Three-component vicinal-diarylation of alkenes: Via direct transmetalation of arylboronic acids

Article abstract of DOI:10.1039/c9sc02182e

Herein, we report three-component vicinal-diarylation of non-conjugated alkenes initiated by transmetalation of arylboronic acids, which provides complementary access to β,γ-diaryl carbonyl compounds. We have also screened a large number of chiral ligands for developing an enantioselective version of this reaction and obtained the preliminary results (up to 79: 21 e.r.). Notably, the methodology developed herein represents the first three component syn-vicinal-dicarbofunctionalization of non-conjugated alkenes involving palladium catalysis.

Full text of DOI:10.1039/c9sc02182e

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Three-Component Vicinal-Diarylation of Alkenes via Directed
Transmetalation of Arylboronic Acids
Received 00th January 20xx,
Accepted 00th January 20xx
Yun Zhang, Gong Chen*, and Dongbing Zhao*
DOI: 10.1039/x0xx00000x
Herein, we report transmetalation of arylboronic acids-initiated three-component vicinal-diarylation of non-conjugated
alkene, which constitutes a complementary access to β,γ-diaryl carbonyl coumpounds. We have also screened a large
number of chiral ligands for developing the enantioselective version of this reaction and got the preliminary results (up to
79:21 e.r.). Notably, the methodology developed herein represents the first three component syn-vicinal-
dicarbofuctionaliztion of non-conjugated alkenes involving palladium catalysis.
www.rsc.org/
documented.7 In recent years, several groups have developed
an array of methods for alkene functionalization, which
triggered by PdII-catalyzed transmetalation of arylboronic acids
Introduction
Vicinal-diaryl structures are a common scaffold in various
medicinally relevant molecules and can also be widely utilized
as chemical feedstocks to access a number of natural products
(Scheme 1, upper panel).1 Traditional reactions to access
vicinal-diaryl structures generally suffer from disadvantages
such as multi-step process, a limited substrate scope, and the
difficulties of accessing starting materials.1, 2
such as oxidative boron Heck reaction.8, 9 We thus questioned
whether three-component heterodiarylation of olefins with
aryl halides and arylboronic acids could also be initiated by
transmetalation step (Scheme 1c, lower panel). Such a reaction
would constitute a complementary access with the previous
two approaches to vicinal-diaryl structures. Herein, we report
the first transmetalation-initiated three-component vicinal-
diarylation of γ-olefinic acids by using directing-group strategy,
which enables rapid construction of syn-β,γ-diaryl carbonyl
coumpounds.
Alkenes are among the most abundant classes of organic
molecules, available in bulk quantities from petrochemical
feedstocks and renewable resources. Thus, the intermolecular
diarylation of olefins represents one of the most powerful and
straightforward way to rapid buildup of vicinal diaryl
structures.3 For example, homodiarylation of alkenes with aryl
metals or halides provides an quick access to introduce two
identical aryl groups across an olefin.4 On the other hand, two
general approaches for introduction of two different aryl
moieties across an olefin has been developed: (1) a sequence
involving formation of a Ar−MX species via oxidation addition
of M0 catalyst (Ni0 or Pd0) to a aryl electrophile (El), alkene
