Arylzinc Halides by Silver Catalyzed Zinc Insertion into Aryl Iodides

Article abstract of DOI:10.1002/ejoc.201801543

A catalytic amount of silver acetate efficiently promotes direct insertion of zinc metal into aryl iodides, having different structure, in ethereal solvent. Electron-rich substrates also rapidly undergo oxidative metalation. The arylzinc iodides formed give Negishi coupling products under mild reaction conditions to obtain biaryls in high yields. Sensitive functional groups like aldehydes and primary amides are well-tolerated.

Full text of DOI:10.1002/ejoc.201801543

A Journal of
Accepted Article
Title: Arylzinc Halides by Silver Catalyzed Zinc Insertion to Aryl Iodides
Authors: Gianluca Casotti, Anna Iuliano, and Adriano Carpita
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10.1002/ejoc.201801543
European Journal of Organic Chemistry
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Arylzinc Halides by Silver Catalyzed Zinc Insertion to Aryl Iodides
Gianluca Casotti,*[a] Anna Iuliano,[a] and Adriano Carpita†,[a]
Abstract: A catalytic amount of silver acetate efficiently promotes
direct insertion of zinc metal into aryl iodides, having different
structure, in ethereal solvent. Electron-rich substrates also rapidly
Results and Discussion
undergo oxidative metalation. The arylzinc iodides formed give
Negishi coupling products under mild reaction conditions to give
biaryls in high yields. Sensitive functional groups like aldehydes and
primary amides are well-tolerated.
Herein we report a novel, simple and general procedure for
the preparation of arylzinc iodides in ethereal solvents, even
starting from electron-rich substrates, in short reaction times.
Inspired by previous works where the zinc-silver couple[17] has
been used together with tetramethylethylenediamine (TMEDA) to
promote zinc insertion in various substrates,[18–20] we tried a
similar approach to obtain arylzinc iodides.
Introduction
Although there are not specific studies on the role of silver in
these couples, it can be assumed to facilitate electron transfer
from zinc to the organic halide, probably the rate determining step
of the metalation.[5] TMEDA, in this context, is supposed to
stabilize the organometallic reagent, providing faster conversion
of the halide.[18]
Organozinc halides are useful reagents for organic synthesis,
as witnessed by their wide use as nucleophiles in the Negishi
coupling, a powerful and versatile reaction for carbon-carbon
bond formation.[1]
Direct insertion of zinc metal to organic halides provides the
most practical and atom-economical way for preparing these
organometallic reagents.
Nevertheless, oxidative metalation often has limited
application due to the long reaction times required by many
substrates.[2,3]
Aryl iodides are known to be unreactive with normal zinc
powder under standard reaction conditions used for other
oxidative metalations, such as the Grignard preparation: as a
matter of fact, special formulation like Rieke zinc,[4] the use of
polar or high-boiling solvents[5–12] or some kind of activation or
additives[6,10,13–16] are required. Despite the great importance of
these methods, some drawbacks, like pyrophoricity of highly
active zinc formulations, affect their use. Furthermore, organozinc
halides, normally, must be directly used in the successive
reactions in the solvent where they are prepared. Therefore the
use of an uncommon medium for organometallic reactions (polar
or high-boiling solvents), as well as additives with a potential
activity in the successive synthetic steps, might constitute a
limitation of these methods, depending on the reactions where
they have to be used.[12]
In our first trials zinc-silver couple was formed following a
previously reported procedure.[18]
In order to verify the efficiency of the method, we chose
substrates that notoriously provide insertion products with long
reaction times even by using additives,[13] as the electron-rich 4-
iodoanisole (1a) and 4-iodotoluene (1b), and, for comparison,
iodobenzene (1c) as well (Table 1, entries 1-3). In all cases, high
conversions were achieved within reasonable reaction times,
even on scarcely reactive substrates.[2]
Encouraged by these results, 1,2-dimethoxyethane (DME) was
used to further shorten the reaction times. Being higher-boiling
than THF, DME could be used both at the reflux temperature and
at 70 °C, which is close to the THF reflux temperature. The solvent
change had practically no effect at 70°C (Table 1, entry 4), while
resulted in a dramatic improvement of the reaction rate when it
was employed at the reflux temperature (ca. 85°C) (Table 1, entry
5). It is noteworthy that under these conditions, direct insertion on
1a was completed in just 10 h (Table 1, entry 6).
