Pd-Catalyzed Stereoselective 1,2-Aryboration of Alkenylarenes

Article abstract of DOI:10.1021/acs.orglett.9b03114

The palladium-catalyzed highly regio- and diastereoselective arylboration of alkenylarenes has been developed. This chemistry afforded the benzylic boronic esters with a broad substrate scope, which are valuable synthetic intermediates for organic synthes

Full text of DOI:10.1021/acs.orglett.9b03114

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Pd-Catalyzed Stereoselective 1,2-Aryboration of Alkenylarenes
Penglin Zhang,† Mimi Xing,† Qitao Guan,† Jinguo Zhang,† Qian Zhao,† and Chun Zhang*,†,‡
†Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Chemistry, Institute of Molecular Plus, Tianjin
University, Weijin Rd. 92, Tianjin 300072, China
‡State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
S
* Supporting Information
ABSTRACT: The palladium-catalyzed highly regio- and diaster-
eoselective arylboration of alkenylarenes has been developed. This
chemistry afforded the benzylic boronic esters with a broad
substrate scope, which are valuable synthetic intermediates for
organic synthesis. The chiral anion phase-transfer strategy was
designed for this transformation to realize the regio-, diastereo-,
and enantioselective control of this reaction simultaneously.
he transition-metal-catalyzed arylboration of alkenes is an
(entry 1, Table 1). We then surveyed the effect of different
solvents. Compared with diethyl ether, some other solvents
afforded much better results (entries 1−3, Table 1). In
particular, when toluene was chosen as the solvent, the product
could be given in 72% yield and with greater than 20:1
diastereoselectivity (entry 3, Table 1). The efficiency of this
reaction could not be improved by increasing the reaction
temperature (entry 4, Table 1). Further studies indicated that
both Pd0 and PdII sources could be used as the catalyst for this
reaction (entries 5 and 6, Table 1), and without a Pd catalyst,
this reaction did not work (entry 7, Table 1). Then, some
stronger bases were tried, such as Na2CO3 and Na3PO4, which
suggested that these reactions with different bases gave similar
results (entries 8 and 9, Table 1). Further condition screening
approved the notion that an additional base is unnecessary for
this transformation (entry 10, Table 1). Interestingly,
decreasing the amount of both the Pd catalyst and the starting
material nearly did not affect the efficiency of this reaction
(entry 11, Table 1). Therefore, the condition of entry 11 was
chosen as the optimal condition.
T
efficient strategy to construct a versatile intermediate in
one step.1 Among these studies, the reactions with 1,2-
disubstituted alkenes are much more challenging due to
additional diastereoselectivity control.2 Because of the
significance of this kind of transformation, some important
achievements have been obtained in recent years ( Scheme 1,
Scheme 1. Arylboration of Internal Alkenes
1).3 By some of the above chemistry, 1,1-diaryl boronic
compounds could be made with good efficiency and selectivity.
However, until now, there have been few examples using the
arylboration reaction of internal alkenes to produce benzylic
boronic esters,4 which are valuable synthetic intermediates for
complex biological molecules because of their ability to
participate in several well-established C−C and C−heteroatom
bond-forming reactions.5,6 Herein we developed a novel Pd-
catalyzed highly selective arylboration of internal alkenes with
high regio- and diastereoselectivity, which could afford benzylic
boronic esters as products (Scheme 1, 2). Importantly, the
enantioselectivity of this transformation could be controlled by
an asymmetric phase-transfer-catalyzed strategy.7
With the optimal reaction condition in hand, the substrate
scope of aryldiazonium tetrafluoroborates was investigated
(Scheme 2). In general, this chemistry afforded the desired
products in modest to good yield and with high diaster-
eoselectivities. As the data of Scheme 2 show, the aryl group
with an electron-withdrawing group, such as −CF3, −CO2Me,
−F, and −Cl, worked very well (3c−g, Scheme 2). Notably,
when bromo-substituted aryldiazonium tetrafluoroborate was
employed as a substrate, the corresponding product could be
afforded in 87% yield and with high selectivity, which could be
used for further transformation (3h, Scheme 2). Further
studies indicated that substituents at the ortho, meta, and para
positions of the arene group nearly did not affect the efficiency
(3i−k, Scheme 2). Notably, the carboxyl group was compatible
with this reaction system (3m, Scheme 2). To our delight, the
Our study commenced with the palladium-catalyzed
reaction of B2Pin2, 1,2-dihydronaphthalene (1a), and 4-
nitrobenzenediazonium tetrafluoroborate (2a) in diethyl
ether. At 25 °C for 24 h, the above reaction gave the desired
product 3a in 8% yield and with a greater than 20:1 d.r. value
Received: September 2, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03114
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Effect of Different Reaction Conditions
b
c
entry
[Pd]
base
solvent
T (°C)
yield (%)
d.r.