Insertion, transmetalation with the aryl nucleophiles (Nu), and
C–C reductive elimination (Scheme 1a, lower panel);5 (2) π-
Lewis acid (PdII as the Lewis acid) activation of the alkene to
enable attack of a aryl C−H nucleophile (limited to indoles and
phenols) to form a carbopalladated Wacker-type intermediate,
followed by oxidative addition of aryl electrophiles (Ar−X) and
C−C reductive elimination (Scheme 1b, lower panel).6
Ar2
Ar2
CF3
O
O
Ar1
Ar1
HO
OH
N
Ar3
H
O
Vitronectin receptor
antagonists
Urokinase receptors
Flocoumafen
O
HO
R
OH
OMe
HO
R
O
O
OMe
H
H
Ar1
X-
Me
Ar2
N
OH
O
OR
HO
OH
Pallidol
O
Macarpine
Anti-estrogenic molecules
(a) Oxidative addition-initiated three-component vicinal-diarylation of alkenes (Ref. 5)
[M]
Ar
(EI)
X
Ar
Ar
(Nu)
[M]
Sigman, Song,
Zhao, Engle, Giri,
Brown's studies
R
R
R'
R
R'
R'
Transmetalation
Reductive ellimination
(M: Zn or B)
Oxidative addition
alkene insertion
(X: N2BF4, OTf, Br, I)
Ar
Ar
(syn-)
(
M: Ni or Pd)
(b) Nucleopalladation-initiated three-component vicinal-diarylation of alkenes (Ref. 6)
Ar
Ar
Ar
(Nu)
X
(EI)
H
[Pd]
R
Transmetalation of arylmetal reagents with palladium(II)
catalyst to generate the Ar−PdX intermediate has been well
R
R
(Engle's study)
R'
R'
R'
Oxidative addition
Nucleopalladation
(limited to indoles and phenols)
Ar
(anti-)
(c) Transmetalation-initiated three-component vicinal-diarylation of alkenes
[Pd]
Ar
Reductive ellimination
Ar
(Nu)
[B]
Ar
(EI)
I
Ar
R
R
(This work)
R'
R
R'
a. State Key Laboratory and Institute of Elemento-Organic Chemistry, College of
Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071 (China).
E-mail: gongchen@nankai.edu.cn; dongbing.chem@nankai.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Transmetalation
Reductive ellimination
([B]: boronic acid/ester)
R'
Oxidative addition
Reductive ellimination
Ar
Ar
(syn-)
Scheme 1 The usefulness of β,γ-diaryl carbonyl structures as well as the previous work
and our design on three-component diarylation of olefins.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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9−11). All others gave the inferior results. We fVuierwthAertriclefoOunlninde
that the addition of extra (-)-sparteine (20 mol%) would
Results and discussion
DOI: 10.1039/C9SC02182E
In our preliminary experiment, 3-butenoic acid derivative 1a
bearing 8-aminoquinoline (AQ)-directing group (0.3 mmol) was
treated with Pd(OAc)2 (10 mol%), K2CO3 (0.3 mmol), 2-
phenylboronic acid 2a (0.6 mmol) and 4-methoxyphenyl iodide
3a (0.9 mmol) in hexafluoroisopropanol (HFIP, 2 mL) at 100 °C
for 24 h, which was completely unreactive (Table 1, entry 1).
Inspired by Toste’s work,10 we changed the solvent to the
mixture of DCM/H2O/CH3CN (2 mL:0.4 mL:0.2 mL) and the
base to Na2CO3 (0.3 mmol). Then a variety of palladium(II)
catalysts were evaluated (Table 1, Entries 2−8). (-)-
SparteinePdCl2 was proved to be the best choice (Entry 5).
Subsequently, the different bases were also screened (Entries
increase the yield to 83% (Entry 12). The effect of each
component of the mixed solvents was also investigated
(Entries 13−16). It has been proved that all the three solvents
are necessary to ensure the satisfied yield. Switching the
solvent back to HFIP dramatically shut off the reaction (Entry
17). Notably, we also checked the enantioselectivity of this
reaction under our optimized condition. However, the product
4a was always racemic at this stage. The different types of aryl
boron compounds were also screened (Entries 18−19).
