Nickel N-heterocyclic carbene catalyst for cross-coupling of neopentyl arenesulfonates with methyl and primary alkyl Grignard reagents

Article abstract of DOI:10.1021/jo902151h

(Chemical Equation Presented) Nickel N-heterocyclic carbene (NHC) catalytic system prepared in situ by the reaction of Ni(acac)₂ with NHC precursor efficiently catalyzed the cross-coupling reaction of alkoxysulfonylarenes with methyl, neopentyl

Full text of DOI:10.1021/jo902151h

pubs.acs.org/joc
electron-donating ligands have been investigated to increase
Nickel N-Heterocyclic Carbene Catalyst for Cross-
Coupling of Neopentyl Arenesulfonates with Methyl
and Primary Alkyl Grignard Reagents
the reactivity and efficiency.2 Since Herrmann reported that
palladium complexes of N-heterocyclic carbene (NHC) cat-
alyzed the Heck reaction,3 NHCs have emerged as attractive
alternatives to phosphine ligands in catalytic transforma-
tions.4 As NHCs, with their strong σ-donor effect combining
with a shielding steric pattern, activate the oxidative addition
step of transition metal-catalyzed reactions,5 metal-NHC
complexes have been recognized as highly reactive catalytic
systems, especially for unactivated alkyl or aryl chlorides.6
Grignard reagents are one of the most widely adopted
organometallic reagents7 in the area of transition metal-
catalyzed cross-coupling reactions. Accordingly, these
metal-NHC complexes have often been applied for the
reactions of organic electrophiles with Grignard reagents.8
However, in reactions with NHC complexes, not only were
the electrophilic compounds limited to organic halides, but
also alkyl Grignard reagents have only rarely been applied.
While organosulfur compounds have not been commonly
used as electrophilic substrates due to their relatively low
reactivity, the recent developments of efficient catalysts
and additives have begun to allow their desulfitative
carbon-carbon cross-coupling reactions.9 We previously
reported that alkyloxysulfonyl moieties attached onto
aromatic compounds could act as chemoselective leaving
groups in reactions with aryl and primary alkyl Grignard
reagents.10 However, a large excess of Grignard reagents was
still required, even at elevated temperatures, in order to
overcome the low reactivity of the alkyloxysulfonyl group
with common nickel catalysts. Therefore, a more electron-
rich metal complex, capable of catalytic activity in an atom-
economical manner at ambient temperature, is desirable.
Recently, we found that neopentyl arenesulfonates 1 read-
ily undergo the cross-coupling reaction with relatively small
amounts of methyl-, neopentyl-, and benzylmagnesium
Chul-Bae Kim, Hyunjong Jo, Bo-Kyoung Ahn,
Chang Keun Kim, and Kwangyong Park*
School of Chemical Engineering and Materials Science,
Chung-Ang University, Seoul 156-756, South Korea
kypark@cau.ac.kr
Received October 7, 2009
Nickel N-heterocyclic carbene (NHC) catalytic system
prepared in situ by the reaction of Ni(acac)2 with NHC
precursor efficiently catalyzed the cross-coupling reac-
tion of alkoxysulfonylarenes with methyl, neopentyl, and
benzyl Grignard reagents at ambient temperature.
Transition metal-catalyzed cross-coupling reactions of
organic electrophiles with organometallic reagents have been
employed as a powerful synthetic tool for carbon-carbon
bond formation in the construction of various types of
organic compounds. Organic halides and pseudohalides
containing a variety of sp-, sp2-, and sp3-hybridized C-X
bonds (X = Cl, Br, I, OTf, etc.) have gained wide acceptance
as electrophilic substrates in these reactions.1
€
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9566 J. Org. Chem. 2009, 74, 9566–9569
Published on Web 11/19/2009
DOI: 10.1021/jo902151h
r
2009 American Chemical Society

