Pd-Catalyzed Regioselective Arylboration of Vinylarenes

Article abstract of DOI:10.1021/acs.orglett.6b02527

A palladium-catalyzed 1,2-arylboration of vinylarenes with aryldiazonium tetrafluoroborates and bis(pinacolato)diboron has been disclosed. It is reported for the first time that styrene derivatives can be successfully employed as good substrates for 1,2-arylboration of alkenes. Mechanistic studies suggest that no Pd-H reinsertion occurred under our standard conditions, which is the key for the success of this transformation.

Full text of DOI:10.1021/acs.orglett.6b02527

Letter
pubs.acs.org/OrgLett
Pd-Catalyzed Regioselective Arylboration of Vinylarenes
Kai Yang† and Qiuling Song*,†,‡
†Institute of Next Generation Matter Transformation, College of Chemical Engineering, Huaqiao University, 668 Jimei Boulevard,
Xiamen, Fujian 361021, P. R. China
‡National Laboratory for Molecular Sciences, Institute of Chemistry, CAS, Beijing 100190, P. R. China
S
* Supporting Information
ABSTRACT: A palladium-catalyzed 1,2-arylboration of vinylarenes with aryldiazonium tetrafluoroborates and bis(pinacolato)-
diboron has been disclosed. It is reported for the first time that styrene derivatives can be successfully employed as good
substrates for 1,2-arylboration of alkenes. Mechanistic studies suggest that no Pd−H reinsertion occurred under our standard
conditions, which is the key for the success of this transformation.
ransition-metal-catalyzed difunctionalization of alkenes
has become an efficient and expedient strategy to
Scheme 2. Challenges in Pd-Catalyzed Arylboration of
Vinylarenes
T
construct molecular complexities in one step in organic
synthesis.1 Among them, carboboration of alkenes has attracted
great attention since diversified alkyl boronates, which are
important intermediates and building blocks in organic
chemistry, were found to be readily accessible.2 Significant
progress on transition-metal-catalyzed carboboration has been
achieved recently by Fu,3a Toste,3b Cheng,3c Yoshida,3d
Hoveyda,3e Brown,3f Liao,3g Semba and Nakao,3h et al.,
rendering 1,2-carboboration (a),3a 2,1-carboboration (b),3d−h
and 1,1-carboboration (c)3b products (Scheme 1a). Recently,
key to solving this challenge. We envisioned that the electron
effects of Ar1 and Ar2 will highly influence the stability of two
intermediates due to their cationic properties.7 Therefore,
vinylnaphthalenes come to mind: compared to benzene
counterparts, naphthalene has more room to accommodate
the cationic charge.7a Herein, we report the first Pd-catalyzed
1,2-arylboration of vinylarenes under very mild conditions with
high regioselectivity and excellent functional group tolerance.
