (C14H13BrO2 + Na): Calc.: 314.9997; found: 314.9989 (d, J = 7.7 Hz, 2 H), 7.32 (t, J = 8.1 Hz, 1 H), 7.29–7.21 (m, 2 H),
(M+ + Na).
7.15 (t, J = 7.7 Hz 1 H), 7.09 (t, J = 7.7 Hz, 1 H), 7.04
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(t, J = 8.8 Hz, 1 H), 6.41 (s, 1 H), 2.65 (s, 1 H); 13C NMR
(150 MHz, CDCl3): δ (ppm) = 160.4 (d, J = 247.6 Hz), 141.0,
132.9, 129.6 (d, J = 8.8 Hz), 129.3, 128.9 (d, J = 13.2 Hz), 128.5
(d, J = 4.4 Hz), 128.4, 127.5, 124.1 (d, J = 3.3 Hz), 122.8, 115.4
(d, J = 22.0 Hz), 69.1 (d, J = 3.3 Hz); IR (Diamond-ATR, neat):
˜ν(cm−1) = 3206.5 (S, br.), 1615.7 (W), 1588.2 (W), 1486.4 (M),
1455.6 (M), 1225.3 (M), 1016.0 (M), 758.3 (S); HRMS
(C13H10BrFO + Na): Calc.: 302.9797; found: 302.9788 (M+ + Na).
Ethyl
3′,5′-bis(trifluoromethyl)-[1,1′-biphenyl]-4-carboxylate
(4i). PdCl2 (16 mg, 0.09 mmol), PPh3 (47 mg, 0.18 mmol) and
THF (1 mL) were placed in an argon-flushed flask. The mixture
was stirred for 2 h at room temperature. To the mixture was
added ethyl 4-iodobenzoate (1q, 497 mg, 1.8 mmol). Sub-
sequently, (3,5-bis(trifluoromethyl)phenyl)manganese(II) chlor-
ide (2i, 10 mL) was added dropwise at 10 °C. The reaction
mixture was stirred for 12 h followed by quenching with
(2-Bromophenyl)(2,4-difluorophenyl)methanol (4g). 2-Bromo- ammonium chloride (5 mL). The aqueous layer was extracted
benzaldehyde (3a, 333 mg, 1.8 mmol) and THF (1 mL) were with ethyl acetate (3 × 20 mL). The combined organic phases
placed in an argon-flushed flask. To this mixture was added were dried over MgSO4, and the solvent was removed in vacuo.
(2,4-difluorophenyl)manganese(II) chloride (2g, 10 mL) drop- Purification by flash column chromatography (SiO2, petroleum
wise at 10 °C. The reaction mixture was continuously stirred ether–ethyl acetate = 50 : 1) provided the pure compound 4i
for 12 h followed by quenching with ammonium chloride (340 mg, 52%) as a white solid. m.p. = 88.1 °C–90.4 °C; 1H
(5 mL). The aqueous layer was extracted with ethyl acetate (3 × NMR (600 MHz, CDCl3): δ (ppm) = 8.17 (d, J = 8.1 Hz, 2 H),
20 mL). The combined organic phases were dried over MgSO4, 8.03 (s, 2 H), 7.90 (s, 1 H), 7.67 (d, J = 8.1 Hz, 2 H), 4.42 (q, J =
and the solvent was removed in vacuo. Purification by flash 7.3 Hz, 2 H), 1.42 (t, J = 6.9 Hz, 3 H); 13C NMR (150 MHz,
column chromatography (SiO2, petroleum ether–ethyl acetate = CDCl3): δ (ppm) = 166.0, 142.3, 142.2, 132.3 (q, J = 33.0 Hz),
30 : 1–15 : 1) provided the pure compound 4g (481 mg, 89%) as 130.9, 130.5, 127.4 (q, J = 2.2 Hz), 127.2, 123.2 (q, J = 272.9 Hz),
a white solid. m.p. = 77.0 °C–78.5 °C; 1H NMR (600 MHz, 121.7 (m), 61.3, 14.3; IR (Diamond-ATR, neat): ˜ν(cm−1) =
CDCl3): δ (ppm) = 7.54 (t, J = 6.6 Hz, 2 H), 7.35 (t, J = 7.3 Hz, 3050.8 (W), 1716.3 (S), 1382.7 (M), 1288.2 (M), 1126.2 (M),
1 H), 7.22–7.14 (m, 2 H), 6.85–6.77 (m, 2 H), 6.36 (d, J = 4.4 Hz, 896.7 (W), 773.3 (W); HRMS (C17H12F6O2 + H): Calc.: 363.0820;
