Nickel(0)-catalyzed linear-selective hydroarylation of unactivated alkenes and styrenes with aryl boronic acids

Article abstract of DOI:10.1039/c8sc02101e

Herein, we describe the first linear-selective hydroarylation reaction of unactivated alkenes and styrenes with aryl boronic acids, which was achieved by introducing a directing group on the alkenes. This efficient, scalable reaction serves as a method for modular assembly of structurally diverse alkyl arenes, including γ-aryl butyric acid derivatives, which are widely utilized as chemical building blocks for the synthesis of various drugs and other biologically active compounds.

Full text of DOI:10.1039/c8sc02101e

View Article Online
View Journal
Chemical
Science
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: H. Lv, L. Xiao, D.
Zhao and Q. Zhou, Chem. Sci., 2018, DOI: 10.1039/C8SC02101E.
This is an Accepted Manuscript, which has been through the
Volume
7 Number 1 January 2016 Pages 1–812
Royal Society of Chemistry peer review process and has been
accepted for publication.
Chemical
Science
Accepted Manuscripts are published online shortly after
www.rsc.org/chemicalscience
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 2041-6539
EDGE ARTICLE
Francesco Ricci et al.
Electronic control of DNA-based nanoswitches and nanodevices
rsc.li/chemical-science

Please do not adjust margins
Chemical Science
Page 1 of 6
View Article Online
DOI: 10.1039/C8SC02101E
Journal Name
ARTICLE
Nickel(0)-Catalyzed Linear-Selective Hydroarylation of
Unactivated Alkenes and Styrenes with Aryl Boronic Acids
Honggui Lv,a Li-Jun Xiao,a Dongbing Zhao*a and Qi-Lin Zhoua
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Herein, we describe the first linear-selective hydroarylation reaction of unactivated alkenes and styrenes with aryl boronic
acids, which was achieved by introducing a directing group on the alkenes. This efficient, scalable reaction serves as a
method for modular assembly of structurally diverse alkyl arenes, including γ-aryl butyric acid derivatives, which are widely
utilized as chemical building blocks for the synthesis of various drugs and other biologically active compounds.
www.rsc.org/
various drugs and other biologically active compounds
Introduction
(Scheme 1). γ-Aryl butyric acids are traditionally prepared by
Friedel–Crafts reactions between arenes and butyrolactones,9
but this method suffers from disadvantages such as harsh
reaction conditions, limited substrate scope (it is suitable only
for electron-rich arenes), and poor regioselectivity.
Transition-metal-catalyzed alkene hydroarylation involving
metal hydrides (M–H)1 has become one of the most widely
used strategies for the synthesis of alkyl arenes.2 To date,
three types of aryl sources have been used for this purpose: (1)
simple arenes, (2) aryl halides, and (3) aryl metals (i.e., aryl
stannanes or boronic acids). The simple arenes are usually
restricted to heteroarenes and arenes with a directing group
because of the challenge of activating the inert C–H bonds of
simple arenes.3 Aryl halides and aryl metals as the aryl sources
require the use of O2 or an excess of a reductant (such as a
a) Hydroarylation of alkenes with (hetero)arylmetals under reductive conditions
[M] catalyst
[M]= [Pd], [Ni], [Cu]
Ar
LG
…
Branch
Selectivity
Ar
R
involving MꢀH species
Excess reductant or O
H
2
R
LG: Halogen, [Sn] or [B]
…
Reductant: silanes, akyl bromides,
b) Hydroarylation of alkenes with (hetero)arylmetals under redox neutral conditions
0
Ar
silane or an alkyl halide), which limits the practicality of alkene
5
[B]
Ni catalyst
Branch
Selectivity
Ar
hydroarylations with these two sources (Scheme 1a).4,
A
R
involving NiꢀH species
Redox Neutral
H
R
(Styrenes and 1,3-dienes)
c) This work
significant breakthrough was made by Zhou et al., who
reported a highly selective Ni-catalyzed hydroarylation of
styrenes and 1,3-dienes with aryl boron compounds under
redox-neutral conditions (Scheme 1b).6 However, this method
still suffers from some limitations: (1) the reaction is efficient
only with styrene and 1,3-diene substrates, and (2) only
branched products can be achieved.
