Thieme journal awardees - Where are they now? on cobalt-catalyzed biaryl coupling reactions

Article abstract of DOI:10.1055/s-0029-1218013

An operationally simple biaryl coupling reaction has been developed. The underlying domino process involves in situ Grignard formation from aryl bromides and subsequent homocoupling with catalytic CoCl² and 1 bar synthetic air as terminal oxidant. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218013

LETTER
2919
Thieme Journal Awardees – Where Are They Now?
On Cobalt-Catalyzed Biaryl Coupling Reactions
C
obalt-Catalyze
d
Biar
a
C
ouplingtthias Mayer, Waldemar Maximilian Czaplik, Axel Jacobi von Wangelin*
Department of Chemistry, University of Cologne, Greinstr. 4, 50939 Köln, Germany
Fax +49(221)4705057; E-mail: axel.jacobi@uni-koeln.de
Received 14 August 2009
Abstract: An operationally simple biaryl coupling reaction has
been developed. The underlying domino process involves in situ
Grignard formation from aryl bromides and subsequent homocou-
pling with catalytic CoCl2 and 1 bar synthetic air as terminal oxi-
dant.
Key words: domino reactions, cross-coupling, Grignard reactions,
biaryls, dimerizations
Biaryls constitute a prevalent structural motif in a plethora
of materials, natural products, pharmaceuticals, fine
chemicals, agrochemicals, and catalysts.1 The formation
of unsymmetrical biaryls is largely dominated by cross-
coupling methodologies.2 Such reactions of a nucleophilic
aryl species with an electrophilic aryl halide readily occur
under transition-metal catalysis. The most prominent
procedures utilize arylboronic acids,3 arylstannanes,4
arylzinc5 or arylmagnesium6 reagents, and more recently
activated hydrocarbon nucleophiles.7 For the synthesis of
symmetrical biaryl compounds, the transition-metal-
catalyzed oxidative dimerization of organometal species
is more practical as it relies on two identical reactants and
thus bypasses the separate preparation and handling of the
two electronic antipodes.8 Especially palladium and nick-
el complexes have exhibited high catalytic activity for a
wide range of aryl substrates in combination with various
oxidants.9 In the context of sustainability, however, these
protocols suffer from the high costs10 of palladium cata-
lysts and the allergenic and cancerogenic toxicity of nick-
el.11 From an economic standpoint, there is clearly a
demand for more efficient coupling methodologies that
obviate the need for complex or toxic catalyst systems as
well as sensitive and hazardous reactants. As early as
1941, Kharasch et al. demonstrated the feasibility of
homo-biaryl coupling using transition-metal salts.12 Stoi-
chiometric metal salts have been used to oxidatively
dimerize arylmetalates.13 Later, optimized protocols for
cobalt-,14 manganese-,15 and iron-catalyzed16 biaryl cou-
pling reactions were reported. We wish to report on a new
ligand-free reaction for the direct cobalt-catalyzed cou-
pling of substituted aryl bromides to give symmetrical bi-
aryls under mild conditions in the presence of cheap
magnesium and synthetic air as ubiquitous and waste-free
oxidant (Scheme 1).
Axel Jacobi von Wangelin (born 1974) enjoyed his youth growing
up in Berlin-Friedrichshain. He studied Chemistry at the University of
Erlangen-Nürnberg and went a long way round to indulge in college
lifes in Germany, Wales, and the USA. Axel was a visiting scientist
at the University of Utah with John A. Gladysz before taking up
graduate work in the group of Matthias Beller (Leibniz-Institute of
Catalysis, Rostock) on carbonylation and cycloaddition reactions. A
DAAD postdoctoral fellow with Barry Trost in Stanford, he worked
on asymmetric zinc-catalyzed reactions. In late 2005, he started his
independent career at the University of Cologne and currently heads
a pack of extraordinarily talented lab rats. His group is engaged in the
development of sustainable metal- and organo-catalyzed transforma-
tions. Axel is an Emmy-Noether fellow of the DFG, recipient of a
2007 Thieme Journal Award, and the 2009 Science Award of the In-
dustrie-Club. When not drudging in the labs, he and his group enjoy
a diverting table football match.