1 H), 2.57 (d, J = 3.7 Hz, 1 H); 13C NMR (150 MHz, CDCl3): found: 363.0811 (M+ + H).
4′-Methoxy-[1,1′-biphenyl]-2-carbonitrile (4j). PdCl2 (8 mg,
0.045 mmol), PPh3 (24 mg, 0.09 mmol) and THF (1 mL) were
placed in an argon-flushed flask. The mixture was stirred for
2 h at room temperature. To the mixture was added 1-iodo-4-
methoxybenzene (1c, 211 mg, 0.9 mmol). Subsequently, (2-cya-
nophenyl)manganese(II) chloride (2j, 10 mL) was added drop-
wise at 10 °C. The reaction mixture was stirred for 12 h
followed by quenching with ammonium chloride (5 mL). The
δ (ppm) = 161.7 (dd, J = 62.7 Hz, 12.1 Hz), 161.6 (dd, J = 562.3
Hz, 12.1 Hz), 140.9, 133.0, 129.6 (dd, J = 9.9 Hz, 5.5 Hz), 129.5,
128.3, 127.7, 125.2 (dd, J = 14.3 Hz, 4.4 Hz), 122.8, 111.3 (dd,
J = 20.9 Hz, 4.4 Hz), 103.9 (t, J = 25.9 Hz), 68.7 (d, J = 3.0 Hz);
IR (Diamond-ATR, neat): ˜ν(cm−1) = 3187.8 (S, br.), 1606.4 (M),
1504.2 (M), 1432.9 (M), 1284.4 (M), 1141.7 (M), 1024.0 (M),
966.2 (M), 955.9 (M), 719.3 (W); HRMS (C13H9BrF2O): Calc.:
297.9805; found: 298.0051 (M+).
Ethyl 2′-(trifluoromethyl)-[1,1′-biphenyl]-4-carboxylate (4h). aqueous layer was extracted with ethyl acetate (3 × 20 mL).
PdCl2 (16 mg, 0.09 mmol), PPh3 (47 mg, 0.18 mmol) and THF The combined organic phases were dried over MgSO4, and the
(1 mL) were placed in an argon-flushed flask. The mixture was solvent was removed in vacuo. Purification by flash column
stirred for 2 h at room temperature. To the mixture was added chromatography (SiO2, petroleum ether–ethyl acetate
=
ethyl 4-iodobenzoate (1q, 497 mg, 1.8 mmol) and DME 30 : 1–15 : 1–10 : 1) provided the pure compound 4j (153 mg,
1
(577 mg, 6.4 mmol). Subsequently, (2-(trifluoromethyl)phenyl)- 40%) as a pale yellow solid. m.p. = 81.5 °C–83.0 °C; H NMR
manganese(II) chloride (2h, 10 mL) was added dropwise at (600 MHz, CDCl3): δ (ppm) = 7.73 (d, J = 8.1 Hz, 1 H), 7.60 (t,
10 °C. The reaction mixture was stirred for 12 h followed by J = 7.3 Hz, 1 H), 7.53–7.45 (m, 3 H), 7.38 (t, J = 7.3 Hz, 1 H),
quenching with ammonium chloride (5 mL). The aqueous 7.01 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3 H); 13C NMR (150 MHz,
layer was extracted with ethyl acetate (3 × 20 mL). The com- CDCl3): δ (ppm) = 159.9, 145.1, 133.7, 132.7, 130.4, 129.9,
bined organic phases were dried over MgSO4, and the solvent 129.8, 126.9, 118.9, 114.1, 110.9, 55.3; IR (Diamond-ATR, neat):
was removed in vacuo. Purification by flash column chromato- ˜ν(cm−1) = 3035.4 (W), 2223.5 (M), 1612.2 (M), 1517.7 (M),
graphy (SiO2, petroleum ether–ethyl acetate = 20 : 1) provided 1481.1 (M), 1253.5 (S), 1481.1 (M), 1035.6 (M), 833.1 (M), 752.1
the pure compound 4h (475 mg, 90%) as a white solid. m.p. = (S); HRMS (C14H11NO + Na): Calc.: 232.0738; found: 232.0732
39.0–40.5 °C; 1H NMR (600 MHz, CDCl3): δ (ppm) = 8.08 (d, J = (M+ + Na).
