Stereoselective synthesis of trisubstituted alkenes via cobalt-catalyzed double dehydrogenative borylations of 1-alkenes

Article abstract of DOI:10.1021/acscatal.7b02104

A highly selective cobalt-catalyzed single and double dehydrogenative borylations (DHBs) of terminal alkenes have been developed for the synthesis of trans-monoborylalkenes and diborylalkenes, respectively. While the cobalt-catalyzed double DHBs of aryl 1

Full text of DOI:10.1021/acscatal.7b02104

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Article
Stereoselective Synthesis of Trisubstituted Alkenes via Cobalt-
Catalyzed Double Dehydrogenative Borylations of 1-Alkenes
Huanan Wen, Lei Zhang, Suzhen Zhu, Guixia Liu, and Zheng Huang
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b02104 • Publication Date (Web): 11 Aug 2017
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Stereoselective Synthesis of Trisubstituted Alkenes via Cobalt-
Catalyzed Double Dehydrogenative Borylations of 1-Alkenes
Huanan Wen, Lei Zhang, Suzhen Zhu, Guixia Liu and Zheng Huang*
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†State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Acadꢀ
emy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
ABSTRACT: A highly selective cobaltꢀcatalyzed single and double dehydrogenative borylations (DHBs) of terminal alkenes have
been developed for the synthesis of transꢀmonoborylalkenes and diborylalkenes, respectively. While the cobaltꢀcatalyzed double
DHBs of aryl 1ꢀalkenes with 2 equiv of bis(pinacolato)diboron (B2pin2) in the presence of 1 equiv of CsF in DMF produce 1,1ꢀ
diborylalkenes selectively, the double DHBs with alkyl 1ꢀalkenes generate cisꢀ1,2ꢀdiborylalkenes in a selective manner. The 1,1ꢀ
diborylalkene products are further applied to stepwise and stereospecific crossꢀcouplings with aryl halides to create trisubstituted
alkenes, including triaryl alkenes.
INTRODUCTION
Lin found that the reaction of 4ꢀvinyl anisole with 2 equiv of
B2pin2 at 80 oC after 4ꢀ5 days formed 1,1ꢀdiborylalkene as the
major product, along with transꢀmonoborylalkene as the minor
product (Scheme 1b).13 More recently, a more general route to
1,1ꢀdiborylalkenes from 1ꢀalkenes was disclosed by the group
of Iwasawa using a pincer Pd catalyst.6a,6b Although this Pd
catalysis represents a remarkable advance, the development of
a catalyst system based on inexpensive, sustainable, and enviꢀ
ronmentally begin baseꢀmetal, such as cobalt, is desirable.
Vinyl boronic acids and boronates are versatile synthetic
intermediates due to their reasonable stability, low toxicity and
wide applications in C–C and C–heteroatom bondꢀforming
reactions.1 Among them, 1,1ꢀdiborylalkenes bearing two
geminal boronate moieties are of particular synthetic interest
because they are useful building blocks for diverse synthesis
of polysubstituted alkenes, which are prevalent motifs
occurring in bioactive compounds and πꢀconjugated
materials.2 Stereodefined triaryl alkenes (TAAs), for example,
have shown interesting biological activities3 and novel optical
properties.4
Scheme 1. Known Catalytic Methods for Synthesis of 1,1-
Diborylalkenes.
While many methods are available for the synthesis of
monoborylalkenes, there are limited approaches to 1,1ꢀ
diborylalkenes.1c,5,6 Traditional routes to the latter involve the
use of reactive lithium reagents, which may pose a challenge
in reactions with sensitive functional groups.7ꢀ9 Recently,
several catalytic methods have been developed for the
synthesis of 1,1ꢀdiborylalkenes using alkynes as the starting
materials (Scheme 1a). In 2015, Sawamura and Ohmiya reꢀ
ported the preparation of 1,1ꢀdiborylalkenes by LiOtBuꢀ
catalyzed reactions of propiolates, propiolamides, and 2ꢀ
ethynylazoles with B2pin2.10 Ozerov disclosed an Irꢀcatalyzed
synthesis of 1,1,2ꢀtriborylalkenes from a twoꢀstep reaction of
terminal alkynes with HBpin.11 More recently, Chirik
developed a Coꢀcatalyzed 1,1ꢀdiboration of terminal alkynes.
While very effective for aliphatic alkynes, the reactions with
aryl alkynes gave moderate yields due to the
homodimerization of alkynes to enynes.12
Driven by our interest in developing baseꢀmetal catalysis for
alkene functionalizations,14 very recently we reported the
synthesis of 1,1,1ꢀtris(boronates) from vinylarene and B2pin2
through a Coꢀcatalyzed tandem sequence comprising the
double DHBs and the hydroboration of resulting 1,1ꢀ
diborylalkenes with HBpin generated in situ.15 Here we report
that a combination of a bipyridylꢀphosphine (PNN)ꢀCo
catalyst with CsF in DMF is effective for selective double
DHBs of terminal vinylarenes with B2pin2, producing 1,1ꢀ
diborylalkenes that can be utilized as building blocks for the
construction of a diverse range of stereodefined trisubstituted
alkenes, including TAAs. Furthermore, selective synthesis of
The synthesis of 1,1ꢀdiborylalkenes from simple alkenes is
of great interest because of the wide accessibility and high
stability of the substrates. During their successful development
of Rhꢀcatalyzed single dehydrogenative borylation (DHB) of
alkenes with B2pin2 to yield monoborylalkenes, Marder and
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transꢀmonoborylalkenes has also been achieved by Coꢀ
Table 1). Unfortunately, the addition of 1 equiv of pꢀ
3
4
5
6
7
8
9
catalyzed single DHB of vinylarenes under slightly modified
conditions. When terminal alkyl alkenes are used as the
substrates, the Coꢀcatalyzed double DHBs form cisꢀ1,2ꢀ
diborylalkenes with high stereoselectivety.
