Nickel-Catalyzed Hydroacylation of Styrenes with Simple Aldehydes: Reaction Development and Mechanistic Insights

Article abstract of DOI:10.1021/jacs.6b00024

The first nickel-catalyzed intermolecular hydroacylation reaction of alkenes with simple aldehydes has been developed. This reaction offers a new approach to the selective preparation of branched ketones in high yields (up to 99%) and branched selectivities (up to 99:1). Experimental data provide evidence for reversible formation of acyl-nickel-alkyl intermediate, and DFT calculations show that the aldehyde C-H bond transfer to a coordinated alkene without oxidative addition is involved. The origin of the reactivity and regioselectivity of this reaction was also investigated computationally, which are consistent with experimental observations.

Full text of DOI:10.1021/jacs.6b00024

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Communication
Nickel-Catalyzed Hydroacylation of Styrenes with Simple
Aldehydes: Reaction Development and Mechanistic Insights
Li-Jun Xiao, Xiao-Ning Fu, Min-Jie Zhou, Jian-Hua Xie, Li-Xin Wang, Xiu-Fang Xu, and Qi-Lin Zhou
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b00024 • Publication Date (Web): 08 Feb 2016
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Nickel-Catalyzed Hydroacylation of Styrenes with Simple Alde-
hydes: Reaction Development and Mechanistic Insights
Li-Jun Xiao,a Xiao-Ning Fu,b Min-Jie Zhou,a Jian-Hua Xie,a,c Li-Xin Wang,a Xiu-Fang Xu,* a,b Qi-
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Lin Zhou* a,c
a State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China
b Department of Chemistry, Nankai University, Tianjin 300071, China
c Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China
E-mail: qlzhou@nankai.edu.cn; xxfang@nankai.edu.cn
as silyl triflate or trimethylaluminum to provide allylic
ABSTRACT: The first nickel-catalyzed intermolecular
alcohol derivatives.11 Thus, the nickel-catalyzed intermo-
hydroacylation reaction of alkenes with simple aldehydes
lecular direct hydroacylation of alkenes with simple alde-
has been developed. This reaction offers a new approach
hydes remains a challenge.
to the selective preparation of branched ketones in high
We have studied nickel-catalyzed asymmetric coupling
yields (up to 99%) and branched selectivities (up to 99:1).
of aldehydes with alkynes and 1,3-dienes for the synthesis
Experimental data provide evidence for reversible for-
mation of acyl-nickel−alkyl intermediate and DFT calcula-
of chiral allylic and bishomoallylic alcohols, respectively,
as well as coupling of imines with alkynes for the synthe-
tions show that the aldehyde C−H bond transfer to a co-
ordinated alkene without oxidative addition is involved.
of the coupling of aldehydes with alkenes and alkynes, we
The origin of the reactivity and regioselectivity of this re-
action was also investigated computationally which are
hydroacylation of alkenes to provide branched ketones in
consistent with experimental observations.
sis of chiral allylic amines.12 As part of our ongoing studies
herein report the first nickel-catalyzed intermolecular
high yields with excellent selectivities. The experiments
and density functional theory (DFT) calculations showed
that the reaction involves an aldehyde C−H bond transfer
to the coordinated alkene, forming an acyl-nickel−alkyl
intermediate reversibly (Scheme 1c), which is different
from the oxidative cyclization pathway (Scheme 1a and
1b).
