Nickel-Catalyzed Cross-Coupling of Aryl Pivalates with Cyclobutanols Involving C—O and C—C Bond Cleavage?

Article abstract of DOI:10.1002/cjoc.202000319

An efficient nickel-catalyzed cross-coupling of aryl pivalates with cyclobutanols is described. The use of Ni(cod)₂/PCy₃/base as the catalytic system enables the cleavage of inert C—O bond and C—C bond under mild conditions, thus providing a facile access to γ-arylated ketones in generally good to excellent yields. This transformation is also characterized by wide substrate scope and functional group compatibility, for example, methoxy, N,N-dimethylamino, keto, ester, fluoro and TMS groups are well-tolerated during the reaction process.

Full text of DOI:10.1002/cjoc.202000319

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Nickel-Catalyzed Cross-coupling of Aryl Pivalates with Cyclobutanols involving
C−O and C−C Bond Cleavage
Authors: Yi Gan, Ninghui Zhang, Shaoxu Huang, and Yuanhong Liu *
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2020, 38, 10.1002/cjoc.202000319.
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Chinese Journal
of Chemistry
nickel catalysis, cross-coupling, aryl pivalates, cyclobutanols
Report
CJC
中
国 化 学 - An International Journal
Nickel-Catalyzed Cross-coupling of Aryl Pivalates with Cyclobutanols
involving C−O and C−C Bond Cleavage
Yi Gan,a Ninghui Zhang,a,b Shaoxu Huang,a and Yuanhong Liu a,*,
aState Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of
Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, People’s Republic of China. bDepartment of Chemistry,
Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan Province, 450001, People’s Republic of China.
Cite this paper: Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
Summary of main observation and conclusion An efficient nickel-catalyzed cross-coupling of aryl pivalates with cyclobutanols is described. The use of
Ni(cod)2/PCy3/base as the catalytic system enables the cleavage of inert C−O bond and C−C bond under mild conditions, thus providing a facile access to
γ-arylated ketones in generally good to excellent yields. This transformation is also characterized by wide substrate scope and functional group
compatibility, for example, methoxy, N,N-dimethylamino, keto, ester, fluoro and TMS groups are well-tolerated during the reaction process.
that of palladium not only due to their low cost but also because
of their high reactivity towards C-O bond oxidative addition. Since
the first report related to the activation of C–O bonds in aryl or
Background and Originality Content
Ketones are highly important structural motifs which are not
vinyl methyl ethers via nickel catalysis in 1979,[8] nickel-catalyzed
reactions have attracted much attention in the transformation of
C−O electrophiles.[9] Although much progress has been achieved,
most of the studies concentrate on the use of relatively reactive
aryl sulfonates such as triflates, mesylates or tosylates as the
coupling partners, the employment of the less reactive aryl
carboxylates[10] is far less developed because it poses formidable
challenges such as high activation barrier for the aryl C−O bond
cleavage (106 kcal/mol for the aryl acetate)[7] and the
site-selectivity issue between the aryl C−O bond and carbonyl C−O
bond (Scheme 1, a vs b). Nevertheless, through the judicious
choice of the catalysts, ligands and other reaction conditions, aryl
carboxylates have recently been used successfully to react with
organoboronic reagents,[11] organozinc reagents,[12] silylboranes,[13]
amines,[14] P−H compounds[15] and ketones[16] etc. under nickel
catalysis. However, nickel-catalyzed cross-coupling reactions of
these “inert” O-based electrophiles with cyclobutanols have not
only widespreadly present in organic compounds but also can be
conveniently transformed to other functional groups. Generally,
α-substituted ketones can be synthesized by electrophilic
substitution of the ketone enolates or metal-catalyzed
α-functionalization of carbonyl compounds.[1] β-Substituted
ketones can be prepared by Michael addition to α,β-unsaturated
ketones etc.[2] Recently, the catalytic ring-opening coupling of
tert-cyclobutanols has proven to be promising protocols for the
construction of γ-substituted ketones.[3] The C−C bond cleavage of
cyclobutane derivatives is prone to occur due to the strain energy
(26.3 kcal/mol for unsubstituted cyclobutane)[4]. There are two
major pathways for the cleavage of C−C bonds in cyclobutanols: (a)
transition metal such as palladium or rhodium-catalyzed
ring-opening of cyclobutanols via β-carbon elimination;[5] (b)
oxidative ring-opening of cyclobutanols via β-carbonyl radical
intermediates.[6] In 1999, Uemura and co-workers reported a
Pd-catalyzed arylative ring-opening of cyclobutanols using aryl
bromides as the coupling reagents leading to γ-arylated
ketones.[5a] However, this reaction was limited to 3-substituted or
3,3-disubstituted cyclobutanols in order to avoid the β-hydride
elimination of the alkyl-Pd intermediates. In 2012, Martin et al.
