Nickel/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of Alkenes

Article abstract of DOI:10.1021/jacs.9b12554

An unprecedented asymmetric acyl-carbamoylation of pendant alkenes tethered on aryl carbamic chlorides with both aliphatic and aromatic aldehydes has been developed via the cooperative catalysis of a chiral nickel-PHOX complex and tetrabutylammonium decatungstate. This reaction represents the first example of merging hydrogen-atom-transfer photochemistry and asymmetric transition metal catalysis in difunctionalization of alkenes. Using this protocol, a variety of oxindoles bearing a challenging quaternary stereogenic center are furnished under mild conditions in highly enantioselective manner.

Full text of DOI:10.1021/jacs.9b12554

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Communication
Nickel/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of Alkenes
Pei Fan, Yun Lan, Chang Zhang, and Chuan Wang
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b12554 • Publication Date (Web): 23 Jan 2020
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Nickel/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of
Alkenes
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Pei Fan†, Yun Lan†, Chang Zhang, and Chuan Wang*
Hefei National Laboratory for Physical Science at the Microscale, Department of Chemistry, Center for Excellence in
Molecular Synthesis, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
Supporting Information Placeholder
envisaged an asymmetric acyl-carbamoylation reaction of alkenes
tethered on carbamic chlorides with aldehydes via the merger of
nickel and photo-catalysis,11-13 to access the oxindole motif bearing
ABSTRACT:
An
unprecedented
asymmetric
acyl-
carbamoylation of pendant alkenes tethered on aryl carbamic
chlorides with both aliphatic and aromatic aldehydes has been
developed via the cooperative catalysis of a chiral nickel-PHOX
complex and tetrabutylammonium decatungstate. This reaction
represents the first example of merging hydrogen-atom-transfer
photochemistry and asymmetric transition metal catalysis in
difunctionalization of alkenes. Using this protocol, a variety of
oxindoles bearing a challenging quaternary stereogenic center are
furnished under mild conditions in highly enantioselective manner.
a
quaternary stereogenic center (Scheme 1B) in highly
enantioselective manner. In this cooperative catalysis the
enantioselective elementary step is controlled by a chiral Ni-
catalyst whereas the coupling partner, the acyl radical, is generated
from the aldehyde through C−H activation by TBADT under
irradiation.
Scheme 1. Asymmetric Dicarbofunctionalizations of Tethered
Alkenes
A) Previous Work of Asymmetric Dicarbofunctionalization of Tethered Alkenes
Transition metal-catalyzed dicarbofunctionalization of alkenes has
emerged as a powerful tool for concomitant installation of two
different carbo-moieties across the π-system.1 Significant advances
have been achieved in both two- and three-component
dicarbofunctionalization by application of redox-neutral or
reductive strategies.2-5 Notably, diverse cyclic compounds can be
approached through dicarbofunctionalization of tethered alkenes,
such as dialkylation,2a diarylation,2b-d,3a aryl-alkylation,2e-h,3b-h aryl-
alkenylation2i,3i-k and aryl-acylation2j,k. Moreover, a few examples
of highly enantioselective dicarbofunctionalization of tethered
olefins have been recently developed by Fu,2e Brown,2c
Kong,2d,3a,j,k Shu,3i Zhang2h and our group3g. However, all these
reactions involve a facially selective arylmetalation of the
incorporated olefinic unit as the enantiodetermining step followed
by termination with an organohalide or an organoboron (Scheme
1A). Therefore, it is highly desirable to establish new strategies for
asymmetric dicarbofunctionalization of alkenes, to allow for new
retrosynthetic disconnections to achieve target molecules
Although acyl-nickel species is also known to undergo
migratory insertion into a tethered alkene,2j,k,6 asymmetric two-
component dicarbofunctionalization relies on enantioselective
acylnicklation remains elusive. Our attention was drawn to the use
of aryl carbamic chlorides7 bearing a reactive pendant alkene as
substrates in the cyclization reaction via intramolecular
carbamoylnicklation, which would provide a rapid construction of
the oxindole scaffold featured in a large number of biologically
active compounds.8 On the other side, aldehydes are abundant and
easily accessible starting materials, and thus serve as an appealing
acyl source in organic synthesis through acyl C-H activation.
