Nickel-Catalyzed Allylic C(sp2)–H Activation: Stereoselective Allyl Isomerization and Regiospecific Allyl Arylation of Allylarenes

Article abstract of DOI:10.1002/ejoc.201600955

Stereoselective allyl isomerization and regiospecific allyl arylation reactions of allylarenes with a catalytic system comprising nickel(II) with an aryl Grignard reagent were studied. Both reactions are triggered by allylic internal C(sp²)–H activation by in-situ-formed Ni⁰, which is inserted into the C–H bond at the 2-position of the allyl moiety without a directing group. The isomerization of allylarene to 1-propenylarene favors the E isomer and proceeds with quantitative conversion. The arylation takes place through oxidative cross-coupling of allylarenes with excess Grignard reagent. It occurs regiospecifically at the position of C(sp²)–H activation and represents a new method for the synthesis of 1,1-disubstituted olefins. The results of deuterium labeling experiments reveal an alkenyl/alkyl mechanism involving allylic internal C(sp²)–H activation and multiple intermolecular 1,2-, 1,3-, and 2,3-hydride shifts. These methods represent new approaches to the functionalization of olefins, and the mechanistic investigations could be helpful for the discovery and design of new strategies for olefin functionalization.

Full text of DOI:10.1002/ejoc.201600955

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Accepted Article
Title: Nickel-Catalyzed Allylic C(sp2)-H Activation: Stereoselective Allyl Isomerizati-
on and Regiospecific Allyl Arylation of Allylarenes
Authors: Qiang Wu; Lanlan Wang; Rizhe Jin; Chuanqing Kang; Zheng Bian; Zhijun
Du; Xiaoye Ma; Haiquan Guo; Lianxun Gao
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201600955
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European Journal of Organic Chemistry
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Nickel-Catalyzed Allylic C(sp2)-H Activation: Stereoselective Allyl
Isomerization and Regiospecific Allyl Arylation of Allylarenes
Qiang Wu,[a, b] Lanlan Wang,[a, b] Rizhe Jin,[a] Chuanqing Kang,*[a] Zheng Bian,[a] Zhijun Du,[a] Xiaoye
Ma,[a] Haiquan Guo,[a] and Lianxun Gao[a]
Abstract: Stereoselective allyl isomerization and regiospecific allyl
arylation of allylarenes with a catalytic system comprising nickel(II)
with aryl Grignard reagent are studied. Both reactions are triggered
by allylic internal C(sp2)-H activation by in situ-formed Ni(0), which is
inserted into the C-H bond at the 2-position of the allyl without a
directing group. The isomerization of allylarene to 1-propenylarene
favors the E-isomer with a quantitative conversion. The arylation
through oxidative cross-coupling of allylarenes with excess Grignard
reagents is regiospecific at the position of C(sp2)-H activation, which
provides a new method for synthesizing 1,1-disubstituted olefins.
Investigations with deuterium labelling experiments reveal an
alkenyl-alkyl mechanism involving the allylic internal C(sp2)-H
activation and multiple intermolecular 1,2-, 1,3-, and 2,3-hydride
shifts. These results provide new approaches to olefin
functionalization and the mechanistic investigations would be helpful
for the discovery and design of new strategy for olefin
functionalization.
mechanisms are dependent on the reagents and reaction
6]
conditions.[3,
According to H/D exchange and crossover
experiments, the former functions via metal hydride addition-
elimination while the latter functions through a 1,3-hydride shift
induced by coordination of π-allyl to a metal. The metal hydride
for the addition-elimination is generated from reductive reagents
or from ligands by H-abstraction.[5c, 6, 7] No metal hydride should
be present in the π-allyl mechanism, or the alkyl mechanism will
take place instead. Recently, a few reports have presented
olefin isomerizations catalyzed with Co(II) and Fe(III) in the
presence of Grignard reagent through a 1,3-hydride shift or an
8]
unspecified mechanism.[5a,
Previously, olefin isomerizations
catalyzed by Ni(0) were carried out under aqueous conditions
showing poor-to-good E/Z selectivity, those studies proposed
that nickel hydride is generated from the aqueous medium
5f]
during the addition-elimination.[5e,
More recently, a Ni(I)-
catalyzed olefin isomerization with excellent Z-selectivity has
been published,[5g] where the hydride addition-elimination is
mediated by diphenylphosphane coordinating to Ni(I). Coversely,
Ni(0) has also been used to mediate isomerization of allylamides
through 1,3-hydride shift with poor-to-excellent E/Z selectivity
depending on the substrate structures.[9] However, no report has
ever demonstrated olefin isomerization through olefinic C(sp2)-H
activation or through the alkyl mechanism without pre-formed
metal hydride.