described a Pd-catalyzed coupling of cyclobutanols with aryl
been reported.[17] Herein, we report
a
nickel-catalyzed
cross-coupling of aryl pivalates with cyclobutanols for the
synthesis of γ-arylated ketones via inert C−O and C−C bond
cleavage under milder reaction conditions (50-80 oC).
o
chlorides at 110 C, in which a bulky and electron-donating ligand
played a key role in facilitating the oxidative addition of the C−Cl
bond and inhibiting the β-hydride elimination.[5d] However,
hazardous halogen-containing waste was generated by using
these electrophiles.
Noticeably, phenol-derived electrophiles are more attractive
coupling partners compared with aryl halides due to their low
toxicity and readily availability. However, the transformations of
phenol derivatives are highly challenging owing to the high
dissociation energy of the C–O bond.[7] In this context,
nickel-based catalyst systems are more attractive compared with
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First author et al.
Report
Scheme 1 Metal-catalyzed ring-opening/coupling of cyclobutanols with aryl
Table 1 Optimization of the Reaction Conditions
electrophiles
5 mol%
Ni(cod)2
.
ligand
base
OH
Ph
emura e
a
l
U
t
OPiv
O
a
Pd2 db 3/BINAP
(
)
+
R2
R3
R1
R1
solvent, 50 oC 12 h
,
K2CO3
Ph
r
+
r
B
r
A
A
,
100 o
R2
1a
2a
3a
oxane
di
equiv)
equiv)
(1.0
R3
(1.2
O
H
C
O
O
yield (%)a
entry
base
solvent
.
ligand (mol%)
(equiv)
ar n e
ti
a
M
t
l
PCy2
PCy2
c
an
d
Pd OA 2/Lig
(
)
LiOtBu
(1.2)
LiOtBu
PBu
H
H
R1
toluene
toluene
toluene
toluene
17
3
1
2
t
3 (10)
a
u
R1
N O B
,
o uene
t l
+
r
A
r
A
•
C
l
110 o
C
PPh
2HBF4
3 (10)
(1.2)
O
H
an
d
Lig
3
4
LiOtBu
(1.2)
15
36
PCyPh2 (10)
s wor
:
k
Thi
LiOtBu
a
b
Ph
(10)
PCy2
(1.2)
R1
.
R2
H
R1
R
O
ca
t Ni
LiOtBu
(1.2)
LiOtBu
87
2
R3
+
PCy
toluene
toluene
toluene
toluene
5
R3
3 (10)
-
R2
,
50 80 o
C
o uene
t l
O
O
H
O
6
dppb (5)
(1.2)
-
-
-
-
ow cos n c e as e ca a
s
ner
on c eava e
t C O b
s
it
e se ec
v
o
on s
d
LiOtBu
(1.2)
l
t
i k th ly t
l
t
i
d
l
g
l
ti ity f C O b
7
5
dppf (5)
8
LiOt
0
Bu
dcype (5)
(1.2)
(1.2)
(1.2)
9b
10
PCy
toluene
toluene
25
5
LiOtBu
LiOtBu
3 (10)
-
c
Results and Discussion
PCy
11
12
13
14
15
16
NaOtBu
KOtBu
toluene
toluene
toluene
toluene
hexane
THF
37
10
15
37
61
37
3 (10)
(1.2)
We began our investigation by examination of the reactivity
of naphthalen-2-yl pivalate (1a) with 1-phenylcyclobutan-1-ol (2a),
and the results were shown in Table 1. To our delight, 17% of the
desired cross-coupling product 3a was detected when PBu3 was
used as ligand in the presence of 5 mol% Ni(cod)2 as the catalyst
and 1.2 equiv LiOtBu as the base. This result encouraged us to
further screen different ligands. Unfortunately, monodentate
ligands such as PPh3 or PCyPh2 provided 3a in only 3-15% yields
(entries 2-3). Higher yield of 3a (36%) could be observed using
PCy2Ph as the ligand (entry 4). Pleasantly, the electron-rich and
bulky ligand PCy3, which was widely used in the inert C−O bonds
activation and functionalization, generated the desired product