(4-Chlorophenyl)(thiophen-3-yl)methanone (4k). 4-Chloroben-
zoyl chloride (3b, 158 mg, 0.9 mmol) and THF (1 mL) were
placed in an argon-flushed flask. To this mixture was added
thiophen-3-ylmanganese(II) chloride (2k, 5 mL) dropwise at
10 °C. The reaction mixture was stirred for 12 h followed by
quenching with ammonium chloride (5 mL). The aqueous
layer was extracted with ethyl acetate (3 × 20 mL). The com-
bined organic phases were dried over MgSO4, and the solvent
was removed in vacuo. Purification by flash column chromato-
graphy (SiO2, petroleum ether–ethyl acetate = 50 : 1) provided
8.1 Hz, 2 H), 7.75 (d, J = 8.1 Hz, 1 H), 7.57 (t, J = 7.7 Hz, 1 H),
7.49 (t, J = 7.3 Hz, 1 H), 7.39 (d, J = 8.1 Hz, 2 H), 7.31 (d, J =
7.3 Hz, 1 H), 4.40 (q, J = 6.9 Hz, 2 H), 1.41 (t, J = 6.9 Hz, 3 H);
13C NMR (150 MHz, CDCl3): δ (ppm) = 166.4, 144.4, 140.3 (q,
J = 2.2 Hz), 131.6, 131.4, 129.8, 129.0, 128.5, 128.3, 127.8, 126.2
(q, J = 5.5 Hz), 123.9 (q, J = 274.0 Hz), 61.0, 14.3; IR (Diamond-
ATR, neat): ˜ν(cm−1) = 2973.7 (W), 1712.5 (S), 1604.5 (M), 1450.2
(W), 1313.3 (VS), 1168.7 (S), 1112.7 (S), 1033.7 (M), 862.0 (M),
771.4 (M); HRMS (C16H13F3O2 + Na): Calc.: 317.0765; found:
317.0758 (M+ + Na).
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the pure compound 4k (131 mg, 65%) as a white solid. m.p. = extracted with ethyl acetate (3 × 20 mL). The combined organic
85.9 °C–87.8 °C; 1H NMR (600 MHz, CDCl3): δ (ppm) = 7.91 phases were dried over MgSO4, and the solvent was removed
(dd, J = 2.9 Hz, 1.5 Hz, 1 H), 7.79 (d, J = 8.8 Hz, 2 H), 7.57 (d, in vacuo. Purification by flash column chromatography (SiO2,
J = 5.1 Hz, 1 H), 7.46 (d, J = 8.1 Hz, 2 H), 7.39 (dd, J = 4.8 Hz, petroleum ether–ethyl acetate = 100 : 1 to 50 : 1) provided the
2.6 Hz, 1 H); 13C NMR (150 MHz, CDCl3): δ (ppm) = 188.7, pure compound 4r (91 mg, 53%) as a pale yellow liquid.
140.9, 138.8, 136.9, 133.9, 130.8, 129.5, 128.7, 128.5; IR 1H NMR (600 MHz, CDCl3): δ (ppm) = 7.89 (d, J = 8.1 Hz, 2 H),
(Diamond-ATR, neat): ˜ν(cm−1) = 3085.6 (W), 1637.3 (S), 1587.1 7.18 (d, J = 8.1 Hz, 2 H), 5.92–5.84 (m, 1 H), 5.05–4.99 (m, 2 H),
(W), 1414.5 (W), 1278.6 (M), 1096.6 (M), 842.7 (M), 748.3 (M), 4.29 (q, J = 7.3 Hz, 2 H), 3.36 (d, J = 6.6 Hz, 2 H), 1.31 (t, J =
687.5 (W); HRMS (C11H7ClOS + H): Calc.: 222.9984; found: 7.3 Hz, 3 H); 13C NMR (150 MHz, CDCl3): δ (ppm) = 166.6,
222.9977 (M+ + H).
145.3, 136.4, 132.8, 129.7, 128.5, 116.5, 60.8, 40.1, 14.3; IR
(Diamond-ATR, neat): ˜ν(cm−1) = 2980 (W), 1717.4 (VS), 1611.7
(W), 1367.1 (W), 1276.5 (VS), 1178.5 (M), 1106.8 (S), 1022.4
(W), 758.7 (W); HRMS (C12H14O2 + Na): Calc.: 213.0891; found:
213.0887 (M+ + Na).