thiolcresol inhibited the catalysis (entry 3). In our previous
attempt to synthesize 1,1,1ꢀtris(boronates) from 4ꢀbromoꢀ
styrene,
a decent amount of the corresponding 1,1ꢀ
diborylalkene was detected.15 Given this observation, mesityl
bromide (1 equiv) was used as an additive. The run gave 77%
3a, but substantial amounts of the hydroboration products
resulted (entry 4). Preforming the reaction with 1 equiv CsF in
toluene was somewhat selective for the formation of
monoborylalkene 3a (81%) (entry 5). Gratifyingly, switching
the solvent from toluene to DMF for an enhanced solubility of
CsF resulted in the formation of 87% 4a (entry 6). A slight
increasing of the catalyst loading (3 mol %) provided the
desired product 4a in 96% yield (entry 7). Switching the
precatalyst 1a to the iPrꢀsubstituted variant 1b gave poor
selectivity (47% 4a, 6% 3a, and 14% 5a，entry 8). A control
experiment without CsF gave only 19% 3a (entry 9). The
reactions with other inorganic additives, KF, LiF and CsCl,
afforded moderate yields of 3a; in none case was 4a observed
(entries 10ꢀ12). In addition, reducing the loading of CsF from
1.0 to 0.7 equiv decreased the yield of 4a from 96% to 36%,
with 59% 3a (entry 13 vs 7). Significantly, the reaction with
0.4 equiv of CsF is highly selective for the formation of the
single DHB product (91% 3a, entry 14). A further decreasing
of the loading of CsF, however, had a detrimental effect on the
yield of 3a (entry 15).
RESULTS AND DISCUSSION
Optimization Studies. To produce vinylboronates in a
selective manner, the Co catalyst system must fulfill the
following requirements: (1) the hydroboration of alkene or
borylalkene, which can occur rapidly using the (PNN)Co
catalyst as shown in our previous works,14c,15 must be entirely
inhibited; (2) the catalyst system should enable a clear
discrimination between the single DHB and the double DHBs
events.
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Table 1. Condition Optimizations for Selective Double
˩
DHBs or Single DHB of Styrene with B2pin2
cat. (x mol %), NaBEt3H (2x mol %)
Bpin
additive (y equiv)
sol., RT, 12 h
Ph
Bpin
Ph
2a
Ph
Bpin
3a
6a
4a
+
B2pin2
Bpin
Bpin
Bpin
Bpin
N
Ph
Ph
Bpin
2 equiv
Ph
R2P
N
Co
Cl2
Bpin
5a
7a
R= tBu, 1a; iPr, 1b
yield (%)b
Entry
cat. (x)
additive (y)
sol.
3a
4a
5a/(6a+7a)
Substrate Scope of Co-Catalyzed Double DHBs and Single
EtOH (1)
DIPAc (1)
Thiocresol (1)
MesBrd (1)
CsF (1)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (2)
1a (3)
1b (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
tol
32
52
8/5
1
DHB of Vinylarenes. Next we evaluated the scope and
limitation of our protocol for the synthesis of gemꢀ
diborylalkenes and transꢀmonoborylalkenes (Table 2). In the
presence of 1 equiv of CsF, the Co catalyst derived from 1a is
effective for double DHBs of various aryl alkenes. The gemꢀ
diborylalkenes products are moistureꢀ and airꢀstable, and can
be purified by flash chromatography. A range of functional
groups, such as halide (4g, 4h), ester (4i), thioether (4k), ether
(4l, 4o), and ketone (4q), can be tolerated. An exception was
the paraꢀMe2Nꢀsubstituted styrene that gave only 14% 4j, but
67% of the monoboryl 3j. Meꢀsubstituents at the ortho
positions are tolerated as demonstrated by the isolation of 4d
and 4e in good yields. Double DHBs of two double bonds in
1,3ꢀdivinylbenzene occurred smoothly to form the tetraboryl
4p. The estroneꢀderived diborylalkene 4q was obtained in a
moderate yield.
tol
24
2
40
6
5/1
0/0
2
tol
3
tol
1
77
5
12/11
14/1
1/<1
3/<1
14/25
<1/0
0/0
4
tol
81
5
5
CsF (1)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
87
96
47
0
6
CsF (1)
<1
6
7
CsF (1)
8
none
19
65
42
36
59
91
33
9
KF (1)
0
10
11
12
13
14
15
LiF (1)
0
2/<1
<1/0
<1/<1
<1/0
<1/0
CsCl (1)
CsF (0.7)
CsF (0.4)
CsF (0.2)
0
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1
Noteworthily, simple modification of the reaction
conditions by using 0.4 equiv of CsF led to the formation of
the corresponding transꢀmonoborylalkenes (3) in excellent
selectivity (Table 2). Most single DHB reactions of aryl
alkenes proceeded with high yields, although a few products
resulted in moderate isolated yields due to decomposition
during the purification by column chromatography.