R
1) Mg
X
2) [CoCl2]
air
R
R
1
2
Scheme 1 Direct cobalt-catalyzed biaryl homocoupling
Model studies (Table 1) with commercial PhMgCl solu-
tions in THF revealed the superiority of pure oxygen as
terminal oxidant at low temperatures. However, safety
concerns and practical considerations prompted us to ap-
ply an atmosphere of ambient air instead. Best results
were achieved with a dry oxygen source. The use of tech-
nical and atmospheric air (open flask) led to low yields;
highest yields were obtained by using a balloon filled with
pure oxygen, albeit at the cost of long reaction times (>8
h). From repetitive runs it became obvious that reactions
under a static layer of oxygen or air were difficult to re-
produce, with the surface-to-volume ratio and the stirring
frequency being crucial parameters. The application of a
constant stream of synthetic air through the solution (20
mL/min) resulted in significantly shorter reaction times
SYNLETT 2009, No. 18, pp 2919–2923
x
x
.x
x
.2
0
0
9
Advanced online publication: 08.10.2009
DOI: 10.1055/s-0029-1218013; Art ID: G26409ST
© Georg Thieme Verlag Stuttgart · New York

2920
M. Mayer et al.
LETTER
Table 1 Selected Optimization Experiments of the Model Reactiona
CoCl2 (5 mol%)
ligand (10 mol%)
[CoCl2]
MgBr
THF, 0 °C, 30 min
synth. air
MgCl
conditions
2b
2a
Ligand
Yield (%)
Temp (°C) CoCl2 (mol%) Oxidantb
Yield (%)
81
71
71
80
no
Me4-DACH
TMEDA
phen
–20
0
O2
0
57
90
2.5
5
Scheme 3 Effect of ligand addition on the oxidative dimerization
0
5
O2
81
synthetic air
synthetic air purge
open
76
89 (86)d
51
materials.18 The operationally simple reaction conditions
for most substrates involved stirring the aryl bromide with
1.2 equivalents of Mg turnings in THF solution (ca. 0.7
M) at room temperature for 3 hours. The presence of
amine ligands in such a domino process proved detrimen-
tal for the initial magnesiation of the aryl bromide, proba-
bly due to surficial deactivation.
–20
20
5
5
synthetic air
80
48
–20
20
synthetic air purge
70c,d
86d
a A 5 mL test tube was sealed with a rubber septum and charged with
CoCl2 in THF (1 mL). A solution of PhMgCl (2 mL, 2 M in THF) was
slowly added, and the mixture exposed to oxygen or synthetic air for
2 h.
Table 2 shows a series of arylbromide substrates that were
subjected to sequential magnesiation and cobalt-catalyzed
oxidative dimerization under optimized conditions.19 Bro-
moarenes with alkyl and alkoxy substituents showed very
good reactivity. The susceptibility for competitive hydrol-
ysis or phenol formation increased with the basicity
(2e,j,k) and steric hindrance (2j,o,p) of the arylmagne-
sium halide. In most cases, the cobalt-catalyzed oxidation
of arylmagnesium halides was complete within 30 min-
utes, while some (electron-deficient) substrates required
longer exposure to synthetic air (1–3 h). Reaction of
1-bromo-4-fluorobenzene (1q) afforded the desired 4,4¢-
difluorobiphenyl (2q, 59%) alongside significant
amounts of 4,4¢¢-difluoro[1,1¢:4¢,1¢¢]-terphenyl (3q, 24%,
Scheme 4).20
b O2 and air were applied via gas-filled balloons (1.25 bar). Air purge
refers to a stream (20 mL/min) of dry synthetic air bubbled through
the solution. Open-vessel reactions were stirred at 500 rpm.
c Phenol as main (by)product, see also Scheme 2.
d Yield in parentheses after 30 min.
(30 min) and good yields (86%). In the absence of cobalt
catalyst, at high oxygen concentrations in solution and at
lower temperatures, rapid conversion to the correspond-
ing phenol was observed (Table 1, Scheme 2). This reac-
tion is believed to involve intermediate organometallic
peroxides that are prone to reductive cleavage to give
alkoxymagnesium species.17 With basic arylmagnesium
halides, the phenol formation becomes highly competi-
tive. The employment of amine ligands, that generally as-
sure high catalytic activity in most cobalt-catalyzed cross-
coupling reactions, showed no beneficial effect
(Scheme 3).
