Cobalt-catalyzed direct arylation and benzylation by C-H/C-O cleavage with sulfamates, carbamates, and phosphates

Article abstract of DOI:10.1002/anie.201202466

Inexpensive cobalt catalysts enable the first direct arylation and benzylation of (hetero)arenes with aryl carbamates, sulfamates, and phosphates with ample scope. The non-radical C-H/C-O arylation reaction even proved viable at ambient temperature. Copyr

Full text of DOI:10.1002/anie.201202466

Angewandte
Chemie
DOI: 10.1002/anie.201202466
Biaryl Synthesis
À
À
Cobalt-Catalyzed Direct Arylation and Benzylation by C H/C O
Cleavage with Sulfamates, Carbamates, and Phosphates**
Weifeng Song and Lutz Ackermann*
Dedicated to Professor Lutz F. Tietze on the occasion of his 70th birthday
Efficient methods for the selective preparation of biaryls are
of key importance, as these structural motifs are crucial
building blocks for natural products, liquid crystals, and
functional materials. Particularly, palladium-catalyzed cross-
coupling reactions between nucleophilic metalated arenes
and electrophilic aryl halides have matured into indispensable
tools for the synthesis of substituted biaryls (Scheme 1a).[1]
However, recent focus has shifted towards catalytic arylations
with phenol derivatives as organic electrophiles, because
these arylating reagents are inexpensive, readily accessible,
and can easily be implemented as directing groups in versatile
arene functionalization strategies.[2] Unfortunately, the high
recent progress in cross-coupling chemistry has been accom-
À
plished with challenging C C bond formations using fluorine-
free, yet difficult to activate, aryl tosylates, phosphates,
sulfamates, or carbamates (Scheme 1b).[4,5] Although these
methods have proven to be highly versatile, they are
inherently limited, as they rely on prefunctionalized organ-
ometallic starting materials. Thus, a significantly more
sustainable strategy is represented by the direct transforma-
[6]
À
tion of ubiquitous C H bonds as latent functional groups.
À
Thus far, C H bond arylations with fluorine-free phenol-
based electrophiles were accomplished on heteroarenes with
the aid of palladium complexes,[7] whereas nickel catalysts
were elegantly utilized by Itami for the most recent direct
À
C O bond strength in phenols calls for the activation of these
arylations of C H acidic azoles.[8] On the contrary, the direct
À
precursors, which has been predominantly achieved with
expensive fluorine-containing reagents.[3] However, notable
arylation of arenes with aryl tosylates or mesylates is, to date,
unfortunately restricted to relatively expensive complexes of
the rare transition metals ruthenium[9,10] and palladium
(Scheme 1c).[11]
Recent seminal contributions by the research groups of
Nakamura and Yoshikai highlighted the power of inexpensive
[13,14]
cobalt[12] catalysts for direct C H bond alkylations.
In
À
considering the most recent success in cobalt-catalyzed direct
arylations through radical intermediates,[6,15–17] as well as the
non-radical direct arylations with Grignard reagents reported
by Wang and Shi,[18] we became fascinated by developing step-
economical cobalt-catalyzed biaryl syntheses through chal-
À
À
lenging C H/C O bond cleavages, which we herein report.
We initiated our studies by exploring the reaction
conditions for the direct arylation with electronically deacti-
vated sulfamate 2a (Table 1). Although mono- or bidentate
phosphine ligands unfortunately provided unsatisfactory
results (entries 1–3), N-heterocyclic carbene (NHC)[19,20]
À
precursors were more effective for catalytic C H bond
transformations, with N,N-bis(mesityl)imidazolium chloride
(IMesHCl) delivering optimal yields (entries 4–8). Notably,
the bases lithium hexamethyldisilazide (LiHMDS) and
KOtBu failed to affect the desired direct arylation with aryl
sulfamates 2, and CyMgCl[21] was instead found to be the
additive of choice (Cy = cyclohexyl; entries 8–12). Among the
solvents tested, polar aprotic 1,3-dimethyl-3,4,5,6-tetrahydro-
2-pyrimidinone (DMPU) proved beneficial for direct alkyla-
tions (entries 8 and 13–15), as was recently noted by
Nakamura.[13b,d] Also, comparable catalytic efficacies were
observed for both cobalt(II) and cobalt(III) complexes
(entries 8 and 17).
Scheme 1. Strategies to achieve a versatile and economically attractive
biaryl synthesis. [TM]=transition metal complex.