1
2
3
4
5
6
7
8
9
10
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(PPh3)4
Pd(OAc)2
none
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
Na2CO3
Na3PO4
none
Et2O
THF
25
25
25
40
25
25
25
25
25
25
25
8
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
37
72
72
17
59
NR
59
69
77
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
>20:1
>20:1
>20:1
>20:1
de
,
f
11
none
76 (73)
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), B2Pin2 (0.4 mmol), Pd catalyst (5 mol %), base (0.4 mmol), and solvent (2.0 mL) at 25 °C
b
c
d
e
for 24 h. Yield was determined by 1H NMR. d.r. was determined by 1H NMR. 2.5 mol % Pd2(dba)3 was used. Amount of 2a and B2Pin2 was
decreased to 0.3 mmol. Isolated yield.
f
a
Scheme 2. Scope of Different Aryldiazonium
Tetrafluoroborates
Scheme 3. Scope of Different Alkenes
a
a
Standard reaction conditions: 1a (0.2 mmol), 2 (0.3 mmol), B2Pin2
(0.3 mmol), Pd2(dba)3 (2.5 mol %), toluene (2 mL), and N2 at 25 °C
b
1
for 24 h. Isolated yield; d.r. was determined by H NMR.
naphthyl and heterocyclic starting materials could be function-
alized under this reaction condition (3n−p, Scheme 2).
The substrate scope of the Pd-catalyzed highly selective
arylboration transformation was further expanded to a variety
of substituted alkenylarenes (1) (Scheme 3). These results
indicated that both cyclic and acyclic substrates proceeded well
in good yield and with high diastereoselectivities (Scheme 3).
Importantly, the bromo-substituted products could be made by
this reaction, which could be used for further transformation
(3s, Scheme 3). Compared with the six-membered alkenyl ring
containing the starting material, the C−C double bond on a
seven- or five-membered ring slightly induced a lower yield
a
Standard reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), B2Pin2
(0.3 mmol), Pd2(dba)3 (2.5 mol %), toluene (2 mL), and N2 at 25 °C
for 24 h. Isolated yield. d.r. was determined by H NMR. E-alkene
was used as the starting material. Z-alkene was used as the starting
material.
b
c
1
d
(3u,v, Scheme 3). To our delight, the oxygen- and nitrogen-
containing alkyl ring part could survive, which afforded the
B
DOI: 10.1021/acs.orglett.9b03114
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
desired product in a synthetically useful yield (3w,x, Scheme
3). For acyclic substrates, different electron densities of the aryl
ring did not affect the efficiency (3y−ad, Scheme 3). Other
internal acylic alkenes besides β-Me styrene derivatives could
be converted into the desired product (3z,aa, Scheme 3).
Notably, both (E)-1,2-diphenylethene and (Z)-1,2-diphenyle-
thene, which possesses a stronger steric hindrance effect,
worked well with similar efficiencies (3ae,af, Scheme 3).
Unfortunately, trisubstitued alkene and aliphatic alkene did not
work. (See the SI.)
Scheme 5. Optimization of Enantioselective 1,2-
Arylborylation
a
The chiral anion phase-transfer (CAPT) reaction is a kind of
powerful strategy for asymmetric synthesis.8 On the basis of
our above studies, we proposed that chiral anion catalyst (L)
and palladium cationic catalyst could control the enantiose-
lectivity of this kind of reaction in a proper solvent system
(Scheme 4). The soluble chiral ion pair could be formed via
Scheme 4. Proposed Catalytic Cycle for Highly Selective
Arylboration of Alkenylarenes
a
Reaction conditions: 1 (0.1 mmol), 2a (0.2 mmol), B2Pin2 (0.2
mmol), Na3PO4 (0.2 mmol), Pd2(dba)3 (5 mol %), L (10 mol %),
b
and N2 for 24 h. The yield was calculated by 1H NMR. Isolated yield
of the corresponding alcohol product d.r. was determined by 1H
c
NMR, and all of them were >20:1. Determined by chiral HPLC
analysis.
