Highly chemoselective cobalt-catalyzed biaryl coupling reactions

Article abstract of DOI:10.1039/c2sc21667a

A practical cobalt-catalyzed hetero-biaryl coupling reaction between aryl chlorides and arylmagnesium halides with unprecedented selectivity has been developed. The protocol utilizes 1 mol% of cheap Co(acac)₃ as pre-catalyst and effects clean reactions of deactivated chlorostyrenes with only 1.1 equiv. of the Grignard reagent under mild conditions (30 °C, 5-30 min). Highly chemoselective reactions were realized even in the presence of activated bromoarenes. The olefin substituent facilitates the activation of the C-Cl bond by coordination to the catalyst. Kinetic studies indicate the operation of an arylcobaltate(i) catalyst species. Catalyst formation during the induction period was studied in the presence of cobalt(iii), (i), and (-i) pre-catalysts. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c2sc21667a

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Highly chemoselective cobalt-catalyzed biaryl coupling
reactions†
Cite this: Chem. Sci., 2013, 4, 776
ab
Samet Gulak, Ondrej Stepanek,bc Jennifer Malberg,d Babak Rezaei Rad,d
¨
c
d
ab
*
Martin Kotora, Robert Wolf and Axel Jacobi von Wangelin
A practical cobalt-catalyzed hetero-biaryl coupling reaction between aryl chlorides and arylmagnesium
halides with unprecedented selectivity has been developed. The protocol utilizes 1 mol% of cheap
Co(acac)3 as pre-catalyst and effects clean reactions of deactivated chlorostyrenes with only 1.1 equiv. of
the Grignard reagent under mild conditions (30 ꢀC, 5–30 min). Highly chemoselective reactions were
realized even in the presence of activated bromoarenes. The olefin substituent facilitates the activation
of the C–Cl bond by coordination to the catalyst. Kinetic studies indicate the operation of an
arylcobaltate(I) catalyst species. Catalyst formation during the induction period was studied in the
presence of cobalt(III), (I), and (ꢁI) pre-catalysts.
Received 4th October 2012
Accepted 22nd November 2012
DOI: 10.1039/c2sc21667a
www.rsc.org/chemicalscience
rubbers, and resins.3 By virtue of their synthetic versatility,
olens are one of the most valuable functional groups with
1 Introduction
Unsymmetrical biaryls (hetero-biaryls) are a fascinating class of
molecules due to their rod-like structure with co-existing
aromatic rigidity and rotational exibility. They nd widespread
applications as building blocks for organic materials, ne
chemicals, and pharmaceuticals.1 Transition metal-catalyzed
cross-coupling reactions constitute the most prominent and
elegant method to assemble a biaryl motif starting from two
discrete aryl entities. The vast majority of such reactions have
been realized with aryl bromides and iodides as electrophilic
reactants under palladium or nickel catalysis.2 Continuing
research efforts are mainly devoted to the utilization of less
reactive substrates, the identication of reaction conditions
that tolerate various functional groups, and the development of
cheaper catalyst systems. Chlorostyrenes are cheap and easily
accessible electrophiles that contain two versatile functional
groups: a rather stable C–Cl moiety and an olen substituent. In
the context of organic synthesis, they constitute an under-
utilized class of substrates. This is even more astonishing when
considering that chlorostyrenes are easily prepared from benz-
aldehydes or chloroarenes and constitute important interme-
diates in the industrial manufacture of functional polymers,
many efficient transformation available. However, olens can
be subject to unwanted side reactions under the mostly basic
and nucleophilic conditions of cross-coupling reactions.4 We
have recently reported the rst iron-catalyzed biaryl coupling
with simple chlorostyrenes.5 The underlying substrate activa-
tion exerted by vinyl substituents exceeds that of conventional
electron-withdrawing groups (CO2R, CN, pyridyl, CF3, etc.)
without the implication of competing side reactions by nucle-
ophilic attack at the electrophilic substituent. Similar to iron,
only a handful of cobalt-catalyzed biaryl coupling reactions with
good selectivity have been reported.6 However, they mostly have
one of the following limitations: use of highly activated elec-
trophiles (i.e. heteroaryl halides, halophenones), elevated
ꢀ
temperatures (60–80 C), high catalyst loadings (>10 mol%), a
special catalyst/ligand system (CoF2/N-heterocyclic carbene), or
a large excess of Grignard reagent (>2 equiv.). Here, we present a
study on practical hetero-biaryl coupling reactions of deacti-
vated chlorostyrenes and various arylmagnesium halides with
only 1 mol% catalyst loading and no excess of Grignard reagent.