Tetrabutylammonium decatungstate (TBADT) has proven to be a
successful hydrogen-atom-transfer (HAT) photocatalyst for acyl
C−H activation of aldehydes by promoting the homolytic acyl C−H
bond cleavage, providing nucleophilic acyl radical for further
reactions with electron-deficient olefins and imines.9,10 Herein, we
R1
X
R2
O
O
Ni, Cu or Pd
+
R2-Y
*
Z
Z
R1
R2: Aryl, Alkyl, Alkenyl;
Y: F, Br, I, OTf, B(OH)2;
Z: CH2, O, N-PG.
+
X: 9-BBN, BPin, Cl, Br, I, OTf, N2
;
B) This Work: Ni/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of Tethered Alkenes
O
TBADT, hv
O
O
R4
R1
R4
R1
Acyl CH
Activation
R4
R1
R3
*
O
[Ni]*
O
R3
R3
N
Chiral Ni-Cat.
R2
*
R2
Cl
N
R2
N
Enantiocontrol
O
For optimization of the reaction conditions, we utilized the
carbamoyl chloride 1a incorporating a terminal olefin and butanal
(2a) as standard substrates (Table 1). Initially, various types of
chiral ligands for nickel were tested under the catalysis of TBADT
irradiated at 390 nm by a LED lamp (entries 1-8). In the cases of
chiral Pyrox L1, PyBOX L2 and BOX-ligands L3-5 the desired
product 3a was afforded in low yields and low to moderate
enantioselectivities (entries 1-5). To our delight, a promising result
was achieved in terms of both efficiency and enantiocontrol when
the chiral PHOX L6 was employed as the ligand (entry 6). In
contrast, the reaction using the chiral bidentate phosphine ligands
L7 and L8 failed to deliver a satisfactory outcome (entries 7 and
8). Next, a series of Ni-complexes were screened (entries 9-14), and
Ni(OTf)2 turned out to be the best precatalyst (entry 14), elevating
the asymmetric induction to an excellent level (93% ee).
Performing the reaction in acetone led to a diminished enantiomeric
excess (entry 15). Furthermore, replacing K3PO4 by Na2CO3 in the
reaction gave rise to an inferior result (entry 16). Finally, increasing
the reaction concentration to 0.2 M improved the reaction yield
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°C). b Yields of the isolated product. c Determined by HPLC-analysis on a
slightly (entry 17). In this case, the hydrocarbamoylation product
3a-1 (15%) and N-methyl-2-(prop-1-en-2-yl)aniline (3a-2) (6%)
turned out to be the major by-products. Remarkably, no desired
product was formed when the reaction was conducted in the
absence of either Ni-precatalyst (entry 18) or TBADT (entry 19),
confirming the synergistic effect of these two catalysts. In addition,
the reaction was completely shut down when it was carried out in
dark (entry 20) or under blue LED irradiation (entry 21).
chiral stationary phase. d Not determined. e Reaction was performed in
acetone. f Na2CO3 was used instead of K3PO4. g Reaction was performed in
1 mL MeCN. h Reaction was performed in the absence of Ni-precatalyst.
i Reaction was performed in the absence of TBADT. j Reaction was
performed in dark. k Reaction was performed under blue LED irradiation.