Scheme 1. Transition-Metal-Catalyzed Carboboration of
Alkenes
our group reported a Pd-catalyzed arylboration of unactivated
bicyclic alkenes through the Catellani intermediate A4 (Scheme
1b).5 However, in all of these pioneering examples, 1,2-
arylboration of vinylarenes has not been investigated due to the
unselectivity and complexity of the reactions: two isomers via
different π-allyl-Pd intermediates, which come from a tandem
process of high-oxidative-state Pd-aryl Heck insertion of
vinylarenes, β-hydride elimination, and reinsertion of Pd−H,
always exist owing to their similarity (Scheme 2).6,3b How to
find a good way to differentiate the two intermediates and make
one of them stable enough for further coupling becomes the
To evaluate our hypothesis, we commenced our study with
2-vinylnaphthalene (1a), 4-fluorophenyldiazonium tetrafluor-
oborate (2a), and B2pin2 as substrates (Table 1). Starting with
Pd2(dba)3 as the catalyst and Na2CO3 as the base in t-amyl-
OH, to our delight, the desired product 3aa was formed in 56%
GC yield, which indicated 1,2-arylboration product 3aa
Received: August 24, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02527
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Development of Optimized Conditions for 1,2-
Arylboration
Scheme 3. Substrate Scope of Aryldiazonium
Tetrafluoroborates 2
a
a
c
c
temp
(°C)
4aa
5a
c
entry
1
base
solvent
3a (%)
(%)
(%)
Na2CO3 tert-amyl-
60
60
60
60
60
60
60
56
59
41
51
61
52
57
59
22
20
20
13
18
21
21
18
21
OH
2
3
4
5
6
7
K2CO3
Cs2CO3
NaOAc
K3PO4
tert-amyl-
OH
20
22
14
20
23
21
17
tert-amyl-
OH
tert-amyl-
OH
tert-amyl-
OH
K2HPO4 tert-amyl-
OH
KOH
tert-amyl-
OH
8
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
THF
60
60
60
60
60
60
60
25
10
10
9
EtOH
DMF
dioxane
toluene
p-xylene
DCE
a
Reaction conditions: 2-vinylnaphthalene (1a) (0.2 mmol), aryldia-
zonium salt 2a (1 equiv), Pd2(dba)3 (5 mol %), B2pin2 (1.1 equiv),
K3PO4 (1 equiv), DCE (1 mL), N2, 12 h, isolated yield.
10
11
12
13
14
15
16
35
69
22
76
87
90
11
14
0
9
13
0
6
7
fluoroborates were demonstrated to be well-tolerated under our
standard conditions, and para, meta, and ortho substitutions all
provided the corresponding products in good yields (3aa−ae,
Scheme 3) that provide feasibility for further structural
manipulation. Moreover, aryldiazonium tetrafluoroborates
with electron-rich substituents (like tBu, Me, and MeO) on
the aromatic rings could proceed smoothly to afford the
corresponding 1,2-arylboration products in moderate to good
yields (3af−aj, Scheme 3), and aryldiazonium tetrafluorobo-
rates bearing strong electron-withdrawing groups (such as
ketone and nitro) were found to be good candidates as well for
this transformation, rendering 3ak and 3al in 69% and 65%
yields, respectively.
Subsequently, the scope of vinylarenes was evaluated with (4-
fluorophenyl)diazonium tetrafluoroborate (2a) or (4-
acetylphenyl)diazonium tetrafluoroborate (2k) under the
standard conditions (Scheme 4). To our delight, 2-vinyl-
naphthalenes bearing both electron-rich and electron-poor
substituents worked well with (4-fluorophenyl)diazonium
tetrafluoroborate (2a) and B2pin2, affording the corresponding
desired products in decent yields (3ba−ea). Both 2-vinyl-
anthracene (1f) and 1-vinylnaphthalene (1g) were good
candidates for this transformation as well. Furthermore,
heteroaromatics, such as 5-vinylbenzo[b]thiophene (1h), were
compatible under the standard conditions, leading to the
desired product 3ha in 59% yield. To our delight, this catalytic
system could be employed for styrenes, whose preparation has
met with hurdles and challenges for 1,2-carboboration products
in previous reports,8 after simple condition optimization (see
Table S1 for details). Byproducts arising from Heck reaction or
hydroboration reactions also existed in these reactions;
however, interestingly, 1,1-arylboration product was not
detected, which is in sharp contrast to the precedents. Both
electron-donating and electron-withdrawing groups were
DCE
7
6
DCE
5
3
b
d
17
DCE
89 (80)
5
5
a
Reaction conditions: 2-vinylnaphthalene 1a (0.2 mmol), aryldiazo-
nium salt 2a (1 equiv), B2pin2 (1.5 equiv), base (1 equiv), solvent (1
b
c
d
mL), N2, 12 h. B2pin2 (1.1 equiv). GC yield. Isolated yield.
predominated over hydroboration product 5a, Heck product
4aa, and trace Suzuki−Miyaura borylative product (Table 1,
entry 1).
