Ligand-Enabled Nickel-Catalyzed Redox-Relay Migratory Hydroarylation of Alkenes with Arylborons

Article abstract of DOI:10.1002/anie.202001742

A redox-relay migratory hydroarylation of isomeric mixtures of olefins with arylboronic acids catalyzed by nickel complexes bearing diamine ligands is described. A range of structurally diverse 1,1-diarylalkanes, including those containing a 1,1-diarylated quaternary carbon, were obtained in excellent yields and with high regioselectivity. Preliminary experimental evidence supports the proposed non-dissociated chainwalking of aryl-nickel(II)-hydride species along the alkyl chain of alkenes before selective reductive elimination at a benzylic position. A catalyst loading as low as 0.5 mol % proved to be sufficient in large-scale synthesis while retaining high reactivity, highlighting the practical value of this transformation.

Full text of DOI:10.1002/anie.202001742

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Ligand-Enabled Nickel-Catalyzed Redox-Relay Migratory
Hydroarylation of Alkenes with Arylborons
Authors: Yuli He, Chuang Liu, Lei Yu, and Shaolin Zhu
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202001742
Angew. Chem. 10.1002/ange.202001742
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10.1002/anie.202001742
Angewandte Chemie International Edition
RESEARCH ARTICLE
Ligand-Enabled Nickel-Catalyzed Redox-Relay Migratory
Hydroarylation of Alkenes with Arylborons
Yuli He,[a] Chuang Liu,[b] Lei Yu,[b] and Shaolin Zhu*[a]
Dedicated to the 70th anniversary of Shanghai Institute of Organic Chemistry
[a]
[b]
Y. He, Prof. S. Zhu
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center
(ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, (China)
E-mail: shaolinzhu@nju.edu.cn
Homepage: http://hysz.nju.edu.cn/slzhu/
C. Liu, Prof. L. Yu
School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225002, (China)
Supporting information for this article is given via a link at the end of the document.
Abstract:
mixtures of olefins with arylboronic acids catalyzed by nickel
complexes bearing diamine ligands is described. range of
A redox-relay migratory hydroarylation of isomeric
a
Previous work (NiI/NiIII): reductive migratory hydroarylation proposed via NiIH
A
remote functionalization
structurally diverse 1,1-diarylalkanes, including those containing a
1,1-diarylated quaternary carbon, were obtained in excellent yields
and with high regioselectivity. Preliminary experimental evidence
supports the proposed non-dissociated chainwalking of aryl-
nickel(II)-hydride species along the alkyl chain of alkenes before
selective reductive elimination at a benzylic position. A catalyst
loading as low as 0.5 mol% proved in large-scale synthesis to be
sufficient while retaining high reactivity, highlighting the practical
value of this transformation.
H
Ar
NiIH
ArX RX ArNO2
R1
R1
+
R2
R2
X
()n
easily accessible
()n
bpy, pyrox
ligands
electrophilic
coupling partners
traceless
via NiIII
OA/RE
remote C–C, C–N, C–S
bond formation
[Si-H]
cat. Ni/L
Ar
NiI
NiI
H
chain-walking
NiI
R
R1
R
R2
()n
R2
R2
()n
()n
chain-walking proceeds:
n w/o coupling reagents n w reductant n w dissociation of NiH from olefin
b
This work (Ni0/NiII): redox-relay migratory hydroarylation proposed via ArNiIIH
Ar
Ar1
()n
Introduction
R
NiIIH
+
Ar[B]
Ar1
R
()n
isomerization
unrefined
Selective introduction of a functional group onto an inert sp3
carbon is of considerable synthetic utility and will allow access to
structures with a more concise synthetic route or from more
readily available starting materials.[1] To distinguish between
multiple, yet similar, inert sp3 C–H bonds, a pre-installed polar
directing group nearby is necessary in most reported processes
and this limits their generality and applicability. Given the
abundance and easy accessibility of alkene feedstock, remote
functionalization through alkene isomerization and sequential
selective cross-coupling has recently emerged as an attractive
alternative in which a non-polar C=C double bond in an arbitrary
position is used as a traceless directing group and the distant C–
H bond is selectively functionalized.[2-6] Previously, starting from
isomeric olefins and a wide variety of electrophilic coupling
nucleophilic
arylboron
diamine
ligands
1,1-diarylalkane
remote C–H arylation
alkenes
Ar[B] & ROH
Ar1
cat. Ni/L
remote C–C bond formation
selective RE
NiIIAr
R
NiIIAr
chain-walking
()n
NiII
H
Ar1
R
Ar1
()n
R
()n
Ar
chain-walking proceedsғ
n w coupling reagents n w/o reductant n w/o dissociation of NiH from olefin
c
Representative bioactive 1,1-diarylalkanes
O
iPr
iPr
N
MeHN
HO
O
Cl
Cl
OMe
OMe
O
OH
O
OMe
podophyllotoxin
(Condylox)
partners,
nickel[7]
catalyzed
reductive
remote
tolterodine
(Detrol)
sertraline
(Zoloft)
hydrofunctionalization[6c-e,g-i,l,m,o-u,x,z] has been developed via
proposed nickel hydride intermediates[8,9] (Figure 1a). Despite
robust investigation, these methods are generally limited by the
need of a stoichiometric amount of extra reductant.