Table 2. Evaluation of the Substrate Scope by Varying the
Carbamic Chlorides a-c
Table 1. Optimization of the Reaction Conditions a
Me
9
R1
O
TBADT (5 mol%)
Ni(OTf)2 (10 mol%)
Ligand L6 (12 mol%)
R3
R1
R3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
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Me
O
O
R2
Cl
O
Me
N
Me
K3PO4 (1.1 equiv)
MeCN
9 h, 390 nm
N
Me
R2
O
O
O
TBADT (5 mol%)
N
Ni-precatalyst (10 mol%)
1
2a
3
3a
Me
Cl
Me
+
Ligand (12 mol%)
N
Me
2a
Me
1
Me
3a
, R = Me, 65%, 93% ee
Me
K3PO4 (1.1 equiv)
MeCN
9 h, 390 nm
Me
O
O
(64%, 94% ee)d
Me
Me
O
R1
O
1a
Ph
1
3b
3c
3d
3e
, R = Et,
1
71%, 95% ee
N
N
H
, R = n-Pr, 67%, 94% ee
Me
3a 2
-
O
3a-1
O
3f
, 39%, 0% ee
(53%, 0% ee)e
1
, R = i-Pr, 70%, 94% ee
N
N
1
, R = c-Hex, 65%, 94% ee
Me
Me
O
N
O
O
N
Me
Me
N
O
Me
Me
Me
O
O
O
O
N
O
O
N
N
Ph
Ph
t-Bu
i-Pr
R1
i-Pr
N
N
N
t-Bu
Ph
Ph
t-Bu
L1
L2
L3
L4
O
O
O
N
N
N
Me
MeO
BnO
Me
Me
Me
O
1
3g
3j, 68%, 95% ee
(70%, 95% ee)f
, 66%, 96% ee
3h
, 63%, 93% ee (R = i-Pr)
O
O
O
,
46%, 92% ee (R1= Me)
NH PPh2
NH PPh2
3i
PPh2
PPh2
N
N
N
PPh2
t-Bu
Me
Me
O
Me
Me
O
O
OMe
Me
i-Pr
O
MeO
MeO
Cl
O
N
O
O
N
L5
L6
L7
L8
N
Me
Me
Me
entry
1
ligand
L1
L2
L3
L4
L5
L6
L7
L8
L6
L6
L6
L6
L6
L6
L6
L6
L6
L6
L6
L6
L6
Ni-precatalyst
NiBr2•dme
NiBr2•dme
NiBr2•dme
NiBr2•dme
NiBr2•dme
NiBr2•dme
NiBr2•dme
NiBr2•dme
NiBr2
yield (%)b
ee (%)c
16
10
n.d.d
n.d.d
61
85
3
n.d.d
89
91
85
77
91
93
86
92
93
-
, 57%, 96% ee
3m
3k
3l
, 62%, 91% ee
, 85%, 90% ee
16
11
trace
trace
17
53
27
trace
60
10
8
Me
Me
Me
O
O
O
i-Pr
i-Pr
i-Pr
2
O
O
O
N
3
N
N
N
R3
Me
Me
Me
O
Me
3q
4
3
3p
, 54%, 94% ee
, 24%, 48% ee
3n
3o
, 62%, 95% ee, (R = Cl)
5
3
, 55%, 94% ee, (R = CF3)
6
Me
O
Unsuccessful Substrates:
i-Pr
7
Me
Me
Me
Me
Me
O
N
R2
Me
8
Me
N
Me
Cl
Me
Me
Cl
9
N
N
N
N
2
3r
, 39%, 92% ee, (R = n-Pent)
O
Cl
O
O
Cl
O
10
11
12
13
14
15e
16f
17g
18h
19i
20j
21k
Ni(BF4)2•6H2O
Ni(ClO4)2•6H2O
Ni(acac)2
2
3s
, 46%, 92% ee, (R = Bn)
2
3t
, 70%, 90% ee, (R = PMB)
51
62
62
58
53
65
0
a Unless otherwise specified, the reactions were performed on a 0.2 mmol
scale of the carbamoyl chloride 1 using 3 equiv of butanal (2a), 10 mol%
Ni(OTf)2, 12 mol% L6, 5 mol% TBADT and 1.1 equiv of K3PO4 in 1 mL
MeCN under the irradiation at 390 nm for 9 h (two lamps 5 cm away, with
adequate fans and a water bath to keep the reaction below 45 °C). b Yields
of the isolated products. c Enantiomeric excesses were determined by
HPLC-analysis on a chiral stationary phase. d Reaction was performed on
2-mmol-scale for 18 h. e Reaction was performed in the absence of Ni(OTf)2
and L6. f Reaction was performed on 1-mmol-scale for 18 h.
Ni(COD)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
0
-
With the optimal reaction conditions in hand, we started to
evaluate the substrate scope of this Ni/photo-cocatalyzed reaction.