Having optimized the reaction conditions, we first
investigated the substrate scope of aryl boronic acid
nucleophiles by using 3-butenoic acid derivative 1a as the
alkene and 4-iodoanisole 3a as the electrophile (Scheme 2). To
our delight, the reaction was found to tolerate an array of
functional groups on the aromatic ring of the boronic acid,
Table 1 Optimization of the directed three-component syn-vicinal-diarylation of alkene
1a with phenylboronic acid 2a and 4-methoxyphenyl iodide 3a.a
OMe
I
B(OH)2
Palladium(II) catalyst (10 mol%)
Ligand (0-20 mol%)
O
including electron-neutral, electron-donating and
-
+
N
O
withdrawing substituents, in both the para- and meta-
positions (4ba−oa). Substituents on the ortho-position led to
diminished yield, presumably due to steric effects (4pa). Multi-
substituted aryl boronic acids (4ra−sa) and heteroaryl boronic
acids were also reactive (4ta−ua). It is important to stress that
these reaction conditions were compatible with a variety of
functional groups such as halogens (F, Cl, and Br), acetyl, ester,
aldehyde, cyano, and methoxy groups on the aryl boronic
acids, which could be subjected to further synthetic
transformations.
Base (1.0 equiv)
Solvent, 24 h, 100 C
H
N
AQ
AQ
OMe
1a
2a
3a
4aa
(1.0 equiv)
(2.0 equiv)
(3.0 equiv)
Entry
1
PdII cat.
Pd(OAc)2
Pd(OAc)2
PdCl2
Base
Solvent
Yield[%]b
NR
54
K2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
HFIP (2 mL)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.1:0.1)
DCM/H2O
(1:0.2)
DCM/CH3CN
(1:0.1)
2
3
44
4
Pd(PhCN)2Cl2
(-)-sparteinePdCl2
69
5
71
OMe
I
[(-)-sparteinePdCl2] (10 mol%)
O
(-)-sparteine (20 mol%)
Ar-B(OH)2
6
(-)-sparteinePd(OAc)2
(Bipy)PdCl2
6
N
O
Na2CO3 (1.0 equiv)
DCM:H2O:MeCN (1:0.2:0.1)
100°C , 24 h
H
N
Ar
2
(2.0 equiv)
AQ
OMe
3a
(3.0 equiv)
AQ
7
60
1a
(1.0 equiv)
OMe
4
OMe
OMe
OMe
8
PddppfCl2
11
BnO
AQ
Me
tBu
F
O
O
O
O
9
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
(-)-sparteinePdCl2
66
AQ
AQ
AQ
4ba, 76%
4ca, 69%
4da 75%b
4ea, 61%
,
10
11
12c
13c
14c
15c
16c
17c
18d
19e
Cs2CO3
K3PO4
44
OMe
OMe
OMe
OMe
Br
F3C
Ac
MeOOC
AQ
53
O
O
O
O
O
AQ
AQ
AQ
AQ
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
83
4fa, 70%
4ga, 59%
4ha, 73%
4ia, 43%
OMe
OMe
OMe
72
Me
OMe
F
OHC
O
O
O
77
AQ
AQ
AQ
4ja, 57%
4ka, 69%
4lb, 72%c
4ma, 63%
14
OMe
OMe
OMe
OMe
Cl
CN
DCM (2 mL)
HFIP (2 mL)
18
O
O
O
O
AQ
AQ
AQ
AQ
NR
81
Me
4pa, 40%
4na, 63%
4qa, 74%
4oa, 68%
OMe
OMe
OMe
OMe
DCM/H2O/MeCN
(1:0.2:0.1)
DCM/H2O/MeCN
(1:0.2:0.1)
Me
OMe
HN
MeO
O
O
O
O
35
S
Me
AQ
AQ
AQ
AQ
4ua, 49%d
4ra, 68%
4ta, 30%
4sa, 81%
a Reactions were carried out by using PdII catalyst (10 mol%), ligand (0-20mol%),
base (0.3 mmol, 1.0 equiv), 1a (0.3 mmol, 1.0 equiv), phenylboronic acid 2a (2.0
equiv), and 4-methoxyphenyl iodide 3a (3.0 equiv) in the mixture of
DCM/H2O/CH3CN (2 mL:0.4 mL:0.2 mL) for 24 h at 100 °C under a N2 atmosphere.