H
0
[B]
Ar
Ni catalyst
Linear
Ar
Selectivity
Ni H
ꢀ species
involving
Redox Neutral
DG
DG
Examples of drugs derived from 4-aryl butyric acids
O
OH
ONa
OH
Inspired by recent work on olefin functionalization reactions
Cl
O
O
O
N
Ph
in which the reactivity and regioselectivity are controlled via
8
Buphenyl
Fenbufen
Leukeran
the introduction of
a
coordinating group,7,
we have
Cl
CF3
N
developed the first method for directing-group-controlled
linear-selective hydroarylation of unactivated alkenes and
styrenes with aryl boronic acids under redox-neutral
conditions (Scheme 1c). This efficient, scalable reaction serves
as a method for modular assembly of structurally diverse alkyl
F
N
N
H
N
N
Cl
NHMe
NH2
O
F
CF3
Janumet
Sensipar
Cl
Sertraline
F
Scheme
1 Transition-metal-catalyzed hydroarylation of alkenes involving M–H and
arenes, including γ-aryl butyric acid derivatives, which are
widely utilized as chemical building blocks for the synthesis of
examples of drugs derived from 4-aryl butyric acids
Results and discussion
In a preliminary experiment, we found that treatment of 3-
butenoic acid derivative 1a (0.2 mmol), which bears an 8-
aminoquinoline (AQ) directing group, with Ni(COD)2 (5 mol%),
PCy3 (10 mol%), and 2-naphthalenylboronic acid 2a (0.3 mmol)
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 2 of 6
View Article Online
DOI: 10.1039/C8SC02101E
ARTICLE
Journal Name
in MeOH (1 mL) at 70 °C for 24 h gave linear product 3a in 21% high yield of 3b could be obtained by hydroarylation of 1a with
yield (Table 1, entry 1). Replacing MeOH with t-amyl alcohol an aryl boroxine or an aryl boronic ester as the aryl source. It is
slightly improved the yield (entry 2), and adding 1.5 equiv of important to stress that these reaction conditions were
K2CO3 improved the yield even further (to 38%, entry 3). compatible with a remarkable variety of functional groups on
Evaluation of different bases revealed that CsOPiv was the best the aryl boronic acids, including halogens (F, Cl, and Br) and
choice (entries 3−7). We also found that changing the 1a/2a acetyl, cyano, and methoxy groups, yielding products (3i–3s)
molar ratio to 1:2 increased the yield to 61% (entry 8). Finally, that could be subjected to further synthetic transformations.
various phosphine ligands were investigated (entries 9–12); In addition, the reaction could be carried out on gram scale
switching from PCy3 to PPh3 dramatically improved the yield without a decrease in the yield (1.5 g of 3b, 86%). The
(to 85%, entry 9). A control experiment confirmed that the structure of 3b was confirmed by X-ray diffraction analysis of a
reaction did not occur in the absence of Ni(COD)2 (entry 13).