In order to check if these results could be reproduced, both the
preparation of the zinc-silver couple and the oxidative metalation
on 1a were repeated several times.
These considerations, together with the request for mild and
efficient protocols for the achievement of these organometallic
reagents, prompted us to search for different synthetic methods.
[a]
G. Casotti, Prof. A. Iuliano, Prof. A. Carpita
Dipartimento di Chimica e Chimica Industriale, Università di Pisa,
Via Giuseppe Moruzzi, 13, 56124, Pisa, Italy
gianluca.casotti@dcci.unipi.it
†
Deceased May 5, 2018.
Supporting information for this article is given via a link at the end of
the document.
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Table 1. Evaluation of Zinc-Silver couple in aryl iodides direct insertion reaction
Entry
Substrate [a]
R
Solvent
THF
Temperature
reflux
Particle size
9.8 µm
9.8 µm
9.8 µm
9.8 µm
9.8 µm
9.8 µm
4 µm
Time
23 h
19 h
10 h
9 h
Conversion [b]
95%
1
2
3
4
5
6
7
8
1a
1b
1c
1c
1c
1a
1a
1a
4-MeO
4-Me
H
THF
reflux
90%
THF
reflux
>99%
>99%
>99%
>99%
48%
H
DME
DME
DME
DME
DME
70°C
H
reflux
3 h
4-MeO
4-MeO
4-MeO
reflux
10 h
24 h
10 h
reflux
reflux
8 µm
99%
* Zn(Ag) activated with Me3SiCl. [a] 1M concentration of aryl iodide. [b] GC conversion (determined by analysis on hydrolyzed aliquots).
resulted unreactive under these conditions (Table 2, entry 2).
Moreover, we have verified that, as previously reported in the
literature for other metalation methods, zinc pre-activation with
Me3SiCl is not strictly required (Table 2, entry 3), even if it
provides more reproducible results.[12]
To verify if silver acetate was the only salt capable to promote this
kind of activation, we decided to try some other silver salts (Table
2, entries 4 and 5). From these trials it emerged that the nitrate is
completely unreactive whereas the tosylate has a little effect,
even if much less significant with respect to the acetate. Moreover,
we have found that copper (II) acetate could not provide the
analogous zinc-copper couple “in situ” (Table 2, entry 6). It is
remarkable that without silver salts, no reaction occurred in 24 h
(Table 2, entry 7). Afterwards, the role of TMEDA as additive was
checked, by performing some tests to verify if it could be used in
substoichiometric amount.
Figure 1. Zn(Ag) made with 4 µm zinc (left) and 9.8 µm (right).
Unfortunately, this procedure seemed to be poorly reproducible.
Further investigations suggested that the success of the method
is strictly dependent on the particle size of the zinc. Specifically,
zinc dust with particle size of 8-10 µm gave good results (Table 1,
entries 6 and 8), while smaller particles provided a less active
zinc-silver couple, resulting in poor conversions during the
oxidative metalation step (Table 1, entry 7). The low reaction rate
is probably due to aggregation of particles during the preparation
of the Zn-Ag couple (Figure 1).
After 7 h, the time needed to have full conversion of the model
substrate with 1 equivalent of TMEDA, the conversion was
substantially proportional to the added TMEDA equivalents (Table
2, entries 8 and 9).
It is noteworthy that even without TMEDA, high conversions could
be achieved, albeit with long reaction times (Table 2, entry 10).
To find if only TMEDA is capable to accelerate the direct insertion
in the presence of silver acetate, the effect of various amounts of
other additives was checked. To this aim another bidentate amine,
1,4-diazabicyclo[2.2.2]octane (DABCO) and LiCl, which is known
to increase the reaction rate of the metalation,[13] were tried.
The obtained results showed that also DABCO has an
accelerating effect, even if smaller than TMEDA (Table 2, entry
13) and LiCl increased the reaction rate with respect to the
additives-free conditions (cfr. Table 2, entry 10 vs entry 15). The
possibility of a double activation with both TMEDA and LiCl in
different amounts (Table 2, entries 11 and 12) was checked as
well, but no substantially different results were obtained. Also the
Despite these interesting results, the preparation of the zinc-silver
couple has to be considered of little interest from a practical
outlook, because it requires a long and tedious procedure of
preparation and a lot of solvent must be used during the work-up.
So, we decided to try a more appealing approach to zinc
activation, attempting to form zinc-silver couple directly during the
oxidative metalation step, by adding a catalytic amount of silver
acetate to the reaction mixture. These results are summarized in
Table 2.