Scheme 2 The substrate scope of aryl boronic acid nucleophiles. aReactions were
carried out by using (-)-sparteinePdCl2 (0.03 mmol, 10 mol%), (-)-sparteine (0.06 mmol,
20 mol%), Na2CO3 (0.3 mmol, 1 equiv), 1a (0.3 mmol, 1.0 equiv), arylboronic acid 2 (0.6
mmol, 2.0 equiv), and 4-methoxyphenyl iodide 3a (0.9 mmol, 3.0 equiv) in the mixture
e
b Isolated yields. c (-)-Sparteine (20 mol%) was added. d (PhBO)3 instead of 2a.
b
of DCM/H2O/CH3CN (2 mL:0.4 mL:0.2 mL) for 24 h at 100 °C under a N2 atmosphere.
PhBNep instead of 2a.
2 | J. Name., 2012, 00, 1-3
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c
the X-ray analysis of the crystal structure of 5m,11 which was in
accordance with our proposed mechanism. Notably, both
Alkene 1a (0.2 mmol) was used in the reaction. Iodobenzene was used as the
electrophile; d The reaction was conducted for 48 h and 4.0 equiv of 3a were used.
View Article Online
DOI: 10.1039/C9SC02182E
diastereomers could be accessed based on the
stereochemistry of the alkene substrate (i.e., E-alkene to 5c, Z-
alkene to 5d), suggesting that the alkene does not undergo
isomerization in our Pd-catalyzed process. In addition, a
pendant phthalimide-protected amine, benzyl-protected
alcohol and ester were also well tolerated in the reaction
(5g−i).
Subsequently, a variety of substituted aryl and heteroaryl
iodide electrophiles were tested under the optimized
conditions, and the results are summarized in Scheme 3. It was
gratifying to find whether aryl iodides are electron-rich,
electron-poor, or sterically hindered, all of them afforded
moderate to high yields (4ac−an). Heteroaryl iodide was also
competent coupling partner (5n). Notably, a lot of important
functional groups such as halogens (F, Br, and I), ester, acetyl
on the aryl iodides were tolerated, presenting the opportunity
for subsequent diversification. Besides diverse (hetero)aryl
iodides, employment of methyl iodide as the electrophile also
smoothly delivered the desired products in moderated yield in
this reaction (Scheme 3, 4aq). X-Ray analysis of single crystal
4ah clearly confirmed that the product connectivity is opposite
to those vicinal-diaryl products approaching by M0 (Ni0 or Pd0)-
catalyzed diarylation of alkenes with aryl electrophile and
nucleophiles.5
OMe
I
B(OH)2
(2 eq)
[(-)-sparteinePdCl2] (10 mol%)
(-)-sparteine (20 mol%)
O
R1
O
N
Na2CO3 (1.0 equiv)
DCM:H2O:MeCN (1:0.2:0.1)
100°C , 24 h
R1
H
R2
N
AQ
AQ
Ph R2
5 (syn-product)
2a
OMe
1
3a
(1 eq)
OMe
OMe
OMe
OMe
OMe
O
O
O
O
O
Bn
Ph
Ph
Me
Et
AQ
AQ
AQ
AQ
AQ
Ph
5e, 76%
(from E-alkene)
Me
5a, 55%b
d.r.: 1.6:1
Ph
5b, 62%
(from E-alkene)
Ph
5c, 72%
(from E-alkene)
Et
5d, 69%
(from Z-alkene)
OMe
OMe
OMe
OMe
O
O
O
O
B(OH)2
[(-)-sparteinePdCl2] (10 mol%)
(-)-sparteine (20 mol%)
O
Ph
PhthN
Ar
O
AQ BnO
AQ
AQ
MeOOC
AQ
Ar-I
3
N
Na2CO3 (1.0 equiv)
DCM:H2O:MeCN (1:0.2:0.1)
100°C , 24 h
Ph
Ph
Ph
Ph
AQ
H
5h, 59%b
5i, 74%b
N
5f, 79%b
5g, 69%b, c
AQ
4
1a
(1 eq)
(from E-alkene)
(from E-alkene)
2a
(from E-alkene)
(2 eq)
(from E-alkene)
Me
F
Br
I
OMe
OMe
OMe
OMe
MeO
O
Br
O
O
O
O
O
O
O
Ph