N
Cy
S
O
CO2H
NMe2
dimetindene
(Fenistil )
anti breast cancer agent
nafenopin
Figure 1. Design plan: redox-relay migratory hydroarylation via the aryl-
nickel(II)-hydride generated in situ.
1
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10.1002/anie.202001742
Angewandte Chemie International Edition
RESEARCH ARTICLE
LNiII precatalyst
ArB(OH)2
Distinct from the previously reported nickel-catalyzed
reductive remote hydroarylation systems,[6e,h,s,z] two precedents
of redox-neutral olefin remote hydroarylation have been reported
by Lee[6a] and by Hartwig[6b]. However, the scope of the arylation
is limited to only trifluoromethylarenes or heteroarenes with low
pKa values. To address these shortcomings, we speculated that
oxidative addition of a ligated nickel(0) with alcohol[10c-f] followed
by a transmetalation with commercial available arylboronic acids
would provide rapid access to a broad range of aryl-nickel(II)-
hydride species, which could also serve as a platform for remote
hydroarylation of alkenes (Figure 1b). Specifically, if the aryl-
nickel(II)-hydride generated in situ is active enough to insert into
an isomer or mixture of isomers of the olefin substrate and
promote a fast and reversible chain-walking process along the
hydrocarbon chain prior to a selective reductive elimination, then
a convergent and regioselective migratory arylation instead of
hydroarylation at the ipso position[10,11] would be achieved.
Ideally, depending on the choice of the ligand, selective
reductive elimination at the benzylic position would provide a
complementary approach to the synthesis of a wide variety of
1,1-diarylalkanes as important pharmacophores[12] (Figure 1c).
Unlike our previously proposed reductive nickel(I)-hydride
catalyst system,[6e,h,s] this proposed aryl-nickel(II)-hydride
process suggests that: (1) no extra reductant is required, (2)
chain-walking happens with the participation of the coupling
partners to form the active catalyst, aryl-nickel(II)-hydride, (3)
chain-walking proceeds efficiently with no dissociation of the
aryl-nickel(II)-hydride catalyst from the alkenes.
Ar
3
Ph
H2N
NH2
Ar Ar
ROH
1,1-diarylalkane
L: diamine ligand
LNi0
I
reductive
elimination
oxidative
addition
NiIIAr
LNiII OR
VII
II
Ph
H
H
Ar B(OH)2
β-hydride elimination
2
transmetalation
/migratory insertion
ROB(OH)2
H
Ni0/NiII
LNiII Ar
VI
III
Ph
H
NiIIAr
Ph
hydrometallation
H
hydrometallation
NiIIAr
1a
Ar
NiII
β-hydride
H
elimination
Ph
Ph
V
IV
H
n ArNiIIH induced chainwalking
n Regioselective & regioconvergent
n Efficient 1,1-diarylalkane synthesis
n Mild & wide scope
Figure 2. Envisioned catalytic cycle.