This kind of activation, which presumably leads to the formation
of a zinc-silver couple “in situ”, had an impressive effect with
various kind of zinc, leading to complete conversion of 1a in just
7 h, with zinc powder having particle size ranging from 4 to 63 µm
(Table 2, entry 1). Only zinc with particle size of 600 – 800 µm
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10.1002/ejoc.201801543
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use of another Lewis acid, instead of LiCl, did not lead to
significant effects (Table 2, entry 16).
in longer times with respect to electron-poor substrates (Scheme
1, compounds 2a and 2g).
Table 2. Effect of various conditions with zinc-silver “in situ” activation
Catalyst
AgOAc
AgOAc
AgOAc
AgNO3
AgOTs
Cu(OAc)2
Amine (eqs.)
TMEDA (1)
TMEDA (1)
TMEDA (1)
TMEDA (1)
TMEDA (1)
TMEDA (1)
TMEDA (1)
TMEDA (0.2)
TMEDA (0.1)
Time
7 h
Conv. [a]
> 99 %
< 5 %
> 99 %
< 1 %
20 %
1 [b]
2 [c]
3 [d]
4
24 h
7 h
24 h
24 h
24 h
24 h
7 h
5
6
< 1 %
< 1 %
19 %
7
8
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
9
7 h
11 %
10
11 [e]
12 [e]
13
14
15 [e]
16 [g]
65 h
7 h [f]
7 h
96 %
TMEDA (1)
TMEDA (0.2)
DABCO (1)
DABCO (0.2)
> 99 %
30 %
[a] Time required for complete conversion (determined by analysis on
hydrolyzed aliquots)
15 h
15 h
40 h
15 h
43 %
21 %
Scheme 1. Preparation of various arylzinc iodides.
97 %
20 %
However, it is noteworthy that also highly electron-rich iodides
provided the corresponding arylzinc halides in acceptable
reaction times (Scheme 1, compound 2d).
To prove the potential of the organozinc halides thus obtained we
decided to test their reactivity in Negishi cross-coupling reactions
under mild conditions (Scheme 2). In all these examples high
yields have been achieved in reasonable reaction times, either
with electron-rich or electron-poor donors. Even sensitive
functional groups like aldehydes and primary amides are well-
tolerated.
* Zn activated with Me3SiCl. [a] GC conversion (determined by analysis on
hydrolyzed aliquots). [b] Zn of various particle size: 4, 8, 9.8 and 63 µm. [c]
Particle size 600-800 µm. [d] Zn was not activated with Me3SiCl. [e] 1.5
equivalents of LiCl were added. [f] Time required to provide complete
conversion. [e] 1.5 equivalents of MgBr2 were added
Once the best reaction conditions had been found, the procedure
was used to obtain arylzinc iodides having different structure
(Scheme 1) to test the general applicability of the procedure. As
expected, electron-rich aryl iodides underwent oxidative additions
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[a] Isolated yield after flash chromatography
Scheme 2. Negishi cross-coupling.
hypodermic syringes. Ethereal solvents were refluxed over
sodium-potassium alloy / benzophenone and distilled before the
use. Liquid tertiary amines were refluxed over calcium hydride
and distilled before the use. All other liquid reagents were distilled
and dried over molecular sieves. Lithium chloride, magnesium
bromide and zinc were flame dried under high vacuum before the
use. Pd(PPh3)4 was freshly prepared according to the literature
procedure.[21] All other solid reagents were dried under high
vacuum before the use. GLC analyses were performed on a
Varian CP-3800 GC instrument with a Split/Splitless injector a FID
detector and a Varian CP-8400 Autosampler, equipped with an
Agilent HP5 FSOT column (30 m x 0.25 mm i.d. x 0.25 µm).
GLC/MS analyses were performed using an Agilent 6890 Network
GC system equipped with an Agilent HP5-MS FSOT column (30
m x 0.25 mm i.d. x 0.25 µm) interfaced with an Agilent 5973
Network Mass Selective Detector. 1H and 13C NMR spectra were
recorded on a Bruker DRX 400 MHz spectrometer. Purifications
were performed by flash chromatography on silica-gel (40-63 µm,
Sigma-Aldrich) employing ethyl acetate – hexane mixtures as
eluents.