Transition metal–catalyzed hydroacylation of alkenes
with aldehydes is a useful and atom-economical method
for the synthesis of ketones.1 This cross-coupling reaction
involves metal-catalyzed activation of a C–H bond and
addition of the aldehyde to the alkene to form a new C–C
bond. The first example of this transformation was report-
ed in 1972 by Sakai et al.,2 who used a stoichiometric
amount of a rhodium catalyst for intramolecular hydroac-
ylation of alkenes to produce cyclopentanones. Since
then, significant progress on rhodium-catalyzed intramo-
lecular hydroacylation of alkenes has been made,3 and
rhodium-catalyzed intermolecular hydroacylation of al-
kenes with aldehydes has also been extensively studied.4
However, because the acyl-rhodium intermediates tend to
undergo undesired decarbonylation during the intermo-
lecular reaction, substrates must usually have additional
coordinating groups.5 This drawback can be partially
avoided by using cobalt,6 ruthenium,7 and N-heterocyclic
carbene catalysts.8
Scheme 1. Nickel-catalyzed Hydroacylation of Al-
kynes and Alkenes
Tsuda and Saegusa et al. reported nickel-catalyzed hy-
droacylation of alkynes to give α,β-enones (Scheme 1a).9
Ogoshi and co-workers developed a nickel-catalyzed in-
tramolecular hydroacylation of alkenes (Scheme 1b).10
Those two reactions are proposed to proceed through an
oxa-nickelacycle intermediate. However, the coupling of
an alkene and an aldehyde via oxidative cyclization with
nickel usually need activation of a third component such
We optimized the hydroacylation reaction conditions
using 3-phenylpropionaldehyde (1a) and styrene (2a) as
substrates (Table 1). The reaction was initially performed
in 1,4-dioxane at 100 °C in the presence of a nickel catalyst
prepared in situ from 10 mol% of Ni(COD)2 (COD = 1,5-
cyclooctadiene) and 20 mol% of a monophosphine ligand.
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Page 2 of 6
and excellent branched/linear ratios (entries 16−20). The
hydroacylation with an aromatic aldehyde (benzaldehyde)
was sluggish, even when the catalyst loading was in-
creased to 20 mol%, and the yield was very low (17% yield,
entry 21). However, moderate or higher yields were
achieved in the reaction of benzaldehyde with 4-
Electron-rich monophosphine ligands, such as P(c-
1
2
3
4
5
6
7
8
pentyl)3 and PCy3, gave good results, providing branched
ketone 3a as the major product, along with minor
amounts of linear product 4a in a 95:5 ratio and overall
yields of 74% and 81%, re-spectively (entries 3 and 4). The
ligand PnBu3, which is less sterically bulky, gave a very low
conversion (38%) and yield (7%) and exhibited lower se-
lectivity for the branched product (entry 2). No reaction
was observed with the very bulky electron-rich phosphine
ligand PtBu3 (entry 5). In addition, when the N-
(trifluoromethyl)styrene
(1v)
or
3,5-
bis(trifluoromethyl)styrene (entries 22, 23). When p-
methoxybenzaldehyde and o-methyl benzaldehyde were
used, the yields increased to 80% and 75%, respec- tively
(entries 24, 25). The N,N-dimethylacrylamide can also
undergo the hydroacylation with aldehydes 1a and 1u in
moderate yields and excellent regioselectivity (entries 26,
27).7b The 1-hexene was inert in the hydroacylation reac-
tion with aldehyde 1a (entry 28).
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heterocyclic carbene ligand IPr (IPr
= 1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene) was used, the hy-
droacylation product was obtained in very low yield (5%)
with a branched/linear ratio of 20:80 (entry 6).13 Adding
additional ligand (ca. 10 mol%), bringing the Ni/ligand
ratio to 1:3, increased both the conversion (95%) and the
yield (86%) of the reaction (entry 7). The reaction could
also be performed at a catalyst loading of 5 mol%, but the
conversion and yield decreased (entry 8).
Table 2. Hydroacylation of Alkenes and Aldehydesa
Table 1. Optimization of Reaction Conditionsa
O
O
O
10 mol% Ni(COD)2
20 mol% Ligand
Ph
+
Ph
Ph
+
Ph
yield B/L
Ph
H
Ph
R1
R2
3
solvent, temp., 24 h
entry
(%)b (3:4)c
Me
3a branched
1a
2a
4a linear
1
2
3d
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5(CH2)2
C6H5CH2
C6H5
4-MeC6H4
4-MeOC6H4
4-PhC6H4
4-FC6H4
3a
3b
3c
3d
3e
3f
83
78
42
89
95
98
99
92
90
86
98
95
98
52
61
96:4
92:8
92:8
98:2
97:3
98:2
99:1
99:1
99:1
99:1
98:2
99:1
98:2
98:2
99:1
99:1
98:2
99:1
B/L
entry
ligand conv. (%)b yield (%)b
(3a:4a)b
1
2
none
PnBu3
PCyp3
PCy3
PtBu3
IPr
0
0
−
38
87
90
0
7
74
76:24
95:5
95:5
−
4
3
5
4
81
6
4-CF3C6H4
4-MeO2CC6H4
4-TMSC6H4
3-MeC6H4
3-MeOC6H4
3-FC6H4
5
0
7
3g
3h
3i
6c
7d
8e
95
95
75
5
20:80
96:4
96:4
8
PCy3
PCy3
86(83)
68
9
10
11
3j
a
3k
3l
Reaction conditions: 1a (0.2 mmol), 2a (0.5 mmol),
Ni(COD)2 (0.02 mmol) and ligand (0.06 mmol) were stirred
in solvents (2.0 mL) for 24 h at 100 °C unless otherwise noted.