F
F
Br
1) Mg (1.2 equiv)
THF, r.t., 3 h
2q 59%
3q 24%
2) CoCl2 (5 mol%)
synth. air
0 °C, 1 h
F
F
We then exploited a one-pot protocol that relies upon in
situ generation of arylmagnesium bromides without re-
sorting to expensive or hazardous organometallic starting
F
1q
Scheme 4 Domino C–Br/C–F activation of 1-bromo-4-fluoroben-
zene
1) 0 °C, 10 min
THF, synth. air
MgBr
OH
+
2) NH4Cl, H2O
Dimethyl-4-bromoaniline and 2-bromopyridine exhibited
moderate reactivity (2e and 2h, Figure 1), while other
substrates with accessible donor atoms such as ethyl 4-
bromobenzoate (1r), 3-bromoquinoline (1s), and 3-bro-
mothiophene (1t) proved very sluggish under the standard
reaction conditions, possibly by inhibitive coordination to
the magnesium surface.21 Treatment of 1r and 1t with i-
PrMgCl·LiCl and subsequent oxidative dimerization gave
low yields (<30%) of the biaryls. In an effort to extend the
reaction scope to also include alkenyl substrates, we sub-
jected b-bromostyrene to the standard conditions. The re-
sultant diene 2u was isolated in 52% yield as a 2:1 mixture
28%
72%
1) 0 °C, 10 min
THF, synth. air
OH
MgBr
+
2) NH4Cl, H2O
38%
62%
O2
H2O
ArMgX
ArMgX
ArOOMgX
2 ArOMgX
2 ArOH
Scheme 2 Formation of phenols in the absence of catalyst
Synlett 2009, No. 18, 2919–2923 © Thieme Stuttgart · New York

LETTER
Cobalt-Catalyzed Biaryl Coupling
Table 2 Substrate Scopea (continued)
2921
of E,E- and E,Z-isomers (Scheme 5). Phenylacetylene
was treated with i-PrMgCl·LiCl and subsequently oxida-
tively dimerized in moderate yield (36%).22
Mg (1.2 equiv)
THF, r.t.
Br
MgBr
R
R
Table 2 Substrate Scopea
CoCl2
(5 mol%)
synth. air, 0 °C
1
Mg (1.2 equiv)
Br
MgBr
THF, r.t.
R
R
R
CoCl2
(5 mol%)
1
R
2
synth. air, 0 °C
Biaryl
Yield (%)
79b,h
R
MeO
MeO
MeO
OMe
OMe
OMe
R
2
Biaryl
Yield (%)
86
2k
F
2a
2b
F
F
65
81b
79
F
2l
48b
2c
MeO
OMe
NMe2
CF3
95
2m
Ph
F
2d
70b,i
Ph
72c,d
73e
Me2N
F
2e
2n
F3C
32j
2f
F
2o
48b
34f
93
F
F
F
54k
2g
2p
N
N
a Standard conditions: Mg turnings (3 mmol), THF (4 mL), aryl bro-
mide (2.5 mmol), r.t., 3 h; then addition of solution of CoCl2 (0.125
mmol) in THF (6 mL). Stream of synthetic air (20 mL/min), 0 °C, 3 h.
b Stream of synthetic air (20 mL/min), 0 °C, 0.5 h.
c Stream of synthetic air (20 mL/min), 0 °C, 1 h.
d N,N-dimethylaniline (14%).
2h
OMe
MeO
e Grignard formation at 0 °C for 3 h.
2i
f Sluggish Grignard formation (<40%).
g 1,3-Dimethoxybenzene (28%).
OMe
h 1,2,3-Trimethoxybenzene (20%).
i 2-Fluoro-4-hydroxybiphenyl (16%).
64g
MeO
OMe
j 2,6-Dimethylphenol (40%).
k Naphthalene (16%).
MeO
2j
Synlett 2009, No. 18, 2919–2923 © Thieme Stuttgart · New York

2922
M. Mayer et al.
LETTER
Br
In summary, we have developed a practical one-pot meth-
odology for the cobalt-catalyzed homocoupling of substi-
tuted aryl bromides. The reaction involves sequential
Grignard formation in the presence of magnesium and
rapid cobalt-catalyzed oxidative dimerization with syn-
thetic air.
