Cobalt-Catalyzed Olefinic C-H Alkenylation/Alkylation Switched by Carbonyl Groups

Article abstract of DOI:10.1021/acs.orglett.9b02717

The first cobalt-catalyzed cross-couplings between olefins has been demonstrated to provide C(alkenyl)-H alkenylation and alkylation products, using complex [Cp?Co(CO)I₂]. While coupling partner acrylates afforded conjugated dienoates, α,β-unsaturated ketones led to γ-alkenyl ketones completely, representing a switchable C-H functionalization controlled by different carbonyl groups.

Full text of DOI:10.1021/acs.orglett.9b02717

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Cobalt-Catalyzed Olefinic C−H Alkenylation/Alkylation Switched by
Carbonyl Groups
Tingyan Li, Cong Shen, Yaling Sun, Jian Zhang,* Panjie Xiang, Xiunan Lu, and Guofu Zhong*
College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 311121, China
S
* Supporting Information
ABSTRACT: The first cobalt-catalyzed cross-couplings be-
tween olefins has been demonstrated to provide C(alkenyl)−
H alkenylation and alkylation products, using complex
[Cp*Co(CO)I2]. While coupling partner acrylates afforded
conjugated dienoates, α,β-unsaturated ketones led to γ-alkenyl
ketones completely, representing a switchable C−H function-
alization controlled by different carbonyl groups.
Recently, the addition of a C−H bond across an inert alkene
has become an important method to realize direct C−H
alkylation, because of attractive features such as byproduct-free
properties and greater availability of alkenes than alkyl halides.6
Although remarkable progress have been made on aromatic
C−H alkylation using alkyl halides or alkenes,6 olefinic C−H
alkylation has still remained undeveloped,7 especially alkenyl
C−H alkylation using alkenes.6,8 Toste and Bergman
previously reported an intramolecular cross-coupling of alkenes
mediated by the [CpCo(NO)2] complex.8a However, there is
still no intermolecular cross-coupling of alkenes via cobalt
catalysis (see Scheme 1a).
irect C−H alkenylation such as Heck reaction is a
Dpowerful synthetic method to form new carbon−carbon
bonds; thus, it is highly desirable in pharmaceutical and
materials chemistry.1 In particular, the oxidative olefinic C−H
alkenylation reactions provided an attractive access toward the
preparation of conjugated dienes with atomic economy.2−4
Two strategies can be used to realize these cross-coupling of
alkenes. One is originated by alkenyl-Pd intermediates to form
(E,E)-conjugated dienes,3 and the other is the functionality-
directed olefinic C−H alkenylation to produce (Z,E)-
butadienes via a cyclometalation event (see Scheme 1a).4
However, one limitation is that only noble metals, such as Rh,
Ru, and Pd, have been utilized in olefinic C−H alkenylation,
and there is still no example by the usage of inexpensive first-
row transition-metal catalyst, such as rather environmentally
benign cobalt complexes.5
Despite the vast majority of catalyzed C(sp2)−H function-
alizations achieved by precious second- and third-row
transition metals, the focus has shifted to the use of
inexpensive and Earth-abundant first-row transition metals,
such as rather environmentally benign cobalt.5,9,10 Remarkable
progress has been made in cobalt-catalyzed C−H activation,
and it is urgent to extend the olefinic C−H alkenylation/
alkylation to cobalt catalysis for the complementary substrate
scope and reaction type, as well as new opportunities to
develop ligand-controlled and site-selective/stereoselective C−
H transformations.9−11 Unfortunately, examples on cobalt-
catalyzed olefinic C−H activation remain scarce, most of which
were restricted to C−H activation/annulations to provide
heterocycles.11 Although our group has made progress in
transition-metal-catalyzed olefinic C−H activation using Rh, Ir,
or Ru complexes,4g−j we are still curious about the reactivity
and selectivity of their lighter congeners such as inexpensive
cobalt. Herein, we disclose the first Co-catalyzed regioselective
and stereoselective cross-coupling of alkenes, leading to
dienoates and γ-alkenyl ketones. The carbonyl group, ester
or ketone, plays a key role in the switchable C(alkenyl)−H
alkenylation and alkylation (see Scheme 1b).