12
13
14d
15e
16
17
18
2-MeC6H4
2-FC6H4
3m
3n
3o
3p
3q
3r
b
Conversions, yields and B/L ratios were determined by GC
2-naphthyl
2-pyrindyl
C6H5
analysis using n-dodecane as an internal standard; isolated
yields are given in parentheses. d The Ni/ligand ratio was 1:3. e
Using 5 mol% catalyst.
73
Using the optimal reaction conditions, we evaluated
various aldehydes 1 and alkenes 2 (Table 2). The substitu-
ent on the phenyl ring of the styrenes had little influence
on the yield and selectivity of the reaction. High yields
(78−99%) and excellent branched/linear ratios (92:8−99:1)
were obtained for most of the tested styrenes (entries
1−13). An exception was p-methoxystyrene (1c), which gave
hydroacylation product 3c in only 42% yield (entry 3).
Hydroacylation of 2-vinylnaphthalene (1n) required a
higher reaction temperature (120 °C) to produce desired
product 3n, which was obtained in 52% yield (entry 14). A
reasonable yield of vinylpyridine (1o) could be obtained
only when 40 mol% PCy3 was used, to prevent coordina-
tion of the pyridyl ring of the substrate to the catalyst (en-
try 15). Various aliphatic aldehydes were examined in the
hydroacylation of styrene, and all of them gave high yields
C5H11
C6H5
92
97
2,6-dimethyl-
oct-5-enyl
C6H5
19
20
21f
22f
23f
24f
25f
26d,f
27d,f
iPr
C6H5
C6H5
3s
3t
85
93
17
93:7
96:4
Cy
C6H5
C6H5
C6H5
C6H5
3u
3v
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
4-CF3C6H4
56
62
80
75
45
68
3,5-(CF3)2C6H3 3w
4-MeOC6H5 3,5-(CF3)2C6H3
3x
3y
2-MeC6H5
C6H5(CH2)2
C6H5
3,5-(CF3)2C6H3
CONMe2
3z
CONMe2
3aa
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To investigate the reaction mechanism, we identified
the by-product generated in the hydroacylation reaction
of benzaldehyde (1u) and 4-(trifluoromethyl)-styrene (2v).
The by-product was found to be a 1,1-diarylethane (byP)
in which one aryl group came from styrene and the other
came from benzaldehyde, after decarbonylation (Scheme
2a). Moreover, the formation of catalytically unreactive
nickel carbonyl complexes Ni(PCy3)2(CO)2 was also ob-
served by 31P NMR analysis.14 To assess whether C−H bond
cleavage is reversible, we conducted the reaction with 1-d-
3-phenylpropionaldehyde (d-1a) and p-phenyl-styrene
(2d) to partial conversion (Scheme 2b). We found that
deuteration rate of the new formed methyl group was not
up to 33% (0.75 D), and the recovered aldehyde was de-
creased deuteration content to 0.50 D. Also, the residual
deuterium was detected from the recovered p-phenyl-
styrene.15 These experimental observations showed that
the reaction proceeds through a mechanism involving
reversible aldehyde C−H bond cleavage and formation of
acyl-nickel−benzyl intermediate.16
28
C6H5(CH2)2
nBu
3ab
0
−
1
2
3
4
5
6
7
8
a
Reaction conditions: 1 (0.2 mmol), 2 (0.5 mmol), Ni(COD)2
(0.02 mmol) and PCy3 (0.06mmol) were stirred in 1,4-dioxane
b
(2.0 mL) for 24−36 h at 100 °C unless otherwise noted. Iso-
lated yields based on 1. Determined by GC analysis. d Per-
c
e
formed in toluene for 36 h at 120 °C. Performed using 40
mol% PCy3 for 36 h at 120 °C. f Performed using 20 mol%
catalyst in toluene.
Scheme
2.