Arylation of allyl compounds through well-known Heck-type
cross coupling with aryl halides and triflates is an efficient path
to linear 1,2-disubstituted ethylene or branched 1,1-disubstituted
ethylene determined by regioselective formation of the C-C bond
at terminal or internal C(sp2).[10] The oxidative Heck-type cross
coupling of olefins with aryl Grignard reagents shows exclusive
regioselectivity at terminal C(sp2) to form linear olefins.[11, 12] To
the best of our knowledge, no report has been published on
oxidative cross coupling with internal C(sp2) selectivity to form
branched olefins. In most cases, oxidative cross coupling
undergoes coordinative addition of the aryl Grignard reagent to
form a complex of a transition metal and a heteroatom-
containing olefin followed by β-hydride elimination.[11] In a few
other cases, the cross coupling is enabled by transition metal-
mediated terminal olefinic C-H activation utilizing a heteroatom
in the substrate as a directing group followed by reductive
elimination.[12] Both mechanisms have been extensively
exploited for the Heck-type cross coupling of olefins with other
nucleophilic substrates, in which a heteroatom in the olefin is
essential for coordination with the transition metal.[13]
Introduction
Isomerization and functionalization of olefins are the most
simple and efficient approaches to building highly substituted
olefins in academic and industrial chemistry.[1] In this field,
allylarenes, which are a type of special olefins, have attracted
much attention for their biological activity and wide applications
for pesticide, fragrance, cosmetics, flavors, pharmaceuticals,
and materials.[2] Transition metal-catalyzed isomerization of
allylarenes has proven to be an effective method for the
synthesis of 1-propenylarenes, molecules with the same
application as allylarenes.[3] Besides noble transition metals,[4]
inexpensive first-row transition metals (Fe, Co, and Ni) have also
shown high catalytic activity and good-to-excellent E/Z selectivity
for olefin isomerization,[5] they are considered to have significant
potential to transform this field owing to their abundance and
their ability to be easily removed. Past mechanistic studies on
olefin isomerization have revealed that the alkyl and π-allyl
[a]
Q. Wu, L. Wang, Dr. R. Jin, Dr. C. Kang, Dr. Z. Bian, Dr. Z. Du, Dr.
X. Ma, Prof. Dr. L. Gao
State Key Laboratory of Polymer Physics and Chemistry
Changchun Institute of Applied Chemistry, Chinese Academy of
Sciences
5625 Renmin Street, Changchun 130022, China
E-mail: kangcq@ciac.ac.cn
Recently, we have been interested in the C-C bond
formation and transformation mediated with inexpensive
transition metals. During our studies on Ni(II)-catalyzed cross
coupling of the aryl Grignard reagent with aryl halides,[14] we
noticed the cross coupling of aryl Grignard reagent with the
[b]
Q. Wu, L. Wang
University of Chinese Academy of Sciences
Beijing 100049, China
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
10.1002/ejoc.201600955
FULL PAPER
olefin of an olefin-containing substrate, resulting in the olefin
arylation. Further studies showed the presence of the olefin
isomerization along with the olefin arylation. We then started
elaborate studies on the olefin arylation and the olefin
isomerization of allylarenes mediated with a Ni(II)-aryl Grignard
reagent system. Here we presented the results. Our studies
demonstrated the isomerization of allylarenes with excellent E/Z
selectivity and the regiospecific arylation of allylarenes to 1,1-
disubstituted olefins (Scheme 1). The reaction conditions subtly
control the direction of the transformation of allylarenes to the
disubstituted ethylene with a moderate yield (Table 1, entry 11).
