C60-catalyzed preparation of aryl and heteroaryl magnesium and zinc reagents using Mg/LiCl

Article abstract of DOI:10.1021/acscatal.5b00273

Addition of a catalytic amount of C₆₀ fullerene (3 mol %) catalyzes the insertion of magnesium to polycyclic aromatic halides, allowing the preparation of the corresponding Grignard reagents in good yields. Furthermore, the use of a cocktail of metallic salts (Mg, ZnCl₂, LiCl) in the presence of C₆₀ fullerene (3 mol %) allows preparation of some functionalized polyaromatic zinc reagents. The resulting organomagnesium and organozinc reagents efficiently underwent reactions with electrophiles, such as an aldehyde, an acid chloride, an allylic bromide, or an aryl iodide.

Full text of DOI:10.1021/acscatal.5b00273

Letter
pubs.acs.org/acscatalysis
C -Catalyzed Preparation of Aryl and Heteroaryl Magnesium and
60
Zinc Reagents Using Mg/LiCl
Zhi-Liang Shen and Paul Knochel*
̈
̈ ̈
Department Chemie, Ludwig-Maximilians-Universitat Munchen, Butenandtstrasse 5−13, Haus F, 81377 Munchen, Germany
*
S Supporting Information
ABSTRACT: Addition of a catalytic amount of C60 fullerene (3 mol %) catalyzes the insertion of magnesium to polycyclic
aromatic halides, allowing the preparation of the corresponding Grignard reagents in good yields. Furthermore, the use of a
cocktail of metallic salts (Mg, ZnCl , LiCl) in the presence of C fullerene (3 mol %) allows preparation of some functionalized
2
60
polyaromatic zinc reagents. The resulting organomagnesium and organozinc reagents efficiently underwent reactions with
electrophiles, such as an aldehyde, an acid chloride, an allylic bromide, or an aryl iodide.
KEYWORDS: C60 fullerene, organomagnesium, organozinc, lithium chloride, allylation, acylation, cross-coupling
he preparation of organometallics by the direct insertion
of a main-group metal, such as magnesium, into
T
Table 1. Screening of Different Additives and Solvents for
Magnesium Insertion into 1-Chloronaphthalene (1a)
Figure 1. Electrophiles used for reactions with the formed organo-
metallic reagents.
6
a
complexes ) have been found to facilitate the magnesium
entry
additive
solvent
DME
yield (%)
insertion to organic halides. The pioneering work of Rieke led
1
2
3
4
5
6
7
LiCl
0
0
to the discovery of much activated magnesium by the in situ
C60
DME
DME
THF
7
reduction of MgCl with lithium naphthalenide. We have
2
LiCl, C60
LiCl, C60
LiCl, C60
LiCl, C60
LiCl, C60
84
29
0
reported that the treatment of magnesium powder or turnings
8,9
with lithium chloride lead to a similar activation. LiCl plays
Et O
2
the role of a Lewis acid and “surface cleaner”. Its promoter
t
BuOMe
0
activity can be enhanced by the presence of activated Lewis
tetrahydropyran
0
9−11
9,11,12
9
13
acids, such as InCl3,
PbCl2,
TiCl , or B(OR) . Aryl
4 3
a
Determined by iodolysis.
chlorides are usually cheaper and more readily available than
the corresponding bromides or iodides; thus, there is still a lot
of interest in converting aryl chlorides to Grignard reagents
using mild conditions. Because the mechanism of the insertion
1
unsaturated organic halides is a very atom-economical method.
Because of the insolubility of metallic powders, such insertion
reactions are heterogeneous and proceed readily only after the
activation of the metal. The preparation of organomagnesium
reagents largely depends on the activation of the magnesium
surface. Numerous methods for the activation of magnesium
have been reported. Several additives (such as catalytic
14
involves electron transfer reaction steps, we have envisioned
that molecules that facilitate electron transfer reactions may be
2
Received: February 9, 2015
Revised: March 9, 2015
3
4
5
amounts of FeCl , DIBAL-H, or transition metal−phosphine
2
©
XXXX American Chemical Society
2324
DOI: 10.1021/acscatal.5b00273
ACS Catal. 2015, 5, 2324−2328