Results and Discussion
Based on this hypothesis, we first examined the proposed
remote hydroarylation with 4-phenyl-1-butene (1a) and (4-
methoxyphenyl)boronic acid (2a). After systematic manipulation
of the reaction parameters and ligand evaluation, the desired
migratory arylation product (3a) was isolated in good yield (84%)
as a single isomer using a combination of bench-stable Ni(OTf)2
as a precatalyst, methanol as a hydride source, and a simple
diamine (L1) as a ligand[13] (Table 1, entry 1). Ni(cod)2 was
originally explored as a nickel source (entry 2), but the air-stable
nickel(II) precatalysts were also effective. Notably, the ligand L1
used is a cis- and trans- mixture (~3:1 cis:trans), in which the
cis-isomer (L2) reacted effectively (entry 3) but the pure trans-
isomer (L3) led to a significantly lower yield and selectivity (entry
4). Since a mixture (L1) is much cheaper than pure cis-isomer
(L2), it was chosen for subsequent investigations. Another
diamine ligand (L4) could also facilitate the migratory arylation,
although only a moderate yield was obtained (entry 5). The
electron-rich phosphine ligand PtBu3 or the 6,6'-dimethyl-2,2'-
bipyridine ligand (L5), which were previously used in reductive
NiH catalyst system[6e,h,s,z], gave no reaction. As expected,
control experiments revealed that the alcohol is crucial. Poor
conversion was observed in the absence of methanol (entry 7);
and ethanol was less effective (entry 8). Use of other solvents
such as THF led to only a moderate yield (entry 9). However,
methanol was shown to be an unsuitable solvent (entry 10).
Inferior results were obtained when replacing CsF as base (entry
11) or using 1.5 equiv of the arylboronic acid (entry 12) or
conducting the reaction at 70 °C (entry 13).
A detailed description of our proposed pathway is outlined
in Figure 2. Initially, the nickel(0) species (I) is formed from a
Ni(II) precursor with a catalytic amount of arylboronic acid. It
then undergoes a reversible oxidative addition with the alcohol
to generate
a nickel(II) hydride adduct (II), followed by
transmetalation with arylboronic acid (2) to form the active aryl-
nickel(II)-hydride species (III) which inserts into the alkene (1a)
to generate an alkyl-nickel-aryl intermediate (IV). This readily
undergoes fast and reversible β-hydride elimination to afford the
isomeric complex (V). A series of isomeric alkyl-nickel(II)-aryl
species (IV, VI, VII, ….) is then accessed through a series of
rapid and reversible iterative β-hydride elimination/migratory
reinsertions. In particular, if selective reductive elimination of
benzyl-nickel(II)-aryl intermediate (VII) is favorable relative to
other alkyl-nickel(II)-aryl isomers, the benzylic arylation product
could be obtained with high regioselectivity, along with a
nickel(0) species (I) thus closing the catalytic cycle. There are
three major challenges to such a mechanistically unique process.
First, the aryl-nickel(II)-hydride species must be sufficiently
stable to avoid the undesired irreversible reductive elimination
producing an arene. Second, the aryl-nickel(II)-hydride species
must be sufficiently reactive to promote a fast and reversible
chain-walking process. Third, the reductive elimination of the
alkyl-nickel(II)-aryl intermediate must be highly selective, a less
reactive alkyl-nickel(II)-aryl species would be converted by
chain-walking into
intermediate.
a
more reactive alkyl-nickel(II)-aryl
Table 1: Variation of reaction parameters.