Ni(COD)2 as a catalyst gave similar results to Ni(acac)2 (Table 1,
entries 13), which suggests that Ni(0) can be used as an active
catalyst for arylation and the isomerization.[5e-g, 9, 15] Apart from its
use as a substrate, PhMgBr is also used to activate the Ni(II)
precatalyst by reducing it to Ni(0),[16] which can be confirmed by
the formation of biphenyl according to GC-MS analysis of the
reaction mixture. The olefin arylation of 1a with PhMgBr
appeared to be an oxidative cross coupling accompanied by the
removal of hydride and magnesium salt. However, the
introduction of oxidative reagents such as oxygen, copper(II)
triflate, and silver carbonate, completely inhibited both arylation
and the isomerization. Ni(0) or active species from Ni(0) likely
decomposed in the presence of oxidatives before being able to
trigger the catalytic cycles. We further found the formation of
propanylbenzene by GC-MS analysis of the reaction mixture,
suggesting that 1a acts as a weak oxidant to receive hydride or
hydride-containing species produced during olefin arylation.[11a]
exclusive isomerization or
a combination with arylation.
Investigations into the mechanism disclosed a new catalysis
method involving allylic internal C(sp2)-H activation of allylarenes
without a directing group followed by an alkenyl-alkyl catalytic
cycle for allyl isomerization. These results provide new
approaches to olefin functionalization and the mechanistic
investigations are helpful for the discovery and design of new
strategy for olefin functionalization.
Table 1. Optimization of the olefin arylation conditions.[a]
Entry
1a :
solvent and other
conditions
Yield
2a (1a)[c]
PhMgBr[b]
3aa[d]
15%
1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
2 : 1
2 : 1
2 : 1
3 : 1
4 : 1
5 : 1
4 : 1
THF
65% (0%)
70%(0%)
Scheme 1. Conditions-controlled isomerization and arylation of allylarenes.
2
THF, 30 mol% TMEDA
THF, 10 mol% TMEDA
THF, no Ni(acac)2
THF, NiCl2 (5 mol%)
THF, NiF2 (5 mol%)
THF
12%
8%
3
75%(0%)
Results and Discussion
4
0% (100%)
69%(0%)
0%
5
13%
7%
Optimization of the reaction conditions
The optimization of the conditions for isomerization and arylation
was carried out with a model reaction between allylbenzene (1a)
and phenylmagnesium bromide (PhMgBr). First, we determined
the conditions that favored the olefin arylation to 1,1-
disubstituted ethylene 3aa (Table 1). Initial experiments with
Ni(acac)2 as the catalyst using equimolar 1a and PhMgBr
showed the formation of 1-propenylbenzene (2a) from the
isomerization and of 3aa from the arylation (Table 1, entries 1-3),
meanwhile, none of these products was formed without nickel
(Table 1, entry 4). NiCl2 showed similar catalytic activity, but NiF2
was a poor catalyst (Table 1, entries 5-6). The yield of the
arylation increased to 22% by the use 2 equivalents of 1a (Table
1, entry 7). Toluene as the solvent gave the same result as THF,
but the replacement of the Grignard reagent solvent of THF with
toluene (THF-free) led to an increase of 32% in the arylation
yield (Table 1, entries 8-9). A higher ratio of 1a to PhMgBr under
neat conditions increased the arylation yield to 56% and
decreased the isomerization yield to 30% (Table 1, entries 10-
12). Nonpolar conditions benefitted the arylation and suppressed
the isomerization. Thus, we could determine the optimized
conditions for regiospecific olefin arylation of 1a to 1,1-
6
34%(44%)
65% (5%)
60% (10%)
60% (3%)
55% (2%)
30% (10%)
32% (12%)
40% (10%)
7
22%
22%
32%
39%
56%
50%
40%
8
toluene
9
toluene (THF-free)[e]
neat (THF-free)[e]
neat (THF-free)[e]
neat (THF-free)[e]
10
11
12
13
neat (THF-free),[e]
Ni(COD)2 (5 mol%)
[a] Reaction conditions: otherwise indicated, 1a (as indicated), PhMgBr (1.0
mmol, THF solution for entries 1-9, toluene solution for others indicated as
THF-free), TMEDA (20 mol%), Ni(acac)2 (5 mol%), solvent (5 ml or neat),
argon atmosphere, rt, 12 h, yields are determined by GC. [b] In molar ratio.