single crystal.10
Table 1 Optimization of directed hydroarylation of unactivated alkene 1a with 2-
naphthalenylboronic acid 2a.a
Ni(COD)2 (5 mol %)
PPh3 (10 mol %)
O
O
Ar
+
Ar-B(OH)2
AQ
AQ
CsOPiv (1.5 equiv),
tꢀAmylOH (1 mL), 24 h, 70
C
1a
3
2
Me
O
O
O
O
AQ
AQ
AQ
AQ
AQ
3b, 78%; 70%;a 91%b
5 mmol scale, 86%
3a, 85%
3c, 65%
3d, 57%
Me
Et
tBu
Ph
O
O
O
O
O
O
O
O
AQ
AQ
AQ
AQ
AQ
AQ
AQ
3e, 84%
3i, 82%
3m, 89%
3f, 88%
3j, 89%
3n, 85%
3g, 74%
3h, 85%
Entry
Ligand
Base
Solvent
Yield [%]b
MeO
F3CO
F
Br
(H source)
O
O
AQ
AQ
AQ
1
PCy3
ꢀꢀꢀ
MeOH
21
3k, 89%
3l, 93%
Me
F
F3C
Ac
O
O
2
PCy3
ꢀꢀꢀ
tꢀAmylOH
tꢀAmylOH
tꢀAmylOH
tꢀAmylOH
tꢀAmylOH
tꢀAmylOH
tꢀAmylOH
t-AmylOH
tꢀAmylOH
tꢀAmylOH
tꢀAmylOH
tꢀAmylOH
29
AQ
3o, 84%
3p, 91%
3
PCy3
K2CO3
KHCO3
K3PO4
NaOtBu
CsOPiv
CsOPiv
CsOPiv
CsOPiv
CsOPiv
CsOPiv
CsOPiv
38
CN
CF3
Me
Cl
Me
O
O
O
O
4
PCy3
23
AQ
AQ
AQ
AQ
AQ
AQ
3s, 87%
5
PCy3
43
3q, 93%
3u, 82%
3r, 87%
3t, 86%
Me
O
O
O
O
6
PCy3
NR
53
S
Me
S
AQ
AQ
3w, 80%
3x, 76%
3v, 66%
7
PCy3
Scheme 2 The reactions of diverse aryl boronic acids 2 with 3-butenoic acid derivative
8c
9c
10c
11c
12c
13e
PCy3
61
a
1a. Yield of isolated product is given. 5,5-Dimethyl-2-phenyl-1,3,2-dioxaborinane was
used as the aryl source. b Triphenylboroxine was used as the aryl source.
PPh3
86(85)d
77
CyPPh2
SꢀPhos
XantPhos
PPh3
33
59
NR
a Reactions were carried out with Ni(COD)2 (5 mol%), ligand (10 mol%), base (0 or
1.5 equiv), 1a (0.2 mmol), and 2-naphthalenylboronic acid (2a, 0.3 mmol) in
solvent (1 mL) for 48 h at 25 °C under a N2 atmosphere. b Yields were determined
by NMR spectroscopy with an internal standard. NR = no reaction. c 2.0 equiv of
d
e
2a was used. The isolated yield is given in parenthesis. Reaction without
Ni(COD)2.
Next, we investigated the substrate scope with respect to the
aryl boronic acid by carrying out reactions with 3-butenoic acid
derivative 1a as the alkene (Scheme 2). To our delight,
electron-rich, electron-poor, and sterically hindered aryl
boronic acids all afforded the desired products in good to
Scheme 3 Reactions of unactivated alkenes with aryl boronic acid 2l. Yield of isolated
product is given. a PhPMe2 (10 mol%) as the ligand at 125 ºC.
We next evaluated the utility of this method for various
unactivated alkenes (Scheme 3). Terminal alkenes bearing a
excellent yields (3a–3u). Heteroaryl boronic acids were also
reactive (3v and 3w), as was an alkenyl boronic acid, which
selectively afforded (E)-6-phenylhexenoic acid derivative 3x
under the optimized conditions. In addition, we found that a
single substituent at the αꢀ or β-position reacted smoothly to
afford the desired products in good to excellent yields (4a and
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 3 of 6
View Article Online
DOI: 10.1039/C8SC02101E
Journal Name
ARTICLE
4b). A sterically congested α,α-disubstituted terminal alkene panel). Specifically, removal of the AQ directing group of 3b
was also reactive, furnishing desired product 4c in moderate smoothly provided 4-phenylbutanoic acid (5b) in 97% yield.
