Ligand-controlled cobalt-catalyzed regiodivergent hydroboration of aryl,alkyl-disubstituted internal allenes

Article abstract of DOI:10.1039/c9sc06136c

We report a stereoselective regiodivergent hydroboration of aryl,alkyl-disubstituted internal allenes with pinacolborane (HBpin) in the presence of cobalt catalysts generated from bench-stable Co(acac)₂ and bisphosphine ligands. An interesting correlation between the regioselectivity of this hydroboration and the bite angles of bisphosphine ligands was identified. When hydroboration was conducted with cobalt catalysts containing bisphosphines with medium bite angles (e.g. 98° for dppb and 96° for dppf), HBpin was selectively added to the alkyl-substituted double bond. However, HBpin was selectively added to the aryl-substituted double bond when the reactions were conducted with cobalt catalysts containing bisphosphines with large bite angles (e.g. 111° for xantphos and 114° for Nixantphos). A range of internal allenes underwent these Co-catalyzed hydroboration reactions in a regiodivergent manner to yield the corresponding (Z)-alkenylboronates in high isolated yields and with high regioselectivity. These reactions show good functional group compatibility and can be readily scaled up to gram scales without using a dry box. In addition, the comparison of regioselectivity between the Co-catalyzed hydrosilylation and hydroboration reactions of the same allene substrate suggests that this Co-catalyzed regiodivergent hydroboration of allenes proceeds through a Co-Bpin intermediate. Deuterium-labeling experiments suggest that the Co-Bpin intermediates react with allenes to form allylcobalt species which then react with HBpin to release (Z)-alkenylboronate products.

Full text of DOI:10.1039/c9sc06136c

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Journal Name
ARTICLE
Ligand-controlled cobalt-catalyzed regiodivergent hydroboration
of aryl,alkyl-disubstituted internal allenes
Caizhi Wu and Shaozhong Ge*
Received 00th January 20xx,
Accepted 00th January 20xx
We report a stereoselective regiodivergent hydroboration of aryl,alkyl-disubstituted internal allenes with pinacolborane
(HBpin) in the presence of cobalt catalysts generated from bench-stable Co(acac)2 and bisphosphine ligands. An interesting
correlation between the regioselectivity of this hydroboration and the bite angles of bisphosphine ligands was identified.
When conducted with the cobalt catalysts containing bisphosphines of medium bite angles (e.g. 98° for dppb and 96° for
dppf), HBpin was selectively added to the alkyl-substituted double bond. However, HBpin was selectively added to the
aryl-substituted double bond when the reactions were conducted with the cobalt catalysts containing bisphosphines of
large bite angles (e.g. 111° for xantphos and 114° for Nixantphos). A range of internal allenes underwent these Co-
catalyzed hydroboration reaction in a regiodivergent manner to yield the corresponding (Z)-alkenylboronates in high
isolated yields and with high regioselectivity. These reactions show good functional group compatibility and can be readily
scaled up to gram-scales without using a dry box. In addition, the comparison of regioselectivity between the Co-catalyzed
hydrosilylation and hydroboration reactions of the same allene substrate suggests that this Co-catalyzed regiodivergent
hydroboration of allenes proceed through a Co-Bpin intermediate. Deuterium-labeling experiments suggest that the Co-
Bpin intermediates react with allenes to form allylcobalt species which turn over with HBpin to release the (Z)-
alkenylboronate products.
DOI: 10.1039/x0xx00000x
www.rsc.org/
pinacolborane (HBpin), do not occur in the absence of metal
catalysts. Accordingly, the hydroboration of allenes with HBpin
has been studied with platinum and copper catalysts,3 and
Introduction
Alkenylboronates are synthetically versatile building blocks in
organic chemistry because they are stable, non-toxic, and can
undergo a range of catalytic cross-coupling reactions to
prepare stereodefined multisubstituted alkenes.1 The
hydroboration of allenes with hydroboranes may be an
effective and atom-economical approach to prepare these
alkenylboronates. However, the development of selective
hydroboration of allenes with hydroboranes to access
alkenylboron compounds is very challenging because this
reaction can potentially yield a series of organoboron products
caused by diverse regio- and stereoselectivity issues. For
example, hydroboranes can add to either of the two double
bonds of allenes, the stereochemistry of the remaining double
bond can be cis or trans, and both monohydroboration and
dihydroboration can take place.
these reactions have been limited to terminal allenes with a
single example employing an internal allene (Scheme 1A).3b
Alternatively, formal hydroboration of terminal allenes with
B2(pin)2 in the presence of MeOH as a proton source has been
achieved with copper catalysts (Scheme 1B).3b,4 To the best of
our knowledge, metal catalysts for hydroboration of 1,3-
disubstituted allenes with HBpin to yield alkenylboronates still
remain unknown. Driven by our interest in developing cobalt
catalysts for selective hydrofunctionalization of unsaturated
hydrocarbons,5 we are interested in identifying selective cobalt
catalysts for hydroboration of internal allenes to prepare (Z)-
alkenylboronate compounds (Scheme 1C).