[c] Yield based on allylbenzene, yield in bracket is recovered 1a. [d] Yield
based on PhMgBr. [e] Using toluene solution of PhMgBr. TMEDA
tetramethylethylenediamine.
=
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European Journal of Organic Chemistry
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6
30
30
30
30
30
30
30
5
5
3
1
5
5
5
5
0
3
1
5
5
5
2
96% (52/1)
35% (10/1)[c]
97% (35/1)
94% (24/1)
96% (28/1)
96% (42/1)
96% (52/1)
7
2
According to above results, isomerization occurs in
synchronization with arylation. We therefore shift our focus to
optimizing the conditions that favor of allyl isomerization. The
reactions with reduced amount of Grignard reagent in
tetrahydrofuran (THF), a polar solvent, were examined, where
the E/Z selectivity of isomerization was considered (Table 2). In
theory, 10 mol% of PhMgBr is enough to reduce 5 mol% of Ni(II)
to Ni(0). However, the reactions with 20 mol% or less of PhMgBr
showed poor results and those with more than 25 mol% of
PhMgBr resulted in excellent yields and E/Z values (Table 2,
entries 1-4). No trace of 3aa was detected in those experiments.
Tetramethylethylenediamine (TMEDA) is essential but remains
effective when used with the same loading amount as that of the
nickel catalyst (Table 2, entries 5-7). Lower catalyst loadings
also gave excellent results with a very limited decrease in E/Z
selectivity (Table 2, entries 8-9). The time evolution of the
experimental data confirmed the rapid isomerization of 1a (Table
2, entries 6 and 10-12). The high E/Z ratio at 0.5 h and limited
increase within the subsequent 2 h indicate the intrinsic
tendency of isomerization to E-form selectivity. However, an E/Z
mixture (1/10) of 2a under catalytic conditions displayed the
transformation of Z- to E-form within 2 h with an E/Z ratio of 41/1
(Scheme 2). Thus, we cannot reach a conclusion on whether
E/Z selectivity is a result of kinetics or thermodynamics.
8
2
9
2
10
11
12
0.5
1
4
[a] Reaction conditions: otherwise indicated, 1a (1.0 mmol), PhMgBr (30
mol%, THF solution), TMEDA (5 mol%), Ni(acac)2 (5 mol%), THF (1 ml),
argon atmosphere, rt, 2 h. [b] Determined by GC. [c] 59% of 1a recovered.
Scheme 2. E/Z-isomerization of 1-propenylbenzene.
Mechanistic investigations
The above results give the optimized conditions for the allyl
isomerization of 1a with excellent yield and E/Z selectivity
catalyzed by 5 mol% of Ni(acac)2 and TMEDA combined with 30
mol% of PhMgBr. No 3aa from arylation was detected during the
optimization of the isomerization conditions. The optimized
conditions for both isomerization and arylation had a similar ratio
of 1a to PhMgBr but used different solvents. The isomerization
using 1 mol% of Ni(acac)2 in THF had similar catalyst loading as
the arylation of 1a and PhMgBr with a ratio of 4/1 under neat
conditions (Table 1, entry 11 and Table 2, entry 9). However, the
two reactions gave distinct results, which indicates the solvent
plays an essential role in controlling the direction of the
conversions to either exclusive isomerization or competitive
arylation and isomerization.
Deep insights into both isomerization and arylation of 1a with
H/D exchange and crossover experiments revealed the
mechanistic complexity in the conversions. Substrates with
deuteration at the 1- and 2-position of the allyl were studied to
sufficiently understand the reactions. All experiments were
carried out under the optimized conditions for isomerization.