First, a variety carbamoyl chlorides were reacted with butanal, and
the results were summarized in Table 2. When the substituent of
the pendant olefin is aliphatic, all the reactions proceeded smoothly,
furnishing the corresponding products 3a-e in moderate yields and
high enantioselectivities. In sharp contrast, when the phenyl-
substituted analogue was used as precursor, a racemic mixture of
3f was obtained. A control experiment for this reaction revealed
Ni(OTf)2
0
-
Ni(OTf)2
0
-
a Unless otherwise specified, the reactions were performed on a 0.2 mmol
scale of the carbamoyl chloride 1a using 3 equiv of butanal (2a), 10 mol%
Ni-precatalyst, 12 mol% ligands, 5 mol% TBADT and 1.1 equiv of K3PO4
in 2 mL MeCN under the irradiation at 390 nm for 9 h (two lamps 5 cm
away, with adequate fans and a water bath to keep the reaction below 45
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that the acyl-carbamoylation still occurred in the absence of the Ni-
Subsequently, we turned to study the substrate spectrum of the
aldehydes (Table 3). In general, both aliphatic and (hetero)aromatic
aldehydes could be successfully employed as precursors for this
asymmetric acyl-carbamoylation reaction under slightly modified
reaction conditions (10 mol% TBADT ， 12 h reaction time),
giving access to a variety of oxindoles 3u-aj in moderate to
excellent yields and high enantioselectivities. Again, we obtained
similar yield and enantioselectivity for the reaction of 1-mmol scale
(3ag).
Since all the products contain a keto group on the side chain,
the product derivatization focused on the conversion of this
carbonyl moiety (Scheme 2). First, compound 3a was subjected to
the Wittig reaction, delivering an alkene 4 in a moderate yield
(Scheme 2A). Moreover, Et3SiH-mediated reduction of compound
3ad under acidic condition provided the oxindole 5 in a high yield
(Scheme 2B). The synthetic value of this method is also
demonstrated in the preparation of compound 6 (Scheme 2C),
which contains a furoindoline core structure found in numerous
naturally occurring products, such as physovenine, madindoline A,
picrinine and aspidophylline A.14
catalyst. Next, introduction of electron-donating or –withdrawing
substituent on the phenyl ring of the carbamic chlorides posed no
problem in most cases for this Ni/photo-cocatalyzed reaction,
providing an array of oxindoles 3g-p in moderate to good yields
and excellent enantiocontrol. The substituent ortho to the
carbamoyl chloride was found to have detrimental effect on both
efficiency and enantioselectivity of the studied reaction (3q).
Furthermore, a number of N-substituted carbamoyl chlorides
turned out to be suitable substrates, affording the products 3r-t on
a high level of asymmetric induction. Notably, similar results could
be achieved for the reaction on 1- or 2-mmol scale (3a and 3j).
Unsuccessful substrates for this reaction include trisubstituted
alkenes, pyridinyl-substituted carbamoyl chloride and the ally
benzene-tethered carbamoyl chloride.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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Table 3. Evaluation of the Substrate Scope by Varying the
Aldehydes a-c
O
i-Pr
TBADT (10 mol%)
Ni(OTf)2 (10 mol%)
R
i-Pr
O
L6
Ligand
(12 mol%)
Scheme 2. Derivatization of the Acyl-Carbamoylation Product
Me
O
N
K3PO4 (1.1 equiv)
MeCN
12 h, 390 nm
R
N
Me
O
Cl
1d
A)
Me
Me
O
Ph3P+CH3Br, n-BuLi
THF, 050 °C, 16 h
2a
3
Me
Me
O
O
n-Bu
i-Pr
t-Bu
O
O
O
N
N
i-Pr
i-Pr
i-Pr
4
, 58%
3a
Me
Me
O
O