(4-Chlorophenyl)(thiophen-2-yl)methanone (4l). 4-Chloroben-
zoyl chloride (3b, 158 mg, 0.9 mmol) and THF (1 mL) were
placed in an argon-flushed flask. To this mixture was added
thiophen-2-ylmanganese(II) chloride (2l, 5 mL) dropwise at
10 °C. The reaction mixture was stirred for 12 h followed by
quenching with ammonium chloride (5 mL). The aqueous
layer was extracted with ethyl acetate (3 × 20 mL). The com-
bined organic phases were dried over MgSO4, and the solvent
was removed in vacuo. Purification by flash column chromato-
graphy (SiO2, petroleum ether–ethyl acetate = 20 : 1) provided
the pure compound 4l (180 mg, 90%) as a white solid. m.p. =
96.5 °C–98.0 °C; 1H NMR (600 MHz, CDCl3): δ (ppm) = 7.81
(d, J = 8.1 Hz, 2 H), 7.73 (d, J = 5.1 Hz, 1 H), 7.63–7.61 (m, 1 H),
7.47 (d, J = 8.1 Hz, 2 H), 7.18–7.15 (m, 1 H); 13C NMR
(150 MHz, CDCl3): δ (ppm) = 186.9, 143.2, 138.7, 136.4,
134.8, 134.5, 130.6, 128.8, 128.0; IR (Diamond-ATR, neat):
˜ν(cm−1) = 3073.9 (W), 1630.5 (S), 1588.1 (W), 1413.6 (M),
1303.6 (M), 1091.5 (M), 852.4 (M), 746.3 (M), 721.3 (S), 687.5
(W); HRMS (C11H7ClOS + Na): Calc.: 244.9804; found: 244.9798
(M+ + Na).
TP2: typical procedure for the homocoupling of aromatic
manganese reagents (5a–l). LiCl (2.2 equiv.) was placed in an
argon-flushed flask and dried for 5 min at 380 °C (heat gun)
under high vacuum (1 mbar). After cooling to room tempera-
ture, this flask was charged with manganese chloride
(1.1 equiv.), and dried for 5 min at 380 °C (heat gun) under
high vacuum (1 mbar). The flask was evacuated and backfilled
with argon three times and THF (6.7 mL) was added. The
mixture was stirred until a clear solution was formed. Mag-
nesium turning (2.5 equiv.) was placed in an argon-flushed
flask and dried for 5 min at 380 °C (heat gun) under high
vacuum (1 mbar). The flask was evacuated and backfilled with
argon three times. The solution of MnCl2·LiCl in THF was
transferred with a syringe at 10 °C. The solution of organic
halide (1 equiv.) was then added at the appropriate tempera-
ture (10 °C to 15 °C) and the reaction mixture was stirred until
the conversion of the organic halide reached >95% (monitored
by GC-analysis of the hydrolyzed reaction aliquots). To the
reaction mixture was added 3,3′,5,5′-tetra-tert-butyldiphenoqui-
none (0.5 equiv.) at 10 °C. The reaction mixture was continu-
ously stirred for 12 h followed by quenching with ammonium
chloride (5 mL). The aqueous layer was extracted with ethyl
acetate (3 × 20 mL). The combined organic phases were dried
over MgSO4, and the solvent was removed in vacuo. Purification
by flash column chromatography (SiO2) afforded the corres-
ponding products.
4-(4-Chlorobenzoyl)benzoate (4q). 4-Chlorobenzoyl chloride
(3b, 158 mg, 0.9 mmol) and THF (1 mL) were placed in an
argon-flushed flask. To this mixture was added (4-(ethoxycar-
bonyl)phenyl)manganese(II) chloride (2q, 10 mL) dropwise at
10 °C. The reaction mixture was stirred for 12 h followed by
quenching with ammonium chloride (5 mL). The aqueous
layer was extracted with ethyl acetate (3 × 20 mL). The com-
bined organic phases were dried over MgSO4, and the solvent
was removed in vacuo. Purification by flash column chromato-
graphy (SiO2, petroleum ether–ethyl acetate = 30 : 1) provided
the pure compound 4q (152 mg, 58%) as a white solid. m.p. =
93.0 °C–95.0 °C; 1H NMR (600 MHz, CDCl3): δ (ppm) = 8.16 (d,
J = 8.8 Hz, 2 H), 7.81 (d, J = 8.1 Hz 2 H), 7.76 (d, J = 8.8 Hz,
2 H), 7.48 (d, J = 8.8 Hz, 2 H), 4.43 (q, J = 7.3 Hz, 2 H), 1.43 (t,
J = 6.9 Hz, 3 H); 13C NMR (150 MHz, CDCl3): δ (ppm) = 194.8,
166.3, 140.8, 135.2, 133.8, 131.5, 130.1, 129.6, 129.5, 128.8,
61.5, 14.3; IR (Diamond-ATR, neat): ˜ν(cm−1) = 1716.3 (S),
1648.8 (S), 1587.1 (W), 1276.6 (S), 1105.0 (M), 933.4 (W), 736.7
1,1′-Biphenyl (5a). According to TP2, bromobenzene (1a,
314 mg, 2 mmol) reacted with magnesium turning (120 mg,
5 mmol), MnCl2 (277 mg, 2.2 mmol), LiCl (187 mg, 4.4 mmol)
in THF (6.7 mL) within 3.5 h at 10 °C, affording the corres-
ponding aryl manganese reagent 2a. To the solution of phenyl-
manganese(II) chloride (2a) was added 3,3′,5,5′-tetra-tert-
butyldiphenoquinone (409 mg, 1 mmol) directly at 10 °C. The
reaction mixture was continuously stirred for 12 h followed by
quenching with ammonium chloride (5 mL). The aqueous
layer was extracted with ethyl acetate (3 × 20 mL). The com-
(M); HRMS (C16H13ClO3
+ Na): Calc.: 311.0451; found:
311.0448 (M+ + Na).