Br
Br
EtO2C
N
S
1r
1s
1t
Figure 1 Substrates exhibiting low conversions. Conditions: Mg,
THF, r.t., 3 h; then 5 mol% CoCl2, synthetic air, r.t., 2 h.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
1) Mg (1.2 equiv)
THF, 0 °C, 1 h
Ph
Br
Ph
2) CoCl2 (5 mol%)
synth. air, 0 °C, 30 min
Acknowledgment
1u E/Z = 4:1
2u 52%, EE/EZ = 2:1
We thank Dr. Mark Sundermeier and Dr. Matthias Gotta (Saltigo
GmbH) for fruitful discussions and Prof. H.-G. Schmalz (University
of Cologne) for excellent technical support. M.M. is a fellow of the
Deutsche Bundesstiftung Umwelt (DBU), W.M.C. received a Max
Buchner stipend of the DECHEMA. A.J.v.W. was a 2007 Thieme
Journal Awardee and is recipient of the 2009 Science Award of the
Industrie-Club Düsseldorf.
1) i-PrMgCl⋅LiCl (1.1 equiv)
THF, 0 °C to r.t., 1 h
Ph
Ph
2) CoCl2 (5 mol%)
synth. air, 0 °C, 30 min
1v
2v 36%
References and Notes
Scheme 5 b-Bromostyrene and phenylacetylene as starting materials
(1) (a) Cepanec, I. Synthesis of Biaryls; Elsevier: Oxford, 2004.
(b) Pu, L. Chem. Rev. 1998, 98, 2405. (c) Bringmann, G.;
Price Mortimer, A. J.; Keller, P. A.; Gresser, M. J.; Garner,
J.; Breuning, M. Angew. Chem. Int. Ed. 2005, 44, 5384;
Angew. Chem. 2005, 117, 5518. (d) Kirsch, P.; Bremer, M.
Angew. Chem. Int. Ed. 2000, 39, 4216; Angew. Chem. 2000,
112, 4384.
(2) (a) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de
Meijere, A.; Diederich, F., Eds.; Wiley-VCH: Weinheim,
2004. (b) Hassan, J.; Svignon, M.; Gozzi, C.; Schulz, E.;
Lemaire, M. Chem. Rev. 2002, 102, 1359. (c) Nicolaou,
K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005,
44, 4442; Angew. Chem. 2005, 117, 4516. (d) Zapf, A.;
Beller, M. Top. Catal. 2002, 19, 101.
We also studied the electronically biased hetero-biaryl
coupling between 1-bromo-4-trifluoromethylbenzene (1f)
and 1-bromo-4-methoxybenzene (1d). Quenching experi-
ments documented that Grignard formation for both aryl
bromides was complete after 2 hours at room temperature.
Cobalt-catalyzed oxidative coupling gave largely statistic
mixtures of all three biaryls. Upon employment of an ex-
cess of one component, moderate yields of the hetero-
biaryl could be obtained, with phenol formation being the
major side reaction (Table 3).
Table 3 Hetero-Biaryl Formationa
(3) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275.
(4) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React.
1997, 50, 1.
Σ 2.5 mmol
Br
Br
Ar1Ar1
+
1) Mg (3 mmol)
THF, r.t., 2 h
(5) Negishi, E. Acc. Chem. Res. 1982, 15, 340.
(6) Selected examples for aryl–aryl coupling reactions using
Grignard reagents: (a) Tamao, K.; Sumitani, K.; Kumada,
M. J. Am. Chem. Soc. 1972, 94, 4374. (b) Corriu, R. J. P.;
Masse, J. P. J. Chem. Soc., Chem. Commun. 1972, 144.
(c) Martin, R.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129,
3844. (d) Hartmann, C. E.; Nolan, S. P.; Cazin, C. S. J.
Organometallics 2009, 28, 2915. (e) Korn, T. J.; Schade,
M. A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725.
(f) Sapountzis, I.; Lin, W.; Kofink, C. C.; Despotopoulou,
C.; Knochel, P. Angew. Chem. Int. Ed. 2005, 44, 1654;
Angew. Chem. 2005, 117, 1682.
(7) For recent reviews, see: (a) Alberico, D.; Scott, M. E.;
Lautens, M. Chem. Rev. 2007, 107, 174. (b) Seregin, I. V.;
Gevorgyan, V. Chem. Soc. Rev. 2007, 36, 1173. Selected
recent examples: (c) Lewis, J. C.; Bergman, R. G.; Ellman,
J. A. Acc. Chem. Res. 2008, 41, 1013. (d) Join, B.;
Yamamoto, T.; Itami, K. Angew. Chem. Int. Ed. 2009, 48,
3644; Angew. Chem. 2009, 121, 3698.