0
aReaction conditions: on 0.5 mmol scale and used 2 mL solvent at
o
b
25 C; Yields were determined by GC with mesitylene as an
internal standard. c2,6ꢀDiisopropylaniline. dMesityl bromide.
Initial efforts focused on the search for an additive that can
suppress the hydroboration, but has no adverse effect on the
DHB process. Considering the successful dehydrocouplings of
alcohols, amines, and thiols with HBpin,16 such reagents were
tested as the HBpin scavenger. In the presence of 1 equiv of
ethanol or 2,6ꢀdiisopropylaniline (DIPA), the reaction of
styrene (2a) with B2pin2 (2 equiv) in toluene at rt using the Co
catalyst generated in situ from 1a (2 mol %) and NaBEt3H (4
mol %),17 mainly formed the double DHBs product 4a and the
single DHB product 3a, with minimal yields of the
hydroboration byꢀproducts (5a, 6a and 7a) (entries 1 and 2,
Substrate Scope of Co-Catalyzed Double DHBs of Alkyl
Alkenes. Compared to the DHB reactions of aryl alkenes, the
DHB reactions of aliphatic alkenes are more challenging,
partly due to competing alkene isomerization. With the
precatalyst 1a, initial attempts employing the conditions
applied for double DHBs of aryl alkenes have been
unsuccessful for the double DHBs of alkyl alkenes.
Gratifyingly, the substitution of the precatalyst 1a for the less
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Table 2. Cobalt-Catalyzed Selective Double DHBs or Single DHB of Various Aryl Alkenesa
3
4
5
6
7
8
9
CsF (0.4 equiv)
1a (3 mol %), NaBEt3H (6 mol %)
CsF (1 equiv)
1a (3 mol %), NaBEt3H (6 mol %)
Bpin
Ar1
B2pin2
+
Ar1
Bpin
Ar1
3
4
2
2 equiv
Bpin
DMF, RT, 12 h
Bpin
DMF, RT, 12 h
Bpin
Bpin
Bpin
Bpin
Bpin
Ph
Ph
Bpin
4b, 87%(83%)
Bpin
Bpin
4c, 91%(84%)
Bpin
Bpin
4a, 92%(84%)
3a, 91%(88%)
3b, 99%(93%)
Bpin
3c, 86%(78%)
3f, 93%(81%)
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Bpin
Bpin
Bpin
Bpin
Bpin
Bpin
Bpin
4e, 85%(84%)
Bpin
tBu
tBu
3d, 65%(63%)
Bpin
3e, 78%(60%)
Bpin
EtO2C
4d, 66%(60%)
4f, 74%(71%)
Bpin
Bpin
Bpin
Bpin
Bpin
4h, 74%(59%)
EtO2C
Bpin
F
Cl
F
Cl
4i, 82%(69%)c
3g, 92%(80%)
3h, 55%(37%)
3i, 90%(77%)
4g, 86%(77%)
Bpin
MeS
Bpin
Bpin
Bpin
Bpin
4k, 79%(73%)
Bpin
Bpin
Bpin
4l, 75%(72%)
Bpin
Me2N
3j, 72%(54%)
MeO
Me2N
MeS
MeO
3k, 74%(71%)
3l, 91%(72%)
4j, 14%
MeO
MeO
MeO
Bpin
MeO
MeO
Bpin
Bpin
Bpin
MeO
Bpin
Ph
3m, 90%(87%)
3o, 88%(79%)
4n, 75%(68%)
Bpin
Bpin
Bpin
4o, 86%(77%)
OMe
OMe
Bpin
H
H
H
H
Bpin
Bpin
H
Bpin
H
O
O
3q, 92%(71%)b
3p, 78%(67%)
4p, 73%(48%)
4q, 46%
Bpin
Bpin
aConditions: on 0.5 mmol scale and used 2 mL DMF; Yields were determined by H NMR and values in parentheses are isolated yields.
1
bThe reaction time was 24 h. cPerformed at 40 oC.
sterically hindered 1b led to selective formation of cisꢀ1,2ꢀ
diborylalkenes (Table 3). The substrate scope is not limited to
1ꢀalkenes bearing branches (8hꢀk) that can prevent undesired
Table 3. Cobalt-catalyzed Double DHBs of Various Alkyl
Alkenesa
isomerization. The challenging linear αꢀolefins, including 1ꢀ
octene and 1ꢀnonene, undergo double DHBs to give 1,2ꢀ
diborylalkenes with satisfactory selectivity (9aꢀg). Ester
functionalities are tolerated as shown by the isolation of 9f and
9g in useful yields. Comparison of the outcomes of the double
DHB reactions with aryl alkenes and alkyl alkenes shows
different selectivity (1,1ꢀ versus 1,2ꢀdiborylalkens), which is
tentatively attributed to the inverted regioselectivity of the
insertion of the monoborylalkene intermediates into the Co–B
bond.15 The formation of cisꢀ1,2ꢀdiborylalkene products is
consistent with the results obtained by Pdꢀcatalyzed double
DHBs of alkyl alkenes.6a,6b
We have also developed procedures for large scale synthesis.