Hydroacylation
of
4-
9
(Trifluoromethyl)styrene with Benzaldehyde and
Deuterium-labeling Experiment
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Pathway I
Pathway II
(b)
(a)
Branched
product (3a) product (4a)
Linear
O
O
PCy3
Ph
Ph
Me
3a-cpx: -3.7
TS3:13.7
PCy3
TS4: 20.0
4a-cpx: -0.5
PCy3
O
PCy3
Ni
PCy3
Ni
Ni
H
2a + PCy3
2a + PCy3
O
O
Ph
TS1
Ph
Me
Cy3P
Cy3P
Ph
Ph
C1: 3.6
C2: 14.6
Ph
A0: 0
PCy3
PCy3
Ni
PCy3
Ni
O
O
Ph
H
PCy3
PCy3
Ph
O
Ni
H
Turnover-
Limiting
Hydrogen
Transfer
Turnover-
Limiting
1a
H
Ph
H
Ph
H
PCy3
H
PCy3
Ni
Ph
Hydrogen
Transfer
Ph
B1: 18.3
Ni
B2: 24.8
O
O
TS2
TS1: 23.0
H
H
TS2: 26.1
H
H
H
Ph
Ph
Ph
A1: 4.7
A2: 5.0
(c)
PCy3
Ni
PCy3
PCy3
Ni
PCy3
Ph
Ni
b1-TS1: 23.0
b2-TS1: 23.1
PCy3
b1-TS5: 24.7
b2-TS5: 22.0
b1-TS6: 29.6
b2-TS6: 22.6
R
R
Ph
Ph
O
Ph
H
O
Ni
O
C
O
CO
PCy3
Me
Me
byp
Me
R = PhCH2CH2, b1
R = Ph, b2
R
H
H
R
R
H
0.5 Ni(PCy3)2
0.5 Ni(PCy3)2(CO)2
H
R
H
byp-cpx
Me
A
C
E
B
Figure 1. (a) Proposed catalytic cycle with DFT-calculated free energies (kcal mol-1) in dioxane for the reaction between 3-
phenylpropionaldehyde 1a and styrene 2a (b) Structures of transition states TS1 and TS2. (c) Proposed decarbonylation process-
es with DFT-calculated free energies of transition states of the reaction of 3-phenylpropionaldehyde 1a and benzaldehyde 1u.
To deeply understand the details of the proposed
mechanism, DFT studies were performed using the reac-
tions of 3-phenylpropionaldehyde (1a) with styrene (2a) as
models.17,18 As shown in Figure 1a, the catalytic cycle ini-
tials with the Ni(0) complex A0, where the nickel catalyst
Ni(PCy3)2 is coordinated to styrene.19 Other possible Ni(0)
complexes were also considered and their energy are
found all higher than that of A0 (see Table S2-1).14 The
coordination of 1a to the nickel center of A0 to replace the
PCy3 ligand forms the complexes A1 and A2 with two dif-
ferent coordinating orientations relative to 2a. Then, the
reaction can proceed along two distinct pathways, path-
way I (in red) and pathway II (in blue). In the pathway I,
A1 undergoes the hydrogen transfer from the bound alde-
hyde to the bound styrene via TS1 (Figure 1b) which is
termed ligand-to-ligand hydrogen transfer (LLHT)20 The
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We thank the Natural Science Foundation of China, the Na-
resulting acyl-nickel−alkyl intermediate B1 isomerizes to a
more stable species C1 by rotating styrene along the Ni-
Cben bond to approach a η3 binding mode. Next, C1 under-
goes the reductive elimination via a transition state TS3 to
produce the product complex 3a-cpx. Finally, 3a-cpx re-
leases the branched product 3a by binding with styrene 2a
and the PCy3 ligand to form A0 complex, which starts the
next catalytic cycle. Similar steps are involved in the
pathway II: the aldehyde hydrogen transfer via TS2 and
the subsequent reductive elimination via TS4 to form the
linear product 4a. The hydrogen transfer processes have
the highest energy barriers (TS1 and TS2) in the pathways
I and II, respectively. Thus, the hydrogen transfer is the
turnover-limiting step of the overall process.21 TS1 is more
stable than TS2 by 3.1 kcal/mol, indicating that the alde-
hyde C−H bond prefers to transfer to the electron-
deficient carbon atom of the styrene. Therefore, the
branched adduct should be the main product, and the
reactions involving the electron-deficient alkenes should
proceed better, which are consistent with the experi-
mental results (entries 3, 6). And the energy of species C1
is close to A0 in the main pathway, which means they
have sufficient stability to interconvert under the reaction
condition. The experiment of H/D exchange of aldehyde
d-1a also showed this process is reversible.