A) Catalytic hydroboration of terminal allenes with HBpin
Bpin
Bpin
Me
Bpin
[Pt] or [Cu]
Allenes can readily undergo uncatalyzed hydroboration with
reactive dialkylboranes to afford allylboron or alkenylboron
products.2 The regio- and stereoselectivity for these
uncatalyzed hydroboration reactions are generally controlled
by allene or dialkylborane reagents. However, hydroboration
of allenes with less reactive dialkoxyboranes, such as
or
or
•
+ HBpin
R
R
R
R
B) Catalytic formal hydroboration of terminal allenes with B2(pin)2 and MeOH
Bpin
Me
Bpin
[Cu]
+ B2(pin)2
or
•
R
+ MeOH
R
R
C)This work: Co-catalyzed hydroboration of 1,3-disubstituted allenes with HBpin
H
Bpin
Co(acac)2/L
•
R
Bpin
or
+ HBpin
Ar
Ar
Ar
Department of Chemistry, National University of Singapore, 3 Science Drive 3,
Singapore 117543 (Singapore). E-mail: chmgsh@nus.edu.sg
R
H
R
†
Electronic
Supplementary
Information
(ESI)
available:
See
Scheme 1. Hydroboration and formal hydroboration of allenes.
DOI: 10.1039/x0xx00000x
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J. Name., 2013, 00, 1-3 | 1
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ARTICLE
In recent years, cobalt complexes have gained increasing
Journal Name
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Table 1. Evaluation of Conditions for the Co-catalyzed Hydroboration of Allene 1a
attention in hydroboration6 and hydrosilylaiton7 of
unsaturated hydrocarbons,8 and the majority of these
reactions occur through cobalt hydride intermediates.9 Very
recently, we have reported Co-catalyzed diborylation of
alkenes and mechanistic studies suggest the existence of a Co-
Bpin species.10 To develop Co-catalyzed hydroboration of
internal allenes, we envisioned that the reaction would
proceed through borylmetallation to afford alkenylboronates.
Herein, we report Co-catalyzed regiodivergent hydroboration
of internal allenes to prepare (Z)-alkenylboronates, and the
regioselectivity of this Co-catalyzed hydroboration is controlled
by bisphosphine ligands employed in these reactions.
DOI: 10.1039/C9SC06136C
with HBpin.a
Co(acac)2 (3 mol %)
ligand (3 mol %)
Bpin
•
Me
Bpin
+
1a
+
Me
THF, rt, 12 h
Me
HBpin
2a
3a
entry
ligand
bite
angleb
--
--
72
85
91
98
--
83
92
96
102
111
114
conversion
(%)c
>99
>99
>99
18
ratio
yield
(2a/3a)c
71:29
83:17
65:35
76:24
86:14
94:6
83:17
74:26
84:16
96:4
(%)
--
--
--
d
1
2
3
4
5
6
7
8
PMe3
d
PPh3
dppm
dppe
dppp
dppb
dpppe
dppbz
--
15
--
78 (2a)
--
--
--
81 (2a)
--
80 (3a)
76 (3a)
>99
>99
>99
91
>99
>99
>99
>99
Results and Discussion
9
rac-binap
dppf
dpephos
xantphos
Nixantphos
We initiated the studies on the Co-catalzyed hydroboration of
allene by identifying selective and reactive cobalt catalysts for
the reaction between buta-1,2-dieny-1-ylbenzene (1a) and
HBpin. The catalysts generated in situ from Co(acac)2 and a
series of phosphine ligands were tested and the results are
summarized in Table 1. In general, these reactions were
conducted with allene 1a as a limiting reagent in the presence
of 1.1 equivalents of HBpin and 3 mol % catalysts at room
temperature for 12 h. This hydroboration reaction yielded two
(Z)-alkenylboronate products 2a and 3a, resulting from the
addition of HBpin to the alkyl-substituted and aryl-substituted
alkene moieties, respectively.
