Palladium(0)-catalyzed cross-coupling of 1,1-diboronates with vinyl bromides and 1,1-dibromoalkenes

Article abstract of DOI:10.1002/anie.201407000

Palladium-catalyzed cross-coupling reactions of 1,1-diboronates with vinyl bromides and dibromoalkenes were found to afford 1,4-dienes and allenes, respectively. These reactions utilize the high reactivities of both 1,1-diboronates and allylboron intermediates generated in the initial coupling.

Full text of DOI:10.1002/anie.201407000

Angewandte
Chemie
DOI: 10.1002/anie.201407000
Synthetic Methods
Palladium(0)-Catalyzed Cross-Coupling of 1,1-Diboronates with Vinyl
Bromides and 1,1-Dibromoalkenes**
Huan Li, Zhikun Zhang, Xianghang Shangguan, Shan Huang, Jun Chen, Yan Zhang, and
Jianbo Wang*
Abstract: Palladium-catalyzed cross-coupling reactions of 1,1-
diboronates with vinyl bromides and dibromoalkenes were
found to afford 1,4-dienes and allenes, respectively. These
reactions utilize the high reactivities of both 1,1-diboronates
and allylboron intermediates generated in the initial coupling.
compounds in the construction of multiple carbon–carbon
bonds.[3d]
In contrast to alkylboron compounds, allyboron com-
pounds show high reactivity and have been explored in
coupling reactions and other reactions.[4] We thus conceived
that the allylboron compound A, generated through palla-
dium-catalyzed coupling of 1,1-diboron alkanes with vinyl
bromides, should undergo subsequent transformations in the
same reaction system (Scheme 1). Herein we report the
Organoboron compounds have found wide applications in
carbon–carbon bond formations, in particular as nucleophiles
in palladium-catalyzed cross-coupling reactions (Suzuki–
Miyaura coupling).[1] In contrast to aryl- or vinylboron
compounds, which are the nucleophilic coupling partners
typically employed in Suzuki–Miyaura coupling reactions,
alkylboron compounds provide opportunities to construct
carbon(sp3)–carbon bonds in similar coupling reactions.
However, these otherwise straightforward coupling reactions
usually encounter difficulties, such as low reactivity and side
reactions. For this reason, alkylboron compounds have not
been appreciably explored in transition-metal-catalyzed cou-
pling reactions.[1c,2]
Recent studies on 1,1-diboron compounds have revealed
some unique reactivity of these compounds in cross-coupling
reactions.[3] It has been observed that in the case of 1,1-
diboron alkanes, the palladium-catalyzed cross-coupling
reactions with aryl,[3a,c] allyl,[3d] and benzyl[3d] bromides are
highly efficient, thus affording monocoupling products, with
one of the two boron groups remaining intact. The interesting
observation is that the adjacent boron group facilitates the
cross-coupling reaction of the other boron group. However,
because of the low reactivity of the produced monoboron
alkanes, further coupling under the same reaction system does
not occur. To utilize the remaining boron group for carbon–
carbon bond formation, a different reaction system has to be
applied upon the completion of the first coupling reaction,
and thus considerably limits the application of 1,1-diboron
Scheme 1. Palladium(0)-catalyzed cross-coupling with 1,1-dibronates.
pin=pinacol.
investigation based on this design. We have found that in the
case of the reaction with vinyl bromides, 1,4-dienes are
formed as the products, while in the reaction with 1,1-
dibromoalkenes, allenes are obtained.
We initially investigated the vinyl bromide 1a in the
coupling reactions with the 1,1-diboronate 2a using [Pd-
(PtBu3)2] as the catalyst and aqueous KOH (10m) as the base
(Scheme 2). As anticipated, the coupling reaction proceeded
efficiently. However, the allyl boronate product 3a could not
be isolated. Instead, it further couples with vinyl bromide to
[*] H. Li, Z. Zhang, X. Shangguan, S. Huang, Dr. Y. Zhang,
Prof. Dr. J. Wang
Beijing National Laboratory of Molecular Sciences (BNLMS) and
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University
Beijing 100871 (China)
E-mail: wangjb@pku.edu.cn
Dr. J. Chen
Beijing Institute of Microchemistry, No.15 Xinjiangongmen Road,
Haidian District, Beijing 100091 (China)
[**] The project is supported by National Basic Research Program of
China (973 Program, No. 2012CB821600) and Natural Science
Foundation of China (Grant No. 21272010 and 21332002).
Scheme 2. Reactions of 1,1-diboronates with vinyl bromide. Reaction
conditions: 1a (0.4 mmol), 2a (0.3 mmol), [Pd(PtBu3)2] (5 mol%),
base, 1,4-dioxane (2 mL). The products were isolated by silica gel
chromatography. The E/Z ratio was determined by 1H NMR analysis of
the final product.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201407000.