3a efficiently in 87% yield (entry 5). Further ligand screening
revealed that bidentate ligands such as dppb and dppf were
ineffective for this reaction (entries 6-7). The use of dcype, which
has been shown to be an active ligand in Ni-catalyzed C−H/C−O
coupling of azoles with aryl pivalates,[18] failed to promote this
coupling (entry 8). Considering the high yield of the product
obtained using PCy3 as the ligand, other reaction parameters
were evaluated in the presence of PCy3. Ni(acac)2 resulted in
lower conversion to 3a (entry 9). Attempt to generation of Ni(0)
species from Ni(PCy3)2Cl2 and a reductant (Zn) failed to catalyze
this transformation (entry 10). It was found that inorganic bases
such as NaOtBu or KOtBu had a deleterious effect on the reaction
efficiency, affording 3a in low yields (10-37%). The results
suggested that the Li+ counter ion may play an important role for
this reaction (entries 11-12). A comparison of entry 5 vs entries 13
and 14 indicated that the use of a strong base with a steric bulk
counter anion is necessary for this reaction. Other solvents were
also examined. Changing the solvent to hexane, THF, or
1,4-dioxane gave the ketone 3a in 37-61% yields (entries 15-17).
However, changing the solvent to CH3CN failed to give the
PCy
3 (10)
(1.2)
PCy
LiOMe
3 (10)
(1.2)
PCy
LiHMDS
LiOtBu
3 (10)
(1.2)
PCy
3 (10)
(1.2)
(1.2)
LiOtBu
PCy
3 (10)
LiOtBu
LiOtBu
17
18
19
20
21
PCy
47
0
1,4-dioxane
CH3CN
3 (10)
(1.2)
(1.2)
PCy
3 (10)
d
LiOtBu
PCy
87
toluene
toluene
3 (10)
(86)
(1.0)
(0.5)
LiOtBu
-
PCy
47
2
3 (10)
PCy
toluene
toluene
toluene
3 (10)
22e
0
0
LiOtBu
LiOtBu
PCy
-
3 (10)
(1.0)
(1.0)
23
aNMR yields using 1,3,5-trimethoxybenzene as the internal standard.
bUsing 5 mo% Ni(acac)2 as the catalyst. 5 mol% Ni(PCy3)2Cl2 and 20 mol%
c
Zn were used. dIsolated yield. eIn the absence of Ni(cod)2.
desired product (entry 18). Reducing the amount of LiOtBu to 1.0
equiv provided 87% yield of 3a (entry 19). However, when the
amount of LiOtBu was decreased to 0.5 equiv, the yield of 3a was
reduced rapidly (entry 20). In the absence of base, only a trace of
3a was observed (entry 21). We envisioned that the base plays a
role in the facilitating the formation of nickel alcoholates. It
should be mentioned that no desired product was observed in the
absence of Ni(cod)2 or PCy3, demonstrating that nickel catalyst
and the ligand are needed for the success of this transformation
(entries 22 and 23).
With the optimized reaction conditions in hand (Table 1, entry
19), the substrate scope of this coupling reaction with respect to
various aryl pivalates was first evaluated using tert-cyclobutanol
2a as the coupling partner. To our delight, a wide range of aryl
pivalates bearing electron-donating and electron-withdrawing
substituents could be accommodated in this reaction (Scheme 2).
For example, a sterically demanding 1-naphthyl pivalate coupled
cleanly with tert-cyclobutanol 2a at 50 °C to afford 3b in 79% yield.
