Nickel(0)-Catalyzed Hydroarylation of Styrenes and 1,3-Dienes with Organoboron Compounds

Article abstract of DOI:10.1002/anie.201710735

A Ni-catalyzed hydroarylation of styrenes and 1,3-dienes with organoboron compounds has been developed. The reaction offers a highly selective approach to diarylalkanes and allylarenes under redox-neutral conditions. In this hydroarylation reaction, a new strategy that uses the proton of methanol to generate the active catalyst species Ni?H was developed. The Ni-catalyzed hydroarylation, combined with a Ir-catalyzed C?H borylation, affords a very efficient and straightforward access to a retinoic acid receptor agonist.

Full text of DOI:10.1002/anie.201710735

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Accepted Article
Title: Nickel(0)-Catalyzed Hydroarylation of Styrenes and 1,3-Dienes
with Organoborons
Authors: Qi-Lin Zhou, Li-Jun Xiao, Lei Cheng, Wei-Min Feng, Mao-Lin
Li, and Jian-Hua Xie
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201710735
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10.1002/anie.201710735
Angewandte Chemie International Edition
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Nickel(0)-Catalyzed Hydroarylation of Styrenes and 1,3-Dienes
with Organoborons
Li-Jun Xiao,[a] Lei Cheng,[a] Wei-Min Feng,[a] Mao-Lin Li,[a] Jian-Hua Xie,[a,b] Qi-Lin Zhou*[a,b]
Abstract: The Ni-catalyzed hydroarylation of styrenes and 1,3-dienes
with organoborons has been developed. The reaction offers a highly
selective approach to the diarylalkanes and allylarenes under redox-
neutral condition. In this hydroarylation reaction, a new strategy that
uses easily available proton of methanol to generate active catalyst
species Ni–H was developed. The Ni-catalyzed hydroarylation,
combining with a Ir-catalyzed C–H borylation, affords a very efficient
and straightforward access to retinoic acid receptor agonist.
(entries 5 and 6). The reaction can also be performed in pure
alcohols, with MeOH giving best result (3a: 70%, b/l >99:1, entry
7). However, under these reaction conditions, a competitive
styrene dimerization reaction occurred, producing 5a in up to 84%
yield. To prevent this side reaction and improve the yield of the
hydroarylation product, various monophosphine ligands were
evaluated. It was delighted to find that the bulky and electron-rich
phosphine ligand PtBu3 not only prevented styrene dimerization
but also allowed the reaction to occur at a lower temperature.
When the reaction was carried out at 60 °C for 1 h, the
hydroarylation product 3a was obtained in 88% yield (entry 14). It
is worth mentioning that the uses of Ni(II) catalysts or chelating
diphosphine ligands give no reaction (see SI).
Transition-metal-catalyzed functionalization of alkenes is a
highly efficient C−C bond forming reaction using abundant
feedstocks to produce value-added products and has received
increasing attention.[1] Hydroarylation, the addition of hydrogen
and aryl to alkenes offers a straightforward method for the
synthesis of alkylarenes. Among the hydroarylations, the reaction
with styrenes could produce 1,1-diarylalkanes, which often show
biological activity.[2] To date, two strategies have been developed
for achieving hydroarylation of alkenes, which are characterized
by using different way to generate active catalyst species M−H.
One uses C−H bond activation of arenes to form M−H (Scheme
1a),[3] and other uses hydride reagents to form M−H (Scheme
1b).[4] The former strategy usually required the arenes having a
directing group or heteroarenes. The latter strategy worked only
under reductive conditions. As a part of our efforts on the
development of earth-abundant nickel catalysis,[5] we herein
report the hydroarylation of alkenes under redox-neutral condition.