While the monoboryl 3a could be isolated in 71% yield (1.6 g)
from 10 mmol of 2a using the standard single DHB conditions
(rt, 12 h), the gram scale preparation of 1,1ꢀdiborylalkene 6a
required an elevated temperature (40 oC) and a longer reaction
time (24 h) in order to gain a high isolated yield (82%, 2.9 g,
eq 1).18
aConditions: On 0.5 mmol scale and used 2 mL DMF, Yields
2a
(10 mmol)
+
CsF (0.4 equiv)
1a (3 mol %)
CsF (1 equiv)
1a (3 mol %)
NaBEt3H (6 mol %)
were determined by 1H NMR and values in parentheses are isolatꢀ
ed yields. bUsed 5.0 mol % of 1b and 10 mol % NaBEt3H and the
reaction time was 24 h.
(1)
NaBEt3H (6 mol %)
3a
4a
2.9 g, 82%
B2pin2
2 equiv
DMF, RT, 12 h
DMF, 40 oC, 24 h
1.6 g, 71%
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Noteworthily, the TAA product with a paraꢀMeS substituent
(11aa) can be readily oxidized to the sulfonyl derivative,
Substrate Scope of Pd-Catalyzed Stepwise Cross-Coupling
of 1,1-Diboryl-1-alkenes. With broad array of 1,1ꢀ
a
Table 5. Stereoselective Synthesis of Triaryl Alkenes via
Cross-Couplings of 10 with Aryl Bromides.a
diborylalkenes in hand, we sought to develop stepwise Suzukiꢀ
Miyaura crossꢀcouplings for stereodefined synthesis of TAAs.
Althoug several approaches, such as Wittigꢀtype carbonyl
olefinations,19 catalytic hydroarylations of alkynes,4d,20 and
crossꢀcouplings of 1,1ꢀdihaloalkenes with organometallic
nucleophiles,21 are known for the synthesis of TAAs, few
methods offer a stereocontrol for the construction of TAAs
with three different aryl substituents.4a,21a,22 Note that Shimizu
and Hiyama have reported Pdꢀcatalyzed consecutive couplings
of 1,1ꢀarylalkylꢀ2,2ꢀdiborylalkenes with aryl iodides to form
tetrasubstituted alkenes,2b yet the trisubstituted type was not
disclosed.
Pd(PtBu3)2 (5 mol %),
K3PO4 (4 equiv)
DME/H2O, 80 oC, 12 h
Ar2
Ar2
Ar1
10
Ar1
Ar3Br
2 equiv
+
Bpin
Ph
Ar3 11
Ph
R
1 = OMe, 11d, 98%
SMe, 11e, 98%
NMe2, 11f, 96%
CN,11g, 96%
CO2Me, 11h, 95%
CONEt2, 11i, 92%
F, 11j, 99%
10
11
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Ph
Ar'
Ph
Ar' = p-tol, 11a, 94%
m-tol, 11b, 98%
o-tol, 11c, 96%
OCF3, 11k, 77%
R1
Ph
Arp-tBu
Arp-tBu
=
Ph
Ph
Ph
tBu
The use of aryl iodides as the coupling reagents was
responsible for the success of selective single arylation of 4.
The couplings using the Pd catalyst of tBuꢀJohnPhos and
KOH as the base occurred under mild conditions (30 oC),
allowing the introduction of the aryl group, Ar2, exclusively at
the position trans to the Ar1 group regardless of the nature of
substituents on the para, meta, and ortho positions of Ar1
(Table 4). The cis or double arylation products were not
observed. In contrast, the reaction with an aryl bromide
required a higher reaction temperature (80 oC), and led to both
of the single and double arylation products (see Supporting
Information for details). A number of functional groups,
including the acetyl group (10e), were compatible with the
catalyst. Most of the transꢀ1,2ꢀdiarylꢀsubstituted monoꢀ
borylalkene products 10 could be obtained in goodꢀtoꢀhigh
isolated yields.