Scheme 1. Catalytic C(alkenyl)−H Alkenylation/Alkylation
Received: August 2, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02717
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a b
,
The amide group has been widely utilized in pharmaceutical
chemistry, as well as directed C−H activation, and we tested
the cross-coupling between acrylamide 1a and acrylate 2a,
using robust Cp*Co(III) cobalt complex as a catalyst.9,10
Although [Cp*Co(CO)I2] combined with AgOAc led to no
product, the addition of AgSbF6 (40 mol %) greatly promoted
the reaction, producing 1,3-diene 3aa in 51% yield (see Table
1, entries 1 and 2). Representative silver salts, such as AgOTf,
Scheme 2. Scope of Alkenyl C−H Alkenylation
a
Table 1. Condition Optimization
b
entry
additive
oxidant
solvent
yield (%)
1
2
3
4
5
−
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
Ag2CO3
Cu(OAc)2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
MeOH
MeCN
DCM
CHCl3
DME
DCE
0
51
21
49
31
60
39
43
15
44
0
AgSbF6
AgOTf
AgNTf2
AgBF4
c
6
AgSbF6/AcOH
AgSbF6/PivOH
AgSbF6/HCOOH
AgSbF6/AcOH
AgSbF6/AcOH
AgSbF6/AcOH
AgSbF6/AcOH
AgSbF6/AcOH
AgSbF6/AcOH
AgSbF6/AcOH
AgSbF6/AcOH
c
7
c
8
c
9
c
10
11
12
13
c
c
0
c
40
58
49
0
c
14
c
15
cd
,
16
a
Reaction conditions 1 (0.2 mmol), 2 (0.4 mmol), [Cp*Co(CO)I2]
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [Cp*Co(CO)-
I2] (10 mol %), additive (40 mol %), oxidant (2.5 equiv), in a solvent
(10 mol %), AgSbF6 (40 mol %), AcOH (40 mol %), AgOAc (2.5
equiv), in DCE (1 mL) at 60 °C, 16 h. Isolated yields.
b
b
c
(1 mL) at 60 °C, 16 h. Isolated yields. Carboxylic acid (40 mol %)
and AgSbF6 (40 mol %) were used. Co(OAc)2 (10 mol %) was used
d
instead of [Cp*Co(CO)I2]. [Legend: DME = 1,2-dimethoxyethane,
DCE = 1,2-dichloroethane, and DCM = dichloromethane.]
tetrahydrofurfuryl alcohol derivated acrylate also converted
well and led to moderate yield (3ag). Unfortunately, phenyl
vinyl sulfone only exhibited limited reactivity (3ah). Differ-
ently N-substituted acrylamides were further investigated.
While secondary amides bearing methyl or isopropyl produced
1,3-diene in good yields, tertiary amide such as pyrrolidine
amide 1d led to moderate yield. Installation of a phenyl ring
and long aliphatic chain to the α-position of acrylamides also
reacted, and the corresponding dienes 3ed and 3fd were
isolated in 43% and 64% yields, respectively. Some other
unsuccessful substrates included acrylamides bearing N−OH,
N-OMe, and N-Ts substituents.
Electron-deficient alkene such as vinyl ketones 4 were also
examined as coupling partners. Interestingly, vinyl ethyl ketone
4a reacted well with acrylamide 1a to provide alkylation
product 5aa in 65% yield under the optimal conditions
(Condition A), without the formation of 1,3-diene 3aa (eq 1):
AgNTf2, and AgBF4, have been screened, but none of them
improved the reaction (see Table 1, entries 3−5). Interestingly,
the addition of acetic acid further improved the C−H
alkenylation, leading to 3aa in 60% yield with complete
(Z,E)-configuration (Z,E/Z,Z > 99/1), supporting a chelation-
assisted vinylic C−H activation via cyclometalation.4,10 (see
Table 1, entry 6). However, other carboxylic acids, such as
PivOH and HCOOH, exhibited decreased efficacy (see Table
1, entries 7 and 8). Different metal oxidants such as Ag2CO3 or
Cu(OAc)2 were examined, but neither of them provided
satisfactory results (see Table 1, entries 9 and 10). Moreover,
replacing the DCE with other solvents, such as methanol
(MeOH), acetonitrile (MeCN), dichloromethane (DCM),
CHCl3, or 1,2-dimethoxyethane (DME) failed to further
improve the coupling reaction (see Table 1, entries 11−15).
Finally, simple cobalt complexes such as Co(OAc)2 did not
catalyze the cross-coupling (see Table 1, entry 16).
Next, we turned to examining the scope of substrates
acrylamides 1 and alkenes 2. As shown in Scheme 2, a wide
variety of acrylates 2 reacted well with N-benzyl methacryla-
mide 1a to provide conjugated diene derivatives successfully,
and phenyl acrylate reacted best (3aa−3af). Notably,
B
DOI: 10.1021/acs.orglett.9b02717
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Letter
The C−H alkylation is redox-neutral and it is supposed to
proceed via a proto-demetalation step-involved mechanism.