In our hydroarylation reaction, proton of methanol was used to
react with Ni0 to generate active catalyst species Ni−H (Scheme
1c), which represents a unique example in which the catalytic
process is initiated by the protonation of a low-valent metal.[6]
We began our study by investigating the hydroarylation of
styrene (1a) with (4-methoxyphenyl)boronic acid (2a) in the
presence of a Ni catalyst generated in situ from Ni(COD)2 and a
monophosphine ligand. The complex Ni0/PCy3 was found to
catalyzed the reaction of 1a with 2a at 80 °C in THF or toluene,
giving branched hydroarylation product 3a, however, in low yield
(Table 1, entries 1 and 2). Adding H2O and MeOH into toluene
increased the yields of 3a to 64% and 36% yield, respectively
Scheme 1. Transition-metal-catalyzed hydroarylations of alkenes
A variety of alkenes 1 and arylboronic acids 2 were investigated
under the aforementioned optimal reaction conditions. As shown
in Table 2, all reactions of styrene 1a with different arylboronic
acids gave hydroarylation products 3a–3g in moderate to high
yields (50–92%) with excellent regioselectiviity (b/l >99:1). Both
electronic and steric properties of the arylboronic acids affected
the yield of the reaction. Arylboronic acids having an electron-
donating group afforded higher yields than those having an
electron-withdrawing group (3a vs 3d). The arylboronic acid with
a 2-methyl group exhibited only a moderate yield (3e, 61%)
because of the steric effect of the 2-methyl on the phenyl ring of
arylboronic acid. Notably, the reaction tolerated a wide range of
functional groups in arylboronic acids, including ketone (3i),
[a]
L.-J. Xiao, L. Cheng, W.-M. Feng, M.-L. Li, Prof. J.-H. Xie, Prof. Q.-
L. Zhou
State Key Laboratory and Institute of Elemento-organic Chemistry,
College of Chemistry, Nankai University
Tianjin 300071, China
E-mail: qlzhou@nankai.edu.cn
Homepage: http://zhou.nankai.edu.cn.
Prof. J.-H. Xie, Prof. Q.-L. Zhou
[b]
Collaborative Innovation Center of Chemical Science and
Engineering (Tianjin)
Tianjin 300071, China
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201710735
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COMMUNICATION
Table 2. Hydroarylation of alkenes with arylboronic acids[a,b]
Table 1. Optimization of reaction conditions[a]
[a] Reaction conditions: styrene 1a (0.5 mmol), (4-methoxyphenyl)boronic acid
2a (0.75 mmol), Ni(COD)2 (0.025 mmol), ligand (0.050 mmol), solvent (1.0 mL).
[b] Yields and b/l ratio were determined by GC with internal standard; isolated
yield is given in parenthesis. [c] H source: 2.0 equiv. [d] At 60 °C for 1 h.
[a] Reaction conditions: alkenes 1 (0.5 mmol), boronic acid 2 (0.75 mmol),
Ni(COD)2 (0.025 mmol), PtBu3 (0.050 mmol), MeOH (1.0 mL) for 1–2 h; the ratio
of b/l >99:1 unless otherwise noted. [b] Isolated yields. [c] b/l = 87:13. [d] b/l =
89:11.
amide (3j), and ester (3k). The boronic acid with a furyl ring also
underwent hydroarylation reaction with 1a albeit the yield was
relatively low (3h, 40%). Next, we carried out hydroarylation
reactions of various styrenes with phenylboronic acid or
naphthylboronic acid. High yield (82–94%) and excellent
regioselectivity (b/l > 99:1) were obtained for the most of tested
Table 3. Hydroarylation of 1,3-dienes[a,b]
styrenes. However, styrenes having
a strongly electron-
withdrawing CF3 group afforded only moderate yield and lower
regioselectivity (3p and 3s). Styrenes with sterically bulky 2-
methyl and 3,4,5-trimethoxyl groups still reacted with
phenylboronic acid and naphthylboronic acid, but gave only
moderate yields (3t and 3v). The internal aromatic alkenes such
as trans-β-methylstyrene or indene and aliphatic alkenes such as
1-hexene were inert in the Ni-catalyzed hydroarylation reaction
with arylboronic acid.
We also examined Ni-catalyzed hydroarylation reactions of 1,3-
dienes 6 with (4-methoxyphenyl)boronic acid (2a) (Table 3). For
these dienes, Ni/PCy3 or Ni/PPh3 catalyst provided better results
than the Ni/PtBu3 catalyst. The aromatic 1,3-dienes and cyclic 1,3-
dienes reacted with 2a at 80 °C, giving exclusively allylic arylation
product in good to high yields (70−95%). However, the aliphatic
1,3-diene 6e provided a mixture of hydroarylation products at C2
and C4 in a 1:1 ratio.
[a] Reaction conditions: diene 6 (0.5 mmol), boronic acid 2a (0.75 mmol),
Ni(COD)2 (0.025 mmol), PR3 (0.050 mmol), MeOH (1.0 mL) for 12 h. [b] Isolated
yield. [c] Performed with PCy3. [d] Performed with PPh3.