2
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10.1002/anie.202001742
Angewandte Chemie International Edition
RESEARCH ARTICLE
5 mol% Ni(OTf)2
6 mol% L1
5 mol% Ni(OTf)2
6 mol% L1
B(OH)2
PMP
Ar
+
+
ArB(OH)2
Ph
Ph
Ph nPr
2.0 equiv MeOH
1.5 equiv K3PO4
Tol (0.25 M)
2.0 equiv MeOH
1.5 equiv K3PO4
Tol (0.25 M), 80 °C, 24 h
Ph
MeO
2a (2.0 equiv)
arylboronic acid
1a
2 (2.0 equiv)
3
3a (remote arylation)
1,1-diarylalkane
1a
alkene
80 °C, 24 h
O
Entry
1
Variation from standard conditions
none
Yield [%][a]
rr[b]
99 (84)
91
>99:1
>99:1
>99:1
89:11
>99:1
–
>99:1
>99:1
>99:1
–
MeO
OMe
OTBS
NPh2
N
2
Ni(cod)2 instead of Ni(OTf)2
L2 instead of L1
L3 instead of L1
L4 instead of L1
PtBu3 or L5 instead of L1
no MeOH
3
99
4
5
71
57
Ph nPr
Ph nPr
Ph nPr
Ph nPr
Ph nPr
6
7
NR
8
3a 84% yield
3b 73% yield
3c 74% yield 3d 48% yield 3e 81% yield
8
9
EtOH instead of MeOH
THF instead of Tol
MeOH as solvent
CsF instead of K3PO4
1.5 equiv 2a
83
76
O
O
OMe
OCF3
CF3
Cl
MeO
OMe
10
11
12
13
NR
77
78
>99:1
>99:1
>99:1
Ph nPr
Ph nPr
Ph nPr
Ph nPr
Ph nPr
70 °C
85
3f 81% yield 3g[b] 77% yield 3h[b,c] 78% yield 3i[b] 80% yield 3j 46% yield
L1 (~3:1 cis:trans)
L2 (cis)
NH2 L3 (trans)
L4
SiMe3
HN
NH
N
N
H2N
L5
F
MeO2C
[a] Yields determined by GC using n-dodecane as the internal standard, the
yield in parentheses is the isolated yield. [b] Regioselectivities (rr) determined
by GC and GCMS analysis. Tol = toluene; THF = tetrahydrofuran; PMP = 4-
methoxyphenyl.
Ph nPr
Ph nPr
Ph nPr
Ph nPr
Ph nPr
3k 87% yield 3l[b,d] 73% yield 3m 81% yield 3n 91% yield 3o 66% yield
NMe
nPr
Ph
With the optimal conditions in hand, we sought to define
the scope of the arylboronic acid partner (Table 2). A wide range
of arylboronic acids including both electron-rich (2a–2e) and
electron-deficient (2f–2l) arylboronic acids, are accommodated
Ph nPr
3p 90% yield 3q[b] 59% yield
Ph nPr
Ph nPr
3r 86% yield
3s 61% yield
well.
A
variety of functional groups are also readily
[a] Yield under each product refers to isolated yield of purified product (0.5
mmol scale, average of two runs), >99:1 regioisomeric ratio (rr) unless
otherwise noted. [b] 6.0 equiv MeOH used. [c] L4 used. [d] 1.0 equiv K3PO4
used.
accommodated, including ethers (2a, 2b, and 2d–2h), amines
(2c, 2d), a trifluoromethyl group (2i), an aryl chloride (2j), an aryl
fluoride (2k), an ester (2l), a silane (2m), and alkyl groups (2n,
2o). Notably, ortho-substituted arylboronic acids (2o, 2q) could
also be coupled in good yields while the corresponding ortho-
substituted aryl halides could not be coupled using our previous
reductive chain-walking protocols[6e,h]. Moreover, heterocycles
such as indole (2s) are also competent coupling partners.
The scope of the alkenes was also explored (Table 3). As
shown in Table 3a, an array of terminal aliphatic alkenes with a
variety of substituents on the remote aromatic ring, including
both electron-withdrawing (1c–1g) and electron-donating (1h–
1k) substituents underwent migratory hydroarylation smoothly.
Moreover, a series of heterocycles frequently found in the
medicinally active agents in place of the aryl group, including
furan (1l), benzofuran (1m), and indole (1n, 1o), were shown to
be viable substrates. The reaction is insensitive to the length of
the chain between the C=C bond and the remote aryl group,
regardless of the starting position of the C=C bond (1a, 1p–1r).
Notably, an alkene (1s) with an internal branching, e.g. a tertiary
sp3 carbon between the C=C double bond and the remote aryl
group, along the alkyl chain was also a suitable substrate.
Moreover, 1,1-disubstituted alkenes (1t, 1u) could also be
employed. In a more striking example, a 1,1-disubstituted alkene
(1v) containing a pre-existing tertiary carbon at the benzylic
position can also undergo migratory hydroarylation to produce a
product with a challenging quaternary carbon at the benzylic
position.