ꢀ
The mild conditions (30 C, 5 min) tolerate various functional
groups and allow chemoselective arylations of chlorostyrenes in
the presence of bromoarenes (Scheme 1). Mechanistic experi-
ments corroborate the facilitation of C–Cl activation by the
olen substituents and the activity of cobalt(ꢁI), cobalt(I), and
cobalt(III) pre-catalysts.
aInstitute of Organic Chemistry, University of Regensburg, Universitaetsstr. 31, 93053
Regensburg, Germany. E-mail: axel.jacobi@ur.de; Fax: +49 (0)941 943 4617; Tel: +49
(0)941 943 4802
bDepartment of Chemistry, University of Cologne, Germany
cDepartment of Organic and Nuclear Chemistry, Charles University, Prague, Czech
Republic
2 Results and discussion
2.1 Discovery of a cobalt-catalyzed cross-coupling
Building on earlier work with iron catalysts,5 we studied the
reaction of 2-chlorostyrene (1) with p-anisylmagnesium bromide
dInstitute of Inorganic Chemistry, University of Regensburg, Germany
† Electronic supplementary information (ESI) available. CCDC 884015. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c2sc21667a
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Scheme 1 Cobalt-catalyzed biaryl coupling with olefin activation.
(ArMgBr) to hetero-biaryl 2 (Table 1). Co(acac)3 (cobalt(III) acety-
lacetonate) and cobalt(II) chloride were equally active pre-cata-
lysts (entries 1, 2). Fe(acac)3 gave slightly lower conversion aer 3
h but exhibited high product selectivity.5 However, reactions with
Co(acac)3 were much faster and displayed no induction period.
Aer 1 min, 70% conversion was achieved (Fig. 1). The high
activity of the cobalt catalyst is mirrored by a turn-over frequency
(TOF) of >7600 hꢁ1 (vs. 850 hꢁ1 for Fe(acac)3). Palladium(II)
chloride and nickel(II) chloride showed neglectable activity
(entries 3 and 4, Table 1). Further experiments resulted in an
optimized set of reaction conditions (THF/NMP (10 : 1 v/v), 30 ꢀC,
1 h) without the requirement to use a large excess of Grignard
reagent as in most literature protocols.6,7 Slow addition of only 1.1
equiv. of ArMgBr (0.5 M in THF) over 20 min to a solution of 1 and
only 1 mol% catalyst afforded hetero-biaryl 2 in up to 87% yield
(entry 10). A direct reductive coupling of 1 and 4-bromoanisole
with stoichiometric magnesium and catalytic Co(acac)3 fared
poor.6e,8
Fig. 1 Reaction rates (1 mol% M(acac)3, 1.1 equiv. ArMgBr (over 2 s), THF/NMP,
30 ꢀC; Ar ¼ p-anisyl. GC yields of 1 and 2 in [%].
bromides manifested the postulate that vinyl groups strongly
activate aryl chlorides in the presence of cobalt catalysts.9 Very
good yields have been obtained with various ortho-, meta-, and
para-chlorostyrenes (Table 2). The high regioselectivity in reac-
tions of 2,4-dichlorostyrene is noteworthy. Obviously, ortho-
substituted chlorostyrenes are most reactive due to the close
proximity of directing group (olen) and reactive site (C–Cl
bond). With disubstituted olen groups, a slower addition of
the 0.5 M solution of the arylmagnesium halide in THF (over 40
min) was benecial. Alkoxy, alkenyl, uoro, chloro, acetal, ester,
enolate, and furan groups are tolerated under the strongly basic
and nucleophilic reaction conditions (Tables 2 and 3).
2.2 Substrate scope and chemoselectivity
Table 3 documents the effect of added functionalized arenes
on the cross-coupling selectivity of the model reaction. Clean
cross-coupling occurred with ester-bearing arylmagnesium
halide (Table 2) and in the presence of 1 equiv. methyl benzoate
(Table 3, entry 2). Free alcohols and acetophenone were
deprotonated by the Grignard reagent, but cross-coupling was
restored when employing 2.1 equiv. of ArMgBr (entries 5, 8).