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In addition to arylboronic acids, arylboroxines, arylboronic
esters, and boranes could also be used as hydroarylation reagent
in this Ni-catalyzed hydroarylation reaction (Table 4). For example,
arylboronic esters 8a–8c and triphenylborane 8d reacted with 4-
methylstyrene (1n), giving hydroarylation product 3n in good to
excellent yields (71–95%) with excellent regioselectivity (b/l >
99:1). Encouraged by these results, we applied this Ni-catalyzed
hydroarylation protocol to the synthesis of 1,1-diarylethane 3w,
which is a retinoic acid receptor agonist.[7] The combination of our
Ni-catalyzed hydroarylation with an Ir-catalyzed C–H borylation
reaction[8] afforded a very efficient and straightforward access to
3w in good yield on a gram scale.
A mechanism was proposed based on the aforementioned
experimental results and previous reports (Scheme 3).[9] First,
oxidative addition of the O‒H bond of methanol to the nickel
atom yields methoxyl-nickel-hydride intermediate A. The
hydride of Ni–H was transferred to the terminal carbon of the
double bond of styrene to form a benzylic nickel intermediate
B in path I. The resulting methoxyl-Ni-benzyl intermediate
underwent transmetalation with arylboron to generate
intermediate C.[10] Finally, reductive elimination of C provided
the hydroarylation product 3. Similar steps were involved in
path II, with the hydride of Ni–H being transferred to the internal
carbon of the double bond of styrene and afforded linear
product 4. Because the methoxyl-nickel-benzylic intermediate
B is stabilized by forming a η3-ally nickel complex,[11] the
branched product (path I) was expected as a main product.
Table 4. Arylboron reagent scope and the synthesis of retinoic
acid receptor agonist[a,b]
Scheme 3. Proposed mechanism.
In summary, we have developed a highly selective Ni-
catalyzed hydroarylation of styrenes and 1,3-dienes with
arylboron compounds under redox-neutral conditions. This
reaction offers a new approach to the selective preparation of
diarylalkanes and allylarenes. In this hydroarylation reaction, a
new strategy that uses easily available proton of methanol to
generate active catalyst species Ni–H has been developed.
These results shed light on the origins of the reactivity and the
regioselectivity of the reaction and may be useful for the
development of new functionalization reaction of alkenes
catalyzed by nickel or other transition metals.
To gain some mechanistic insight on the hydroarylation
reaction, deuterium-labeling experiments using CH3OD and
CD3OH were conducted. As shown in Scheme 2, the H NMR
spectroscopic analysis of the products revealed that the Ni−H
intermediate was generated from methanol O−H, instead of C−H
bond of alcohol like that in the previous work.[4a-c] The observation
of H/D scrambling at methyl and benzyl of the hydroarylation
product suggested that the reaction involves reversible formations
of methoxyl-nickel–hydrogen and methoxyl-nickel–benzyl
intermediates.
1
Experimental Section
In an argon-filled glove-box, an oven-dried sealed tube was charged with
a stir bar, catalyst precursor Ni(COD)2 (7.0 mg, 0.025 mmol), and (4-
methoxyphenyl)boronic acid (2a, 114 mg, 0.75 mmol). A solution of PtBu3
in toluene (25 μL, 0.050 mmol, 50 wt%), styrene 1a (58 μL, 0.50 mmol),
and methanol (1.0 mL) was injected into the tube under argon. The mixture
was heated at 60 ºC for one hour, and then cooled down to room
temperature. The resulting mixture was passed through a short silica gel
column eluted with ethyl acetate, and analyzed branched/linear ratio of
product 3a by GC using n-dodecane as an internal standard. The pure
product was obtained by column chromatography on silica gel (PE/EA =
40:1, v/v) in 88% yield as a colorless oil.
Scheme 2. Deuterium-labeling experiment.
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Acknowledgements
We thank the National Natural Science Foundation of China (Nos.
21325207, 21421062, 21532003) and the “111” project (B06005)
of the Ministry of Education of China for financial support.
Keywords: Nickel Catalyst • Coupling • Hydroarylation• Alkene •
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COMMUNICATION
COMMUNICATION
Li-Jun Xiao, Lei Cheng, Wei-Min Feng,
Mao-Lin Li, Jian-Hua Xie, Qi-Lin Zhou*
Page No. – Page No.
Nickel(0)-Catalyzed Hydroarylation of
Styrenes and 1,3-Dienes with
Organoborons
A nickel(0)-catalyzed hydroarylation of alkenes with organoborons using alcohol O−H
as H-atom source is reported. The reaction offers a highly selective approach to the
diarylalkanes and allylarenes under redox-neutral conditions.
This article is protected by copyright. All rights reserved.