Conclusions
In conclusion, we have shown that a catalytic amount of silver
acetate activates normal zinc powder of different particle size,
allowing oxidative metalation of various aryl iodides, even
electron-rich, under straightforward conditions and short reaction
times. The effect of several additives and their synergies has been
verified. Arylzinc iodides obtained with the protocol described
have been used in Negishi cross-coupling reactions with aryl
iodides bearing various functional groups to give the
corresponding biaryls in high yields.
Experimental Section
General Information
All reactions were performed in flame dried glassware under
argon atmosphere. Solutions and liquids were transferred with
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Zinc was purchased from Sigma-Aldrich: powders of 4, 8 and 9.8
µm (Aldrich, product number 209988), lot numbers, respectively:
SHBG9711V, SHBG1827V and SHBF7346V; zinc of 63 µm (EMD
Millipore, product number 1.08774.1000) lot number
K48461974645, zinc of 600-800 µm (Aldrich, product number
243469) lot number MKBZ3503V.
and 4-methylphenylzinc iodide (2b) as donor 511 mg (3.04 mmol,
92%) were obtained.
The NMR data agree with the literature.[22]
1H NMR (401 MHz, CDCl3) δ 7.69 (d, J = 7.4 Hz, 2H), 7.61 (d, J =
8.1 Hz, 2H), 7.53 (t, J = 7.6 Hz, 2H), 7.43 (t, J = 7.4 Hz, 1H), 7.35
(d, J = 7.9 Hz, 2H), 2.50 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
141.3, 138.5, 137.1, 129.6, 128.9, 128.8, 127.1, 127.1, 21.2.
General procedure for the preparation of ArZnX by direct
insertion
1,1'-biphenyl (3c)
In a typical procedure, zinc powder (490 mg, 7.5 mmol) was flame
dried under high vacuum (10-2 mbar) and cooled under argon
atmosphere in a round-bottomed flask equipped with reflux
condenser and magnetic stirrer; silver acetate (8.4 mg, 0.05
mmol) was then added under argon and the mixture dried again
under high vacuum; the flask was refilled with argon and
anhydrous DME (5 mL) and chlorotrimethylsilane (15 µL, 0.075
mmol) were added. The mixture was stirred and heated at the
reflux for 5 minutes. After cooling, anhydrous TMEDA (750 µL, 5
mmol) and the aromatic iodide (5 mmol) were added.
Purification by flash chromatography (SiO2, hexane) afforded the
product as a white solid: by using iodobenzene (1c) as acceptor
and phenylzinc iodide (2c) as donor 479 mg (3.11 mmol, 94%)
were obtained.
The NMR data agree with the literature.[22]
1H NMR (401 MHz, CDCl3) δ 7.64 (d, J = 7.5 Hz, 4H), 7.48 (t, J =
7.5 Hz, 4H), 7.39 (t, J = 7.3 Hz, 2H). 13C NMR (101 MHz, CDCl3)
δ 141.4, 128.9, 127.4, 127.3.
3,5-dimethoxy-1,1'-biphenyl (3d)
The mixture was heated at the reflux and stirred for the time
needed for each substrate (see Scheme 1), then was cooled,
settled down and the supernatant was used in the following
coupling reaction. To verify full conversion, an aliquot of the
supernatant solution was quenched with NH4Cl and extracted with
Et2O and another aliquot was iodolyzed and extracted with Et2O,
both the samples were analysed by GLC.
Purification by flash chromatography (SiO2, hexane / ethyl acetate
96:4) afforded the product as a white solid: by using iodobenzene
(1c) as acceptor and 3,5-dimethoxyphenylzinc iodide (2d) as
donor 600 mg (2.80 mmol, 85%) were obtained.
The NMR data agree with the literature.[23]
1H NMR (401 MHz, CDCl3) δ 7.60 (d, J = 7.4 Hz, 2H), 7.45 (t, J =
7.5 Hz, 2H), 7.37 (t, J = 7.3 Hz, 1H), 6.76 (d, J = 2.2 Hz, 2H), 6.49
(t, J = 2.2 Hz, 1H), 3.86 (s, 6H). 13C NMR (101 MHz, CDCl3) δ
161.2, 143.6, 141.3, 128.8, 127.7, 127.3, 105.6, 99.4, 55.5.