Naphthyl derivatives bearing methoxy, amide or ester groups
were tolerated, providing the corresponding ketones 3c-3e in
41-82% yields. Good yield was also obtained with the substrate
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Running title
Chin. J. Chem.
bearing a silyl group, which might be transformed to other
functional groups through coupling reactions (3f). Although
nickel-catalyzed reactions of aryl silyl ethers have previously been
reported,[19] the aryl−OTBS bond could be tolerated under the
present reaction conditions (3g). Phenyl pivalates, which were
proved to be more challenging electrophiles than naphthyl
pivalates in Ni-catalyzed cross-coupling via C−O bond activation,
were also proved to be good substrates. In these cases, increasing
the reaction temperature to 80 oC was required. Biphenyl
pivalates showed a high reactivity for this reaction. For example,
biphenyl 1h provided 3h in 81% yield. Biphenyl pivalates bearing a
methyl or methoxy group were also compatible to provide 3i and
might also occur. However, the reaction of aryl pivalate bearing a
benzoyl group proceeded efficiently to give 3s in 78% yield. When
the substrate bearing an ortho-substituent on the aryl ring was
employed, the desired 3t was formed in a lower yield (32%).
Next, the scope of cyclobutanols 2 was examined (Scheme 3).
The reaction of C1-aryl-substituted cyclobutanols bearing an
electron-donating group such as 4-Me, 4-OMe on the phenyl ring
worked well to give 3u and 3v in 75-88% yields. A 4-F substituent
on the phenyl ring was compatible (3w). In addition, the presence
of a sterically demanding ortho-methoxy group was also suitable,
furnishing 3x in 56% yield. Substrates bearing a 1,3-benzodioxole
or a 1,4-benzodioxan ring showed a high reactivity for this
reaction, affording 3y-3z in 87-89% yields. Coupling of
heteroaryl-substituted cyclobutanol with 1a afforded 3za in 53%
yield. Besides, alkyl-substituted cyclobutanols also coupled well
(3zb). Moreover, cyclobutanols with a C-3-substitutent such as Ph
Scheme 2 Scope of aryl pivalatesa
5 mol%
Ni(cod)2
10 mol% PCy3
1.0
LiOtBu
OH
Ph
OPiv
O
equiv
R
+
or CO2
Me group also worked well, leading to the corresponding
R
toluene, 50-80 o 12 h
C,
Ph
products 3zc-3zd in 43-91% yields.
1
2a
3
equiv)
(1.2
naphthyl pivalates
Scheme 3 Scope of cyclobutanolsa
For
O
O
O
5 mol%
Ni(cod)2
10 mol% PCy3
1.2
LiOtBu
Ph
Ph
Ph
OMe
50 o 86%
C,
50 o 79%
,
C,
50 o 79%
3a
3c
,
OH
R1
3b
,
C,
R2
OPiv
equiv
O
O
+
R
OTBS
toluene, 50 o 12 h
O
O
R1
O
C,
R2
Ph
Ph
Ph
1a
2
3
equiv)
(1.2
o
=
NHPiv
Ph
3e
3f
R
CO2
Me,
50
82%
,
C,
75%
80 o
C,
41%
50 o 70%
3g
,
C,
3d
,
SiMe3,
50 o
=
R
,
C,
O
O
O
For
phenyl pivalates
R
O
O
O
OMe
3v 75%
,
3u
88%
,
Me
MeO
Ph
Ph
Ph
o
=
3i
3j
R
Me,
77%
C,
80
,
,
80 o 81%
80 o 81%
3k
,
C,
3h
,
C,
=
R
80 o 85%
O
F,
C,
OMe
O
O
O
O
O
Ph
Ph
Ph
Me
Ph
Ph
OMe
O
3w 72%
3x
56%
,
,
F
80 o 61%
C,
80 o
72%
80 o
3n
,
C,
72%
3l
3m
,
,
C,
F
O
O
O
O
O
O
O
Ph
CO2Et
NMe2
80 o 85%
80 o 73%
80 o
3q
,
C,
71%
3o
3p
,
,
3y
, 87%
C,
C,
3z
89%
,
O
O
O
O
O
Me
O
Ph
O
Ph
Ph
Ph
80 o 52%
C,
80 o 78%
80 o 32%
C,
46%b
3zb
,
O
3za
53%
,
3r
3s
,
3t
,
,
C,
CO2Me
aIsolated yield.