yield, although a higher temperature (125 °C) and a higher Acid 5b could undergo intramolecular cyclization to yield
loading(10 mol%) of a different ligand, PhPMe2, were required. tetralin-derivative 6a, or the carboxyl group could be replaced
Furthermore, internal alkenes bearing a variety of substituents with an iodine atom (6b). Five-membered lactone 6c could be
at the
γ-position could also be efficiently converted into the obtained by treatment of 5b with a hypervalent iodine
corresponding products (4d
–
4l); the steric and electronic reagent, and 5b readily underwent attack by CH3NO2 to afford
effects of the substituents appeared to be negligible. Notably, corresponding ketone derivative 6d. To further demonstrate
the yields of 4e from trans- and cis-3-hexenoic acid were the synthetic usefulness of our method, we synthesized the
essentially the same. In addition, α,γ-disubstituted alkenes drug Sensipar from 3s (Scheme 5, lower panel). First, free acid
gave desired products 4i and
4
j
.
Surprisingly,
a
γ,γ
disubstituted alkene could also be hydroarylated to produce then the acid was transformed into the corresponding alkyl
-
5s was synthesized by removal of the AQ directing group, and
compound 4l (88%), which has a quaternary carbon center.
iodide (6s) by treatment with NIS/I2 in DCE. Simple amination
of 6s gave Sensipar in 97% yield.
To probe the reaction mechanism, we carried out a control
experiment and a series of deuteration experiments (Scheme
6). We found that no reaction occurred when N-
(naphthalenyl)butenamide
7 and 2-naphthalenylboronic acid
(
1a) were used as the substrates (eq. 1). This result indicates
that the presence of the AQ directing group on the unactivated
alkene was indispensable. Treatment of PhB(OD)2 2b-D with
alkene 1a in MeOH or treatment of (PhBO)3 with 1a in CD3OH
gave undeuterated product 3b (eqs. 2 and 3). However, the
use of MeOD as the solvent led to the formation of 3b that
Scheme 4 Reactions of styrene derivative 1m with aryl boronic acids.
We wondered whether the introduction of the AQ directing
group at the ortho-position of styrene would result in linear
selectivity rather than the branched selectivity reported by
Sigman et al. and Zhou et al. for hydroarylation of styrenes
with aryl metals.4, 6 After extensive investigation, we found, to
our delight, that reactions of styrene derivative 1m with
various aryl boronic acids occurred smoothly with completely
linear selectivity and in moderate yield by employment of
PhPCy2 as the ligand and higher catalyst loading (10 mol%
Ni(COD)2), higher temperature (125 °C), and longer reaction
time (Scheme 4). This result clearly proved that the directing
group controlled the regioselectivity of the hydrometalation.
was only partially deuterated at both the αꢀ and
(eq. 4), which reveals that the hydrogen atom of the Ni–H
intermediate (Scheme 7) came from the methanol O–H
β-positions
A
group and hydrometalation of Ni-H is irreversible in the
presence of aryl boronic acid. Further experiment suggests
that hydrometalation of starting material 1a via Ni-H species
would also happen to form 5-membered nickelacycle and is
reversible in the absence of aryl boronic acid under our
reaction conditions (eqs.
5 and 6). Additionally, the
deuteration of
α
-positions might be because of CsOPiv base.
O
B(OH)2
"standard conditions"
No reaction
(1)
(2)
N
H
7
2a
Ni(COD)2 (5 mol %)
PPh3 (10 mol %)
O
0 D
B(OD)2
O
AQ
AQ
CsOPiv (1.5 equiv.),
CH3OH (1 mL), 24 h, 70
C
1a
2b-D
0 D
0 D
3b
Ni(COD)2 (5 mol %)
PPh3 (10 mol %)
O
Ph
O
Ph
Ph
O
B
B
(3)
AQ
O
O
CsOPiv (1.5 equiv.),
CD3OH (1 mL), 24 h, 70
AQ
AQ
B
1a
C
C
Ph
3b
0 D
0.82 D
Ni(COD)2 (5 mol %)
PPh3 (10 mol %)
O
Ph
O
B
B
O
O
(4)
AQ
O
O
CsOPiv (1.5 equiv.),
CH3OD (1 mL), 24 h, 70
B
AQ
1a
3b-D
0.58 D
Ph
(recovery)
1.26 D
Ni(COD)2 (5 mol %)
PPh3 (10 mol %)
O
1.17 D
O
OMe O
0.34 D
AQ
CsOPiv (1.5 equiv.),
(5)
AQ
AQ
CH3OD (1 mL), 24 h, 70
C
8-D
0.90 D
9-D
1a
Ni(COD)2 (5 mol %)
PPh3 (10 mol %)
O
O
Scheme 5 Transformations of hydroarylation products 3b and 3s.