Nitrobenzene was reduced to the N-arylaniline.10 Surprisingly,
bromobenzene remained untouched, while 1 showed full
conversion (entry 9). This high chemoselectivity is in stark
contrast to the general order of reactivity in cross-couplings
(ArBr > ArCl)11 and underpins the strong activating effect exer-
ted by the vinyl substituents.
Application of the optimized conditions (entry 9, Table 1) to a
series of substituted chlorostyrenes and arylmagnesium
Table 1 Selected optimization experimentsa
Entry
Deviation from above conditions
2b[%]
The (slight) steric hindrance in ortho-chlorostyrenes and a- or
b-substituted vinyl groups generally impedes polymerization and
renders the cross-coupling highly chemoselective. Another
advantage of the cobalt-catalyzed protocol is its applicability to
1
2
3
4
5
6
7
8
9
—
65
53
0 (4)
0 (7)
CoCl2
PdCl2
NiCl2
Fe(acac)3
51 (69) capricious 4-chlorostyrene (3). Mostly polymeric products were
0
ꢀC
26 (72)
36
68
76
87
observed with iron catalysts (by GPC-MS, Scheme 2).5,12 Selective
cross-coupling occurred under cobalt catalysis and polymeriza-
tion was effectively suppressed (Table 4).
w/out NMP
Slow addition of ArMgBr (20 min)
As entry 8, 1 mol% Co(acac)3
As entry 9, 1.1 equiv. ArMgBr
When subjecting 2- and 4-chlorotolane to the standard
conditions with para-anisylmagnesium bromide, only traces of
cross-coupling products and 1,1,2-triarylethylene isomers (from
carbo-metalation) were observed (<5%, Scheme 3). Furthermore,
10
a
b
NMP ¼ N-methyl-2-pyrrolidinone; Ar ¼ 4-MeO–C6H4. GC yields (in
parentheses conversion of 1 if not >95%).
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Table 2 Arylations of ortho-, meta-, para-chlorostyrenesa
Table 3 Chemoselectivity in the presence of additivesa
Hetero-biarylb
Entry
Additive
None
Yield of 2b [%]
1
2
3
4
5
6
7
8
9
89
82
FG ¼ CO2Me
CN
COMe
COMe
NO2
OH
OH
Br
22 (28)
6 (13)
81c
0 (3)d
0 (1)
69c
86
10
79
a
Ar ¼ p-anisyl. b GC yields; conversion of 1 in parentheses. c 2.1 equiv.
ArMgBr. d N-4-anisyl aniline detected by GC-MS.
Scheme 2 Fe- vs. Co-catalyzed arylation of 4-chlorostyrene (3); Ar ¼ p-anisyl; GC
yields given.
cross-coupling (<8%), while the employed chlorostyrenes were
cleanly converted to the corresponding vinylbiaryls (entries 3–
6). With strongly activated di- and triuorophenyl bromides
(entries 7, 8) signicant generation of Ar–Ar0 was observed.
a
Ar ¼ p-anisyl. b Isolated (GC) yields. c ArMgBr addition over 40 min.
2.3 Mechanistic studies
addition of 1 equiv. 1-(4-chlorophenyl)-2-phenylacetylene, 1,2- The activation of aryl halides by an olen substituent can also be
diphenylacetylene, or phenylacetylene (the last with 1.1 and 2.1 exploited with aryl bromides. Consistently, the concomitant
equiv. ArMgBr), respectively, to the model reaction of 1 and employment of 2-bromostyrene and 2-chlorostyrene (1) resulted
ArMgBr resulted in low conversion and no biaryl formation. in a slightly more rapid consumption of the bromoarene (kBr/kCl
Strong alkyne coordination is believed to prohibit productive ¼ 3.5, Scheme 4, top). Conclusive intramolecular competition
pathways.13 1-Chloronaphthalene fared also poorly (<7%).
experiments between a deactivated chloroarene (EDG ¼ –vinyl,
The high chemoselectivity observed under standard condi- –OCH2Ar) and a slightly activated bromoarene (EWG ¼ –CH2OAr)
tions (cf. entry 9, Table 3) is especially useful for organic were designed by employment of 4-(bromobenzyloxy)-2-chloro-1-
synthesis. We further studied such competition experiments by vinylbenzene derivatives under standard conditions (Scheme 4,
concomitant employment of chlorostyrenes and aryl bromides middle). Exclusive substitution of the chlorides was observed,
(Table 5).