Ethyl 4-(4-chlorobenzoyl)benzoate (4r). Allyl bromide (3c, bined organic phases were dried over MgSO4, and the solvent
109 mg, 0.9 mmol) and THF (1 mL) were placed in an argon- was removed in vacuo. Purification by flash column chromato-
flushed flask. To this mixture was added (4-(ethoxycarbonyl)- graphy (SiO2, petroleum ether) provided the pure compound 5a
phenyl)manganese(II) chloride (2q, 10 mL) dropwise at 10 °C. (94 mg, 61%) as a white solid. m.p. = 67.5 °C–69.3 °C; 1H NMR
The reaction mixture was stirred for 6 h followed by quenching (600 MHz, CDCl3): δ (ppm) = 7.61–7.58 (m, 4 H), 7.46–7.42
with ammonium chloride (5 mL). The aqueous layer was (m, 4 H), 7.36–7.33 (m, 2 H); 13C NMR (150 MHz, CDCl3):
7806 | Org. Biomol. Chem., 2014, 12, 7800–7809
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δ (ppm) = 141.2, 128.7, 127.2, 127.1; IR (Diamond-ATR, neat): 3,3′,5,5′-tetra-tert-butyldiphenoquinone (409 mg,
1 mmol)
˜ν(cm−1) = 3033.5 (W), 1568.8 (W), 1480.1 (M), 1428.9 (M), directly at 10 °C. The reaction mixture was continuously stirred
1169.6 (W), 728.9 (S), 696.2 (M); HRMS (C12H10): Calc.: for 12 h followed by quenching with ammonium chloride
154.0783; found: 154.0786 (M+ + H).
(5 mL). The aqueous layer was extracted with ethyl acetate (3 ×
20 mL). The combined organic phases were dried over MgSO4,
the solvent was removed in vacuo. Purification by flash column
chromatography (SiO2, petroleum ether–ethyl acetate = 50 : 1)
3,3′-Dimethoxy-1,1′-biphenyl
(5b). According
to
TP2,
1-bromo-3-methoxybenzene (1b, 281 mg, 1.5 mmol) reacted
with magnesium turning (90 mg, 3.75 mmol), MnCl2 (208 mg,
1.65 mmol), LiCl (140 mg, 3.3 mmol) in THF (5 mL) within 3 h
at 10 °C, affording the corresponding aryl manganese reagent
2b. To the solution of (3-methoxyphenyl)manganese(II) chlor-
ide (2b) was added 3,3′,5,5′-tetra-tert-butyldiphenoquinone
(307 mg, 0.75 mmol) directly at 10 °C. The reaction mixture
was continuously stirred for 12 h followed by quenching with
ammonium chloride (5 mL). The aqueous layer was extracted
with ethyl acetate (3 × 20 mL). The combined organic phases
1
provided the pure compound 5d (228 mg, 71%) as an oil. H
NMR (600 MHz, CDCl3): δ (ppm) = 7.56 (d, J = 8.8 Hz, 4 H),
7.29 (d, J = 8.1 Hz, 4 H); 13C NMR (150 MHz, CDCl3): δ (ppm) =
148.9 (q, J = 2.2 Hz), 138.6, 128.5, 121.3, 120.5 (q, J = 257.5 Hz);
IR (Diamond-ATR, neat): ˜ν(cm−1) = 3047.9 (W), 1496.5 (S),
1258.3 (VS), 1206.3 (VS), 1166.7 (VS), 1008.6 (W), 808.0 (W);
HRMS (C14H8F6O2): Calc.: 322.0428; found: 322.0445 (M+).