Further base screening suggested that K3PO4 was optimal
compared to K2CO3, Cs2CO3, NaOAc, K2HPO4, and KOH
(Table 1, entries 2−7). Subsequently, solvent optimization
demonstrated that DCE was the best one among THF, EtOH,
DMF, dioxane, toluene, and p-xylene (Table 1, entries 8−14).
Interestingly, a significant improvement in yield of 3aa was
observed when the temperature was decreased from 60 to 10
°C (GC yield from 76 to 90%), and superior selectivity of the
desired product over other byproducts was also detected
simultaneously (Table 1, entry 14−16). When the loading of
B2pin2 was dropped to 1.1 equiv, the yield of desired product
3aa was not affected and obtained in 89% in GC with 80%
isolated yield (Table 1, entry 17). It is of note that when aryl
iodide and triflate such as PhI and PhOTf took place of
aryldiazonium salt 2a no reaction occurred under the current
conditions.
With the optimized conditions in hand, we next turned our
attention to the substrate scope of this palladium-catalyzed
regioselective 1,2-arylboration. A very broad range of
substituted aryldiazonium tetrafluoroborates (2a−n, Scheme
3) with 1a and B2pin2 could be smoothly converted into the
corresponding 1,2-arylboration products with high regioselec-
tivity. To our delight, halo-substituted aryldiazonium tetra-
B
DOI: 10.1021/acs.orglett.6b02527
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 4. Substrate Scope of Vinylarenes 1
Scheme 5. Related Mechanistic Experiments
a
Reaction conditions: 2-vinylarene 1 (0.2 mmol), aryldiazonium salt 2
Scheme 6. Plausible Catalytic Cycle for 1,2-Arylboration of
Vinylarenes
(1 equiv), Pd2(dba)3 (5 mol %), B2pin2 (1.1 equiv), K3PO4 (1 equiv),
DCE (1 mL), N2, 12 h, isolated yield. Reaction conditions: 2-
b
vinylarene 1 (0.2 mmol), aryldiazonium salt 2 (1 equiv), Pd2(dba)3
(15 mol %), B2pin2 (1.1 equiv), Na2CO3 (1 equiv), THF (1 mL), N2,
24 h, isolated yield. Using 4-acetylphenyldiazonium tetrafluoroborate
was convenient for isolation, and 1,1-arylboration product was not
observed when other aryldiazonium salts were used.
introduced into the corresponding products smoothly in
moderate to good yields (1j−n). Moreover, a heteroaromatic
alkene, such as 2-vinylthiophene, was also a good substrate for
this transformation without generating any byproducts (3ol).
To understand the inherence for the high regioselectivity of
this 1,2-arylboration, isotope-labeled experiments were carried
out with 4-t-Bu β,β-bisdeuterated styrene (1k-D2) (Scheme
5B). To improve the yields of the Heck product and
hydroboration product, we decreased the loading of
Pd2(dba)3 to 5 mol % and raised the temperature to 70 °C.
Under these conditions, we purified the reaction mixture and
obtained 38% yield of 3kk, 13% yield of 4kk, and 14% yield of
5k (Scheme 5A). At the same time, with deuterated styrene 1k-
D2, similar results were obtained. It was surprising that the
hydroboration product 5k-D is the branched boronate (α-
boronate) with three deuterium atoms observed on the same
carbon (methyl group); meanwhile, 1,1-bisdeuterated 1,2-
arylboration product 3kk-D2 was obtained in 27% yield along
with 8% of 1-deuterated Heck product 4kk-D. On the basis of
previous experiments, the additional deuterium atom on 5k-D3
might come from the Pd-D intermediate which was generated
from β-D elimination of the Heck reaction between 1k-D and
2k, leading to product 4kk-D. This reaction also explained why
Heck product 4kk and hydroboration product 5k always appear
in identical amounts.
intermediate D. The intermediate D directly reacts with a
nucleophile, diboron, under basic conditions to generate the
desired 1,2-arylboration product 3. Meanwhile, β-H elimination
of the intermediate II will lead to Heck product 4 as a
byproduct along with 1 equiv of LnPd−H, which attacks
vinylarene 1 to render intermediate III, and eventually
branched alkyl boronate 5 was obtained in the presence of
B2pin2. Interestingly, reinsertion of LnPd−H over Heck product
4 was not observed at all under our standard conditions, which
is in sharp contrast to the previous report, probably owing to
the steric hindrance of Heck product 4 over vinylarene 1.