N
O
N
N
B)
H
O
t-Bu
t-Bu
Me
, 64%, 94% ee
Bn
Me
Me
H
i-Pr
i-Pr
Et3SiH, TFA
0 °CRT, 16 h
3u
3v
3w
, 88%, 96% ee
, 71%, 95% ee
O
O
N
N
5
Me
3ad
O
O
O
, 84%
OBz
OTBDPS
Me
i-Pr
i-Pr
i-Pr
O
O
C)
O
O
t-Bu
N
N
N
i-Pr
t-Bu
LiAlH4, 0 °CRT
THF, 2 h
i-Pr
Me
Me
Me
O
3x
3y
, 95%, 95% ee
3z
, 39%, 96% ee
, 48%, 94% ee
O
N
N
3ad
H
Me
6
, 51%, dr> 98:2
Me
O
O
O
NBoc
Ph
i-Pr
i-Pr
i-Pr
NHBoc
In order to shed some light on the mechanism of this
Ni/TBADT-cocatalyzed reaction, we carried out a series of
control experiments (Scheme 3). As reported in the literature,10
TBADT is able to promote the hydroacylation of electron-
deficient alkenes with aldehydes wherein the addition of acyl
radical to the C−C double bond is the key step. To verify
whether our reaction is also initiated by addition of an acyl
radical to the aryl-substituted olefinic unit, we performed a
reaction between the carbamoyl chloride 1d and butanal (2a)
under the photo catalysis of TBADT. In this case, no
hydroacylation occurred (Scheme 3A). Moreover, the
carbamate 8 bearing a tethered alkene with similar electronic
property like the one of 1d was subjected to the reaction with
butanal under the standard reaction conditions, giving neither
the hydroacylation product 9 nor the acyl-carbamoylation
product 3d (Scheme 3B). The results mentioned-above argue
against a reaction pathway engaging the acylation of the
pendant alkene as the initial step. Thus we wonder if the studied
reaction starts with the interaction of the carbamoyl chloride
and a low-valent Ni species. Then a stoichiometric reaction of
the carbamic chloride 1d with Ni(COD)2 was conducted
(Scheme 3C). After quenching with water the formation of the
hydrocarbamoylation product 10 was not observed, while the
carbamoyl-hydroxylation product 11 was obtained in 55% yield
and 76% ee. This result indicates that Ni(II)-mediated
O
N
O
N
O
N
Me
Me
Me
3aa
3ab
3ac
, 38%, 89% ee
, 96%, 95% ee
, 58%, 95% ee
O
O
O
R
OMe
OMe
i-Pr
i-Pr
i-Pr
Me
O
O
O
N
N
N
Me
Me
Me
3ad
3ae
, R= Me, 53%, 94% ee
, R= t-Bu, 60%, 94% ee
3ag
, 61%, 94%ee
(58%, 94%ee)d
3af
, 41%, 92% ee
Me
NEt
N
O
O
O
F
i-Pr
i-Pr
i-Pr
O
O
O
N
N
N
Me
Me
Me
3ai
3aj
, 43%, 91% ee
, 91%, 95% ee
3ah
, 38%, 90% ee
a Unless otherwise specified, the reactions were performed on a 0.2 mmol
scale of the carbamoyl chloride 1d using 3 equiv of aldehydes 2, 10 mol%
Ni(OTf)2, 12 mol% L6, 10 mol% TBADT and 1.1 equiv of K3PO4 in 1 mL
MeCN under the irradiation at 390 nm for 12 h (two lamps 5 cm away, with
adequate fans and a water bath to keep the reaction below 45 °C). b Yields
of the isolated products. c Enantiomeric excesses were determined by
HPLC-analysis on a chiral stationary phase. d Reaction was performed on
1-mmol-scale for 18 h.
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a different ligand is employed in our reaction, a similar process
enantioselective migratory insertion proceeds very rapidly, but
the enantiocontrol is much lower than the acyl-carbamoylation
process (>90% ee). . Interestingly, the use of the carbamoyl
chloride 13 without a pendant alkene as substrate in the reaction
with butanal led to the production of the amide 15, suggesting
the presence of the Ni(III) species 14 in this catalytic reaction,
which is possibly formed via oxidative addition of the
carbamoyl chloride to an acyl Ni(I) species (Scheme 3D). When
1,4-cyclohexadiene was employed instead of butanal in this
Ni/TBADT-cocatalyzed reaction, the hydrocarbamoylation
product 10 was obtained in a moderate yield (Scheme 3E).