R2 = Me, 11n, 97%
OMe, 11o, 98%
COPh, 11p, 79%
R2
11l
84%
11m
90%
O
F
Arp-tBu
Arp-tBu
Arp-tBu
Arp-tBu
R3
=
R3
MeO
F
OHC
F
F
F, 11t, 97%
Ph, 11u, 98%
11q, 86%
11r, 86%
11s, 96%
Arp-tBu
Arp-tBu
Ph
F
tBu
S
N
11x, 80%
tBu
F
F
11v, 82%
11w, 74%
F
SMe
F
Table 4. Synthesis of Stereodefined trans-1,2-Diaryl-1-
borylalkenes via Cross-Couplings of 4 with Aryl Iodides.a
Ph
F
Pd(OAc)2 (3 mol %)
11y, 96%
S
11z , 97%
11aa, 94%
tBu-JohnPhos (3.3 mol %)
KOH (2 equiv)
DMF, 30 oC, 12 h
Bpin
Ar2
10
CO2Me
Ar1
Ar1
Ar2I
+
4
Arp-tBu
Arp-tBu
Bpin
Bpin
Ph
Ph
R1 R1 = H, 10a, 91%
tBu, 10b, 86%
Ph
R2 = Me, 10f, 73%
OMe, 10g, 77%
F, 10h, 80%
F, 10c, 76%
OCF3, 10d, 77%
Ph
Ph
Ph
CO2Et
Bpin R2
COMe, 10e, 58%b
Bpin
Bpin
F
F
MeO
11ad, 84%
11ae, 87%
11ab, 84%
11ac, 92%
CF3 Ph
Ph
N
Bpin
Bpin
MeO
10i, 54%
10j, 73%
10k, 65%
F
tBu
R3
S
S
R3
=
tBu, 10m, 78%
F, 10n, 69%
Bpin
Bpin
10l, 74%
F
11af, 93%b
11ag, 97%b
aConditions: on 0.2 mmol scale. Yields shown are of isolated
products. bUsed 1 equiv of KOH.
F
F
F
F
aConditions: on 0.1 mmol scale. Yields shown are of isolated
products. bUsed 0.1 mmol ArBr and 0.2 mmol 10k.
Next we developed a procedure for the installation of the
second aryl group (Ar3) to complete the synthesis of TAAs.
Using Pd(PtBu3)2 as the catalyst and K3PO4 as the base, the
couplings of 10 with various aryl bromides proceeded at 80 °C,
furnishing the desired products 11 in high yields (Table 5).
The alkene geometry was effectively preserved in all cases. A
wide range of reactive functionalities, including the formyl
(11q), ketone (11p), cyanide (11g) groups, were tolerated.
which is a novel inhibitor of the cyclooxygenaseꢀ2 isozyme.19a
Thiophenyl (11v, 11y, 11af) and pyridyl (11w) bromides were
suitable coupling reagents. In addition, allyl (11ad), benzyl
(11ae), and vinyl (11m, 11ab, 11ac) bromides gave high
yields and high selectivities for the desired trisubstituted alꢀ
kenes. The coupling with ethyl (Z)ꢀ3ꢀbromoacrylate produced
1,3,4ꢀtrisubstitued cis,transꢀ1,3ꢀbutadiene (11ac) as the single
stereoisomer. Finally, two extended πꢀsystems, 11af and 11ag,
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were obtained in high isolated yields, demonstrating the utility
firmed by Xꢀray diffraction analysis.25 Note that the 11B{1H}
of diborylalkenes in the synthesis of conjugated materials.
Thus, the synthetic scheme provides a general route to
stereospecific trisubstituted alkenes, including those bearing
three different substituents (11nꢀ11ag). Some products bearing
reactive functionalities (for examples, 11p, 11q, 11ac) would
be difficut to access by the couplings of 1,1ꢀdihaloalkenes
with Grignard or zinc reagents.21a
(both solidꢀstate and simulation), 19F, 13C{1H} NMR data of 12
are very similar with those of [nBu4N][B2pin2F] and
[Me4N][B2pin2F],25 suggesting that 12 is likely an anionic
fluoride adduct. Treatment of the isolated 12 with 2a and
B2pin2 in a 1:1:1 ratio under the catalytic conditions formed
17% 3a and 81% 4a (eq 6). The data suggest that the diboron
adduct 12 is likely an active source of boryl species in the
double DHBs process.24d
Importantly for the user, the transformation of the simple
terminal alkenes to TTAs can be performed in a oneꢀpot,
threeꢀstep fashion without the requirement for isolation of the
intermediates. For example, the sequence comprising the Coꢀ
catalyzed double DHBs of 2a and Pdꢀcatalyzed arylations with
iodobenzene and 4ꢀbromoanisole gave 11d in 66% overall
yield (eq 2).
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O
O
Cs
B B
CsF + B2pin2
12, 91%
(5)
(6)
DMF, RT
O
O
F
assigned tentatively
1a (3 mol %), NaBEt3H (6 mol %)
3a
+ 4a
B2pin2
2a + 12 +
DMF, RT, 12 h
17% 81%
To test the possibility of the formation of 1,1ꢀdiborylalkenes
via CsFꢀmediated dehydroboration of 1,1,1ꢀtris(boronates), 7a
was submitted to the reaction with CsF in DMF under the
standard catalytic conditions. The product observed in this
reaction was the protodeboronation product 6a (92% yield, eq
7),26 instead of 4a. Moreover, a deuterium labeling experiment
was performed using styreneꢀβ,βꢀD2 2a-D2 as the substrate.
The reaction gave 4a and 4a-D1 in a 3:1 ratio (eq 8), indicating
that the competing 1,2ꢀinsertion of vinylarene or monoꢀ
borylalkene into a Co−D bond occurs during catalysis. These
data, combined with the mechanistic insights obtained in our
earlier studies on the Coꢀcatalyzed synthesis of
tris(boronates),15 are consistent with a pathway of Coꢀ
catalyzed double DHBs. Following the 2,1ꢀinsertion insertion
of vinyarene 2 into the Co−B bond, βꢀH elimination gives
monoborylalkene 3, which undergoes the second DHB to form
1,1ꢀdiborylalkene 4 (Scheme 2).