Table 2: Scope of arylboronic acid coupling partner.[a]
Unactivated aliphatic internal alkenes are also competent
substrates, regardless of the E/Z configuration or the starting
position of the C=C bond (Table 3b, 1w–1a') and even a
trisubstituted internal alkene could also be well-tolerated (1a').
To get better yields, CsF is used as base in most cases.
Additionally, the current transformation could also be applied to
3
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10.1002/anie.202001742
Angewandte Chemie International Edition
RESEARCH ARTICLE
styrenes themselves, to producing the desired 1,1-diarylalkanes
exclusively (Table 3c). Both E (1b') and Z (1c') styrenes, as well
as styrenes with a variety of substituents on the remote aryl ring
(1f', 1g') are suitable substrates. Remarkably, with α-alkyl
substituted styrenes (1d'–1g'), benzylic arylation exclusively
producing the challenging products bearing a quaternary carbon
were still preferred in all cases.
Table 3: Scope of alkene coupling component.[a]
5 mol% Ni(OTf)2
6 mol% L1
R1 R2 R3
R2 R3
R1
PMP
B(OH)2
n Remote and proximal olefins
R4
+
R4
n Regioconvergent process
Ar
()m ()n
Ar
()m ()n
2.0 equiv MeOH
1.5 equiv K3PO4
MeO
2a (2.0 equiv)
arylboronic acid
R5
R5
n Highly functional group tolerance
n Form challenging quaternary carbons
1
4
Tol (0.25 M), 80 oC, 24 h
alkene
(remote C–H arylation)
a) from terminal aliphatic olefins
R1 R2 R3
PMP
PMP
PMP
PMP
PMP
MeO
RO
EtO2C
MeO2C
Ar
()m ()n
CF3
4f R=TBS, 93% yield
4g R=Bn, 94% yield
from 1b–1v
4b 69% yield
4c 56% yield
4d 76% yield
4e 61% yield
PMP
O
()3
()3
O
PMP
PMP
()3
H
PMP
MeO
MeO
()3
O
O
H
H
O
PMP
O
PMP
estrone derivative
4j[c] 89% yield, 1:1 dr
δ-tocopherol derivative
4k[c] 91% yield, 1:1 dr
4h[b] 95% yield
4i 43% yield
4l 45% yield
4m 60% yield
PMP
PMP
()n
PMP
PMP
PMP
Ph
PMP
Ph
Ph
nPr
Ph
()n
Ph
N
R
PMP
4p n=3, 87% yield
4q n=6, 74% yield
4r[d] n=10, 68% yield
4n R=Bn, n=2, 83% yield
4o R=Boc, n=0, 74% yield
>20:1 dr
4s[c,d] 68% yield, 2:1 dr
4t 62% yield
4u[c,d] 56% yield, 2:1 dr
4v 48% yield, 95:5 rr
b) from unactivated internal olefins
nPent
Cy
Ph
Ph
Ph
Ph
1w
1x
1y
1z
1a'
PMP
PMP
PMP
PMP
PMP
Ph
nPent
Cy
Ph
Ph
Ph
4w[e] 65% yield
4x[e] 47% yield
4y[e] 43% yield
4z 98% yield
4a'[e] 45% yield
c) from styrenes
PMP
PMP
PMP
PMP
PMP
Ph
PMP
Ph nPent
Ph
N
MeO2C
Me2N
CO2Me
4b' 87% yield
4c' 69% yield
4d' 99% yield
4e' 79% yield
4f' 57% yield
4g' 79% yield
[a] Yield under each product refers to isolated yield of purified product (0.5 mmol scale, average of two runs), >99:1 regioisomeric ratio (rr) unless otherwise noted.
[b] 0.25 mmol 1h used. [c] Diastereomeric ratio (dr) determined by crude 1H NMR analysis. [d] 2.5 equiv 2a used. [e] 2.5 equiv 2a, 2.0 equiv CsF, and 4.0 equiv
MeOH used.