Solvent effects are examined because of the different reactivities
of the isomerization and arylation of 1a in THF, toluene, and
under neat conditions.
The olefin isomerization of (allyl-2-d)benzene (1a-2-d) under
various conditions showed a 2,3-hydride shift (Scheme 3). In
both THF and toluene, the isomerization of 1a-2-d produced 2a
with partial deuteration at the 2- and 3-positions. The hydride
shift seemed to be in agreement with the alkyl mechanism.[3, 6]
However, isomerization did not proceed under the neat
conditions at room temperature, nor did arylation, but
successfully yielded 3aa and 2a at 80 ºC with partial deuteration
at the 2- and 3-positions. These results strongly support that the
C-D bond is broken during both isomerization and arylation.
Therefore, the activation of C(sp2)-H bond at the 2-position of
the allyl of 1a is essential for both isomerization and arylation.
The fact that the arylation product 3aa using the neat conditions
did not show any deuteration suggests that there is no H/D
exchange in arylation. We therefore propose that the in situ-
formed Ni(0) species from Ni(II) reduction by PhMgBr inserts into
the C(sp2)-H bond prior to isomerization and arylation.
Table 2. Optimization of the isomerization conditions.[a]
Entry
X (mol%)
Y (mol%)
Z (mol%)
Time (h) Yield (E/Z)[b]
1
2
3
4
5
15
20
25
30
30
5
5
5
5
5
20
20
20
20
10
2
2
2
2
2
2% (n.d.)
55% (15/1)
95% (28/1)
98% (32/1)
96% (44/1)
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European Journal of Organic Chemistry
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Further investigations into the mechanisms were carried out
with H/D crossover experiments using deuterated 1a-2-d and
1a-1-d2 and undeuterated 1b as substrates; these experiments
clearly demonstrated the presence of multiple intermolecular
hydride shifts. In all investigated conditions, the reactions of 1a-
2-d and 1b showed an intermolecular 2,3-hydride shift (Scheme
5), while those of 1a-1-d2 and 1b showed intermolecular 1,2-
and 1,3-hydride shifts (Scheme 6). This is the first observation of
intermolecular 1,3-hydride shift for olefin isomerization.[3, 6] The
intermolecular hydride exchanges led to the deuteration of the 2-
and 3-positions of all isomerization products. No allyl arylation
was observed in the reactions in THF or toluene, while the allyl
arylation worked for the neat conditions but did not show a
hydride shift. Cross coupling without a hydride shift suggests
that the arylation is independent on isomerization.
Scheme 3. Olefin isomerization with 2,3-hydride shift. Reaction condtions:
Ni(acac)2 (5 mol%), TMEDA (5 mol%), PhMgBr (30 mol%), argon, 2 h, others
as indicated.
The above result led us to propose mechanisms for allyl
isomerization and allyl arylation to address the hydride shifts in
the catalytic cycles (Scheme 7). The initial 2-C(sp2)-H activation
of allyl via the oxidative insertion of the in situ-prepared Ni(0)
generates alkenyl-nickel-hydride I, the activated nickel hydride
for forward conversions. Then, the intermolecular 2,3-hydride
shift starts with the complexation of I into another molecule of 1a
to form II. Subsequently, the 2-H of I is transferred to another
molecule at the 3-position through a nickel-hydride addition in
accordance with Markovnikov's rule. The 1,2-elimination of the
alkyl molecule trapped in intermediate III produces the unstable
complex IV. Dissociation of IV releases product 2a and
regenerates alkenyl-nickel-hydride which takes the 1-H to the 3-
position of another molecule of 1a in the above sequence, which
is the 1,3-hydride shift. The complexation of I with 1a and the
addition of nickel-hydride to form III are reversible, which leads
to 2,3-hydride exchange. The combination of 1,3-hydride shift
and 2,3-hydride exchange results in the formal 1,2-hydride
exchange, which is probably the reason for the lower deuteration
rate at the 2-position compared with that at the 3-position
(Scheme 6). Another possible pathway for the addition of nickel-
hydride to 1a is via the unfavorable anti-Markovnikov's rule to
form V. The reversible anti-Markovnikov's addition causes 2,2-
hydride exchange. From the catalytic cycle, the alkenyl nickel
hydride I is the real active species that is trapped in the catalytic
cycle and promotes allyl isomerization following the alkyl
mechanism,[3, 6] which we refer to as alkenyl-alkyl mechanism.