Mechanistic Studies. To probe the role of DMF and CsF in the
double DHBs process, stoichiometric experiments were
carried out. Treatment of HBpin with DMF (2 equiv) and the
Co catalyst in C6D6 resulted in the reduction of DMF, giving
85% or 74% yield of Me3N in the reaction with (1 equiv) or
without CsF, respectively (eq 3). Treatment of HBpin with
CsF in DMF, but without the Co catalyst, led to a rapid deꢀ
composition of HBpin to form multiple unidentified hydrido
boron compounds; however, no Me3N was detected in this
reaction, suggesting the reduction of DMF with HBpin occurs
under the Co catalysis (eq 4). Though the identity of these
hydrido boron compounds is not known definitively,
1
1
comparison of the Hꢀcoupled and Hꢀdecoupled 11B NMR
data of the reaction mixture with those of previously reported
hydrido boron compouds23 implies the formation of cesium
boron trihydride, dihydride, and monohydride species (see
spectral data in the Supporting Information) (eq 4).24 Note that
HBpin remains intact in DMF in the absence of the Co catalyst
and CsF. All together, these results imply that DMF can inhibꢀ
it the undesired hydroboration by consuming HBpin derived
from the Coꢀcatalyzed DHBs. While CsF does react with
HBpin, the addition of CsF is not required for suppressing the
hydroboration, which is in accord with the lack of the hydrobꢀ
oration products in the control without CsF (entry 9, Table 1).
1a (3 mol %)
NaBEt3H (6 mol %)
Bpin
Bpin
Bpin
4a
Ph
7a
CsF
Ph
(7)
+
not observed
DMF, RT, 12 h
Bpin
Bpin
6a, 92%
B2pin2 (2 equiv), CsF (1 equiv)
1a (3 mol %), NaBEt3H (6 mol %)
D
D
Bpin
Ph
4a +
(8)
D
Ph
Bpin 4a-D1
2a-D2
DMF, RT, 12 h
95% D content
69%, 4a:4a-D1 = 3:1
Scheme 2. Proposed Mechanism.
NaBEt3H
[Co]Cl2
[Co]-H
12 or B2pin2
1a (3 mol %), NaBEt3H (6 mol %)
[Co] = (PNN)-Co
Me3N (3)
HBpin + DMF
2 equiv
+ CsF
C6D6, RT, 12 h
0 or 1
equiv
1 equiv CsF: 85%
no CsF: 74%
HBpin/
CsF
HBpin/
CsF
Ar
w/o cat.
DMF, RT, 12 h
2
Cs[BH X ] Cs[BHX ]
Cs[BH3X]
(Me3N not formed; multiple
unidentified hydrido borons detected)
+
+
[Co]-Bpin
2
2
3
+
(4)
CsF
HBpin
12 or B2pin2
2 equiv
Bpin
[Co]-H
H
[Co]
Ar
On the other hand, CsF has an important effect on promotꢀ
ing the DHBs (entry 7 vs 8, Table 1). The reaction of CsF with
1 equiv of B2pin2 in DMF formed a putative anionic fluoride
diboron adduct, Cs[B2pin2F] 12, in 91% yield (eq 5). This
compound exhibits very low solubility in common organic
solvents, but was fully characterized by combustion analysis
H
Ar
Bpin
Bpin
4
H
[Co]
Ar
Bpin
Bpin
Bpin
[Co]-H
Ar
1
and solidꢀstate 11B{1H}, 19F, 13C{1H}, and H NMR spectrosꢀ
3
copies (see spectral data in the Supporting Information).
Similar fluoride diboron adducts [nBu4N][B2pin2F] and
[Me4N][B2pin2F] have been reported by Marder and
colleagues, and the structure of [Me4N][B2pin2F] was conꢀ
12 or B2pin2
[Co]-Bpin
Bpin
HBpin consumed
by reaction with
CsF and DMF
HBpin/
CsF
3
Ar
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(3) (a) Collins, D. J.; Hobbs, J. J.; Emmens, C. W. J. Med. Chem. 1971,
14, 952ꢀ957. (b) Emmens, C. W. Reproduction 1973, 34, 23ꢀ28. (c)
Borgna, J. L.; Coezy, E.; Rochefort, H. Biochem. Pharmacol. 1982, 31,
3187ꢀ3191.
CONCLUSIONS
In summary, we have developed
a
controlled,
(4) (a) Itami, K.; Ohashi, Y.; Yoshida, J. J. Org. Chem. 2005, 70, 2778ꢀ
2792. (b) Yuan, W. Z.; Tan, Y.; Gong, Y.; Lu, P.; Lam, J. W. Y.; Shen, X.