Kim et al.
JOCNote
FIGURE 1. Structures of neopentyl arenesulfonates 1.
FIGURE 2. Structures of NHC precursors 3 and Ni-NHC cata-
lyst 5.
SCHEME 1. Ni-NHC-Catalyzed Cross-Coupling Reaction of
Arenesulfonates with Alkyl Grignard Reagents
TABLE 1. Effect of Reaction Conditions on the Cross-Coupling of 1a
with 2aa
entry catalystb 2a (equiv)
3
solvent temp (°C) yield (%)c
1
2
3
4
5
6
7
8
9
dppeNiCl2
dppfNiCl2
Ni(acac)2
Ni(acac)2
none
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
5
5
5
5
5
5
3
1.5
1.5
1.5
1.5
1.5
1.5
none THF
none THF
none THF
67
67
67
25
67
25
25
25
25
25
25
25
92
86
22
99
no rxn
98
98
87
84
bromides 2 in the presence of Ni(acac)2 and NHC precursor
3 to produce the corresponding alkylarenes 4 at room
temperature (Scheme 1). The results of these reactions are
presented and discussed below.
3a
3a
3a
3a
3a
3a
3b
THF
THF
THF
THF
DME
Et2O
THF
Arenesulfonates 1 were prepared according to the procedure
of our previous report (Figure 1).11 The neopentyl group was
selected to avoid the competitive substitution or elimination of
arenesulfonate moiety in the reactions with alkyl Grignard
reagents. NHC precursors 3, 1,3-bis(2,6-diisopropylphenyl)imi-
dazolium trifluoroborate (3a), and 1,3-bis(2,6-diisopropyl-
phenyl)imidazolium chloride (3b), andbis[1,3-di(20,60-diisopropyl-
phenyl)imidazolin-2-ylidene]nickel(0) (Ni(IPr)2, 5) were prepared
by a modified version of the literature procedure (Figure 2).12
The reaction of 4-biphenylsulfonate 1a with methylmag-
nesium bromide (2a) was initially investigated in order to
determine the optimum reaction conditions (Table 1). While
the reaction gave a good yield in the presence of dppeNiCl2
or dppfNiCl2 (entries 1-2),10 Ni(acac)2 alone was a poor
catalyst even at the elevated temperature (entry 3). However,
its activity was dramatically increased by the addition of 3a
to facilitate the reaction to proceed at room temperature
(entry 4). This indicated that the reactive Ni-NHC catalyst is
generated in situ from Ni(acac)2 and 3a.
Although the NHC-coordinated metals were generally pre-
pared and isolated prior to the coupling reactions, the catalytic
complexes generated in situ from the transition metals and
NHC precursors were also efficient in some coupling reac-
tions.13 Herrmann et al. first demonstrated the ability of the in
situ generated Ni-NHC complexes to successfully mediate the
cross-coupling reactions of aryl chlorides with arylmagnesium
brimides and thereby afford unsymmetrical biaryls.12b Fort
et al. also disclosed in situ preparation of Ni-NHC.14
10
11
12
96
92
85
none THF
3ad
Ni(acac)2
THF
aReactions of 1a (0.300 mmol) with 2a were carried out in the
indicated solvent (10 mL) by using the indicated catalyst (0.015 mmol)
and 3 (0.015 mmol) at the indicated temperature for 12 h. bdppe = 1,2-
bis(diphenylphosphino)ethane, dppf = 1,10- bis(diphenylphosphino)-
ferrocene. cYields were determined by GC analyses, using naphthalene
as an internal standard. d0.0300 mmol of 3a was used.
With only 3a, the reaction did not proceed without a nickel
catalyst (entry 5). Addition of 1.5 equiv of 2a was sufficient
for reaction completion (entry 7) because additional 2a did
not improve the reaction conversion by a meaningful margin
(entries 4 and 6). THF was the best ethereal solvent in this
catalytic system (entries 7-9). The counteranion of the salt 3
did not greatly influence the catalytic power of the resulting
Ni-NHC catalyst, although the catalytic system with 3b was
slightly less efficient than that system with 3a (entry 10).
The use of 5 prepared in advance exhibited a lower
efficiency (entry 11). This was consistent with the superiority
of the 1:1 mixture of Ni(acac)2 and 3a compared to the 1:2
mixture (entry 12). The zerovalent nickel coordinated by
only one NHC ligand has been postulated as the catalytically
active species.12,14 In summary, the best results in the opti-
mization studies were obtained by using 1.5 equiv of 2a in the
presence of Ni(acac)2 and 3a in THF at room temperature.
Cross-coupling reactions were performed between various
arenesulfonates 1 and alkyl Grignard reagents 2 under
the optimized conditions, and the results are summarized
in Table 2. Arenesulfonates 1 underwent reaction with 2a
to produce the corresponding methylarenes, 4a-h, in high
yields within 12 h at ambient temperature (entries 1-8).
Neopentylmagnesium bromide (2b), not possessing a
β-hydrogen to magnesium, also showed high reactivity
toward the arensulfonates 1a-c and 1e to produce the
(11) Kim, C.-B.; Cho, C.-H.; Park, K. Bull. Korean Chem. Soc. 2007, 28,
281.
€
(12) (a) Bohm, V. P. W.; Gstottmayr, C. W. K.; Weskamp, T.; Herrmann,
W. A. Angew. Chem., Int. Ed. 2001, 40, 3387. (b) Bohm, V. P. W.; Weskamp,
€
€
€
T.; Gstottmayr, C. W. K.; Herrmann, W. A. Angew. Chem., Int. Ed. 2000, 39,
1602. (c) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889.
(13) (a) Addis, D.; Enthaler, S.; Junge, K.; Wendt, B.; Beller, M. Tetra-
hedron Lett. 2009, 50, 3654. (b) Nordstrom, L. U.; Vogt, H.; Madsen, R. J.
Am. Chem. Soc. 2008, 130, 17672. (c) Adonin, N. Y.; Babushkin, D. E.;
Parmon, V. N.; Bardin, V. V.; Kostin, G. A.; Mashukov, V. I.; Frohn, H.-J.
Tetrahedron 2008, 64, 5920. (d) Jia, Y.-X.; Hillgren, J. M.; Watson, E. L.;
€
Marsden, S. P.; Kundig, E. P. Chem. Commun. 2008, 4040.
(14) Gradel, B.; Brenner, E.; Schneider, R.; Fort, Y. Tetrahedron Lett.
2001, 42, 5689.
(15) Hartwig, J. F.; Paul, F. J. Am. Chem. Soc. 1995, 117, 5373.
J. Org. Chem. Vol. 74, No. 24, 2009 9567