Ph
AQ
AQ
AQ
AQ
AQ
AQ
AQ
AQ
Ph
5j, 49%b
(from E-alkene)
Ph
5k, 49%b
Ph
5l, 43%b
(from E-alkene)
4ac, 87%
4ad, 67%
4ae, 68%
4af, 67%b
5m, 29%b
CCDC: 1852877
CF3
COCH3
COOEt
(from E-alkene)
Scheme 4 The scope of various non-conjugated alkenes. a Reactions were carried out by
using (-)-sparteinePdCl2 (0.03 mmol, 10 mol%), (-)-sparteine (0.06 mmol, 20 mol%),
Na2CO3 (0.3 mmol, 1.0 equiv), 1 (0.3 mmol, 1.0 equiv), phenylboronic acid 2a (0.6 mmol,
O
O
O
AQ
AQ
AQ
AQ
AQ
AQ
4ag, 54%
4ah, 70%
CCDC: 1852875
4ai, 63%
2equiv), and 4-methoxyphenyl iodide 3a (0.9 mmol,
3 equiv) in the mixture of
Me
MeO
Br
DCM/H2O/CH3CN (2 mL:0.4 mL:0.2 mL) for 24 h at 100 °C under a N2 atmosphere. b The
reaction was conducted for 36 h and 4.0 equiv of 3a were used. c Alkene substrate (0.2
mmol) was used in the reaction.
OMe
O
O
O
O
AQ
4aj, 72%
4ak, 69%
4al, 60%
4am, 55%
Me
S
Me
MeO
OMe
In light of our success on the transmetalation-initiated three-
component vicinal-diarylation of alkenes to synthesize racemic
syn-β,γ-diaryl carbonyl coumpounds, we have tried to develop
the enantioselective version of this reaction. After much work
on ligand evaluation and optimization of the reaction
conditions (see Figure S2-3 in SI for details of the optimization
studies), we identified pyridyl-oxazolidine ligand L41 as an
effective ligand, producing chiral product with moderate
enantioselectivity (79:21 er) and 60% yield (eq 1).
O
Me
O
O
O
AQ
AQ
AQ
AQ
4aq, 36%d
4ap, 48%c
4an, 70%
4ao, 73%
Scheme 3 The scope of aryl iodide electrophiles. a Reactions were carried out by using (-)-
sparteinePdCl2 (0.03 mmol, 10 mol%), (-)-sparteine (0.06 mmol, 20 mol%), Na2CO3 (0.3
mmol, 1.0 equiv), 1a (0.3 mmol, 1.0 equiv), phenylboronic acid 2a (0.6 mmol, 2 equiv),
and aryl iodide 3 (3-10 equiv) in the mixture of DCM/H2O/CH3CN (2 mL:0.4 mL:0.2 mL)
b
for 24 h at 100 °C under a N2 atmosphere.
By-product 4afʹ with 8% yield was
observed in this reaction from the activation of the second C–I bond in the aromatic
ring. c The reaction was conducted for 36 h and 4.0 equiv of aryl iodide were used. d The
reaction was conducted for 48 h and 10.0 equivalent of methyl iodide were used.
OMe
OMe
B(OH)2
+
I
10 mol% [Pd(allyl)Cl]2
L41
O
We next evaluated the utility of this method for various non-
conjugated alkenes by using phenylboronic acid 2a as the
nucleophile and 4-methoxyphenyl iodide 3a as the electrophile
(Scheme 4). The terminal alkene bearing mono-substitution at
the α-position proceeded smoothly to afford the desired
product in moderate yield nevertheless more forcing
conditions are needed (Scheme 4, 5a). Furthermore, we
proved that a variety of internal alkenes could also be
efficiently converted into the syn-diastereomers with nearly
neglectable electronic effect of substituents (Scheme 4,
5b−m). The syn-selectivity of the reaction was confirmed by
24 mol%
, K2CO3
O
N
O
N
+
eq 1
AQ
DCM/H2O/MeCN (5/2/1)
N
AQ
60% yield; 79: 21 e.r
80 C, 24 h
OMe
L41
To demonstrate the practicality of our method, we first scaled
up the reaction to obtain ~1 g of 4aa (Scheme 5, upper panel).