Y.; Feng, C.; Sung, H. H. Y.; Lu, Y.; Williams, I. D.; Sun, J. Z.; Zhang,
Y.; Tang, B. Z. Adv. Mater. 2013, 25, 2837ꢀ2843. (c) Wen, W.; Shi, Z.;
Cao, X.; Xu, N. Dyes Pigm. 2016, 132, 282ꢀ290. (d) Masai, H.; Matsuda,
W.; Fujihara, T.; Tsuji, Y.; Terao, J. J. Org. Chem. 2017, 82, 5449ꢀ5455.
(5) Recent reviews on the synthesis of monoborylalkenes: (a) Yun, J.
Asian J. Org. Chem. 2013, 2, 1016ꢀ1025. (b) Yoshida, H. ACS Catal.
2016, 6, 1799ꢀ1811. (c) Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.;
Westcott, S. A.; Marder, T. B. Chem. Rev. 2016, 116, 9091ꢀ9161.
(6) Recent works on the monoborylalkenes via catalytic alkene dehydroꢀ
genative borylation: (a) Takaya, J.; Kirai, N.; Iwasawa, N. J. Am. Chem.
Soc. 2011, 133, 12980ꢀ12983. (b) Kirai, N.; Iguchi, S.; Ito, T.; Takaya, J.;
Iwasawa, N. Bull. Chem. Soc. Jpn. 2013, 86, 784ꢀ799. (c) Sasaki, I.; Doi,
H.; Hashimoto, T.; Kikuchi, T.; Ito, H.; Ishiyama, T. Chem. Commun.
2013, 49, 7546ꢀ7548. (d) Brown, A. N.; Zakharov, L. N.; Mikulas, T.;
Dixon, D. A.; Liu, S.ꢀY. Org. Lett. 2014, 16, 3340ꢀ3343. (e) Morimoto,
M.; Miura, T.; Murakami, M. Angew. Chem., Int. Ed. 2015, 54, 12659ꢀ
12663. (f) Mazzacano, T. J.; Mankad, N. P. ACS Catal. 2017, 7, 146ꢀ149.
(g) Wang, C.; Wu, C.; Ge, S. ACS Catal. 2016, 6, 7585ꢀ7589.
(7) Matteson, D. S. Synthesis 1975, 147ꢀ158.
(8) (a) Hata, T.; Kitagawa, H.; Masai, H.; Kurahashi, T.; Shimizu, M.;
Hiyama, T. Angew. Chem. Int. Ed. 2001, 40, 790ꢀ792. (b) Kurahashi, T.;
Hata, T.; Masai, H.; Kitagawa, H.; Shimizu, M.; Hiyama, T. Tetrahedron
2002, 58, 6381ꢀ6385. (c) Shimizu, M.; Shimono, K.; Schelper, M.; Hiyaꢀ
ma, T. Synlett 2007, 1969ꢀ1971.
(9) (a) Weber, L.; Eickhoff, D.; Halama, J.; Werner, S.; Kahlert, J.;
Stammler, H.ꢀG.; Neumann, B. Eur. J. Inorg. Chem. 2013, 2013, 2608ꢀ
2614. (b) Hyodo, K.; Suetsugu, M.; Nishihara, Y. Org. Lett. 2014, 16,
440ꢀ443. (c) Ho, H. E.; Asao, N.; Yamamoto, Y.; Jin, T. Org. Lett. 2014,
16, 4670ꢀ4673.
dehydrogenative borylation(s) approach (double versus single
DHB) for selective synthesis of 1,1ꢀdiborylalkenes and transꢀ
monoborylalkenes from aryl alkenes. On the contrary, the
double DHBs of alkyl alkenes yield cisꢀ1,2ꢀdiborylalkenes
with high stereoselectivity. The boronate groups introduced in
the diboryl products offer flexible synthetic manipulations as
demonstrated by the stepwise Suzuki crossꢀcouplings of 1,1ꢀ
diborylalkenes, allowing
synthesis of trisubstituted alkenes, such as triaryl alkenes,
utilizing simple to access starting materials, 1ꢀalkenes.
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a
convenient, stereoselective
EXPERIMENTAL SECTION
General Procedure for Cobalt-Catalyzed Double DHBs of
Various Aryl Alkenes. In an Arꢀfilled glovebox, a sealed tube
(10 mL) was charged with complex 1a (6.7 mg, 15 ꢁmol, 3.0
mol %), CsF (76.0 mg, 0.5 mmol, 1.0 equiv), and DMF (2
mL). NaBEt3H (30 ꢁmol, 6 mol %, 1.0 M in THF) was added
to the mixture. After stirring for 3 min, 2 (0.5 mmol, 1.0 equiv)
and B2pin2 (254 mg, 1.0 mmol, 2.0 equiv) were added. The
mixture s stirred at room temperature for 12 h, and then
quenched by exposing the solution to air. The mixture was
filtered through silica gel. H2O (10 mL) was added to the
filtrate and the aqueous phase was extracted with diethyl ether
(3x20 mL). The combined organic extracts were washed with
H2O and brine, dried (MgSO4) and concentrated in vacuo. The
crude product was dissolved in CDCl3 to obtain 1H NMR yield,
and then purified by flash chromatography on silica with ethyl
acetate and petroleum ether (v/v, 1:30 to 1:5) to afford the
pure products 4.