(6)
AQ
AQ
CsOPiv (1.5 equiv.),
CH3OD (1 mL), 24 h, 70
C
3b-D
3b
0.62 D
The products obtained by the method described herein could
provide access to structurally diverse synthetic building blocks
by means of additional transformations (Scheme 5, upper
Scheme 6 Control experiment and deuteration experiments.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 4 of 6
View Article Online
DOI: 10.1039/C8SC02101E
ARTICLE
Journal Name
498; (b) C. Deutsch, N. Krause and B. H. Lipshutz, Chem. Rev.,
2008, 108, 2916; (c) M. T. Pirnot, Y.-M. Wang and S. L.
Buchwald, Angew. Chem. Int. Ed., 2016, 55, 48; (d) M. D.
Greenhalgh, A. S. Jones and S. P. Thomas, ChemCatChem
On the basis of literature reports and our own mechanistic
experiments, we propose two catalytic cycles that starts with
the reversible formation of Ni–H species
A (Scheme 7). For
Path A, coordination and subsequent hydrometalation of the
C=C bond affords the sixꢀmembered nickelacyclic intermediate
2015, 7, 190; (e) R. M. Maksymowicz, A. J. Bissette and S. P.
Fletcher, Chem. Eur. J., 2015, 21, 5668; (f) S. W. M. Crossley,
C. Obradors, R. M. Martinez and R. A. Shenvi, Chem. Rev.,
2016, 116, 8912; (g) K. D. Nguyen, B. Y. Park, T. Luong, H.
Sato, V. J. Garza and M. J. Krische, Science 2016, 354, 300.
For some reviews on hydroarylation of alkenes, see: (a) F.
Kakiuchi and S. Murai, Acc. Chem. Res., 2002, 35, 826; (b) S.
C
, and then transmetalation of the aryl boronic acid generates
intermediate D 11
Finally, reductive elimination gives the
desired product and regenerates the Ni(0) catalyst.
Alternatively, intermediate could also undergo
transmetalation first to form ArylꢀNiꢀH species C , and then
alkene insertion to form fiveꢀmembered nickelacyclic
intermediate , which would involve reductive elimination to
.
2
3
A
'
Pan and T. Shibata, ACS Catal., 2013, 3, 704; (c) X. Zeng,
Chem. Rev., 2013, 113, 6864; (d) L. Yang and H. Huang,
Chem. Rev., 2015, 115, 3468; (e) G. E. M. Crisenza and J. F.
Bower, Chem. Lett., 2016, 45, 2; (f) Z. Dong, Z. Ren, S. J.
Thompson, Y. Xu and G. Dong, Chem. Rev., 2017, 117, 9333.
For some examples on hydroarylation of alkenes using
arenes as the aryl source, see: (a) Z.-M. Sun, J. Zhang, R. S.
Manan and P. Zhao, J. Am. Chem. Soc., 2010, 132, 6935; (b)
Y. Nakao, Y. Yamada, N. Kashihara and T. Hiyama, J. Am.
Chem. Soc., 2010, 132, 13666; (c) K. Gao and N. Yoshikai, J.
Am. Chem. Soc., 2011, 133, 400; (d) B.-T. Guan and Z. Hou, J.
Am. Chem. Soc., 2011, 133, 18086; (e) J. Oyamada and Z.
Hou, Angew. Chem. Int. Ed., 2012, 51, 12828; (f) S. Pan, N.