Then, the AQ-directing group was directly removed by
treatment with NaOH to yield the free carboxylic acid 6 via two
steps with an overall yield of 81%. Furthermore, the carboxylic
acid 8, which has been employed as the intermediate to
approach the natural product Pallidol, has been efficiently
synthesized with 92% yield by using the Pd(II)-catalytic method
This journal is © The Royal Society of Chemistry 20xx
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(Scheme 5, lower panel). In contrast, the literature’s method alkene was indispensable. The heck reaction between aryl
View Article Online
involved a non-catalytic procedure with three steps (86% yield), iodide and alkene 1a did not happenedDuOnI:d1e0r.10t3h9e/Co9pSCti0m2i1z8e2dE
which shows the advantage and usefulness of our method in condition and 80 % starting material 1a was recovered (eq. 3).
modular synthesis of β,γ-diaryl carbonyl coumpounds.12
It indicates that the Pd0 species might not formed in our
reaction system. Notably, the homodiarylated product with 8%
yield was observed (eq. 3). To obtain the intermediate C, the
reaction of alkene 1a and phenylboronic acid 2a was run in the
presence of a stoichiometric amount of PdII catalyst (eq. 4).
The heck product 1k (40% yield) and the starting material 1a
(51% recovery) were isolated. It means transmetalation of aryl
boronic acid and carbopalladation would preferentially
occurred in the presence of PdII catalyst, which followed a β-H
elimination step in the absence of electrophile to form Heck
product. To rule out the possibility of the Heck product 11 as
the intermediate for this three-component vicinal-diarylation
of alkenes, we carried out the reaction of the Heck product 11
with aryl iodide under a stoichiometric amount of Pd0 catalyst
(eq. 5). No desired product 4aa was observed. Finally, we
exclude the possibility of the hydrocarbofunctionalized
product 13 as the competent intermediate. Because, only 7%
diarylated product 4aa was yielded when the prepared
hydrocarbofunctionalized intermediate 13 was exposed to the
standard conditions in the absence of additional nucleophile
(eq. 6).
OMe
OMe
B(OH)2
O
1) "Standard Condition"
O
+
AQ
2) NaOH (15 equiv), EtOH, reflux
OH
I
[scale up experiment]
1a
6, 641 mg
81% yield (two steps)
2a
B(OH)2
3a
(3 mmol)
MeO
OMe
O
I
[(-)-sparteinePdCl2] (10 mol%)
O
MeO
(-)-sparteine (20 mol%)
Na2CO3 (1.0 equiv)
OMe
+
AQ
MeO
AQ
1a
DCM:H2O:MeCN (1:0.2:0.1)
100°C , 24 h
OMe
MeO
7, 66% yield
HO
HO
MeO
OMe
OH
NaOH (15 eq)
EtOH, reflux
Ref. 14
O
H
H
OH
HO
8
92% yield
,
OH
OH
Pallidol
Scheme 5 The synthetic usefulness of our methods.
On the basis of literature reports,7-9 we propose the PdII/PdIV
catalytic cycle that starts with the transmetalation (TM) of
arylboronic acids to form Ar−PdX species A (Scheme 6). Then
the Ar−PdX species would coordinate with the directing group
and alkene to form the intermediate B, which would involve
the carbopalladation step resulting in the intermediate C.
Because of the exclusive syn-addition at the carbopalladation
step, the stereoselectivity of our diarylated products are
opposite to the presented diarylation method of alkenes
involving Wacker-type anti-nucleopalladation step.6 Moreover,
the intermediate C would be intercepted by oxidative addition
of aryl iodide to form PdIV species D. Finally, reductive
elimination from the high-valent palladium center and
subsequent ligand exchange produce the product and
regenerate the PdII catalyst.13 Alternatively, alkene
coordination with PdII catalyst could also happened first to
form the intermediate A', and then transmetalation of aryl
boronic acid to form the intermediate B.