However, the enantioselectivity (70% ee) was similar to the
stoichiometric carbamoyl-hydroxylation, but significantly
lower than the corresponding catalytic acyl-carbamoylation
reaction. The formation of compound 10 may be attributed to
hydrogen-atom abstraction of the cage-bound radical 16 with
1,4-cyclohexadiene as a hydrogen atom donor.15 The distinct
level of enantiocontrol in the hydrocarbamoylation and acyl-
carbamoylation suggests that the enantiodetermining migratory
insertion step in the acyl-carbamoylation possibly proceeds
after addition of the acyl radical to the Ni-center.
could also occur, and the generated Ni(0) is then oxidized by the
acyl radical I, providing the Ni(I) species II. Next, the carbamoyl
chlorides 1 perform oxidative addition to the acyl Ni-species II,
affording the Ni(III) intermediate III, which then undergoes the
enantiodetermining migratory insertion to the tethered olefinic unit.
Notably, the formation of complex III via initial oxidative addition
of carbamoyl chloride to Ni(0) followed by addition of acyl radical
I could not be excluded. Upon reductive elimination from the
resultant Ni(III) complex IV, the cyclization product 3 is furnished
with the generation of Ni(I)Cl. The closure of the Ni-catalytic cycle
requires the reduction of Ni(I)Cl to Ni(0), which is likely realized
via single electron transfer with the [W]6-2H+.
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54
55
56
57
58
59
60
Scheme 4. Proposed Reaction Mechanism for the Ni/Photo-
Cocatalyzed Acyl-Carbamoylation
O
O
R4
R4
2
I
HAT
[W]4
[W]5H+
TBADT-Catalytic Cycle
Scheme 3. Control Experiments for the Ni/Photo-Cocatalyzed
Acyl-Carbamoylation
hv
[W]5H+
O
HCl
A)
i-Pr
O
i-Pr
O
R4
[W]4
TBADT (5 mol%)
X
I
Me
Ni(0)
[W]62H+
Me
SET
Me
N
N
K3PO4 (1.1 equiv)
MeCN
9 h, 390 nm
O
Me
O
Cl
Ni(I)-Cl
O
Cl
O
R4
R4
(I)Ni
R1
R3
II
R1
N
R3
1d
2a
7
O
N
R2
Ni-Catalytic Cycle
TBADT (5 mol%)
Ni(OTf)2 (10 mol%)
B)
i-Pr
O
i-Pr
O
R2
Cl
3
R4
n-Pr
O
O
i-Pr
L6
(12 mol%)
X
n-Pr
R1
N
1
O
R1
N
or
R3
Ni(III)Cl
O
Me
Me
O
R3
N
N
K3PO4 (1.1 equiv)
MeCN
9 h, 390 nm
N
Me
2a
O
OMe
R2
Me
O
OMe
(III)
Ni
R2
III
Cl
R4
8
9
3d
IV
O
C)
i-Pr
1) Ni(COD)2 (1 equiv)
L6
OH
O
i-Pr
i-Pr
(1 equiv), MeCN,
20 min
Me
i-Pr
Me
Cl
O
O
+
+
In summary, we demonstrated in this protocol the successful
combination of HAT photo and asymmetric nickel catalysis in the
difunctionalization of alkenes. This new method enables the highly
enantioselective synthesis of diverse 3,3-disubstituted oxindoles
starting from aryl carbamoyl chloride-tethered alkenes and
aldehydes under the cooperative catalysis of TBADT and Ni-
PHOX complex. According to the preliminary mechanistic
investigations, a Ni(III)-mediated migratory insertion might be
engaged as the enantiodetermining step in the catalytic cycle
wherein the coupling partner, the acyl radical, is generated by
TBADT from the aldehyde through acyl C−H activation.