(10) Morinaga, A.; Nagao, K.; Ohmiya, H.; Sawamura, M. Angew. Chem.
Int. Ed. 2015, 54, 15859ꢀ15862.
(11) Lee, C.ꢀI.; Shih, W.ꢀC.; Zhou, J.; Reibenspies, J. H.; Ozerov, O. V.
Angew. Chem., Int. Ed. 2015, 54, 14003ꢀ14007.
(12) Krautwald, S.; Bezdek, M. J.; Chirik, P. J. J. Am. Chem. Soc. 2017,
139, 3868ꢀ3875.
(13) (a) Westcott, S. A.; Blom, H. P.; Marder, T. B.; Baker, R. T. J. Am.
Chem. Soc. 1992, 114, 8863ꢀ8869. (b) Coapes, R. B.; Souza, F. E. S.;
Thomas, R. L.; Hall, J. J.; Marder, T. B. Chem. Commun. 2003, 614ꢀ615.
(c) Mkhalid, I. A. I.; Coapes, R. B.; Edes, S. N.; Coventry, D. N.; Souza,
F. E. S.; Thomas, R. L.; Hall, J. J.; Bi, S.ꢀW.; Lin, Z.; Marder, T. B. Dalꢀ
ton Trans. 2008, 1055ꢀ1064.
(14) (a) Peng, D.; Zhang, Y.; Du, X.; Zhang, L.; Leng, X.; Walter, M. D.;
Huang, Z. J. Am. Chem. Soc. 2013, 135, 19154ꢀ19166. (b) Zhang, L.;
Peng, D.; Leng, X.; Huang, Z. Angew. Chem. Int. Ed. 2013, 52, 3676ꢀ
3680. (c) Zhang, L.; Zuo, Z.; Leng, X.; Huang, Z. Angew. Chem., Int. Ed.
2014, 53, 2696ꢀ2700. (d) Zhang, L.; Zuo, Z.; Wan, X.; Huang, Z. J. Am.
Chem. Soc. 2014, 136, 15501ꢀ15504. (e) Du, X.; Zhang, Y.; Peng, D.;
Huang, Z. Angew. Chem. Int. Ed. 2016, 55, 6671ꢀ6675. (f) Jia, X.; Huang,
Z. Nat. Chem. 2016, 8, 157ꢀ161.
(15) Zhang, L.; Huang, Z. J. Am. Chem. Soc. 2015, 137, 15600ꢀ15603.
(16) Romero, E. A.; Peltier, J. L.; Jazzar, R.; Bertrand, G. Chem. Comꢀ
mun. 2016, 52, 10563ꢀ10565.
(17) NaBEt3H acts as the the catalyst activator, see: Bouwkamp, M. W.;
Bowman, A. C.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2006,
128, 13340ꢀ13341.
(18) Note that CsF has limited solubility in DMF, and the product derived
from the reaction of CsF and B2pin2 also exhibits very poor solubility in
DMF (see the characterization of compound 12 in the Mechanistic Studies
section). Thus, the reaction mixture of 2a, 2 equiv of B2pin2, and 1 equiv
of CsF on 10 mmol scale contains a large amount of solids, making the
stirring of the mixture much more difficult than that on 0.5 mmol scale.
Therefore, performing the reaction on a large scale required a higher temꢀ
perature and a longer reaction time relative to the run on 0.5 mmol scale.
In fact, the large scale reaction under standard conditions (at 25 °C for 12h)
resulted in the formation of a mixture of diborylalkene (4a, 55% GC yield)
and monoborylalkene (3a, 43% GC yield), while increasing the reaction
ASSOCIATED CONTENT
Supporting Information. Experimental procedures, full spectroꢀ
scopic data for all new compounds, and copies of NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: huangzh@sioc.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The National Key R&D Program of China (2015CB856600,
2016YFA0202900), National Natural Science Foundation of Chiꢀ
na (21422209, 21432011, 21421091, 21572255), and Chinese
Academy of Sciences (XDB20000000) support this work.
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temperature (to 40 °C) and prolonging the reaction time (to 24 h) signifiꢀ
cantly enhanced the yield of 4a.
(19) (a) Uddin, M. J.; Rao, P. N. P.; McDonald, R.; Knaus, E. E. Bioorg.
Med. Chem. Lett. 2005, 15, 439ꢀ442. (b) Huo, C.; He, X.; Chan, T. H. J.
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5
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Dominey, A. P.; Thomas, S. P. Nat. Chem. 2017, 9, 595ꢀ600.
(24) Note that unidentified white solid also precipitated from the solution
of the reaction shown in eq 4.
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(25) Pietsch, S.; Neeve, E. C.; Apperley, D. C.; Bertermann, R.; Mo, F.;
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10581ꢀ10584.
For Table of Contents Only
Bpin
Bpin
Ar1
Ar2
I. Pd cat., Ar1I
II. Pd cat., Ar2Br
(
tBuPNN)-[Co] (3%)
Ar
+
CsF (1 equiv)
DMF
Ar
Ar
2 B2pin2
alkyl
Bpin
Bpin
(
iPrPNN)-[Co] (2%)
alkyl
+
2 B2pin2
CsF (1 equiv)
DMF
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