Therefore, this reaction can highly regioselectively afford 1,2-
arylboration product without the formation of 1,1-arylboration
product.
According to the previous literature reports9 as well as our
control experimental results, we gave a proposed mechanism
(Scheme 6): oxidative addition of aryldiazonium tetrafluor-
oborate 2 over Pd(0) affords aryl-Pd intermediate I. Heck
reaction between vinylarene 1 and intermediate I would yield
intermediate II, which further can convert into π-allyl-Pd
In conclusion, a highly regioselective palladium-catalyzed 1,2-
arylboration of vinylarenes with aryldiazonium tetrafluorobo-
rates and bis(pinacolato)diboron has been disclosed for the first
time. Isotope-labeled experiments clearly demonstrated that no
C
DOI: 10.1021/acs.orglett.6b02527
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(7) (a) Johns, A. M.; Tye, J. W.; Hartwig, J. F. J. Am. Chem. Soc. 2006,
128, 16010−16011. (b) Marquard, S. L.; Rosenfeld, D. C.; Hartwig, J.
F. Angew. Chem., Int. Ed. 2010, 49, 793−796. (c) Marquard, S. L.;
Hartwig, J. F. Angew. Chem., Int. Ed. 2011, 50, 7119−7123. (d) Blessley,
G.; Holden, P.; Walker, M.; Brown, J. M.; Gouverneur, V. Org. Lett.
2012, 14, 2754−2757. (e) Poverenov, E.; Efremenko, I.; Leitus, G.;
Martin, J. M. L.; Milstein, D. Organometallics 2013, 32, 4813−4819.
(8) (a) Crudden, C. M.; Ziebenhaus, C.; Rygus, J. P. G.; Ghozati, K.;
Unsworth, P. J.; Nambo, M.; Voth, S.; Hutchinson, M.; Laberge, V. S.;
Maekawa, Y.; Imao, D. Nat. Commun. 2016, 7, 11065. (b) Zhang, L.;
Lovinger, G. J.; Edelstein, E. K.; Szymaniak, A. A.; Chierchia, M. P.;
Morken, J. P. Science 2016, 351, 70−74. (c) Scheuermann, M. L.;
Johnson, E. J.; Chirik, P. J. Org. Lett. 2015, 17, 2716−2719.
(9) (a) Saini, V.; O’Dair, M.; Sigman, M. S. J. Am. Chem. Soc. 2015,
137, 608−611. (b) Stokes, B. J.; Liao, L.; de Andrade, A. M.; Wang,
Q.; Sigman, M. S. Org. Lett. 2014, 16, 4666−4669. (c) Wu, X.; Lin, H.-
C.; Li, M.-L.; Li, L.-L.; Han, Z.-Y.; Gong, L.-Z. J. Am. Chem. Soc. 2015,
137, 13476−13479. (d) Zhu, Y.; Cornwall, R. G.; Du, H.; Zhao, B.;
Shi, Y. Acc. Chem. Res. 2014, 47, 3665−3678. (e) Yeh, M.-C. P.; Tsao,
W.-C.; Tu, L.-H. Organometallics 2005, 24, 5909−5915. (f) Liao, L.;
Jana, R.; Urkalan, K. B.; Sigman, M. S. J. Am. Chem. Soc. 2011, 133,
5784−5787. (g) McCammant, M. S.; Liao, L.; Sigman, M. S. J. Am.
Chem. Soc. 2013, 135, 4167−4170.