Ryu and T. Shibata, J. Am. Chem. Soc., 2012, 134, 17474; (g)
D'
yield the same linear product. Note, that we have detected the
production of naphthalene under our reaction condition. It
indicated that cycle B might be the real process. However, at
this stage, we still can’t rule out cycle A.
P.-S. Lee and N. Yoshikai, Angew. Chem. Int. Ed., 2013, 52
,
1240; (h) T. Andou, Y. Saga, H. Komai, S. Matsunaga and M.
Kanai, Angew. Chem. Int. Ed., 2013, 52, 3213; (i) W. Xu and
N. Yoshikai, Angew. Chem. Int. Ed., 2014, 53, 14166; (j) G. E.
M. Crisenza, N. G. McCreanor and J. F. Bower, J. Am. Chem.
Soc. 2014, 136, 10258; (k) J. S. Bair, Y. Schramm, A. G.
Sergeev, E. Clot, O. Eisenstein and J. F. Hartwig, J. Am. Chem.
Soc., 2014, 136, 13098; (l) G. E. M. Crisenza, O. O. Sokolova
and J. F. Bower, Angew. Chem. Int. Ed., 2015, 54, 14866; (m)
Y. Schramm, M. Takeuchi, K. Semba, Y. Nakao and J. F.
Hartwig, J. Am. Chem. Soc., 2015, 137, 12215; (n) Y. Ebe and
T. Nishimura, J. Am. Chem. Soc., 2015, 137, 5899; (o) C. M.
Filloux and T. Rovis, J. Am. Chem. Soc., 2015, 137, 508; (p) M.
Hatano, Y. Ebe, T. Nishimura and H. Yorimitsu, J. Am. Chem.
Soc., 2016, 138, 4010; (q) N. Kimura, T. Kochi and F. Kakiuchi,
J. Am. Chem. Soc., 2017, 139, 14849; (r) J. Loup, D. Zell, J. C.
A. Oliveira, H. Keil, D. Stalke and L. Ackermann, Angew.
Chem. Int. Ed., 2017, 56, 14197.
(a) K. M. Gligorich, S. A. Cummings and M. S. Sigman, J. Am.
Chem. Soc., 2007, 129, 14193; (b) Y. Iwai, K. M. Gligorich and
M. S. Sigman, Angew. Chem. Int. Ed., 2008, 47, 3219; (c) L.
Liao and M. S. Sigman, J. Am. Chem. Soc., 2010, 132, 10209.
(a) K. Semba, K. Ariyama, H. Zheng, R. Kameyama, S. Sakaki
and Y. Nakao, Angew. Chem. Int. Ed., 2016, 55, 6275; (b) S. D.
Friis, M. T. Pirnot and S. L. Buchwald, J. Am. Chem. Soc.,
2016, 138, 8372; (c) S. D. Friis, M. T. Pirnot, L. N. Dupuis and
S. L. Buchwald, Angew. Chem. Int. Ed., 2017, 56, 7242; (d) X.
Lu, B. Xiao, Z. Zhang, T. Gong, W. Su, J. Yi, Y. Fu and L. Liu,
Scheme
7 Proposed mechanism of the Ni(0)-catalyzed directing-group-controlled
hydroarylation of unactivated alkenes with aryl boronic acids.
Conclusions
In conclusion, we have described the first method for Ni(0)-
catalyzed
directing-group-controlled
linear-selective
hydroarylation of unactivated alkenes and styrenes with aryl
boronic acids under redox-neutral conditions. Our efficient,
scalable method provides a general route to structurally
4
5
diverse alkyl arene derivatives, including γ-aryl butyric acid
derivatives, which are widely utilized as chemical feedstocks
for the preparation of drugs and other biologically active
compounds.
Conflicts of interest
There are no conflicts to declare.
Nat. Commun., 2016, 7, 11129; (e) S. A. Green, J. L. M.