O
Ph
O
3k in 77% and 81% yield, respectively. Especially, the presence of
an aryl fluoride moiety did not interfere, providing the
corresponding product 3j in 85% yield. Strikingly, less reactive aryl
pivalate possessing an electron-rich group at the para position
91%b
3zd
43%
,
3zc
,
aIsolated yield. b80 oC.
converted to ketone 3l in 61% yield. Substrate with
a
Next, the reactivity of phenol derivatives with different
protection groups was also investigated. Gratifyingly, good
product yields were achieved using 2-naphthyl triflate, mesylate
or tosylate as the substrates (Table 2, entries 1-3). Aryl sulfamate,
which shows a low reactivity towards coupling with Grignard
reagents under palladium catalyst,[20] afforded the product 3a in
76% yield (entry 4). Further studies indicated that 2-naphthyl
methylenedioxy group also showed a high reactivity (3m). Phenyl
pivalates with methyl, N,N-dimethylamino or ester groups in the
meta-position coupled well with 2a, leading to 3n-3p in 72-85%
yields. Aryl pivalate with an electron-withdrawing fluoro
substituent converted efficiently to 3q. The presence of an acetyl
group on the aryl ring resulted in moderate yield (52%) of 3r,
possibly due to that the side reactions such as ketone α-arylation
Chin. J. Chem. 2019, 37, XXX－XXX
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First author et al.
Report
carbamate (4e) showed low reactivity and the desired product 3a
was obtained in 18% yield (entry 5). When 2-naphthyl acetate 4f
was employed as the substrate, only 10% NMR yield of 3a was
obtained, accompanying with the byproduct derived from
hydrolysis of 4f (entry 6). The results indicated that the substrate
of aryl acetate is less stable in the presence of strong base than
that of aryl pivalates. Aryl methyl ether (4g) was failed to give the
desired product possibly due to the inertness of the aryl−OMe
bond toward oxidative addition to nickel complex under the
standard conditions (entry 7).
Conclusions
In summary, we have developed
a
nickel-catalyzed
cross-coupling of aryl pivalates with cyclobutanols via the
cleavage of inert C−O bond and C−C bond under mild conditions.
The method provides an efficient route to γ-arylated ketones with
wide functional group compatibility. A broad variety of aryl
pivalates or cyclobutanols are suitable for use in this catalytic
system. In addition, aryl triflates, mesylates, tosylates and
sulfamates all coupled well with cyclobutanols. Further
investigations on the coupling of cyclobutanols with other
electrophiles are in progress in our laboratory.
Table 2 Scope of phenol derivatives
5 mol%
Ni(cod)2
10 mol% PCy3
1.0
LiOtBu
Experimental
OH
Ph
OR
O
equiv
+
Typical
4-(naphthalen-2-yl)-1-phenylbutan-1-one (3a).
The reaction was conducted in an oven-dried screw-cap vial
(volume: mL) equipped with magnetic stir bar. In
procedure
for
the
synthesis
of
toluene, 50 oC 12 h
,
Ph
4
2a
3a
equiv)
entry
1
(1.2
yield(%)a
R
8
a
a
nitrogen-filled glove box, 1-phenylcyclobutan-1-ol (44.5 mg, 0.3
mmol), naphthalen-2-yl pivalate (82.2 mg, 0.36 mmol), LiOtBu
(24.0 mg, 0.3 mmol), Ni(cod)2 (4.1 mg, 0.015 mmol), PCy3 (8.4 mg,
0.03 mmol) and toluene (3 mL) were added sequentially to a
screw-cap vial. The vial was sealed with a screw cap featuring a
PTFE/silicone septum and taken outside the glove box. The vial
87
80
73
76
18
10b
4a
Tf
(
)
4b
2
3
4
5
6
Ms
Ts
(
)
4c
(
)
4d
SO2NMe2
(
)
4e
CONMe2
(
)
o
4f
Ac
(
)
was immersed into an oil bath preheated at 50 C. After stirring
0b
4g
7
Me
for 12 h, the mixture was cooled down to room temperature,
filtered through a short pad of silica gel and washed with ethyl
acetate. The organic solvent was evaporated under the reduced
pressure and the residue was purified by column chromatography
on silica gel (eluent: petroleum ether/ethyl acetate = 50/1) to
afford the desired product 3a in 86% yield (70.5 mg) as a white
(
)
aIsolated yield. bNMR yields using 1,3,5-trimethoxybenzene as internal
standard.