and the corresponding benzyloxy biaryl products isolated in 69%
It becomes obvious from Table 5, that chlorostyrenes and 70% yield, respectively. This documents that the activation
constitute much more reactive substrates than aryl bromides by the vinyl group far exceeds that of a uoride substituent. The
(Ar0Br). Even activated substrates such as 1-bromo-4-uoro- pre-requisite of a conjugated styryl moiety was further proven by
benzene, 1-bromo-4-triuoromethylbenzene, and methyl the selective arylation of the 4-chlorostyrene dimer at the conju-
bromobenzoates exhibited little tendency to undergo gated terminus (Scheme 4, bottom).
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Table 4 Arylations of 4-chlorostyrene (3)a
Table 5 Cross-coupling in the presence of aryl bromidesa
Hetero-biarylb
Entry
Ar0-Br
40-R-vinylbiaryl
Yieldb [%]
1
2
4-OMe
4-H
80
82
3
4-F
76
4
5
6
7
8
9
10
4-CF3
68
2-CO2Me
4-CO2Me
3,4-F2
2,3,4-F3
4-NMe2
75c
63c
53 (33)
39 (35)
69
R ¼ OMe
F
76
a
Ar ¼ p-anisyl. b Isolated yields (GC yields in parentheses).
11
12
PhBr
4-F
69
68
a
Employment of equimolar chlorostyrene and Ar0-Br; Ar ¼ p-anisyl.
Yields of the vinylbiaryl; yield of biaryl Ar–Ar0 in parentheses if >8%.
ꢂ10% loss of Ar0Br due to carbonyl addition.
b
c
Scheme 3 Unreactive substrates (Ar ¼ p-anisyl).
The activation of olen-bearing aryl chlorides toward cross- factors (intramolecular process) are likely to contribute to the
coupling is much more pronounced than with “conventional” observed activation of aryl chlorides even when carrying elec-
electron-withdrawing groups (i.e. F, CO2Me, pyridyl).6 The tron-donor substituents (–Cl, –OR, –NR2). Competitive experi-
crucial role of the olen becomes apparent from a comparative ments with a-deuterated chlorostyrene proved the essential
study of substituents as shown in Table 6. Treatment of various olen coordination. The arylation of 4-chlorostyrene (3) dis-
chloroarenes with p-anisylmagnesium bromide (ArMgBr) – but played signicant 3-positional secondary kinetic isotope effects
(to simplify the procedure) with rapid addition of the 0.5 M of 1.32 (with Co(acac)3 and (Ph3P)3CoCl as pre-catalyst), which
Grignard solution (over 2 s) – resulted mostly in little or no attest to a rate determining olen coordination to the catalyst
conversion (<9%). Activated methyl chlorobenzoate gave merely (Scheme 5).
11% cross-coupling. Solely chlorostyrenes were converted to the
The catalytic reactions are initiated by reduction of the Co(III)
corresponding biaryls in moderate yields (entries 5, 6, 9, 11). pre-catalyst with the Grignard reagent (ArMgBr). This catalyst
These results and the chemoselective arylation in Scheme 4 pre-formation can easily be followed by visual inspection (color
(bottom) already suggest the essential role of olens for change from green to brown) and is accompanied by the
substrate activation possibly by catalyst coordination and formation of one equivalent of homo-biaryl (Ar2) per [Co] (2eꢁ-
migration along the conjugated system.14 Steric repulsion of the redox, vide infra). We thus postulate a mechanistic scenario
ortho-substituents in 2-chloro isopropenylbenzene results in a which involves a catalytically active cobalt(I) species under these
non-planar conformation which prohibits coordination of the conditions.15 We also studied catalyst formation from the
conjugated system (entry 10). It is important to note that the opposite side of the redox scale. In an effort to suppress homo-
presence of styrene or a-methylstyrene in the reactions of biaryl formation during the induction period and thereby
chlorobenzene and ArMgBr exhibited no activating effect and facilitate preparative work-up (separation of hetero-biaryl from
resulted in low cross-coupling yields (ꢂ3%, see entry 2, Table 6). homo-biaryl), we employed the anionic bis(anthracene) cobal-
The vinyl moiety of chlorostyrenes is believed to function as a tate [K(dme)2{Co(C14H10)2}] (4). The synthesis of this formal
directing group for catalyst coordination which ultimately cobalt(ꢁI) complex followed a procedure for the analogous
results in an activation of the aryl chloride toward C–Cl bond [K([18]crown-6)(thf)2)][Co(C14H10)2] and [K([2.2.2]cryptand)]
cleavage. Both, electronic (p-donating olen) and entropic [Co(C14H10)2] by Brennessel and Ellis (Scheme 6).16a The
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Table 6 Substituent effects on the arylation of aryl chloridesa
Entry
Product
Yieldb [%]
1
2
3
R ¼ H
H
CO2Me
(3)
(3)c
(11)
4
(8)
5
6
R ¼ H
68
63
Me
7
8
R ¼ F
(1)
(3)
Allyl
9
10
R ¼ H
72
(9)
Me
Scheme 4 Top: competitive ortho-halostyrene arylations; middle and bottom:
chemoselective arylations at the chlorostyrene moiety (Ar ¼ 4-anisyl). (a): 1 mol%
Co(acac)3, THF/NMP (10/1), 0.5 equiv. ArMgBr (ꢂ20 min), 30 ꢀC, 0.5 h; (b): as (a),
but with 0.9 equiv. ArMgBr.