We then examined the isomerization of (allyl-1-d2)benzene
(1a-1-d2) under various conditions, which clearly demonstrates
1,2- and 1,3-hydride shifts that result in partial deuteration at the
2- and 3-positions of 2a (Scheme 4). The deuterium at the 1-
position was abstracted and transfered to the 2- and 3-positions.
Under the neat conditions, the arylation product 3aa-3-d2
showed no deuterium shift. These observations are in
agreement with the results from the isomerization of 1a-2-d
(Scheme 3), which support that olefin arylation occurs via a
direct cross coupling between C(sp2)-H-activated 1a and
PhMgBr.
Scheme 4. Olefin isomerization with 1,2- and 1,3-hydride shifts. Reaction
condtions: Ni(acac)2 (5 mol%), TMEDA (5 mol%), PhMgBr (30 mol%), argon, 2
h, others as indicated.
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European Journal of Organic Chemistry
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Scheme 5. Olefin isomerization with intra- and intermolecular 2,3-hydride shift. Reaction condtions: Ni(acac)2 (5 mol%), TMEDA (5 mol%), PhMgBr (30 mol%),
argon, 2 h, others as indicated.
Scheme 6. Olefin isomerization with intra- and intermolecular 1,2- and 1,3-hydride shift. Reaction condtions: Ni(acac)2 (5 mol%), TMEDA (5 mol%), PhMgBr (30
mol%), argon, 2 h, others as indicated.
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We then check the catalytic activity of the Ni(acac)2-PhMgBr
system with the isomerization of other terminal alkenes (Scheme
9). Interestingly, but-2-en-1-ylbenzene (4a) is converted to but-1-
en-1-ylbenzene (5a) with a yield of 91% and but-2-en-1-
ylbenzene (5a’) with a yield of 3%, which indicates a continuous
olefin shift along the carbon chain during the olefin isomerization.
However, alkenes 4b and 4c are inert to the reaction conditions;
the latter chemical bears no aryl group. In comparison with 4a,
4b has one more CH2 between the terminal olefin and the
phenyl, which suggests that the appropriate distance of an aryl
and an olefin in the substrate is a primary factor in forming an
activated species for triggering the isomerization. The aryl group
in the allylarenes may be involved in the olefin C(sp2)-H
activation as an electron-rich ligand to stabilize nickel-inserted
intermediate. Furthermore, diene isomerization is observed for
compound 6, in which diene shifts along the carbon chain to
form 7 with an E,E/E,Z ratio of 5/1.
Scheme 7. Proposed alkenyl-alkyl mechanism for the isomerization and cross
coupling for the arylation. A: C(sp2)-H activation; B: complexation; C: addition
in Markovnikov's rule; D: 1,2-elimination; E: dissociation; F: addition in anti-
Markovnikov's rule; G: transmetalation; H: reductive elimination.
Under neat conditions, the C(sp2)-H-activated intermediate I
has a chance to bind with the phenyl from excess PhMgBr
through transmetalation to form VI, probably because of slightly
lower tendency to be complex with and add to 1a in nonpolar
conditions. The transmetalation involves hydride transfer from I
to a magnesium hydride intermediate captured by 1a to form
17]
phenylpropane upon quenching,[11a,
which is confirmed by
GC-MS analysis with the detection of phenylpropane in the
reaction mixture.‡ Reductive elimination of VI releases Ni(0)
catalyst and the cross-coupling product 3a, by which the allyl of
1a is arylated.
Substrate scope and limitations
Various allylarenes (1s) are converted into 1-propenylarenes
(2s) with excellent yields and E/Z selectivities (Scheme 8).