[*] M. Sc. W. Song, Prof. Dr. L. Ackermann
Institut fꢀr Organische und Biomolekulare Chemie
Georg-August-Universitꢁt
Tammannstrasse 2, 37077 Gçttingen (Germany)
E-mail: lutz.ackermann@chemie.uni-goettingen.de
Homepage: http://www.org.chemie.uni-goettingen.de/ackermann/
[**] Support by the DFG, the Georg-August-Universitꢁt Gçttingen, and
the Chinese Scholarship Council (fellowship to W.S.) is gratefully
acknowledged. We thank Ayesha Babar for the synthesis of starting
materials, as well as Dr. Benudhar Punji for helpful discussions and
preliminary experiments with aryl chlorides.
À
We next explored the scope of the cobalt-catalyzed C H
bond arylation with aryl sulfamates 2 using the optimized
catalytic system (Scheme 2). Notably, electron-rich, and thus
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201202466.
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Table 1: Optimization of the direct arylation reaction with sulfamate
2a.[a]
Entry
Ligand
Base
Solvent
Yield [%][b]
1
–
CyMgCl
CyMgCl
CyMgCl
CyMgCl
CyMgCl
CyMgCl
CyMgCl
CyMgCl
KOtBu
LiHMDS
MeMgCl
tBuMgCl
CyMgCl
CyMgCl
CyMgCl
CyMgCl
CyMgCl
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
DMPU
NMP
15
–
2[c]
3
dppe
PCy3
phenanthroline
sIPrHCl
sIMesHCl
IPrHCl
IMesHCl
IMesHCl
IMesHCl
IMesHCl
IMesHCl
IMesHCl
IMesHCl
IMesHCl
IMesHCl
IMesHCl
21
11
42
40
47
82
–
4
5
6
7
8
9
10
11
12
13
14
15[d]
16[e]
17[f]
–
59
40
–
–
38
–
toluene
DMPU
DMPU
DMPU
80
[a] Reaction conditions: 1a (0.75 mmol), 2a (0.5 mmol), Co(acac)2
(10 mol%), ligand (20 mol%), base (2.0 equiv), solvent (1.0 mL), 608C,
16 h. [b] Yield of isolated product. [c] 10 mol% of ligand was used.
[d] Reaction run at 238C. [e] Reaction run without Co(acac)2. [f] Co-
(acac)3 (10 mol%). acac=acetyl acetonate, dppe= 1,2-bis(diphenyl-
phosphino)ethane, Cy=cyclohexyl, DMPU=1,3-dimethyl-3,4,5,6-tetra-
hydro-2-pyrimidinone, IPrH=N,N-bis(2,6-diisopropylphenyl)imidazo-
lium, IMesH=N,N-bis(mesityl)imidazolium, LiHMDS=lithium hex-
amethyldisilazide, NMP=N-methyl-2-pyrrolidone, sIPrH=N,N-bis(2,6-
diisopropylphenyl)imidazolinium, sIMesH=N,N-bis-
Scheme 2. Cobalt-catalyzed direct arylations with aryl sulfamates 2.
strategies that merge directed ortho metalation (DoM) and
À
C H bond functionalization.
Likewise, heteroarenes 5 served as valuable substrates for
the cobalt-catalyzed direct arylation with aryl sulfamate 2g
and carbamates 4 (Scheme 4). Indeed, mono-N-substituted
indoles 5 were selectively arylated at the C2 position, which
allowed for the synthesis of, among other products, sterically
encumbered heterobiaryl 6bd, a feature that should prove
(mesityl)imidazolinium.
deactivated for an oxidative addition, aryl sulfamates 2 were
effectively converted, even when bearing sterically hindered
ortho substituents. Moreover, various pyridyl-substituted
arenes chemoselectively provided the desired mono-arylated
products 3.
À
instrumental for future applications to asymmetric C H bond
arylations.
The cobalt catalyst was not restricted to the use of
Remarkably, the inexpensive cobalt catalyst also enabled
sulfamates 2 as electrophiles, but also allowed for the first C
direct benzylation[22–24] reactions on indoles 5 (Scheme 5).
À
À
H bond arylations of arenes with widely accessible aryl
carbamates 4 (Scheme 3). Both electron-rich carbamates and
functionalized, electron-deficient aryl carbamates were con-
verted with remarkably high catalytic efficacy, even at
ambient temperature (3aa). Furthermore, both arenes with
electron-donating substituents and arenes with electron-with-
drawing substituents delivered the desired products 3 in high
yield. A variety of different pyridyl-directing groups could be
employed to ensure site-selectivity, as could a less electron-
donating 2-pyrimidyl-substituent (3ha). As to the reaction
mechanism, an intramolecular competition experiment[13a]
with meta-fluoro-substituted arene 1i site-selectively fur-
nished biaryl 3ia through functionalization of the kinetically
Indeed, the Csp2 Csp3 bond formation was realized with benzyl
phosphate 7 under remarkably mild reaction conditions,[25]
that is, at ambient temperature.