Kim et al.
JOCNote
TABLE 2. Coupling Reactions of 1 with 2a
TABLE 3. Coupling Reactions of 1 with Benzyl Grignard Reagentsa
aReactions of sulfonates 1 (0.300 mmol) with 2 (0.900 mmol) were
carried out in THF (10 mL) by using Ni(acac)2 (0.015 mmol) and 3a
(0.015 mmol) at room temperature for 12 h . b2d: X = Br; 2e: X = Cl.
cYields based on 1. d0.450 mmol of 2 was used.
Their low reactivity toward traditional nickel catalysts sup-
ports the potential value of this Ni-NHC catalytic system.
In summary, the Ni-NHC catalyst generated in situ by the
reaction of Ni(acac)2 with NHC precursor efficiently cata-
lyzed the cross-coupling reaction of alkoxysulfonylarenes
with methyl, neopentyl, and benzyl Grignard reagents. The
reactions rapidly proceeded to afford high yields with only
1.5 equiv of methyl and neopentyl nucleophiles at room
temperature. Moreover, 3 equiv of benzyl Grignard re-
agents, which showed low reactivity toward traditional
catalysts, successfully underwent reaction at room tempera-
ture. This reaction provides an efficient synthetic route for
alkylarenes, via the mild and versatile transformation of
various arenesulfonates. The application of this catalytic
system to solid-phase organic synthesis is currently under
investigation.
aReactions of sulfonates 1 (0.300 mmol) with 2 (0.450 mmol) were
carried out in THF (10 mL) by using Ni(acac)2 (0.015 mmol) and 3a
(0.015 mmol) at room temperature for 12 h. 2a = methylmagnesium
bromide; 2b = neopentylmagnesium bromide; 2c = n-butylmagnesium
chloride. cYields based on 1. dYields were determined by GC analyses,
using p-terphenyl as an internal standard.
b
neopentylarenes 4i-l in good yields (entries 9-12). How-
ever, reactions of n-butylmagnesium chloride (2c) with 1a
and neopentyl 2-naphthalenesulfonate (1h) proceeded via
the competition between the cross-coupling reaction and the
hydrogenolysis, with the latter dominating by a 5-fold factor,
presumably due to the β-hydride elimination (entries 13
and 14).
Cross-coupling reactions between 1 and benzyl Grignard
reagents 2d,e, which showed low reactivity toward dppe-
NiCl2 in our previous report,10a were performed with this
catalytic system (Table 3). Although 1.5 equiv of benzyl-
magnesium bromide (2d) was insufficient to complete the
reaction (entry 1), the reaction with 3 equiv of 2d afforded a
good yield within 3 h under the standard reaction condition
(entry 2). Benzylmagnesium chloride (2e) was less reactive
than 2d (entry 3). When three arenesulfonates, 1a, 1c, and 1d,
were allowed to react with 2d, the corresponding coupled
products 4p-r were produced in good yields (entries 4-6).
Experimental Section
General Procedure for the Preparation of Arenesulfonates. To
2,2-dimethyl-1-propanol (58.7 mmol) in chloroform (50 mL) at
0 °C were added pyridine (9.28 g, 117 mmol) dropwise over a
period of 20 min and arenesulfonyl chloride (39.0 mmol) in small
portions. The reaction mixture was stirred at room temperature
for 12 h and diluted with EtOAc. The organic layer was washed
with 1% aqueous HCl, water, and brine, dried over MgSO4, and
concentrated in vacuo. The crude sulfonates were purified by
recrystallization.
General Procedure for the Preparation of Neopentyl Biphenyl-
sulfonates (1). To the solution of neopentyl 4-bromobenzene-
sulfonate (5.22 mmol) and Pd(PPh3)4 (0.157 mmol) in toluene
(12.0 mL) was added 2.0 M aqueous Na2CO3 (6.0 mL) under Ar
atmosphere. To the resulting mixture was added arylboronic
acid (5.74 mmol), which was dissolved in ethanol (3.0 mL). The
reaction mixture was heated at reflux for 7 h with vigorous
stirring and diluted with EtOAc (100 mL). The organic layer was
washed with 1% aqueous HCl, water, and brine, dried over
9568 J. Org. Chem. Vol. 74, No. 24, 2009