Under the optimized conditions, the isomerization of allylarenes
with methyl, methoxy, dimethylamino, and fluoro gives 1-
propenylbenzenes in yields over 95% and E/Z ratios of up to
52/1. Allylnaphthalene (1l) shows a little lower E/Z selectivity of
9/1 compared with allylbenzene derivatives (E/Z > 16/1).
Although the isomerization of fluoro-substituted substrates 1m
and 1n demonstrates high reactivity and excellent E/Z selectivity,
the substrates with trifluoromethyl and chloro, 1o and 1p, are
converted to the products in low-to-moderate yields with a
relatively low E/Z selectivity. Unexpectedly, the bromide
substrate 1q is not suitable for isomerization. The catalytic
system is also unable to trigger the conversions of allyl ether 1r
and allylic thiophene 1s.
Scheme 8. Scope of the olefin isomerization of allylarenes.
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European Journal of Organic Chemistry
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We have developed a novel method for the olefin isomerization
and arylation of allylarenes triggered by allylic C(sp2)-H
activation. The method provides new approaches to olefin
functionalization, and the proposed mechanism would facilitate
the discovery and design of new strategy for olefin
functionalization. The inexpensive and wide available nickel is
used as catalyst. In situ-formed Ni(0) induces C(sp2)-H activation
by insertion into the allylic internal C(sp2)-H bond of the
allylarenes without
a
directing group, which results in
isomerization and arylation at the activated position. The
tendency of allylarene toward exclusive isomerization or a
combination of isomerization and arylation is controlled by the
solvent, where isomerization is favored by THF, while arylation
is favored by neat condtions. The isomerization of allylarenes to
1-propenylarenes shows excellent E-form selectivity and yield.
The arylation of allylarenes with aryl Grignard reagent is a new
method for the synthesis of 1,1-disubstituted ethylene through
regiospecific oxidative cross coupling. According to D/H
exchange and crossover investigations, we propose an alkenyl-
alkyl mechanism in which an alkenyl nickel from C(sp2)-H
activation is used as the active species in the catalytic cycle,
similar to the alkyl mechanism. The alkenyl nickel mediates the
hydride addition and elimination to form intermolecular 1,2- 1,3-,
and 2,3-hydride shifts. Particularly, this is the first observation of
intermolecular 1,3-hydride shift for olefin isomerization.[3, 6] The
functionalization of allyl using the strategy of allylic C(sp2)-H
activation should benefit this field and are therefore valuable for
further investigations.
Scheme 9. Olefin isomerization of 1-alkene and diene compounds.
The olefin arylation of a few allylarenes with aryl Grignard
reagents provides a method for regiospecific synthesis of 1,1-
disubstituted ethylenes in moderate isolated yields (Scheme 10).
However, substrates containing methoxy and fluoro inhibit
arylation with trace products detected. It is remarkable that
methoxy on either allylarene or aryl Grignard reagent results in
poor reactivity (3eb and 3ac). In H/D crossover experiments, no
cross coupling product from the arylation of 1b is detected
(Schemes 5 and 6). The results suggest that methoxy only
influences the cross coupling of the substrate containing it, but
does not influence the cross coupling of other substrates in the
reaction system.
Experimental Section
General methods
All substrates and reagents are commercial available and used without
further purification. The nickel catalysts are purchased from Alfa-Aesar.
All the deuterated substrate are prepared from phenylacetic acid and 2,3-
dibromopropene according to the literatures.[18] 1H and 13C NMR spectra
are recorded on Bruker AVX 300 MHz and 400 MHz spectrometer in
CDCl3 with TMS (δ = 0 ppm) and solvent (δ = 77.0 ppm) as internal
standard for chemical shift of 1H NMR and 13C NMR, respectively. All
known compounds are confirmed with 1H NMR according to respective
literatures. GC analyses are performed on Shimidzu GC2010A with DB-
WAX column by comparison with authentic compounds. GC-MS
analyses are performed on Agilent 5975-6890N system with Agilent
19091G-133 column. Known products of allyl isomerization and allyl
arylation are confirmed with 1H and 13C NMR by comparison with
literatures. New structures, which are all the products of allyl arylation,
are confirmed with 1H and 13C NMR and GC-MS.