phase transfer from L and insoluble aryldiazonium tetrafluor-
oborate (2).9 The palladium species 5 was generated due to
the oxidative addition reaction of 4 and the Pd0 catalyst.10 The
intermediate 5 inserted into alkenylarene could give compound
6.11 The following transmetalation reaction with B2Pin2 and
reductive elimination would give the desired product and
regenerate L and Pd0.12
tetrafluoroborate (2) (Scheme 6). The aryl group of
diazonium salt with an electron-withdrawing group could be
a
Scheme 6. Enantioselective 1,2-Arylborylation
The feasibility of the regio-, diastereo-, and enantioselective
control of this reaction at same time by CAPT was studied
from the reaction of B2Pin2, 1,2-dihydronaphthalene (1a), and
4-nitrobenzenediazonium tetrafluoroborate (2a), which was
catalyzed by Pd2(dba)3 and L1 (Scheme 5). To our delight,
the reaction gave a 36:64 e.r. value with 74% yield and high
regio- and diastereoselectivities. As shown in Scheme 5, to
improve the enantioselectivity of this reaction, different kinds
of the asymmetric phosphoric acids had been selected as
phase-transfer catalysts for this reaction. First, the data
suggested that the Ar group of phosphoric acid with an
electron-donating group (L2, Scheme 5) did not affect the
selectivity, but Ar with an electron-withdrawing group (L3,
Scheme 5) had a negative effect. Second, the Ar group with
stronger steric hindrance afforded better enantioselectivity but
lower yield (L4−L14, Scheme 5). Improving the lipid
solubility by installing an alkyl group (L9 and L14) or
changing the dihedral angle (L10) of the catalyst did not
provide a positive effect. The results of solvent screening
suggested that toluene/MTBE 3:2 was the best choice (eq 1,
Scheme 5; see the Supporting Information (SI)). When the
temperature decreased to 0 °C, the enantioselectivity could be
improved to 93:7 (eq 1, Scheme 5; see the SI).
a
Standard reaction conditions: 1 (0.1 mmol), 2a (0.2 mmol), B2Pin2
(0.2 mmol), Na3PO4 (0.2 mmol), Pd2(dba)3 (5 mol %), L12 (10 mol
b
%), and N2 for 24 h. Isolated yield of the corresponding alcohol
product. d.r. was determined by 1H NMR, and all of them were >20:1.
c
Determined by chiral HPLC analysis.
transferred to a desired product with good enantioselectivity,
such as 3a and 3e with 93:7 and 94:6 er, respectively. To our
delight, the chloro- and bromo-substituted alkenylarene
derivative could give good enantioselectivity. Under this
reaction system, all of the above transformations afforded
high regio- and diastereoselectivities. Unfortunately, the yields
of these reactions are <30% because of the side Heck reaction
of 1 and 2.
After testing the influence of different conditions on the
enantioselectivity of this CAPT reaction, we continued to
detect the effect of alkenylarenes (1) and aryldiazonium
In conclusion, we have demonstrated a novel Pd-catalyzed
highly regio- and diastereoselective arylboration of alkenylar-
C
DOI: 10.1021/acs.orglett.9b03114
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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formation could be controlled by a CAPT strategy. Further
studies of synthetic applications are ongoing in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
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̈
■
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(o) Li, X.; Meng, F.; Torker, S.; Shi, Y.; Hoveyda, A. H. Angew. Chem.,
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The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03114.
Experimental procedures, details of experiment, and
spectral data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ChunZhang@tju.edu.cn
ORCID
(7) Carter, C.; Fletcher, S.; Nelson, A. Tetrahedron: Asymmetry
2003, 14, 1995.
Chun Zhang: 0000-0001-6848-2868
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge financial support from Tianjin University,
National Science Foundation of China (no. 21801181),“1000-
Youth Talents Plan”, and State Key Laboratory of Elemento-
Organic Chemistry (Nankai University).
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DOI: 10.1021/acs.orglett.9b03114
Org. Lett. XXXX, XXX, XXX−XXX