The practical value of this transformation was further
highlighted by large-scale synthesis using lower catalyst loading
(Scheme 1a). When conducting the reaction on the 10 mmol
group as a hydride source. To verify this hypothesis, isotopic
labeling experiments of an alkene (1h') and arylboroxine (2T)
were carried out using CD3OH or CH3OD, respectively (Scheme
scale, it could proceed to completion with only 0.5 mol% catalyst. 1c). No deuterium incorporation was observed in 3a when
By treating Ni(OTf)2 and L1 in methanol, a dark yellow air-stable
solid Ni(OTf)2⋅(L2)2 was obtained.[14] Accordingly, with 0.5 mol%
loading of this stable precatalyst, the standard reaction on 10
mmol-scale also proceeds well. Further experiments were
conducted to assess the reactivity of different olefins. As shown
in Scheme 1b, competition experiments indicate that terminal
alkenes are more reactive than internal alkenes.
CD3OH was used. However, deuterium incorporation in 3a-D
was observed when CH3OD was used. These results indicate
that the nickel-hydride intermediate was initially generated from
the O−H group of the alcohol instead of the C−H bond of the
methanol.
To gain more insight into the chain-walking process, the
alkene (1e) was subjected to the reaction conditions in the
absence of arylboronic acid but using more reactive Ni(cod)2
instead of pre-catalyst Ni(OTf)2 and CH3OD instead of CH3OH.
As suggested in the initial mechanistic proposal,
a
stoichiometric amount of alcohol could provide the alcohol O−H
4
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10.1002/anie.202001742
Angewandte Chemie International Edition
RESEARCH ARTICLE
a
Large-scale migratory hydroarylation with lower catalyst loading
After 24 hours, with or without base, the alkene 1e was fully
recovered without any observation of isomerization or H/D
exchange (Scheme 1d). These results are consistent with a
mechanism in which chain-walking happens only with the
participation of the cross-coupling partner through an aryl-
nickel(II)-hydride. Further experiments were conducted to
assess whether the nickel-hydride catalyst disengages during
the chain-walking process. Two crossover experiments using a
1:1 mixture of deuterium-labeled olefin and undeuterated olefin
were carried out. Unlike in our previous proposed Ni(I)H catalyst
system,[6e,h,s] no H/D scrambled crossover products were
obtained (Scheme 1e). This observation indicates that as the
nickel-hydride catalyst proceeds through the iterative β-hydride
elimination/migratory insertion, no dissociation of the catalyst
from the olefin substrate occurs throughout the relay process. To
support the chain-walking proposal further, alkene (R)-1s
containing a pre-existing stereogenic center in the alkyl chain
was evaluated (Scheme 1f). Preservation of the chiral integrity
was observed in this case which is also consistent with the non-
dissociated chain-walking mechanism, in contrast to the partial
racemization of this stereocenter under our previous reductive
PMP
0.5 mol% Ni(OTf)2, 0.6 mol% L1
+
2a
Ph
Ph nPr
3a 81% yield
2.0 equiv MeOH, 1.5 equiv K3PO4
Tol (0.25 M), 80 °C, 24 h
1a (10 mmol)
(2.0 equiv)
0.5 mol% Ni(OTf)2·(L2)2 complex used: 87% yield
H2N
NH2
Ni2+
CCDC
1976289
OTf-
H2N
OTf-
NH2
X-ray of Ni(OTf)2·(L2)2 complex
b
Competition experiment (terminal olefin vs internal olefin)
PMP
PMP
standard conditions
+
+
Ph
()3
Ph
internal alkene
1w (1.5 equiv)
Ph nPent
Ph nBu
1.0 equiv 2a
terminal alkene
1p (1.5 equiv)
4p 39% yield
4w 3% yield
c
Isotopic labelling experiments
5 mol% Ni(OTf)2
6 mol% L1
Ph
O
Ph
B
B
(0 D) Ph
PMP
(0 D)
+
+
O
O
PMP
B
2.0 equiv CD3OH
1.5 equiv K3PO4
Tol (0.25 M), 80 °C, 24 h
(0 D) (0 D)
3a (w/o D)
Ph
2T
1h'
5 mol% Ni(OTf)2
6 mol% L1
Ph
O
Ph
B
B
(0 D) Ph
(0.10 D)
O
O
PMP
B
2.0 equiv CH3OD
1.5 equiv K3PO4
Tol (0.25 M), 80 °C, 24 h
PMP
(0.06 D)(0.80 D)
Ph
2T
1h'
3a-D
chain-walking conditions[6e,h]
.