Ar1Ar2
+
2) CoCl2 (5 mol%)
synth. air, 0 °C, 0.5 h
+
Ar2Ar2
OMe
CF3
(Ar1Br)
(Ar2Br)
Ar1Br/Ar2Br Ar1Ar1
(mmol)
Ar1Ar2
Ar2Ar2
1.72/0.78
1.46/1.04
1.25/1.25
1.04/1.46
0.78/1.72
70%
64%
0.50 mmol
10%
0.04 mmol
0.60 mmol
69%
44%
10%
0.05 mmol
0.50 mmol
0.46 mmol
27%
39%
35%
0.22 mmol
0.17 mmol
0.49 mmol
17%
50%
63%
0.46 mmol
(8) For recent catalyst-free protocols, see: (a) Krasovskiy, A.;
Tishkov, A.; del Amo, V.; Mayr, H.; Knochel, P. Angew.
Chem. Int. Ed. 2006, 45, 5010; Angew. Chem. 2006, 118,
5132. (b) Maji, M. S.; Pfeifer, T.; Studer, A. Angew. Chem.
Int. Ed. 2008, 47, 9547; Angew. Chem. 2008, 120, 9690.
0.09 mmol
0.52 mmol
0%
54%
0.42 mmol
70%
0.60 mmol
0.00 mmol
a Yields refer to minor component.
Synlett 2009, No. 18, 2919–2923 © Thieme Stuttgart · New York

LETTER
Cobalt-Catalyzed Biaryl Coupling
2923
(9) Selected examples: (a) Tsou, T. T.; Kochi, J. K. J. Am.
Chem. Soc. 1979, 101, 7547. (b) Yoshida, H.; Yamaryo, Y.;
Ohshita, J.; Kunai, A. Tetrahedron Lett. 2003, 44, 1541.
(c) Adamo, C.; Amatore, C.; Ciofini, I.; Jutand, A.; Lakmini,
H. J. Am. Chem. Soc. 2006, 128, 6829. (d) Liégault, B.;
Lee, D.; Huestis, M. P.; Stuart, D. R.; Fagnou, K. J. Org.
Chem. 2008, 73, 5022.
(10) The current world market prices of palladium (370 USD/oz)
and nickel (14.4 USD/lb) are expected to increase due to the
request from emerging countries such as China, Russia,
India, and Brazil.
mmol), fitted with a rubber septum, and purged with argon
(1 min). Dry THF (4 mL) and the arylbromide (2.5 mmol)
were added via a syringe. The solution was stirred at r.t. for
1–3 h under argon. Cooled to 0 °C, a solution of CoCl2 (16.1
mg, 0.12 mmol, 5 mol%) in dry THF (6 mL) was added.
Synthetic air (20 mL/min) was added through a needle to the
solution. After 0.5–3 h, the reaction was quenched with sat.
aq NH4Cl (5 mL), extracted with EtOAc (3 × 10 mL).
The combined organic phases were dried (Na2SO4),
concentrated, and subjected to flash chromatography
(cyclohexene–EtOAc).
(11) (a) Handbook on the Toxicology of Metals; Friberg, L.;
Nordberg, G. F.; Vouk, V. B., Eds.; Elsevier: Amsterdam,
1986. (b) Nickel and the Skin: Absorption, Immunology,
Epidemiology, and Metallurgy; Hostynek, J. J.; Maibach,
H. I., Eds.; CRC Press: Boca Raton, 2002.
(12) Kharasch, M. S.; Fields, E. K. J. Am. Chem. Soc. 1941, 63,
2316.
(13) (a) Gilman, H.; Lichtenwalter, M. J. Am. Chem. Soc. 1939,
61, 957. (b) Wittig, G.; Bickelhaupt, F. Chem. Ber. 1958, 91,
883. (c) Wittig, G.; Klar, G. Justus Liebigs Ann. Chem.
1967, 704, 91.