1
2
3
4
5
6
7
8
tional Basic Research Program of China (2012CB821600), the
Ministry of Education of China (B06005), and the Tianjin
Natural Science Foundation (14JCYBJC20100) for financial
support.
SUPPORTING INFORMATION PARAGRAPH.
Experimental procedures and and analytical data of the
products (PDF). This material is available free of charge via
the Internet at http://pubs.acs.org.
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The
decarbonylation
processes
of
3-phenyl-
propionaldehyde and benzaldehyde were also computed
(Figure 1c).14 The highest energy of transition state of reac-
tion of benzaldehyde (b2-TS1, 23.1 kcal/mol) is lower than
that in the reaction of 3-phenyl-propionaldehyde (b1-TS6,
29.6 kcal/mol), indicating that the aromatic aldehydes are
easier to undergo the decarbonylation than the aliphatic
aldehydes. This consequently rationalizes the low yield of
aromatic aldehydes in the hydroacylation reaction.
Our computed results indicate that an alternative
pathway, which involves the oxidative addition of the al-
dehyde C−H bond and the migratory insertion of the al-
kene into the nickel-hydride bond, is less favorable (Fig-
ure S2-3).14 In addition, we also consider another possible
reaction mechanism, which mainly involves the sequential
steps of oxidative cyclization, hydrogen migration and
reductive elimination to form the product. The computa-
tional results show that this pathway requires a very high
activation energy of 56.2 kcal/mol (Figure S2-4).14
In summary, we have developed a highly selective
nickel-catalyzed hydroacylation reaction of styrenes with
aldehydes that does not require chelating groups. This
reaction offers a new approach to the selective prepara-
tion of branched ketones in high yields. The experimental
and computational studies show that the reaction pro-
ceeds through a LLHT pathway which involves the alde-
hyde hydrogen transfer to a coordinated alkene to form
acyl-nickel−benzyl intermediate without oxidative addi-
tion. These results also disclosed that the origins of the
reactivity and regioselectivity of the reaction, which may
provide useful insights for developing new intermolecular
hydroacyaltion reactions with nickel or other transition
metal catalysts.
(6) (a) Lenges, C. P.; Brookhart, M.; J. Am. Chem. Soc. 1997, 119,
3165. (b) Lenges, C. P.; White, P. S.; Brookhart, M. J. Am. Chem.
Soc. 1998, 120, 6965. (c) Chen, Q.-A.; D. Kim, K.; Dong, V. M., J.
Am. Chem. Soc. 2014, 136, 3772. d) Yang, J.-F.; Yoshikai, N. J. Am.
Chem. Soc. 2014, 136, 16748.
(7) (a) Kondo, T.; Tsuji, Y.; Watanabe, Y.; Tetrahedron Lett.
1987, 28, 6229. (b) Fukuyama, T.; Doi, T.; Minamino, S.; Omura,
S.; Ryu, I. Angew. Chem. Int. Ed. 2007, 46, 5559. (c) Shibahara, F.;
Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14120.
(8) (a) Hirano, K.; Biju, A. T.; Piel, I.; Glorius, F. J. Am. Chem.
Soc. 2009, 131, 14190. (b) DiRocco, D. A.; Rovis, T. Angew. Chem.
Int. Ed. 2011, 50, 7982. (c) Schedler, M.; Wang, D.-S.; Glorius, F.
Angew. Chem. Int. Ed. 2013, 52, 2585.
(9) Tsuda, T.; Kiyoi, T.; Saegusa, T. J. Org. Chem. 1990, 55,
2554.
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Journal of the American Chemical Society
(10) (a) Ogoshi, S.; Arai, T.; Ohashi, M.; Kurosawa, H. Chem.
1
2
3
4
5
6
7
8
Commun. 2008, 1347. (b) Hoshimoto, Y.; Hayashi, Y.; Suzuki, H.;
Ohashi, M.; Ogoshi, S. Angew. Chem. Int. Ed. 2012, 51, 10812.
(11) (a) Ogoshi, S.; Oka, M.-a.; Kurosawa, H. J. Am. Chem. Soc.