I
B(OH)2
O
"Standard Condition"
eq. 2
No Reaction
N
H
9
OMe
OMe
I
O
O
"Standard Condition"
MeO
AQ
O
eq. 3
AQ
80% recovery
AQ
AQ
OMe
10, 8% yield
O
B(OH)2
[(-)-sparteinePdCl2] (1 eq)
(-)-sparteine (2 eq)
O
O
eq. 4
AQ
Na2CO3 (1.0 equiv)
DCM:H2O:MeCN (1:0.2:0.1)
100°C , 24 h
AQ
1k, 40% yield
51% recovery
OMe
I
MeO
Pd(dba)2 (1 eq)
(-)-sparteine (2 eq)
O
MeO
AQ
O
O
eq. 5
Ph
Na2CO3 (1.0 equiv)
DCM:H2O:MeCN (1:0.2:0.1)
100°C , 24 h
AQ
AQ
Ph
Ph
OMe
I
11, 53% yield (Z:E: 1.4/1)
12, 19%
1k
OMe
Ar-[B]
syn-diarylated product
path A
N
N
O
Pd
O
on
ti
Ligand
exchange
"Standard Condition"
a
l
Ar
O
N
O
N
eq. 6
Cl
Cl
R
Transmeta
Pd
N
R
AQ
N
H
Ar Cl
AQ
B
OMe
3a
N
Alkene
A
Ar
I
Pd
N
alkene
4a, 7% yield
13
on
path
L
E
n
O
Ar-[B]
coordinati
N
O
Pd
Cl
N
Reductive
on
ti
a
l
eliminatio
Conclusions
O
N
A'
N
Transmeta
R
Carbo-
I
Pd
Ar
N
palladatio
O
In conclusion, we have described the transmetalation-initiated
three-component syn-β,γ-diarylation heterodiarylation of
olefins with aryl halides and arylboronic acids. The process is
not only simple and convenient in terms of reaction condition,
but also tolerant of a variety of functional groups, thus
Ar
Pd
syn
Ar
R
-addi
t
n
N
Oxidative
additio
B
N
Pd
L
L
n
i
on
R
N
D
Ar-I
Ar
C
Scheme
alkenes.
6 Proposed catalytic cycle of this three-component vicinal-diarylation of
constituting
a
practical route to β,γ-diaryl carbonyl
To support our aforementioned continuous mechanism,
several control experiments were performed. We found that
no reaction occurred when N-(naphthalenyl)butenamide 9 was
used as the alkene substrate (eq. 2). This result indicates that
the presence of the AQ directing group on the unconjugated
coumpounds prevalent in bioactive molecules.
Conflicts of interest
4 | J. Name., 2012, 00, 1-3
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Journal Name
ARTICLE
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15586; (c) P. Gao, L.-A. Chen and M. KD. OBIr:o1w0.1n0,3VJ9ie./wCAA9mrStiC.cl0Ce2hO1en8lmi2nEe.
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There are no conflicts to declare.
Acknowledgements
We are grateful for the financial support from the National
Natural Science Foundation of China (21602115), 1000-Talent
Youth Program (020/BF180181), the Natural Science
Foundation of Tianjin (18JCYBJC20400), the Fundamental
Research Funds for the Central Universities and Nankai
University.
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Chemical Science
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DOI: 10.1039/C9SC02182E
Table of Contents
Transmetalation-Initiated Three-Component Vicinal-Diarylation of Alkenes
Ar2
O
O
PdII/PdIV cycle
R1
R1
Ar1-B(OH)2
Ar2-I
AQ
N
H
Ar1
R2
R2
N
Nucleophiles
Electrophiles
AQ
syn-product
Alkenes
1