5,5′-Difluoro-2,2′-dimethoxy-1,1′-biphenyl (5e). According to
were dried over MgSO4, and the solvent was removed in vacuo. TP2, 2-bromo-4-fluoro-1-methoxybenzene (1e, 482 mg,
Purification by flash column chromatography (SiO2, petroleum 2 mmol) reacted with magnesium turning (120 mg, 5 mmol),
ether–ethyl acetate = 100 : 1 to 50 : 1) provided the pure com- MnCl2 (277 mg, 2.2 mmol), LiCl (187 mg, 4.4 mmol) in THF
pound 5b (129 mg, 80%) as a pale yellow liquid. 1H NMR (6.7 mL) within 3 h at 10 °C, affording the corresponding aryl
(600 MHz, CDCl3): δ (ppm) = 7.34 (d, J = 8.1 Hz, 2 H), 7.17 (d, manganese reagent 2e. To the solution of (5-fluoro-2-methoxy-
J = 8.1 Hz, 2 H), 7.12–7.11 (m, 2 H), 6.89 (dd, J = 8.1 Hz, 2.2 Hz, phenyl)manganese(II) chloride (2e) was added 3,3′,5,5′-tetra-
2 H), 3.86 (s, 6 H); 13C NMR (150 MHz, CDCl3): δ (ppm) = tert-butyldiphenoquinone (409 mg, 1 mmol) directly at 10 °C.
159.9, 142.6, 129.7, 119.7, 112.9, 112.8, 55.3; IR (Diamond- The reaction mixture was continuously stirred for 12 h fol-
ATR, neat): ˜ν(cm−1) = 2957.5 (W), 1599.7 (S), 1575.2 (S), 1477.8 lowed by quenching with ammonium chloride (5 mL). The
(S), 1412.5 (M), 1279.1 (M), 1234.6 (S), 1031.4 (M), 853.5 (M), aqueous layer was extracted with ethyl acetate (3 × 20 mL). The
774.8 (S), 695.4 (M); HRMS (C14H14O2): Calc.: 214.0994; found: combined organic phases were dried over MgSO4, and the
214.0994 (M+).
solvent was removed in vacuo. Purification by flash column
chromatography (SiO2, petroleum ether–ethyl acetate = 50 : 1)
provided the pure compound 5e (196 mg, 78%) as a white
4,4′-Dimethoxy-1,1′-biphenyl (5c). According to TP2, 1-iodo-4-
methoxybenzene bromobenzene (1c, 468 mg, 2 mmol) reacted
with magnesium turning (120 mg, 5 mmol), MnCl2 (277 mg,
2.2 mmol), LiCl (187 mg, 4.4 mmol) in THF (6.7 mL) within
1.5 h at 10 °C, affording the corresponding aryl manganese
reagent 2c. To the solution of (4-methoxyphenyl)manganese(II)
chloride (2c) was added 3,3′,5,5′-tetra-tert-butyldiphenoqui-
none (409 mg, 1 mmol) directly at 10 °C. The reaction mixture
was continuously stirred for 12 h followed by quenching with
ammonium chloride (5 mL). The aqueous layer was extracted
with ethyl acetate (3 × 20 mL). The combined organic phases
were dried over MgSO4, the solvent was removed in vacuo. Puri-
1
solid. m.p. = 122.2 °C–123.8 °C; H NMR (600 MHz, CDCl3): δ
(ppm) = 7.04–6.96 (m, 4 H), 6.92–6.87 (m, 2 H), 3.75 (S, 6 H);
13C NMR (150 MHz, CDCl3): δ (ppm) = 156.6 (d, J = 238.8 Hz),
153.0 (d, J = 2.2 Hz), 127.8 (d, J = 6.6 Hz), 118.1 (d, J = 23.1 Hz),
114.8 (d, J = 22.5 Hz), 116.1 (d, J = 7.5 Hz), 56.3; IR (Diamond-
ATR, neat): ˜ν(cm−1) = 3072.1 (W), 2957.3 (W), 1590.9 (W),
1487.8 (VS), 1426.1 (S), 1245.8 (S), 1182.2 (S), 1034.6 (S), 869.7
(M), 819.6 (M), 751.1 (M); HRMS (C14H12F2O2): Calc.: 250.0805;
found: 250.0814 (M+).