General procedure for the Negishi cross-coupling reactions
In a typical procedure, Pd(PPh3)4 (38 mg, 0.033 mmol) was dried
under high vacuum (10-2 mbar) in a round-bottomed flask
equipped with magnetic stirrer; the flask was refilled with argon
and the aromatic iodide (3.3 mmol) and the organozinc halide
solution (5 mL) were added. The mixture was heated at 60 °C and
stirred for the time needed for each substrate (see Scheme 2)
before being quenched with NH4Cl and extracted with Et2O (3 x
10 mL). Flash chromatography purification on silica gel with
hexane or hexane / ethyl acetate mixtures afforded the pure
compounds.
2-methoxy-1,1'-biphenyl (3e)
Purification by flash chromatography (SiO2, hexane / ethyl acetate
98:2) afforded the product as a white solid: by using iodobenzene
(1c) as acceptor and 2-methoxyphenylzinc iodide (2e) as donor
545 mg (2.96 mmol, 90%) were obtained.
The NMR data agree with the literature.[22]
1H NMR (401 MHz, CDCl3) δ 7.55 (d, J = 7.6 Hz, 2H), 7.43 (t, J =
7.5 Hz, 2H), 7.34 (t, J = 6.5 Hz, 3H), 7.09 – 6.96 (m, 2H), 3.83 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 156.6, 138.7, 131.0, 130.9,
129.7, 128.7, 128.1, 127.0, 121.0, 111.4, 55.7.
3-methoxy-1,1'-biphenyl (3f)
4-methoxy-1,1'-biphenyl (3a)
Purification by flash chromatography (SiO2, hexane / ethyl
acetate 98:2) afforded the product as a white solid: by using
iodobenzene (1c) as acceptor and 3-methoxyphenylzinc iodide
(2f) as donor 559 mg (3.03 mmol, 92%) were obtained.
The NMR data agree with the literature.[22]
1H NMR (401 MHz, CDCl3) δ 7.63 (d, J = 7.5 Hz, 2H), 7.47 (t, J =
7.6 Hz, 2H), 7.39 (dt, J = 7.9, 4.3 Hz, 2H), 7.22 (d, J = 7.7 Hz, 1H),
7.17 (s, 1H), 6.94 (dd, J = 8.2, 2.1 Hz, 1H), 3.89 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 160.1, 142.9, 141.2, 129.9, 128.9, 127.5,
127.3, 119.8, 113.0, 112.8, 55.4.
Purification by flash chromatography (SiO2, hexane / ethyl
acetate 98:2) afforded the product as a white solid: by using
iodobenzene (1c) as acceptor and 4-methoxyphenylzinc iodide
(2a) as donor 549 mg (2.98 mmol, 90%) were obtained, by using
4-iodoanisole (1a) as acceptor and phenylzinc iodide (2c) as
donor 543 mg (2.95 mmol 89%) were obtained.
The NMR data agree with the literature.[22]
1H NMR (401 MHz, CDCl3) δ 7.57 (t, J = 8.5 Hz, 4H), 7.44 (t, J =
7.6 Hz, 2H), 7.32 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 8.7 Hz, 2H), 3.87
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.3, 141.0, 133.9, 128.9,
128.3, 126.9, 126.8, 114.3, 55.5.
methyl [1,1'-biphenyl]-4-carboxylate (3g)
Purification by flash chromatography (SiO2, hexane / ethyl
acetate 98:2) afforded the product as a white solid: by using
4-methyl-1,1'-biphenyl (3b)
Purification by flash chromatography (SiO2, hexane) afforded the
product as a white solid: by using iodobenzene (1c) as acceptor
iodobenzene
(1c)
as
acceptor
and
(4-
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(methoxycarbonyl)phenyl)zinc iodide (2g) as donor 649 mg (3.09
mmol, 93%) were obtained.
The NMR data agree with the literature.[22]
acceptor and phenylzinc iodide (2c) as donor 585 mg (2.97 mmol,
90%) were obtained.
The NMR data agree with the literature.[26]
1H NMR (401 MHz, CDCl3) δ 8.12 (d, J = 8.4 Hz, 2H), 7.65 (m, J
= 14.9, 7.8 Hz, 4H), 7.47 (t, J = 7.4 Hz, 2H), 7.40 (t, J = 7.3 Hz,
1H), 3.95 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.1, 145.8,
140.1, 130.2, 129.0, 128.3, 127.4, 127.2, 52.2.
1H NMR (401 MHz, DMSO-d6) δ 8.05 (s, 1H), 7.99 (d, J = 8.4 Hz,
2H), 7.79 – 7.70 (m, 4H), 7.49 (t, J = 7.5 Hz, 2H), 7.45 – 7.36 (m,
2H). 13C NMR (101 MHz, DMSO) δ 167.58, 142.76, 139.23,
133.10, 129.02, 128.18, 128.01, 126.87, 126.45.