New Compounds
3¢,3¢¢-Difluoro[1,1¢:4,1¢¢:4¢,1¢¢¢]quarter-phenyl (2n): mp
182 °C. 1H NMR (300 MHz, CDCl3): d = 7.75 (d, 4 H, J = 6
Hz), 7.65–7.05 (m, 12 H). 13C NMR (75 MHz, CDCl3):
d = 160.0 (d, J = 246 Hz), 140.4 (d, J = 6.8 Hz), 135.3 (d, J
= 12.4 Hz), 131.1 (d, J = 3.4 Hz), 128.9, 128.5, 128.1, 122.7,
114.4 (d, J = 24.1 Hz). MS (EI, 70 eV): m/z (%) = 342 (100)
[M+], 320 (7), 264 (5), 170 (7), 77 (5). HRMS: m/z =
342.122. IR (ATR): 1550 (m), 1473 (s), 1403 (m), 1246 (m),
1183 (m), 1130 (m), 1040 (m), 911 (s), 823 (s), 766 (s), 695
(s) cm–1.
(14) Selected examples: (a) Moncomble, A.; Le Floch, P.;
Gosmini, C. Chem. Eur. J. 2009, 15, 4770. (b) Amatore,
M.; Gosmini, C. Angew. Chem. Int. Ed. 2008, 47, 2089;
Angew. Chem. 2008, 120, 2119.
3,3¢,4,4¢-Tetrafluorobiphenyl (2g): mp 83 °C; 1H NMR (300
MHz, CDCl3): d = 7.39–7.32 (m, 2 H), 7.30–7.25 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 152.1 (dd, J = 12.7, 23.9
Hz), 148.8 (dd, J = 12.6, 24.8 Hz), 136.2, 123.0 (q, J = 3.4
Hz), 117.8 (d, J = 17.3 Hz), 116.0 (d, J = 17.9 Hz). MS (EI,
70 eV): m/z (%) = 226 (100 [M+], 206 (22), 175 (8), 156 (7),
138 (7), 112 (8). HRMS: m/z = 226.041. IR (ATR): 3064
(w), 1881 (w), 1599 (s), 1495 (s), 1339 (s), 1316 (m), 1265
(s), 1184 (s), 1150 (m), 117 (s), 1028 (m), 943 (m), 909 (m),
885 (m), 865 (s), 805 (s), 766 (s), 739 (s) cm–1.
(15) Recent examples: (a) Zhou, Z.; Xue, W. J. Organomet.
Chem. 2009, 694, 599. (b) Cahiez, G.; Moyeux, A.;
Buendia, J.; Duplais, C. J. Am. Chem. Soc. 2007, 129, 13788.
(16) (a) For a recent review, see: Czaplik, W. M.; Mayer, M.;
Cvengroš, J.; Jacobi von Wangelin, A. ChemSusChem 2009,
2, 396. Selected recent examples: (b) Nagano, T.; Hayashi,
T. Org. Lett. 2005, 7, 491. (c) Cahiez, G.; Chaboche, C.;
Mahuteau-Betzer, F.; Ahr, M. Org. Lett. 2005, 7, 1943.
(d) Liu, W.; Lei, A. Tetrahedron Lett. 2008, 49, 610.
(17) (a) Porter, C. W.; Steel, C. J. Am. Chem. Soc. 1920, 42,
2650. (b) Davies, A. G.; Roberts, B. P. Acc. Chem. Res.
1972, 5, 387.
(20) For nucleophilic substitutions of Ar–F with Grignard
compounds, see for example: (a) Yoshikai, N.; Matsuda, H.;
Nakamura, E. J. Am. Chem. Soc. 2009, 131, 9590.
(b) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am. Chem.
Soc. 2005, 127, 17978. (c) Böhm, V. P. W.; Gstöttmayr,
C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem.
Int. Ed. 2001, 40, 3387; Angew. Chem. 2001, 113, 3500.
(21) Lee, J.-S.; Velarde-Ortiz, R.; Guijarro, A.; Wurst, J. R.;
Rieke, R. D. J. Org. Chem. 2000, 65, 5428.
(18) For a related direct aryl–alkyl cross-coupling, see: Czaplik,
W. M.; Mayer, M.; Jacobi von Wangelin, A. Angew. Chem.
Int. Ed. 2009, 48, 607; Angew. Chem. 2009, 121, 616.
(19) General Procedure
(22) Cahiez, G.; Duplais, C.; Buendia, J. Angew. Chem. Int. Ed.
A 10 mL flask was charged with Mg ribbons (74 mg, 3.0
2009, 48, 6731; Angew. Chem. 2009, 121, 6859.
Synlett 2009, No. 18, 2919–2923 © Thieme Stuttgart · New York

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