Pd−H reinsertion occurred under the standard conditions
perhaps due to the steric hindrance of Heck product 4 over
vinylarenes 1, which also explained why this protocol can highly
regioselectively afford 1,2-arylboration product. Enatioselective
1,2-arylboration of vinylarenes with aryldiazonium tetrafluor-
oborates and bis(pinacolato)diboron is underway in our
laboratory and will be reported in due course.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b02527.
General procedures, mechanistic experiemnts, and NMR
spectroscopic data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: qsong@hqu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (21202049), the Recruitment Program
of Global Experts (1000 Talents Plan), the Natural Science
Foundation of Fujian Province (2016J01064), Fujian Hundred
Talents Plan and Program of Innovative Research Team of
Huaqiao University (Z14X0047), and Graduate Innovation
Fund (for K.Y.) of Huaqiao University are gratefully acknowl-
edged. We also thank the Instrumental Analysis Center of
Huaqiao University for analysis support.
REFERENCES
■
(1) (a) Wolstenhulme, J. R.; Gouverneur, V. Acc. Chem. Res. 2014,
47, 3560−3570. (b) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev.
2011, 111, 2981−3019. (c) Minatti, A.; Muniz, K. Chem. Soc. Rev.
2007, 36, 1142−1152.
(2) (a) Hall, D. G., Ed. Boronic Acids: Preparation and Applications in
Organic Synthesis and Medicine; Wiley-VCH: Weinheim, 2005.
(b) Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003, 2003,
4695−4712. (c) Suginome, M. Chem. Rec. 2010, 10, 348−358.
(d) Yun, J. Asian J. Org. Chem. 2013, 2, 1016−1025.
(3) (a) Su, W.; Gong, T.-J.; Lu, X.; Xu, M.-Y.; Yu, C.-G.; Xu, Z.-Y.;
Yu, H.-Z.; Xiao, B.; Fu, Y. Angew. Chem., Int. Ed. 2015, 54, 12957−
́
12961. (b) Nelson, H. M.; Williams, B. D.; Miro, J.; Toste, F. D. J. Am.
Chem. Soc. 2015, 137, 3213−3216. (c) Yang, F.-Y.; Wu, M.-Y.; Cheng,
C.-H. J. Am. Chem. Soc. 2000, 122, 7122−7123. (d) Yoshida, H.;
Kageyuki, I.; Takaki, K. Org. Lett. 2013, 15, 952−955. (e) Meng, F.;
Haeffner, F.; Hoveyda, A. H. J. Am. Chem. Soc. 2014, 136, 11304−
11307. (f) Logan, K. M.; Smith, K. B.; Brown, M. K. Angew. Chem., Int.
Ed. 2015, 54, 5228−5231. (g) Jia, T.; Cao, P.; Wang, B.; Lou, Y.; Yin,
X.; Wang, M.; Liao, J. J. Am. Chem. Soc. 2015, 137, 13760−13763.
(h) Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 7567−7570.
(4) (a) Catellani, M.; Motti, E.; Della Ca’, N. Acc. Chem. Res. 2008,
41, 1512−1522. (b) Candito, D. A.; Lautens, M. Angew. Chem., Int. Ed.
2009, 48, 6713−6716. (c) Gericke, K. M.; Chai, D. I.; Bieler, N.;
Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 1447−1451.
(5) Yang, K.; Song, Q. J. Org. Chem. 2016, 81, 1000−1005.
(6) (a) Urkalan, K. B.; Sigman, M. S. Angew. Chem., Int. Ed. 2009, 48,
3146−3149. (b) Werner, E. W.; Urkalan, K. B.; Sigman, M. S. Org.
Lett. 2010, 12, 2848−2851. (c) Satterfield, A. D.; Kubota, A.; Sanford,
M. S. Org. Lett. 2011, 13, 1076−1079. (d) Kalyani, D.; Satterfield, A.
D.; Sanford, M. S. J. Am. Chem. Soc. 2010, 132, 8419−8427.
D
DOI: 10.1021/acs.orglett.6b02527
Org. Lett. XXXX, XXX, XXX−XXX