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To further study the scope of the reaction, vinyl bromides
with different structures were investigated (Scheme 4). When
cis-1-bromo-1-propene (1n) was used, the 1,4-diene product
4p with an E configuration was isolated in high yield. For the
reactions with 1-substituted 1-bromoethylenes 1o and 1p, the
corresponding products 4q and 4r were obtained. Interest-
ingly, when 1-bromo-2-methylpropene (1q) was used as the
substrate, the allyl boronate 3s could be isolated in moderate
yield, with only trace amount of the 1,4-diene product. This
outcome is presumably attributed to the steric hindrance of
two methyl substituents in 3s, which suppress the subsequent
transmetallation process.
Next, we proceeded to study the palladium-catalyzed
coupling reaction of the 1,1-dibromoalkene 6a with 2a.
Through experiments on the reaction conditions,[5] it was
concluded that under the reaction conditions shown in
Equation (1), the allene product 7a could be isolated in
good yield.
Allenes are highly useful in organic chemistry and their
synthetic methods are still rather limited.[7,8] Under the
reaction conditions shown in Equation (1), the substrate
scope was next investigated. First, various dibromoalkenes
Scheme 3. Proposed reaction mechanism.
form the 1,4-diene 4a as the main product, together with 5a as
the side product. The side-product 5a is formed through
protodeboronation of the allyl boronates intermediate 3a. By
switching the base from KOH to LiOH, the yield of 4a could
be slightly improved.[5]
Table 1: Palladium(0)-catalyzed cross-coupling of vinyl bromides with
1,1-diboronates.[a]
A possible reaction mechanism has been proposed as
shown in Scheme 3. First, oxidative addition of vinyl bromide
to Pd0 generates the intermediate B, which is followed by
transmetallation with 1,1-diboronates to form the PdII species
C. Reductive elimination from C gives 3a (cycle A). As
a result of the high reactivity of 3a, it effectively competes
with 1,1-diboronate substrate to form the PdII species D,
which follows reductive elimination to give the linear 1,4-
pentadiene product 4a (cycle B). Because of the bulky ligand
PtBu3, the isomerization of D to the intermediate F through
the p-allylic PdII species E is slow, while the reductive
elimination of D to form 4a is fast. As a result, only the linear
product 4a is obtained and the branched 4a’ is not observed.
This result is consistent with the g-selectivity commonly
observed for the palladium-catalyzed cross-coupling of ally-
boron compounds.[4d–h,j]
Since the synthetic methodology for 1,4-dienes is highly
demanded in organic synthesis,[6] we subsequently studied the
scope of this reaction. First, a series of vinyl bromides 1a–m
were subjected to the reaction with 2a (Table 1). In most
cases, the yields were moderate to good, however, the E/
Z ratio varied depending on the structure of vinyl bromides.
For the 1,1-diboronate, 2b and 2c were studied. In both cases,
the E/Z selectivity is excellent (Table 1, entries 11 and 12).
For the vinyl bromides, several substrates with R = H or alkyl
groups were also studied, the reaction gave comparable
results (Table 1, entries 13–15).
Entry
1
2
Yield [%][b]
E/Z
11:1
15:1
10:1
8:1
1
2
3
4
R=Ph, 1a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2a
2a
2a
4a, 80
4b, 59
4c, 72
4d, 74
4e, 63
4 f, 58
4g, 86
4h, 83
4i, 67
4j, 45
4k, 57
4l, 45
4m, 74
4n, 94
4o, 84
R=o-FC6H4, 1b
R=p-FC6H4, 1c
R=p-MeC6H4, 1d
R=3,4-(-OCH2O-)C6H3, 1e
R=p-MeOC6H4, 1 f
R=o-MeC6H4, 1g
R=o-MeOC6H4, 1h
R=1-naphthyl, 1i
R=2-thienyl, 1j
R=Ph, 1a
5[b]
6[b]
7
6:1
2:1
17:1
14:1
19:1
14:1
>20:1
>20:1
8
9
10
11[b]
12[b]
13
14
15[d]
R=Ph, 1a
R=H, 1k
R=Me, 1l
R=cyclohexyl, 1m
4:1[c]
2:1
2:1[c]
[a] Reaction conditions: 1 (1.0 mmol), 2 (0.75 mmol), [Pd(PtBu3)2]
(5 mol%), LiOH (4m, 625 mL), 1,4-dioxane (5 mL). Reactions were
monitored by TLC analysis. Products were isolated by silica gel
chromatography and the E/Z ratios were determined by 1H NMR
analysis. [b] The vinyl bromides were not completely consumed in these
cases. [c] The ratio was estimated according to the 13C NMR spectra.
[d] Reaction conditions: 1 0.6 mmol), 2 (0.45 mmol), [Pd(PtBu3)2]
(5 mol%), LiOH (4m, 375 mL), 1,4-dioxane (3 mL).