11
R ¼ Me
66
a
Rapid addition of p-anisyl-MgBr (ArMgBr, 0.5 M in THF) over 2 s.
Isolated yields (GC yields in parentheses). In the presence of
b
c
composition of 4 was conrmed by 1H and 13C{1H} NMR
spectra. Single crystal X-ray diffraction of [K(dme)2{-
Co(C14H10)2}] (4) conrmed the h4-coordination of two anthra-
cenes (Fig. 2).16b,c
styrene or a-methylstyrene, respectively (1 equiv.).
study with cobaltate 4 lies within the observation of highly
competent stoichiometric C–Cl bond activation while catalytic
reactions are limited by the availability of very strong reductant.
Arene cobaltates have never been employed as catalysts in
cross-coupling reactions,17 although the presence of a reduced
metal center almost certainly implies activity in formal oxidative
addition events with suitable electrophiles. Furthermore,
there's a conceptual interest in p-coordinated arene complexes
of transition metals as intermediates in arene functionalization
reactions.18 Initial studies of the general reactivity of 4 toward
chloroarenes were performed with three model substrates.
Treatment of 4 with 1 equiv. 2-chlorostyrene (1), 4-chloro-a-
methylstyrene (5), or 1-chloronaphthalene (6) in the absence of
Grignard reagent rapidly afforded hydrodechlorinated arenes
aer aqueous work-up in low to moderate yields (Scheme 6).
The lower reduction selectivity of the two styrene derivatives 1
and 5 can be attributed to signicant polymer formation (GPC
analysis)12 in the presence of 1 equiv. of the anionic cobalt
complex 4. Despite the lower propensity for polymerization in
catalytic reactions, less than 7% conversion of 1-chloronaph-
thalene was observed in the presence of p-anisylmagnesium
bromide (ArMgBr) and 1 mol% Co(acac)3 or 4, respectively (see
also Scheme 3). These results testify to a rapid oxidation of the
cobalt(ꢁI) complex by the chloroarene (possibly to Co(+I))
without turn-over back to the cobalt(ꢁI) state by the Grignard
reagent. Higher oxidation states of cobalt are thus not compe-
2.4 Comparison of Co(III), Co(I), Co(ꢁI) pre-catalysts
If a catalytically active cobalt(I) species is formed from both pre-
catalysts, Co(acac)3 (by reduction with ArMgBr) and 4 (by
oxidation with Ar0Cl), similar catalytic results can be expected
(Table 7). Reactions were thus performed with Co(acac)3,
cobalt(ꢁI) complex 4, and commercially available cobalt(I)
chloride [CoCl(PPh3)3] (7)19 as pre-catalysts (1 mol%). Indeed,
similar cross-coupling selectivities were observed for Co(acac)3
and 4 despite their different formal oxidation states of +III and ꢁI.
tent in activating chloronaphthalene. The signicance of our Scheme 5 Secondary kinetic isotope effect (average of two runs).
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5 mol% catalyst loadings and incremental addition of the
Grignard reagent based on quantitative GC analyses of all
organic materials (Fig. 3). When employing 5 mol% Co(acac)3 as
pre-catalyst, no cross-coupling takes place until 10 mol%
ArMgBr have been added. When >10 mol% ArMgBr were
generated, homo-biaryl (Ar2) and, shortly aer, cross-coupling21
commenced while the styrene (Ar0–H) concentration remained
low (<2%).