2,2′-Difluoro-1,1′-biphenyl (5f). According to TP2, 1-fluoro-2-
fication by flash column chromatography (SiO2, petroleum iodobenzene (1f, 444 mg, 2 mmol) reacted with magnesium
ether–ethyl acetate = 50 : 1) provided the pure compound 5c turning (120 mg, 5 mmol), MnCl2 (277 mg, 2.2 mmol), LiCl
1
(149 mg, 70%) as a white solid. m.p. = 175.5 °C–176.4 °C; H (187 mg, 4.4 mmol) in THF (6.7 mL) within 3 h at 10 °C,
NMR (600 MHz, CDCl3): δ (ppm) = 7.47 (d, J = 8.8 Hz, 4 H), affording the corresponding aryl manganese reagent 2f. To the
6.95 (d, J = 8.8 Hz, 4 H), 3.83 (s, 6 H); 13C NMR (150 MHz, solution of (2-fluorophenyl)manganese(II) chloride (2f) was
CDCl3): δ (ppm) = 158.7, 133.5, 127.7, 114.1, 55.3; IR added 3,3′,5,5′-tetra-tert-butyldiphenoquinone (409 mg,
(Diamond-ATR, neat): ˜ν(cm−1) = 2958.3 (W), 1607.4 (M), 1502.3 1 mmol) directly at 10 °C. The reaction mixture was continu-
(S), 1276.7 (S), 1250.6 (S), 1184.1 (M), 1041.4 (S), 1012.5 (M), ously stirred for 12 h followed by quenching with ammonium
824.4 (S), 809.9 (M), 782.9 (W); HRMS (C14H14O2): Calc.: chloride (5 mL). The aqueous layer was extracted with ethyl
214.0994; found: 214.0988 (M+).
acetate (3 × 20 mL). The combined organic phases were dried
over MgSO4, and the solvent was removed in vacuo. Purification
by flash column chromatography (SiO2, petroleum ether–ethyl
acetate = 200 : 1) provided the pure compound 5f (123 mg,
64%) as a white solid. m.p. = 115.9 °C–117.8 °C; 1H NMR
(600 MHz, CDCl3): δ (ppm) = 7.41–7.34 (m, 4 H), 7.24–7.20 (m,
2 H), 7.18–7.14 (m, 2 H); 13C NMR (150 MHz, CDCl3): δ (ppm)
= 159.8 (dd, J = 249.8 Hz, 2.2 Hz), 131.6 (d, J = 2.2 Hz), 129.7
4,4′-Bis(trifluoromethoxy)-1,1′-biphenyl (5d). According to
TP2, 1-bromo-4-(trifluoromethoxy)benzene (1d, 482 mg,
2 mmol) reacted with magnesium turning (120 mg, 5 mmol),
MnCl2 (277 mg, 2.2 mmol), LiCl (187 mg, 4.4 mmol) in THF
(6.7 mL) within 3.5 h at 10 °C, affording the corresponding
aryl manganese reagent 2d. To the solution of (4-(trifluoro-
methoxy)phenyl)manganese(II) chloride (2d) was added
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(dd, J = 4.4 Hz, 3.3 Hz), 124.0 (d, J = 2.2 Hz), 123.5 (dd, J = 12.0 10 °C. The reaction mixture was continuously stirred for 12 h
Hz, 4.4 Hz), 115.8 (dd, J = 17.6 Hz, 4.4 Hz); IR (Diamond-ATR, followed by quenching with ammonium chloride (5 mL). The
neat): ˜ν(cm−1) = 3037.3 (W), 1582.3 (M), 1500.4 (S), 1479.1 (VS), aqueous layer was extracted with ethyl acetate (3 × 20 mL).