Based on the previous reports,[5a,21] a plausible reaction
mechanism is proposed as depicted in Scheme 4. Initially,
oxidative addition of aryl pivalate to Ni(0) species gives an
arylnickel(II) intermediate 5. Subsequently, a ligand exchange
between 5 and cyclobutanol in the presence of a base occurs to
give a nickel(II)-alcoholate 6, which is followed by β-carbon
elimination to produce an alkylnickel complex 7. Finally, reductive
elimination of 7 delivers the γ-arylated ketones 3 and regenerates
the Ni(0) species.
o
1
solid. M.p.: 83.2-84.4 C. H NMR (400 MHz, CDCl3): δ 2.11-2.19
(m, 2H), 2.85 (t, J = 7.6 Hz, 2H), 2.96 (t, J = 7.0 Hz, 2H), 7.33 (d, J =
8.4 Hz, 1H), 7.37-7.44 (m, 4H), 7.49 (t, J = 7.6 Hz, 1H), 7.61 (s, 1H),
7.74-7.79 (m, 3H), 7.88 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz,
CDCl3): δ 25.37, 35.17, 37.50, 125.11, 125.85, 126.50, 127.20,
127.35, 127.53, 127.91, 128.44, 131.96, 132.86, 133.49, 136.84,
139.09, 199.99. IR (neat): 3055, 2953, 2888, 2846, 1681, 1597,
1576, 1449, 1370, 1330, 1258, 1199, 977, 846, 822, 748, 732, 689
cm-1. HRMS (ESI) for C20H19O [M+H]+: calcd 275.1430, found
275.1439.
Scheme 4 Possible Reaction Mechanism
O
r
A
r
v
Pi
O
1
A
LnNi 0
( )
R
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
3
re uc ve
ox a ve
id ti
d
ti
e m na on
li ti
a
dditi
on
i
r
A
r
A
O
LmNi II
( )
LmNi II
( )
Acknowledgement
R
v
Pi
O
7
5
We thank the National Key R&D Program of China
(2016YFA0202900), the Strategic Priority Research Program of the
Chinese Academy of Sciences (XDB20000000), Science and
Technology Commission of Shanghai Municipality (18XD1405000)
for financial support.
R
-
H
O
car on
b
+
ase
b
β
e m na on
li ti
2
i
r
A
an exc an e
lig
d
h
g
R
LmNi II
( )
O
6
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Running title
Chin. J. Chem.
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© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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First author et al.
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(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
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Chin. J. Chem. 2019, 37, XXX－XXX
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Running title
Chin. J. Chem.
Entry for the Table of Contents
Page No.
Nickel-Catalyzed
Pivalates with Cyclobutanols involving C−O and
C−C Bond Cleavage
co
Ni
d
P
y
2/ C
3
H
(
)
O
,
O
t
u
B
Cross-coupling
of
Aryl
O
u
B
R3
t
O
Li
R2
R1
r
A
+
R1
r
A
-
O
o
t l
5
0 80 C R2
o uene
R3
,
=
H Ph
,
=
R2
lkyl R
3
ar or a
yl
e
M
CO2
;
-
-
-
w
n
i k l
ner
o
cos c e as e ca a
s
an
on c eava e
l
t
th
r u
t ly t
i
t
d
b
d
l
C O
C C
g
w
un
n
m reac on con ons
ild ti
e
c o a
o
co a
m
id
f
ti
l
p
p tibility
diti
g
An efficient nickel-catalyzed cross-coupling of aryl pivalates with cyclobutanols is described. The
use of Ni(cod)2/PCy3/base as the catalytic system enables the cleavage of inert C−O bond and C−C
bond under mild conditions, thus providing a facile access to γ-arylated ketones in generally good
to excellent yields. This transformation is also characterized by wide substrate scope and
functional group compatibility, for example, methoxy, N,N-dimethylamino, keto, ester, fluoro and
TMS groups are well-tolerated during the reaction process.
Yi Gan, Shaoxu Huang and Yuanhong Liu
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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This article is protected by copyright. All rights reserved.