ACS Catalysis
Letter
Table 2. Preparation of Organomagnesium Reagents and Further Reactions with Electrophiles
a
b
c
d
Determined by iodolysis. Yield of isolated, analytically pure product. 20 mol % CuCN·2LiCl was used. 4 mol % Pd(OAc) and 8 mol % S-Phos
2
were used, and the reactions were performed at 60 °C for 12 h.
Scheme 1. One-Pot Preparation of Organozinc Reagents
with Improved Functional Group Tolerance and Their
Subsequent Reactions with Electrophiles
activated by the addition of 1,2-dibromoethane (5 mol %) and
TMSCl (5 mol %). No reaction was observed with Mg turnings
alone or in the presence of either LiCl (2 equiv) or C (3 mol
6
0
%) (Table 1, entries 1−2). The addition of C60 (3 mol %) led
to a complete conversion in the presence of LiCl, and the
formation of the corresponding Grignard reagent (2a) was
achieved in 84% yield as determined by iodolysis (Table 1,
entry 3). It was important to use 99.9% pure C60 because we
noticed that 98% pure C60 did not catalyze the magnesium
1
8
insertion to an appreciable extent. Under the same
conditions, the insertion performed in other ethereal solvents
led to either poor yields of Grignard reagent 2a (THF, 29%,
Table 1, entry 4) or no insertion reaction (Table 1, entries 5−
good catalysts for the magnesium insertion. After several
unsuccessful attempts, we turned our attention to C fullerene
6
0
because it is known that this highly unsaturated molecule
15−17
readily accepts and transfers electrons.
Herein, we report
7
). Quenching with various electrophiles (Figure 1), such as a
that the addition of catalytic amounts of C60 catalyzes the
magnesium insertion in the additional presence of LiCl,
allowing the synthesis of aryl and heteroaryl magnesium or
zinc reagents under mild conditions.
First, we tested the magnesium insertion to 1-chloronaph-
thalene (1a) using various ethereal solvents. Initially, the
reaction of 1a (1 equiv) with Mg turnings (3 equiv) in DME at
benzaldehyde (3a), an acid chloride (3e), an allylic bromide
19
(3g), or an aryl iodide (3h, after transmetalation with ZnCl ;
2
2
0
21
Negishi cross-coupling using Pd(OAc)
and S-Phos ),
2
produced the expected products (4a−d) in 77−91% yields
(Table 2, entries 1−4).
With 99.9% pure C , it was possible to convert aryl chlorides
60
25 °C for 12 h was examined. The magnesium turnings were
(1b−c) into the corresponding Grignard reagents (2b,c; Table
2
325
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ACS Catalysis
Letter
Table 3. Preparation of Organozinc Reagents and Subsequent Reactions with Electrophiles
a
b
c
d
Determined by iodolysis. Yield of isolated, analytically pure product. 20 mol % CuCN·2LiCl was used. 4 mol % Pd(OAc) and 8 mol % S-Phos
2
were used, and the reactions were performed at 60 °C for 12 h.
2
, entries 5−7). Similarly, these two organomagnesium reagents
Trapping of these organozinc species with electrophiles, such as
an allyl bromide, an acid chloride, or an aryl iodide, led to the
desired products (7c−i) in 63−88% yields (entries 3−9).
In summary, we have shown that the addition of a catalytic
amount of C60 fullerene catalyzes the insertion of magnesium
turnings to polycyclic aromatic halides (X = Cl or Br), allowing
the preparation of the corresponding Grignard reagent in good
were capable of undergoing either direct reactions with an
aldehyde (3b) or CuCN·2LiCl-catalyzed allylation with ethyl 2-
22
(bromomethyl)acrylate (3g), affording the corresponding
products (4e−g) in 65−70% yields. Interestingly, it was found
that several aryl bromides (1d−g) smoothly underwent the
magnesium insertion reactions to generate the corresponding
Grignard reagents (2d−g) in 10 min to 4 h (Table 2, entries
yields. The use of a cocktail of metallic salts (Mg, ZnCl , LiCl)
2
8
−11). In a same manner, reactions of the resulting
in the presence of 3 mol % of C fullerene (99.9% purity) also
60
organomagnesium reagents with aromatic aldehydes (with
functional groups such as ester and nitrile) proceeded
efficiently to produce the benzylic alcohols (4h−k) in 75−
allows preparation of some functionalized polyaromatic zinc
reagents. Extension to other metal insertions is currently
underway in our laboratories.
85% yields. It should be noted that polyaromatic halides are by
far the best substrates, and attempts to activate simple aryl
chlorides failed.
EXPERIMENTAL SECTION
■
(
Typical Procedure for the Magnesium Insertion. LiCl
0.17 g, 4 mmol, 2 equiv) was added to a 20 mL Schlenk flask,
By simultaneously using Mg (3 equiv), ZnCl (1 equiv), LiCl
2
(
2 equiv), and 3 mol % C , it was possible to convert
60
equipped with a magnetic stirrer and a rubber septum, and
dried at 380 °C by heat gun for 5 min under high vacuum. After
cooling, the flask was flushed with nitrogen gas, and magnesium
turnings (0.144 g, 6 mmol, 3 equiv) and anhydrous
dimethoxyethane (DME, 6 mL) were introduced into the
flask. The magnesium was sequentially activated by using 1,2-
dibromoethane (5 mol %) and TMSCl (5 mol %). Then aryl
functionalized organic bromides such as 1-bromonaphthalen-2-
yl pivalate (5a) to the corresponding organozinc reagent 6a in
8
3% yield at −10 °C within 4 h reaction time (Scheme 1 and
Table 3, entry 1). It should be noted that under the same
conditions, in the absence of C , only a poor conversion was
6
0
obtained (<5%). The generated organozinc reagent 6a
efficiently underwent either copper-catalyzed allylation with
allylic bromide 3g or palladium-catalyzed cross-coupling with
aryl iodide 3i, leading to the respective products 7a−b in 62−
halide (2 mmol, 1 equiv), internal standard (C10H22, 0.2 mL),
and C60 (0.044 g, 0.06 mmol, 3 mol %, 99.9% purity) were
added to the flask, and the reaction mixture was stirred at room
temperature for the time indicated in Table 2. The reaction
progress was monitored by GC analysis of reaction aliquots
8
0% yields (entries 1−2). The same one-pot protocol was also
successfully applied to aromatic bromides (5b−d), affording
the desired organozinc reagents (6b−d) in 75−84% yields.
2
326
DOI: 10.1021/acscatal.5b00273
ACS Catal. 2015, 5, 2324−2328