N
Me
N
N
N
H
2) H2O
Me
Me
O
1d
10
11
12
, 9%
, 0%
, 55%, 76 %ee
TBADT (5 mol%)
Ni(OTf)2 (10 mol%)
L6
D)
O
O
O
O
(12 mol%)
(III)
Ni
Ph
O
Me
Ph
Ph
n-Pr
N
N
n-Pr
N
K3PO4 (1.1 equiv)
MeCN
Me Cl
Me
O
Cl
Me
9 h, 390 nm
13
2a
14
15
, 31%
TBADT (5 mol%)
Ni(OTf)2 (10 mol%)
E)
i-Pr
i-Pr
i-Pr
Ni(I)
Me
L6
(12 mol%)
+
Me
Cl
O
O
N
K3PO4 (1.1 equiv)
MeCN
9 h, 390 nm
N
N
3 equiv
ASSOCIATED CONTENT
Supporting Information
Me
Me
O
1d
16
10
, 43%, 70% ee
Representative experimental procedures and necessary
characterization data for all new compounds are provided. This
material is available free of charge via the Internet at
http://pubs.acs.org.
On the basis of the results of the control experiments and the
previous reports, we proposed a plausible mechanism for this
Ni/TBADT cocatalyzed reaction in Scheme 4. Initially, the
TBADT [W]4− is activated to its excited state [W]4−* under the
irradiation, which is capable of abstracting a hydrogen atom from
the aldehydes 2, leading to the formation of the acyl radical I and
[W]5-H+. The latter is known to disproportionate into the original
[W]4− and the doubly reduced [W]6-2H+.16 According to the work
of MacMillan et al.,11 [W]6-2H+ is able to reduce Ni(dtbbpy)Br2
(dtbbpy = 4,4’-di-tert-butyl-2,2’-bipyridine) to the corresponding
Ni(0) species via two successive single-electron transfer. Although
AUTHOR INFORMATION
Corresponding Author
chuanw@ustc.edu.cn
Author Contribution
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Journal of the American Chemical Society
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Peng, Y.; Xu, X.-B.; Xiao, J.; Wang, Y.-W. Nickel-Mediated
Stereocontrolled Synthesis of Spiroketals via Tandem
†These authors contributed equally.
Cyclization–Coupling of β-Bromo Ketals and Aryl Iodides. Chem.
Commun. 2014, 50, 472−474. (f) Jin, Y.; Wang, C. Ni-Catalysed
Reductive Arylalkylation of Unactivated Alkenes. Chem. Sci.
2019, 10, 1780−1785. (g) Jin, Y.; Wang, C. Nickel-Catalyzed
Asymmetric Reductive Arylalkylation of Unactivated Alkenes.
Angew. Chem. Int. Ed. 2019, 58, 6722−6726. (h) Jin, Y.; Yang, H.;
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Wang, C. Nickel-Catalyzed Reductive Arylalkylation via
a
This work is supported by National Natural Science Foundation of
China (Grant No. 21772183), Fundamental Research Funds for the
Central Universities (WK2060190086), “1000-Youth Talents
Plan” start-up funding, as well as University of Science and
Technology of China.
Migratory Insertion/Decarboxylative Cross-Coupling Cascade.
Org. Lett. 2019, 21, 7602−7608. (i) Tian, Z.-X.; Qiao, J.-B.; Xu,
G.-L.; Pang, X.; Qi, L.; Ma, W.-Y.; Zhao, Z.-Z.; Duan, J.; Du, Y.-
F.; Su, P.; Liu, X.-Y.; Shu, X.-Z. Highly Enantioselective Cross-
Electrophile Aryl-Alkenylation of Unactivated Alkenes. J. Am.
Chem. Soc. 2019, 141, 7637−7643. (j) Ma, T.; Chen, Y.; Li, Y.;
Ping, Y.; Kong, W. Nickel-Catalyzed Enantioselective Reductive
Aryl Fluoroalkenylation of Alkenes. ACS Catal. 2019, 9,
9127−9133. (k) Li, Y.; Ding, Z.; Lei, A.; Kong, W. Ni-Catalyzed
Enantioselective Reductive Aryl-Alkenylation of Alkenes:
Application to the Synthesis of (+)-Physovenine and (+)-
Physostigmine. Org. Chem. Front. 2019, 6, 3305−3309.
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2010, 8, 4158-4164. (d) Supranovich, V. I.; Levin, V. V.; Dilman,
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M. Solution Photochemistry of Tetrakis(tetrabutylammonium)
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