2-methyl-1,1'-biphenyl (3h)
3-chloro-1,1'-biphenyl (3m)
Purification by flash chromatography (SiO2, hexane) afforded the
product as a white solid: by using iodobenzene (1c) as acceptor
and 2-methylphenylzinc iodide (2i) as donor 494 mg (2.94 mmol,
89%) were obtained.
Purification by flash chromatography (SiO2, hexane) afforded the
product as a white solid: by using 1-chloro-3-iodobenzene (1j) as
acceptor and phenylzinc iodide (2c) as donor 577 mg (3.06 mmol,
92%) were obtained.
The NMR data agree with the literature.[22]
The NMR data agree with the literature.[24]
1H NMR (401 MHz, CDCl3) δ 7.54 – 7.42 (m, 2H), 7.43 – 7.34 (m,
3H), 7.36 – 7.23 (m, 4H), 2.33 (s, 3H). 13C NMR (101 MHz, CDCl3)
1H NMR (401 MHz, CDCl3) δ 7.62 – 7.54 (m, 3H), 7.51 – 7.42 (m,
3H), 7.43 – 7.30 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 143.21,
δ 142.10, 142.07, 135.46, 130.43, 129.92, 129.32, 128.19, 127.37, 139.95, 134.78, 130.11, 129.03, 127.99, 127.43, 127.39, 127.25,
126.88, 125.89, 20.60.
125.43.
4-(trifluoromethyl)-1,1'-biphenyl (3i)
4,4'-dimethoxy-1,1'-biphenyl (3n)
Purification by flash chromatography (SiO2, hexane / ethyl
acetate 99:1) afforded the product as a white solid: by using
iodobenzene (1c) as acceptor and 4-(trifluoromethyl)phenylzinc
iodide (2h) as donor 695 mg (3.13 mmol, 95%) were obtained.
The NMR data agree with the literature.[22]
1H NMR (401 MHz, CDCl3) δ 7.71 (s, 4H), 7.62 (d, 2H), 7.49 (t,
2H), 7.45 – 7.40 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 144.88,
139.91, 129.13, 128.33, 127.56, 127.42, 125.85 (q, JC-F = 3.7 Hz).
Purification by flash chromatography (SiO2, hexane / ethyl
acetate 98:2) afforded the product as a white solid: by using 4-
iodoanisole (1a) as acceptor and 4-methoxyphenylzinc iodide
(2a) as donor 670 mg (3.13 mmol, 94%) were obtained.
The NMR data agree with the literature.[27]
1H NMR (401 MHz, CDCl3) δ 7.50 (d, J = 8.7 Hz, 4H), 6.98 (d, J =
8.7 Hz, 4H), 3.86 (s, 5H). 13C NMR (101 MHz, CDCl3) δ 158.82,
133.59, 127.84, 114.29, 55.46.
3-chloro-4'-(trifluoromethyl)-1,1'-biphenyl (3j)
Purification by flash chromatography (SiO2, hexane / ethyl
acetate 99:1) afforded the product as a white solid: by using 1-
Acknowledgements
chloro-3-iodobenzene
(1j)
as
acceptor
and
4-
This work was supported by the University of Pisa.
(trifluoromethyl)phenylzinc iodide (2h) as donor 770 mg (3.00
mmol, 91%) were obtained.
The NMR data agree with the literature.[24]
1H NMR (401 MHz, CDCl3) δ 7.78 – 7.63 (m, 4H), 7.59 (s, 1H),
7.52 – 7.33 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 143.41, 141.68,
135.08, 130.36, 128.35, 127.55, 125.99 (q, JC-F = 3.7 Hz), 125.56.
Keywords: metalation • zinc • synthetic methods • C-C coupling
• biaryls
[1]
[2]
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Entry for the Table of Contents (Please choose one layout)
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Organozinc halides preparation
Gianluca Casotti,* Anna Iuliano, Adriano
Carpita
Page No. – Page No.
Arylzinc Halides by Silver Catalyzed
Zinc Insertion to Aryl Iodides
A catalytic amount of silver acetate efficiently promotes direct insertion of zinc metal
into aryl iodides, having different structure, in ethereal solvent. Electron-rich
substrates also rapidly undergo oxidative metalation. The arylzinc iodides formed
give Negishi coupling products under mild reaction conditions.
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