These data suggest the occurrence of an initial ligand
exchange with the anionic aryl group. Subsequent reduction of
such arylcobalt(III) complexes to the Co(+I) state produces Ar2 as
oxidative by-product and triggers cross-coupling. More than 5
mol% electrons were consumed in the reduction of Co(III) until
the beginning of product formation.21 On the other hand,
Co(ꢁI) complex 4 undergoes instantaneous oxidation in the
presence of 2-chlorostyrene (1) before addition of the Grignard
reagent (see also Scheme 6). This results in the formation of ꢂ4–
7 mol% styrene (Ar0–H) due to oxidative catalyst formation. The
overall electron balance indicates a 5–7 mol% electron surplus
within the organic materials (see also Fig. 3, top), so the oper-
ation of a cobalt(0) or cobalt(I) species could be discussed.15
These quantitative results can be interpreted as indications that
catalysts of identical oxidation states – most likely Co(I) – are
operative in all three cases. This requires redox pre-formations
when Co(acac)3 and 4 are used as pre-catalysts (Fig. 3, top),
which are accompanied by (partial) loss of the ligands acac and
anthracene, respectively. The resultant cobalt species could be
stabilized by THF, NMP, olen, or aryl coordination.
Scheme 6 Synthesis of potassium bis(anthracene) cobaltate(ꢁI) 4 and stoi-
chiometric C–Cl bond activation studies.
Table 7 Comparison of Co(III), Co(I), and Co(ꢁI) pre-catalystsa
Fig. 2 ORTEP plot of 4 (ellipsoids with 40% probability; one of two crystallo-
graphically independent molecules shown; H atoms and disorder in DME mole-
ꢀ
˚
cules omitted). Selected bond lengths (A) and angles ( ): Co1–C1 2.150(4), Co1–
C2 2.005(5), Co1–C3 1.975(5), Co1–C4 2.130(5), Co1–C15 2.133(5), Co1–C16
1.978(5), Co1–C17 1.999(5), Co1–C18 2.154(4), C1–C2 1.420(6), C2–C3 1.405(6),
C3–C4 1.435(6), C15–C16 1.434(6), C16–C17 1.412(6), C17–C18 1.410(6), dihe-
dral between planes C1,C2,C3,C4/C1,C11,C12,C4 32.7(2), C1,C2,C3,C4/
C1,C11,C12,C4 29.0(2).
Entry
Chlorostyrene
[Co]
Hetero-biarylb [%]
However, phosphine cobalt(+I) complex 7 showed a slightly
different behavior, affording higher yields with 4-isopropenyl-
styrene and the 2-chlorostyrenes while signicant polymeriza-
tion was observed with 4-chlorostyrene (3). The different
oxidation states of the catalyst precursors Co(acac)3, 4, and 7
should result in different amounts of the homo-biaryl (Ar–Ar,
from oxidation of ArMgBr) and dehalogenated styrene (Ar0–H,
from reduction of chlorostyrene Ar0–Cl) as by-products. It is
important to note that reductive dimerization of chlorostyrenes
was never observed. However, quantitative analyses of the by-
products generated by redox adjustment of the pre-catalysts will
only be diagnostic of the composition and oxidation state of the
active catalyst during the induction period of the reaction.20
Therefore, we recorded kinetic proles of the cross-coupling
between 1 and p-anisyl-magnesium bromide (ArMgBr) with
1
2
3
4
5
6
Co(acac)3
4
7
Co(acac)3
4
7
78
76
88
12 (23)
13 (25)
20 (34)
7
8
9
Co(acac)3
4
7
82
76c
45c
10
11
12
Co(acac)3
4
7
69
68
79
a
b
Ar
¼
p-ansiyl.
GC yields; conversions of chlorostyrenes in
c
parentheses. Polymer formation detected by GPC.