d
e
No alkene isomerization in the absence of arylboron
5 mol% Ni(cod)2
(0 D) (0 D)
MeO2C
6 mol% L1
MeO2C
(0 D) (0 D)
w/o D
2.0 equiv CH3OD
w or w/o 1.5 equiv K3PO4
Tol (0.25 M), 80 °C, 24 h
1e
1e fully recovered
Crossover experiments: no intermolecular H/D scrambled crossover products
PMP
(0 D)
(0.89 D) (0.89 D)
(0 D)
standard
conditions
(0.88 D)
Ph
PMP
(0.67 D)
D
D
+
+
Ph
(0 D)
w/o D
4g
1.0 equiv 1g
4.0 equiv 2a
BnO
BnO
(1.70 D) (0.13 D)
3a-d4
D
D
(0.87 D) (0.87 D)
OMe
(0 D)
1a-d4
PMP
(0 D)
standard
conditions
(0 D)
PMP
(0.24 D)
D
Ph
(0 D)
w/o D
4g
Ph
1.0 equiv 1g
4.0 equiv 2a
D
(0.08 D) (1.66 D)
1a-d2
3a-d2
OMe
f
Retention of configuration of pre-existing stereocenters along the hydrocarbon chain
Ph
standard
PhB(OH)2
+
Ph
(R)-1s 95% ee
conditions
Ph
(2.0 equiv)
(S)-5s 68% yield, 95% ee
reductive chain-walking conditions:[6e,h]
5 mol% NiCl2
6 mol% L5
Ph
+
+
PhI
2.5 equiv PMHS
2.0 equiv CsF
THF (0.20 M), rt
Ph
(R)-1s 95% ee
Ph
(S)-5s 10% yield
54% ee, 78:22 rr
(1.5 equiv)
5 mol% Ni(ClO4)2·6H2O
Ph
6 mol% L5
2.5 equiv nPrBr
2.5 equiv Mn
PhBr
Ph
(R)-1s 95% ee
Ph
(S)-5s 7% yield
20% ee, 95:5 rr
(2.0 equiv)
DMAc (0.20 M), rt
Scheme 1. Large-scale and mechanistic experiments.
Conclusion
In conclusion, we have developed a highly efficient and
robust nickel-catalyzed redox-relay migratory hydroarylation
reaction from two readily available chemicals, olefins and
arylboronic acids. An array of structurally diverse 1,1-
diarylalkanes, including some containing
a
1,1-diarylated
quaternary carbon, were obtained with excellent regio- and
chemoselectivity, from a reaction with high functional group
tolerance. The practical value of this transformation is
highlighted by the large-scale synthesis with low catalyst loading.
5
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10.1002/anie.202001742
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RESEARCH ARTICLE
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Finally, mechanistic experiments are consistent with the
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non-dissociated chain-walking before selective reductive
elimination at a benzylic position to produce the final product.
The development of an asymmetric version of this
transformation is currently in progress.
Acknowledgements
Support was provided by NSFC (21822105, 21772087). We
gratefully acknowledge Dr. Genfeng Feng (Professor Congqing
Zhu group) for acquiring X-ray crystal structure.
G.
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S.
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6
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RESEARCH ARTICLE
D. H. S. Silva, S. C. Davino, S. B. de Moraes Barros, M. Yoshida, J.
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7
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Entry for the Table of Contents
cat. NiII/L
L: diamine
R1 R2 R3
R1 R2 R3
R1 R2 R3
Ar
Ar1
R4
R4
R4
Ar1
Ar1
()m ()
n NiII
()m ()n
()m ()n
Ar[B] & ROH
R5
unrefined alkenes
(easily accessible)
R5
1,1-diarylalkane
(drug pharmacophore)
H
Ar
n regioconvergent
n mild/broad scope
n form 4o carbon
proposed chainwalking
via Ar-Ni(II)-H
A highly efficient and selective nickel-catalyzed redox-relay migratory hydroarylation process was reported. This mild process was
proposed to proceed through non-dissociated chain-walking of aryl-nickel(II)-hydride along the hydrocarbon chain of alkene.
Institute and/or researcher Twitter usernames: ((optional))
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