Considering the unique reactivity of the cobalt catalyst,
we became interested in probing its mode of action. To this
end, intermolecular competition experiments between aryl
sulfamates 2 and carbamates 4 revealed the latter to display
a significantly higher inherent reactivity (Scheme 6a,b) and
electron-deficient carbamates were preferentially converted
(Scheme 6c).
A direct arylation with aryl sulfamate 2a in the presence
of one equivalent of 2,2,6,6-tetramethyl-1-piperidinyloxyl
(TEMPO) led to the formation of desired product 3aa in
a yield of 68%. This result is comparable to the that obtained
in the absence of the radical scavenger (Table 1, entry 8). This
finding suggests that a radical reaction mechanism in the
À
more acidic C H bond. Moreover, aryl carbamates 4h and 4i,
which are functionalized with sterically hindered substituents
in the ortho position, delivered the desired products 3ah and
3ai, thereby illustrating the power of aryl carbamates for
À
À
direct C H/C O arylation is unlikely, as was previously noted
2
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Scheme 5. Cobalt-catalyzed direct benzylation with phosphate 7.
Scheme 6. Competition experiments with electrophiles 2 and 4.
À
À
Scheme 3. Cobalt-catalyzed C H/C O arylations with carbamates 4.
Scheme 7. Competition experiments with different (hetero)arenes.
À
by Wang and Shi for C H bond functionalizations with
Grignard reagents.[18] Moreover, intermolecular competition
experiments with differently substituted arenes and hetero-
arenes provided strong support for a non-SEAr-type reaction
manifold (Scheme 7a).[26] Instead, the reactivity of the arene
Scheme 4. Cobalt-catalyzed direct arylation of heteroarenes 5 with aryl
carbamates 4 and sulfamates 2.
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À
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In summary, we have reported the first use of inexpensive
cobalt catalysts for direct C H bond arylation and benzyla-
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À
À
À
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À
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À
À
and the C H/C O bond arylation proved viable even at
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[17] See also: C. T. To, T. L. Chan, B. Z. Li, Y. Y. Hui, T. Y. Kwok,
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2011, 50, 1109 – 1113.
Received: March 29, 2012
Revised: June 15, 2012
Published online: && &&, &&&&
Keywords: biaryls · carbamates · cobalt · phosphates ·
.
sulfamates
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yield of isolated product.
[24] The direct arylation of substrate 1a with an aryl triflate only
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À
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groups have thus far provided only unsatisfactory results.
4
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Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Communications
Biaryl Synthesis
W. Song, L. Ackermann*
&&&& — &&&&
Cobalt-Catalyzed Direct Arylation and
À
À
Benzylation by C H/C O Cleavage with
Sulfamates, Carbamates, and Phosphates
À
À
Inexpensive cobalt catalysts enable the
first direct arylation and benzylation of
(hetero)arenes with aryl carbamates, sul-
famates, and phosphates with ample
scope. The non-radical C H/C O aryla-
tion reaction even proved viable at
ambient temperature.
Biarylsynthese
W. Song, L. Ackermann*
&&&& — &&&&
Cobalt-Catalyzed Direct Arylation and
À
À
Benzylation by C H/C O Cleavage with
Sulfamates, Carbamates, and Phosphates
Preiswerte Cobalt-Katalysatoren ermçgli-
chen die erste direkte Arylierung und
Benzylierung von (Hetero)arenen mit
einer Vielzahl von Arylcarbamaten, -sul-
famaten und -phosphaten. Die nicht-
radikalische C-H/C-O-Arylierung gelang
sogar bei Umgebungstemperatur.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Biaryl Synthesis
W. Song, L. Ackermann*
&&&& — &&&&
Cobalt-Catalyzed Direct Arylation and
À
À
Benzylation by C H/C O Cleavage with
Sulfamates, Carbamates, and Phosphates
À
À
Inexpensive cobalt catalysts enable the
first direct arylation and benzylation of
(hetero)arenes with aryl carbamates, sul-
famates, and phosphates with ample
scope. The non-radical C H/C O aryla-
tion reaction even proved viable at
ambient temperature.
6
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!