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The notion of a catalytically active cobalt(I) complex is
further supported by the lack of an induction period and the
absence of any redox-byproducts in cross-coupling reactions
with catalyst 7 (see Fig. 3, bottom). Instantaneous product
formation upon Grignard addition was observed. Fig. 3
(bottom) illustrates the formation of the initial products in
reactions employing Co(acac)3, 4, and 7, respectively. With
catalytic Co(acac)3 and 4, cross-coupling commences only aer
Scheme 7 Order of addition in stoichiometric reactions with 7 (Ar ¼ 4-anisyl; 1
redox-adjustment of the pre-catalysts (not shown in Fig. 3, equiv. ArMgBr added in each case; yields of 2 given,).
bottom). For pre-catalyst 7, we postulate the operation of an
initial transmetalation (rather than aryl chloride activation)
based upon stoichiometric experiments which indicate the
presence of ate-complexes.15,22 When treating [CoCl(PPh3)3] (7)
with 1 equiv. 2-chlorostyrene (1) in THF/NMP solution at 20 ꢀC,
no reaction occurred (Scheme 7).23 Sequential addition of 1
equiv. ArMgBr (Ar ¼ p-anisyl) and chlorostyrene 1 gave no
conversion. Aer addition of the second equiv. ArMgBr, rapid
generation of 2 was observed in 70% yield. The reverse order of
addition (rst 1, then ArMgBr) afforded 2 in 63% yield, which
increased to 72% upon addition of a second equivalent ArMgBr.
Scheme 8 shows a plausible mechanism that involves initial
(redox) catalyst formation. Transmetalation between ArMgBr
and the cobalt(I) species affords a cobaltate complex. Rate-
determining olen coordination and activation of the
Scheme 8 Proposed mechanism involving a cobalt(I) catalyst species (L ¼
14H10, PPh3, NMP, THF; Y ¼ anionic ligand such as halide, acac, Ar).
C
chlorostyrene (formally an oxidative addition or single electron
transfer) render a diaryl complex which rapidly undergoes
elimination of the hetero-biaryl and regeneration of the cobalt(I)
catalyst. The operation of a bimetallic activation can be
excluded based upon a reaction order with respect to the cata-
lyst species of 0.85–1.02 for highly diluted catalyst
concentrations.
3 Conclusions
We have developed a practical protocol for the hetero-biaryl
coupling between deactivated aryl chlorides and aromatic
Grignard reagents in the presence of only 1 mol% Co(acac)3.
Remarkable activation of the electrophiles was observed with
olen substituents. The optimized set of reaction conditions is
operationally simple and highly sustainable (no excess of
Grignard reagent, THF, 30 ꢀC, 5–30 min). The protocol displays
a wider substrate scope and almost 10-fold catalyst activity
(>7600 vs. 850 hꢁ1 TOF) at decreased catalyst loadings (1 vs. 5
mol%) than related iron-catalyzed reactions.5 For the rst time,
chlorostyrenes bearing terminal vinyl moieties were cleanly
arylated with no detectable polymer formation under the reac-
tion conditions. The reactions display tolerance of uoro,
chloro, bromo, ester, enolate, alkoxy, amine, and furan groups.
Chemoselective cross-couplings can be executed even in the
Fig. 3 Top: cross-coupling product (Ar–Ar0) and redox by-products (Ar0–H, Ar2);
bottom: initial products of the induction periods with pre-catalysts Co(acac)3, 4,
and 7 (each 5 mol%). Ar0 ¼ 2-vinylphenyl (from 1); Ar ¼ p-anisyl (from ArMgBr). presence of activated aryl bromides. The synthesized biaryls
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contain vinyl substituents, one of the most versatile functional
groups in organic synthesis, which provide numerous oppor-
tunities for post-coupling manipulations. Well-dened cobal-
tate [K(dme)2{Co(C14H10)2}] (4) and commercial [CoCl(PPh3)3]
(7) have been employed as catalysts in cross-coupling reactions
for the rst time. Comparative studies of Co(acac)3 with 4 and 7
gave nearly identical selectivities. This constitutes a striking
argument for the utilization of the cheap and easy to handle
Co(acac)3 as pre-catalyst for the biaryl cross-coupling reactions
in this study (0.65 V per mmol (98%), 2.70 V per mmol
(99.99%)).24 Kinetic studies provided good indications of a
catalytically active cobalt(I) species. Extensions of the under-
lying mode of activation to other reactions are currently being
pursued.
Y. Ikeda, T. Nakamura, H. Yorimitsu and K. Oshima, J. Am.
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24 2011 Catalogue prices of Sigma Aldrich Co. LLC.
784 | Chem. Sci., 2013, 4, 776–784
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