Matos, A.Yagi and R. A. Shenvi, J. Am. Chem. Soc., 2016, 138,
12779; (f) Y. He, Y. Cai and S. Zhu, J. Am. Chem. Soc., 2017,
139, 1061; (g) F. Chen, K. Chen, Y. Zhang, Y. He, Y.-M. Wang
and S. Zhu, J. Am. Chem. Soc., 2017, 139, 13929; (h) W. Li, J.
K. Boon and Y. Zhao, Chem. Sci., 2018, 9, 600.
L.-J. Xiao, L. Cheng, W.-M. Feng, M.-L. Li, J.-H. Xie and Q.-L.
Zhou, Angew .Chem. Int. Ed., 2018, 57, 461.
For some recent examples on directed unactivated alkenes
functionalization without metal hydride species, see: (a) E. P.
A. Talbot, T. A. Fernandes, J. M. McKenna and F. D. Toste, J.
Am. Chem. Soc., 2014, 136, 4101; (b) A. Archambeau and T.
Rovis, Angew. Chem. Int. Ed., 2015, 54, 13337; (c) Z. Liu, T.
Zeng, K. S. Yang and K. M. Engle, J. Am. Chem. Soc., 2016,
138, 15122; (d) K. S. Yang, J. A. Gurak Jr., Z. Liu and K. M.
Acknowledgements
We are grateful for the financial support from the National
Natural Science Foundation of China (21602115), 1000-Talent
Youth Program (020/BF180181), the Fundamental Research
Funds for the Central Universities and Nankai University.
6
7
Notes and references
1
For some reviews on metal-hydride chemistry, see: (a) S.
Rendler and M. Oestreich, Angew. Chem. Int. Ed., 2007, 46
,
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 5 of 6
View Article Online
DOI: 10.1039/C8SC02101E
Journal Name
ARTICLE
Engle, J. Am. Chem. Soc., 2016, 138, 14705; (e) J. A. Gurak,
Jr., K. S. Yang, Z. Liu and K. M. Engle, J. Am. Chem. Soc., 2016,
138, 5805; (f) J. Derosa, V. T. Tran, M. N. Boulous, J. S. Chen
and K. M. Engle, J. Am. Chem. Soc., 2017, 139, 10657; (g) Z.
Liu, Y. Wang, Z. Wang, T. Zeng, P. Liu and K. M. Engle, J. Am.
Chem. Soc., 2017, 139, 11261; (h) J. A. Gurak Jr and K. M.
Engle, Synlett 2017, 28, 2057; (i) B. Shrestha, P. Basnet, R. K.
Dhungana, S. KC, S. Thapa, J. M. Sears and R. Giri, J. Am.
Chem. Soc., 2017, 139, 10653; (j) S. Guin, A. Deb, P. Dolui, S.
Chakraborty, V. K. Singh and D. Maiti, ACS Catal., 2018, 8,
2664; (k) A. Deb, A. Hazra, Q. Peng, R. S. Paton and D. Maiti, J.
Am. Chem. Soc., 2017, 139, 763; (l) A. Deb, S. Bag, R.
Kancherla and D. Maiti, J. Am. Chem. Soc., 2014, 136, 13602.
For some directed hydrofunctionalizations involving M−H
species, see: hydrogenation: (a) R. H. Crabtree and M. W.
Davis, J. Org. Chem., 1986, 51, 2655; (b) S. Song, S.-F. Zhu, Y.-
B. Yu and Q.-L. Zhou, Angew. Chem. Int. Ed., 2013, 52, 1556;
hydrosilyation: (c) J. B. Perales and D. L. Van Vranken, J. Org.
Chem., 2001, 66, 7270; (d) Y. Kawasaki, Y. Ishikawa, K. Igawa
and K. Tomooka, J. Am. Chem. Soc., 2011, 133, 20712;
hydroboration: (e) D. A. Evans and G. C. Fu, J. Am. Chem. Soc.,
1991, 113, 4042; (f) C. E. Garrett and G. C. Fu, J. Org. Chem.,
1998, 63, 1370; (g) M. Rubina, M. Rubin and V. Gevorgyan, J.
Am. Chem. Soc., 2003, 125, 7198; (h) S. M. Smith and J. M.