Kim et al.
JOCNote
MgSO4, filtrated through a small pad of silica gel in a sintered
glass filter, and concentrated in vacuo. The crude compound
was purified by recrystallization from n-hexane to give 1 as a
white solid. The sulfonates 1a-c and 1e were identified accord-
ing to the literature.11
General Procedure for Cross-Coupling Reactions of 1 with 2a,
2b, and 2c. To a stirred solution of 1 (0.300 mmol), Ni(acac)2
(0.0150 mmol), and 3a (0.0150 mmol) in THF (10.0 mL) was
slowly added Grignard reagents 2 (0.450 mmol) at room tem-
perature under an Ar atmosphere. The reaction mixture was
stirred at room temperature for 12 h. The resulting mixture was
diluted with Et2O. The organic layer was washed with 1%
aqueous HCl, water, and brine, dried over MgSO4, and con-
centrated in vacuo. The crude biphenyls 4 were purified by
column chromatography.
General Procedure for Cross-Coupling Reactions of 1 with 2d
and 2e. To a stirred solution of 1 (0.300 mmol), Ni(acac)2 (0.0150
mmol), and 3a (0.0150 mmol) in THF (10.0 mL) was slowly
added Grignard reagents 2 (0.900 mmol) at room temperature
under an Ar atmosphere. The reaction mixture was stirred at
room temperature for 3 h. The resulting mixture was diluted
with Et2O. The organic layer was washed with 1% aqueous HCl,
water, and brine, dried over MgSO4, and concentrated in vacuo.
The crude products 4 were purified by recrystallization in
2-propanol.
Supporting Information Available: Synthetic procedures,
1
characterization data, and copies of H NMR and 13C NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 24, 2009 9569