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the aromatic ring bears two ortho-methyl substituents (7g).
Heteroarenes were also compatible in the reaction (7i,j).
When R is an alkyl group, the yields are moderate to good
for various substrates (7k–p; Scheme 5). When R is an
alkenyl group, the allene products are also obtained in
moderate to good yields (7q–s). However, when R is alkynyl,
no allene product can be observed as a result of the HBr
elimination of the dibromoalkene substrates. In the case of
the dibromoalkene 6t, only low yield of the trisubstituted
allene 7t was obtained. In general, the reactivity is signifi-
cantly diminished for the dibromoalkenes derived from
ketones.
Next, we investigated the scope of diboronates
(Scheme 6). It was observed that the reaction was affected
by steric hindrance of the 1,1-diboronate substrates. For 1,1-
diboronates 2b and 2c, high catalyst loading was needed to
achieve moderate yields (8a,b). For the 1,1-diboronate
bearing a bulky tBu substrate, the coupling reaction did not
work (8c). Notably, functional groups, such as formyl and
hydroxy, could tolerate the reaction (8d,e).
Scheme 4. Reactions of 1,1-diboronates with various vinyl bromides.
were examined (Scheme 5). When the R substituent in 6 was
an aryl group, the reaction worked well with those bearing
electron-donating groups (7b,c). However, for these bearing
strong electron-withdrawing groups the reaction gave poor
results, presumably because of direct HBr elimination under
the basic conditions.[9] Halide substituents tolerated the
reaction conditions (7d–f). The yield was moderate when
Scheme 6. Substrate scope of 1,1-diboronates. Reaction conditions: 6
(0.5 mmol), 2 (0.75 mmol), [Pd(PPh3)4] (0.025 mmol), CsOH (5m,
500 mL), 1,4-dioxane (5 mL). Products were isolated by silica gel
chromatography. [a] 10 mol% of [Pd(PPh3)4] (0.1 mmol) was used.
To further demonstrate the scope of the reaction, 1,4-
bis(2,2-dibromovinyl)benzene (9) was applied as the sub-
strate in the reaction with 2a. The reaction afforded the
symmetric diallene 10 in moderate yield. Moreover, with
a 1,1-dibromoalkene bearing a terminal alkynyl group as the
substrate, the palladium(0)-catalyzed coupling with 2a can be
followed by CuI-catalyzed allenation reaction with N-tosyl-
hydrazones.[10] In this manner, the unsymmetric diallene 13
could be obtained (Scheme 7).
A possible reaction mechanism has been proposed as
shown in Scheme 8. The allylboronate intermediate I is
formed from 6 and 2 via the intermediates G and H. Under
basic conditions, from intermediate I B-Br elimination
(Zweifel olefination)[11] occurs to afford the allene product.
=
Zwiefel olefination is a useful method to construct C C bonds
Scheme 5. Substrate scope of 1,1-dibromoalkenes. Reaction condi-
tions: 6 (0.5 mmol), 2a (0.75 mmol), [Pd(PPh3)4] (0.025 mmol), CsOH
(5m, 500 mL), 1,4-dioxane (5 mL). Products were isolated by silica gel
chromatography. TIPS=triisopropylsilyl.
by B-Br elimination. However, reactions involving allenic
C C bond formations have not been reported previously. An
indirect evidence to support the mechanistic rationale is that
=
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Scheme 7. Synthesis of symmetric and unsymmetric diallenes.
Ts =4-toluenesulfonyl.
Scheme 8. Proposed reaction mechanism.
b-bromoallylsilane has been reported to undergo similar
elimination under basic conditions to give allene.[12]
[5] For the details of the reaction conditions optimization, see the
Supporting Information.
In conclusion, the unique reactivity of allylboronates has
been explored in the palladium(0)-catalyzed cross-coupling of
1,1-diboronates with vinyl bromides and 1,1-dibromoalkenes.
1,4-Dienes or allenes can be synthesized through this method.
The high reactivity of the 1,1-diboronates and the intermedi-
ate allylboronates may open up new possibilities in this type
of coupling reaction, including asymmetric catalysis. Research
along these lines is ongoing in our laboratory.
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Received: July 8, 2014
Revised: August 7, 2014
Published online: && &&, &&&&
Keywords: alkenes · boron · cross-coupling · palladium ·
.
synthetic methods
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Communications
Synthetic Methods
H. Li, Z. Zhang, X. Shangguan, S. Huang,
J. Chen, Y. Zhang,
J. Wang*
&&&& — &&&&
Palladium(0)-Catalyzed Cross-Coupling
of 1,1-Diboronates with Vinyl Bromides
and 1,1-Dibromoalkenes
It takes two B: The title reactions afford
1,4-dienes and allenes. These reactions
utilize the high reactivities of both 1,1-
diboronates and allylboron intermediates
generated in the initial coupling reaction.
6
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These are not the final page numbers!