Takacs, J. Am. Chem. Soc., 2010, 132, 1740; (i) C. Sun, B.
Potter and J. P. Morken, J. Am. Chem. Soc., 2014, 136, 6534;
(j) Z.-D. Yang, R. Pal, G. L. Hoang, X. C. Zeng and J. M. Takacs,
8
ACS Catal., 2014, 4, 763; (k) G. L. Hoang, Z.-D. Yang, S. M.
Smith, R. Pal, J. L. Miska, D. E. Pérez, L. S. W. Pelter, X. C.
Zeng and J. M. Takacs, Org. Lett., 2015, 17, 940; (l) V. M.
Shoba, N. C. Thacker, A. J. Bochat and J. M. Takacs, Angew.
Chem. Int. Ed., 2016, 55, 1465; (m) S. Chakrabarty and J. M.
Takacs, J. Am. Chem. Soc., 2017, 139, 6066; hydroacylation;
(n) M. M. Coulter, P. K. Dornan and V. M. Dong, J. Am. Chem.
Soc., 2009, 131, 6932; (o) M. M. Coulter, K. G. M. Kou, B.
Galligan and V. M. Dong, J. Am. Chem. Soc., 2010, 132
,
16330; (p) S. K. Murphy, A. Bruch and V. M. Dong, Angew.
Chem. Int. Ed., 2014, 53, 2455; (q) S. K. Murphy, A. Brucha
and V. M. Dong, Chem. Sci., 2015, 6, 174; hydroformylation;
(r) C. L. Joe, T. P. Blaisdell, A. F. Geoghan and K. L. Tan, J. Am.
Chem. Soc., 2014, 136, 8556; (s) I. J. Krauss, C. C.-Y. Wang
and J. L. Leighton, J. Am. Chem. Soc., 2001, 123, 11514; (t) A.
D. Worthy, . L. Joe, T. E. Lightburn and K. L. Tan, J. Am. Chem.
Soc., 2010, 132, 14757; (u) B. Breit and D. Breuninger, J. Am.
Chem. Soc., 2004, 126, 10244.
9
(a) A. F. Döbber, R. H. Phoa, B. W. Abbassi, B. W. Stringer, T.
G. Day, M. Johns, C. P. Abadleh, and L. Munoz, ACS Med.
Chem. Lett., 2017, 8, 395; (b) P. Prusevich, J. H. Kalin, S. A.
Ming, M. Basso, J. Givens, X. Li, J. Hu, M. S. Taylor, A. M.
Cieniewicz, P.-Y. Hsiao, R. Huang, H. Roberson, N. Adejola, L.
B. Avery, R. A. Casero Jr., S. D. Taverna, J. Qian, A. J. Tackett,
R. R. Ratan, O. G. McDonald, A. P. Feinberg and P. A. Cole,
ACS Chem. Biol., 2014, 9, 1284; (c) Y.-Z. Xu, X.-Y. Gu, S.-J.
Peng, J.-G. Fang, Y.-M. Zhang, D.-J. Huang, J.-J. Chen and K.
Gao, Eur. J. Med. Chem., 2015, 94, 284.
10 CCDC 1838875
(
3b
)
contains the supplementary
crystallographic data. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
https://www.ccdc.cam.ac.uk/structures.
11 (a) G. Huang and P. Liu, ACS Catal., 2016, 6, 809; (b) M. Liu,
P. Yang, M. K. Karunananda, Y. Wang, P. Liu and K. M. Engle,
J. Am. Chem. Soc., 2018, 140, 5805; (c) Z. Liu, H.-Q. Ni, T.
Zeng and K. M. Engle, J. Am. Chem. Soc., 2018, 140, 3223.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Chemical Science
Page 6 of 6
View Article Online
DOI: 10.1039/C8SC02101E
DG Controlled-Linear Selectivity! The first nickel(0)-catalyzed linear-selective hydroarylation of
unactivated alkenes and styrenes with organoboronic acids are achieved under redox-neutral conditions.
1