ACS Catalysis
Letter
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4
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0, 1021−1032. (i) Xi, Z. Acc. Chem. Res. 2010, 43, 1342−1351.
conversion of the starting material. The yield of the insertion
reaction was determined by GC analysis of the reaction aliquot
quenched with a solution of iodine in anhydrous THF. The
supernatant solution was carefully transferred to another
predried and nitrogen-flushed Schlenk flask by a syringe and
used in subsequent reactions with electrophiles.
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(
Typical Procedure for the Magnesium Insertion in the
9
Presence of ZnCl . LiCl (0.17 g, 4 mmol, 2 equiv) was added
2
to a 20 mL Schlenk flask, equipped with a magnetic stirrer and
a rubber septum, and dried at 380 °C by heat gun for 5 min
under high vacuum. After cooling, the flask was flushed with
nitrogen gas, and magnesium turnings (0.144 g, 6 mmol, 3
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22
60
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of reaction aliquots quenched by sat. NH Cl solution until it
4
7
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showed >95% conversion of the starting material. The yield of
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reaction aliquots quenched with a solution of iodine in
anhydrous THF using an internal standard. The supernatant
solution was carefully transferred to another predried and
nitrogen-flushed Schlenk flask by a syringe and used in
subsequent reactions with electrophiles.
(
̈
2
(
(
̈
̈
̈
ASSOCIATED CONTENT
Supporting Information
The following file is available free of charge on the ACS
■
̈
*
S
(
Marek, I.; Knochel, P. Org. Lett. 2014, 16, 956−959.
Publications website at DOI: 10.1021/acscatal.5b00273.
(
(
11) Peng, Z.; Knochel, P. Org. Lett. 2011, 13, 3198−3201.
12) (a) Takai, K.; Ueda, T.; Hayashi, T.; Moriwake, T. Tetrahedron
Experimental details and characterization data (PDF)
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AUTHOR INFORMATION
Corresponding Author
E-mail: paul.knochel@cup.uni-muenchen.de.
Notes
Ishiyama, T.; Matsushita, H. Bull. Chem. Soc. Jpn. 2003, 76, 347−353.
■
(
13) Haag, B. A.; Sam
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̈
ann, C.; Jana, A.; Knochel, P. Angew. Chem., Int.
*
(
Studer, A.; Curran, D. P. Nat. Chem. 2014, 6, 765−773.
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Eds.; Wiley-VCH: Weinheim, 2005.
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organic synthesis, see: (a) Li, B.; Xu, Z. J. Am. Chem. Soc. 2009, 131,
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The research leading to these results has received funding from
the European Research Council under the European
Community’s Seventh Framework Programme (FP7/2007−
1
6380−16382. (b) Shi, Y.; Gan, L.; Wei, X.; Jin, S.; Zhang, S.; Meng,
F.; Wang, Z.; Yan, C. Org. Lett. 2000, 2, 667−669.
17) On the basis of the high reduction potential of magnesium (E =
2.37 V), the transfer of an electron from the magnesium surface to
0
(
−
2
(
013) ERC Grant Agreement No. 227763. We thank BASF SE
Ludwigshafen), W. C. Heraeus GmbH (Hanau), and Rock-
wood Lithium GmbH (Hoechst) for the gift of chemicals.
the absorbed C60 fullerene should readily proceed. For the reduction
potential of magnesium and C60 fullerene, see: (a) Reed, C. A.;
Bolskar, R. D. Chem. Rev. 2000, 100, 1075−1120. (b) CRC Handbook
of Chemistry and Physics, 87th ed.; Lide, D. R., Ed.; CRC Press: Boca
Raton, 2006.
(18) Both 99.9% and 98% pure C60 powders were purchased from
Aldrich company (Product Nos. 572500 and 483036). It should be
noted that the use of only 1 mol % of C60 (99.9%) did not lead to a
metal activation; the minimum amount of C60 was ∼3 mol%. We
suggest that C60 facilitates the electron transfer from the magnesium
surface to the organic halide. In addition, attempts to extend this
activation to zinc dust failed.
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NOTE ADDED AFTER ASAP PUBLICATION
■
This paper was published ASAP March 13, 2015. Production
errors were corrected in two table references and in the
Supporting Information, and the corrected version was
reposted March 13, 2015.
2
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DOI: 10.1021/acscatal.5b00273
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