General procedure for the allyl isomerization: A 15 mL oven-dried
flask was added Ni(acac)2 (12.8 mg, 0.05 mmol) and TMEDA (7.5 μL,
0.05 mmol) in anhydrous THF (1.0 mL) under argon. Then, PhMgBr (0.3
mL, 0.3 mmol, 1M in THF) was added, the solution was turn to black and
stirred for 3 minutes at room temperature, and 1a (132.0 μL, 1.0 mmol)
was added. After 3 h at room temperature, the reaction was quenched
with aqueous HCl (0.5 M) and extracted with ethyl acetate, the yield and
E/Z ratio was determined by GC analysis.
Scheme 10. Cross coupling of allylarenes with aryl Grignard reagents.
Conclusions
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201600955
FULL PAPER
General procedure for the allyl arylation: A 15 mL oven-dried flask
was added Ni(acac)2 (12.8 mg, 0.05 mmol), TMEDA (0.03 mL, 0.20
mmol) and 1a (0.53 mL, 4.0 mmol) under argon. Then, dropwise addition
of PhMgBr (1.0 mL, 1.0 mmol, 1.0 M in toluene) to the stirred solution at
room temperature. After 12 h at room temperature, the reaction was
quenched with aqueous HCl (0.5 M) and extracted with ethyl acetate.
The organic layer was washed with H2O and brine, dried with anhydrous
MgSO4, and concentrated under reduced pressure. The crude material
was purified by silica gel column chromatography (petroleum as eluent)
to give 87.3 mg product 3aa as colorless oil in 53% yield.
Keywords: C-H activation • isomerization • cross-coupling •
allylic compounds • nickel
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3ab: colorless liquid; H NMR (300 MHz, CDCl3) δ 7.35 (d, J = 8.13 Hz,
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3ba: colorless liquid; H NMR (300 MHz, CDCl3) δ 7.47 (d, J = 6.90 Hz,
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137.73, 136.78, 120.17, 129.94, 128.35, 127.54, 126.46, 125.96, 113.92,
38.92,19.45. GC-MS (M/Z): 208.
1
3bb: colorless liquid; H NMR (300 MHz, CDCl3) δ 7.38 (d, J = 8.15 Hz,
2H), 7.17-7.12 (m, 6H), 5.43 (s, 1H), 4.68 (s, 1H), 3.75 (s, 2H), 2.34 (s,
3H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.11, 138.57, 137.85,
137.28, 136.76, 139.13, 129.90, 129.03, 126.40, 125.97, 125.80, 113.13,
38.90, 21.12, 19.44. GC-MS (M/Z): 222.
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3ca: colorless liquid; 1H NMR (300 MHz, CDCl3) δ 7.44-7.42 (m, 2H),
7.30-7.12 (m, 4H), 7.04-6.97 (m, 3H), 5.49 (s, 1H), 5.00 (s, 1H), 3.79 (s,
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137.89, 129.73, 127.45, 126.88, 126.15, 126.00, 114.55, 41.55, 21.44.
GC-MS (M/Z): 208.
1
3cb: colorless liquid; H NMR (300 MHz, CDCl3) δ 7.33 (d, J = 8.07 Hz,
2H), 7.13-6.98 (m, 6H), 5.47 (s, 1H), 4.96 (s, 1H), 3.78 (s, 2H), 2.31 (s,
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The authors appreciate financial supports by Technology R&D
Program of Jilin, China (No. 20140203003GX).
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
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Stereoselective allyl isomerization and
regiospecific allyl arylation of
C-H activation
Q. Wu, L. Wang, R. Jin, C. Kang,* Z.
Bian, Z. Du, X. Ma, H. Guo, L. Gao
allylarenes are triggered by allylic
internal C(sp2)-H activation without a
directing group, in which an alkenyl
nickel hydride from the C(sp2)-H
activation is the active species
trapped in the catalytic cycles.
Page No. – Page No.
Nickel-Catalyzed Allylic C(sp2)-H
Activation: Stereoselective Allyl
Isomerization and Regiospecific Allyl
Arylation of Allylarenes
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