1443.5 (VS), 1251.6 (M), 1210.1 (S), 1098.3 (M), 831.2 (M), 757.9 The combined organic phases were dried over MgSO4, and the
(S), 704.8 (W); HRMS (C12H8F2): Calc.: 190.0594; found: solvent was removed in vacuo. Purification by flash column
190.0604 (M+).
chromatography (SiO2, petroleum ether–ethyl acetate = 50 : 1)
provided the pure compound 5l (40 mg, 24%) as a white solid.
m.p. = 30.5–31.7 °C; 1H NMR (600 MHz, CDCl3): δ (ppm) =
7.22 (d, J = 5.1 Hz, 2 H), 7.19 (d, J = 3.7 Hz, 2 H), 7.04–7.01
(m, 2 H); 13C NMR (150 MHz, CDCl3): δ (ppm) = 137.4,
2,2′,4,4′-Tetrafluoro-1,1′-biphenyl (5g). According to TP2,
1-bromo-2,4-difluorobenzene (1g, 386 mg, 2 mmol) reacted
with magnesium turning (120 mg, 5 mmol), MnCl2 (277 mg,
2.2 mmol), LiCl (187 mg, 4.4 mmol) in THF (6.7 mL) within
3.5 h at 10 °C, affording the corresponding aryl manganese
reagent 2g. To the solution of (2,4-difluorophenyl)manganese(II)
chloride (2g) was added 3,3′,5,5′-tetra-tert-butyldiphenoqui-
none (409 mg, 1 mmol) directly at 10 °C. The reaction mixture
was continuously stirred for 12 h followed by quenching with
ammonium chloride (5 mL). The aqueous layer was extracted
with ethyl acetate (3 × 20 mL). The combined organic phases
were dried over MgSO4, and the solvent was removed in vacuo.
Purification by flash column chromatography (SiO2, petroleum
ether–ethyl acetate = 100 : 1) provided the pure compound 5g
127.7, 124.3, 123.7; IR (Diamond-ATR, neat): ˜ν(cm−1
) =
3063.4 (W), 1416.5 (M), 1208.2 (M), 1050.1 (M), 828.3 (S), 697.1
(S); HRMS (C8H6S2 + H): Calc.: 166.9989; found: 166.9997
(M+ + H).
Acknowledgements
We thank the Shandong Provincial Natural Science Foundation
(ZR2012BQ006 and 201203109), the National Natural Science
Foundation of China (21202205), Fundamental Research
Funds for the Central Universities (13CX02005A) and China
Postdoctoral Science Foundation Funded Project (2013T60688
and 2012M521382) for their financial support.
1
(157 mg, 69%) as a white solid. m.p. = 137.4 °C–138.7 °C; H
NMR (600 MHz, CDCl3): δ (ppm) = 7.35–7.29 (m, 2 H),
6.98–6.89 (m, 4 H); 13C NMR (150 MHz, CDCl3): δ (ppm) =
156.6 (d, J = 238.8 Hz), 153.0 (d, J = 2.2 Hz), 127.8 (d, J = 6.6
Hz), 118.1 (d, J = 23.1 Hz), 114.8 (d, J = 22.5 Hz), 116.1 (d, J =
7.5 Hz); IR (Diamond-ATR, neat): ˜ν(cm−1) = 3091.3 (W), 1609.3
(S), 1489.7 (S), 1416.5 (S), 1267.0 (M), 1141.7 (S), 955.7 (S),
860.1 (M), 823.5 (M), 732.8 (W); HRMS (C12H6F4): Calc.:
226.0406; found: 226.0414 (M+).
Notes and references
3,3′-Bithiophene (5k). According to TP2, 3-bromothiophene
(1k, 326 mg, 2 mmol) reacted with magnesium turning
(120 mg, 5 mmol), MnCl2 (277 mg, 2.2 mmol), LiCl (187 mg,
4.4 mmol) in THF (6.7 mL) within 5 h at 10 °C, affording the
corresponding aryl manganese reagent 2k. To the solution of
thiophen-3-ylmanganese(II) chloride (2k) was added 3,3′,5,5′-
tetra-tert-butyldiphenoquinone (409 mg, 1 mmol) directly at
10 °C. The reaction mixture was continuously stirred for 12 h
followed by quenching with ammonium chloride (5 mL). The
aqueous layer was extracted with ethyl acetate (3 × 20 mL).
The combined organic phases were dried over MgSO4, and the
solvent was removed in vacuo. Purification by flash column
chromatography (SiO2, petroleum ether–ethyl acetate = 50 : 1)
provided the pure compound 5k (74 mg, 45%) as a white solid.
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m.p. = 126.1–127.6 °C; H NMR (600 MHz, CDCl3): δ (ppm) =
7.38–7.36 (m, 2 H), 7.35–7.32 (m, 4 H); 13C NMR (150 MHz,
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4.4 mmol) in THF (6.7 mL) within 5 h at 10 °C, affording the
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tetra-tert-butyldiphenoquinone (409 mg, 1 mmol) directly at
7808 | Org. Biomol. Chem., 2014, 12, 7800–7809
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Paper
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