2004, 126, 11802. (b) Ogoshi, S.; Ueta, M.; Arai, T.; Kurosawa, H. J.
Am. Chem. Soc. 2005, 127, 12810. (c) Ng, S.-S.; Ho, C.-Y.; Jamison,
T. F. J. Am. Chem. Soc. 2006, 128, 11513.
(12) (a) Yang, Y.; Zhu, S.-F.; Duan, H.-F.; Zhou, C.-Y.; Wang, L.-
X.; Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129, 2248. (b) Yang, Y.;
Zhu, S.-F.; Zhou, C.-Y.; Zhou, Q.-L. J. Am. Chem. Soc. 2008, 130,
14052. (c) Zhou, C.-Y.; Zhu, S.-F.; Wang, L.-X.; Zhou, Q.-L. J. Am.
Chem. Soc. 2010, 132, 10955.
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(13) The major product was 3-phenylpropionate generated by
Tishchenko reaction process. For Nickel-catalyzed Tishchenko
reaction, see: (a) Ogoshi, S.; Hoshimoto, Y.; Ohashi, M. Chem.
Commun. 2010, 46, 3354. (b) Hoshimoto, Y.; Ohashi, M.; Ogoshi,
S. J. Am. Chem. Soc. 2011, 133, 4668.
(14) See the Supporting Information (SI) for details.
(15) The H/D exchange between aldehydes and alkenes were
confirmed by conducting the reaction with β-d2-p-phenyl-
styrene (d2-2d) and 3-phenylpropionaldehyde (1a). For details,
see the SI-2(b). (16) For mechanistic study on the C−H activation
of aldehydes catalyzed by Rh, see: (a) Shen, Z.; Dornan, P. K.;
Khan, H. A.; Woo, T. K.; Dong, V. M. J. Am. Chem. Soc. 2009, 131,
1077. (b) Prades, A.; Fernández, M.; Pike, S. D.; Willis, M. C.;
Weller, A. S. Angew. Chem. Int. Ed. 2015, 54, 8520, and ref. 4e.
(17) All reported free energies are in kcal/mol and calculated
using M06/SDD-6-311+G(d,p)/SMD(1,4-dioxane)//B3LYP/SDD-6-
31G(d) method. For details, see the SI.
(18) For recent review of DFT studies of nickel-catalyzed
reactions, see: Sperger, T.; Sanhueza, I. A.; Kalvet, I.;
Schoenebeck, F. Chem. Rev. 2015, 115, 9532.
(19) A similar structure of nickel complex has been confirmed
by single crystal X-ray diffraction, see: (a) Cornella, J.; Gómez-
Bengoa, E.; Martin, R. J. Am. Chem. Soc. 2013, 135, 1997. (b)
Ohashi, M.; Shibata, M.; Saijo, H.; Kambara, T.; Ogoshi, S. Or-
ganometallics 2013, 32, 3631.
(20) (a) Vastine, B. A.; Hall, M. B. J. Am. Chem. Soc. 2007, 129,
12068. (b) Guihaumé, J.; Halbert, S.; Eisenstein, O.; Perutz, R. N.
Organometallics 2012, 31, 1300. (c) Bair, J. S.; Schramm, Y.;
Sergeev, A. G.; Clot, E.; Eisenstein, O.; Hartwig, J. F. J. Am. Chem.
Soc. 2014, 136, 13098. (d) Schramm, Y.; Takeuchi, M.; Semba, K.;
Nakao, Y.; Hartwig, J. F. J. Am. Chem. Soc. 2015, 137, 12215.
(21) (a) Whittaker, A. M.; Dong, V. M. Angew. Chem. Int. Ed.
2015, 54, 1312. (b) Gu, L.-J.; Jin, C.; Zhang, H.-T. Chem. Eur. J. 2015,
21, 8741.
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SYNOPSIS TOC.
1
2
3
4
O
O
Ni(0)
27 examples
up to 99% yield
up to 99:1 B/L
Ar
Me
+
Ar
R
R
H
5
R = Alkyl, Aryl
6
7
8
9
PCy3
PCy3
Ni
O
R
Ar
No chelation assistance
Highly branched selectivity
Hydroacylation via LLHT
Ar
Ni
O
LLHT
H
H
H
H
H
R
H
10
11
12
13
14
15
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