Therefore, the optimization was performed without AgOAc,6,7
leading to γ-alkenyl ketone 5aa in 75% yield (Condition B).
Consequently, various acrylamides were employed to react
with unsaturated ketones to construct γ-alkenyl ketones
(Scheme 3). Aromatic acrylamides bearing F, Cl, Br, or
Scheme 4. Deuterium-Labeled Experiments
a b
,
Scheme 3. Scope of Alkenyl C−H Alkenylation
a
Reaction conditions: 1 (0.2 mmol), 4 (0.4 mmol), [Cp*Co(CO)I2]
(see Scheme 4e). Parallel and competitive kinetic isotope effect
(KIE) experiments confirmed the directed alkenyl C−H
activation to be the rate-determining step (see Scheme 4f).13
Intermolecular competition experiments between acryla-
mides 1j and 1i under Conditions A and B were performed to
gain some preliminary understanding of the reaction
mechanisms. Both experiments showed that the electron-rich
alkene reacts preferentially, thereby exhibiting an electrophilic
C−H activation (see Scheme 5).4,14
Plausible catalytic mechanism is presented in Scheme 6.
First, AgSbF6-abstracted halide from the [CoCp*(CO)I2]
complex in the presence of acetate, leading to a monocationic
and catalytically active species [Cp*Co(III)(OAc)]+ (I). Next,
Co(III)-O chelation-assisted9,10 vinyliv C−H bond cleavage
(10 mol %), AgSbF6 (40 mol %), AcOH (40 mol %), in DCE (1 mL)
at 60 °C, 16 h. Isolated yields. 2.0 mmol scale (1a, 0.35 g).
b
c
OMe were all well-converted, regardless their electron-
donating or electron-withdrawing properties (5ea−5ka,
64%−82% yields). Tertiary amide 1l and acrylamide 1m
bearing a larger aromatic naphthalene were proven to be good
substrates to react with ketones, including 1-octen-3-one 4b
(5lb, 5ma, and 5mb). Notably, gram-scale preparation of 5aa
was also successful, leading to a yield of 78%.
Treatment of acrylamides 1e or 1l under Condition A or
Condition B, in the presence of CD3COOD (10 equiv), led to
significant vinylic deuterium incorporation in both cases,
exhibiting reversible cyclometalation events (see Schemes 4a
and 4b). The reaction between deuterium-labeling acrylamide
1e-d2 and acrylate 2a under Condition A provided only 3ed-d
in 23% yield, exhibiting a complete cis-C(alkenyl)-D cleavage
and alkenylation. The olefinic H/D exchange in recovered
substrate 1l-d2 supported the hypothesis that the olefin
insertion was competitive with the reversibility of the C−H
activation step (see Scheme 4c). Deuterium-labeling acryl-
amide 1e-d2 was also reacted with ketone 4a under conditions
B, but no olefinic H/D exchange to recovered substrate 1l-d2
was observed, exhibiting that the alkylation step is much faster
to outcompete the reversibility of the C−H cleavage step (see
Scheme 4d). If CD3COOD is used instead, H/D exchange in
the α-position of ketone in product 5la was observed,
supporting a keto/enol like isomerization involved mechanism
Scheme 5. Competition Experiments
C
DOI: 10.1021/acs.orglett.9b02717
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Letter
Scheme 6. Proposed Mechanisms
Guofu Zhong: 0000-0001-9497-9069
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge National Natural Science Founda-
tion of China (NSFC) (Nos. 21502037 and 21672048),
Natural Science Foundation of Zhejiang Province (ZJNSF)
(No. LY19B020006) and the Pandeng Plan Foundation of
Hangzhou Normal University for Youth Scholars of Materials,
Chemistry and Chemical Engineering for financial support.
G.Z. acknowledges a Qianjiang Scholar award from Zhejiang
Province, China.
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In summary, the first Co-catalyzed cross-couplings between
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complexes [Cp*Co(CO)I2], leading to regioselective and
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ketones produced C−H alkylation products by proto-
demetalation. Further explorations on the cobalt-catalyzed
C−H functionalizations are underway in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02717.
Experimental procedures and spectral data for all new
compounds (PDF)
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Loh, T.-P. Stereo- and Chemoselective Cross-Coupling between Two
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AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: zhangjian@hznu.edu.cn (J. Zhang).
*E-mail: zgf@hznu.edu.cn (G. Zhong).
ORCID
Jian Zhang: 0000-0001-8734-3003
D
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Letter
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