10
11
12
13
61:39
6:94
8:92
X
Ph2P
PPh2
PPh2
PPh2
n
PPh2
PPh2
O
n = 1, dppm
n = 2, dppe
n = 3, dppp
n = 4, dppb
n = 5, dpppe
Fe
PPh2
PPh2
PPh2
PPh2
dppf
X = 0, dpephos
X = CMe2, xantphos
X = NH, Nixantphos
dppbz
rac-binap
a Conditions: buta-1,2-dien-1-ylbenzene (0.400 mmol), HBpin (0.440 mmol),
Co(acac)2 (12 µmol), ligand (12 µmol), toluene (1 mL), room temperature,
12 h; bThese values are taken from ref. 11, and the bite angle of dpppe has
not been reported; cDetermined by GC analysis with dodecane as the
internal standard; d6 mol % of ligand was used.
The reactions conducted with monophosphine ligands, such
as PMe3 and PPh3, proceeded to complete conversion of 1a
affording a mixture of 2a and 3a with a modest selectivity to
2a (entries and 2). The catalysts generated by the
,
more sterically hindered than the methyl-substituted one,
which means that the methyl-substituted double bond is
sterically more accessible for hydroboration. Meanwhile, the
phenyl-substituted double bond is more reactive towards
hydroboration due to the electron-withdrawing effect of the
phenyl group. Therefore, the observed ligand effect (Figure 1)
on the regioselectivity of this Co-catalyzed hydroboration of
allene 1a could be explained by the steric and electronic
interactions between the substrate 1a and the cobalt catalysts.
The data in Figure 1 suggest that steric effects dominate with
1
combination of Co(acac)2 and a series of bisphosphine ligands
were subsequently evaluated, and the majority of these cobalt
catalysts (entries 3 and 6-13) were highly active for the
hydroboration of 1a, except the catalysts containing dppe and
dppp ligands (entries 4 and 5). These reactions showed varied
selectivity for products 2a and 3a. In addition, we also tested
other hydroboranes, such as HB(cat) and 9-BBN, for this Co-
catalyzed hydroboration of 1a. However, the reactions with
these hydroboranes became less selective and multiple
products were obtained (see the ESI for details).
While studying the ligand effect on the Co-catalyzed
hydroboration of allene 1a, we found that the selectivity of
this reaction was sensitive to the bite angles of the
bisphosphine ligands,11 and the correlation between the
selectivity to product 2a and the bite angles of bisphosphines
is depicted in Figure 1. The selectivity of product 2a increased
with the increase of bite angles till the highest selectivity was
100
90
80
70
60
50
40
30
20
10
0
reached for dppf and dppb ligands with bite angles of 96
° and
98 , respectively (entry 6 and 10). However, in the presence of
°
ligands with large bite angles, such as xantphos and
Nixantphos, the hydroboration of 1a afforded the (Z)-
alkenylboronate 3a as the major product in high isolated yields
with high selectivity (entries 12 and 13).
The two internal double bonds in allene 1a have different
steric properties and the phenyl-substituted double bond is
70
75
80
Bite Angle of Bisphospine Ligand (o)
Figure 1. Plotting of the selectivity of 2a vs bite angles of ligands
85
90
95 100 105 110 115
2 | J. Name., 2012, 00, 1-3
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bisphosphine ligands of medium bite angles (such as dppb and reactions that produce the alkenylboronate
ARTICLE
2
. For example,
View Article Online
DOI: 10.1039/C9SC06136C
dppf) and that electronic activation dominates with allenes containing electron-rich (2k
bisphosphine ligands of large bite angles (such as xantphos and neutral (2a and 2m), and electron-deficient (2l
Nixantphos). groups reacted with similarly high regioselectivity, and the
,
2v, and 2w), electron-
,
2r, and 2u) aryl
Under the identified conditions (entry 10 in Table 1), we isolated yields of the corresponding (Z)-alkenylboronates are
studied the scope of internal allenes that undergo this cobalt- similarly high as well. This is likely because the hydroboration
catalyzed hydroboration to yield the alkenylboronate 2 and the does not take place on the aryl-substituted double bond. As
results are summarized in Table 2. In general, a wide range of HBpin was added to the alkyl-substituted double bond, the
internal allenes reacted smoothly with HBpin in the presence steric property of the aliphatic groups has a noticeable effect
of 3 mol % Co(acac)2/dppf at room temperature, affording the on the regioselectivity. For example, the regioselectivity to the
corresponding (Z)-alkenylboronates (2a
-
2u) in high yields alkenylboronate
2
decreased when the aliphatic groups
2d). Most significantly, hydroboration
(68 85%) with high regioselectivity ( ratio up to 97:3). The become more bulky (2a-
-
2:
3
GC-MS analysis on crude mixtures of these reactions showed of alkyl-substituted double bond was inhibited when the alkyl
the formation of trace amounts (< 5%) of the corresponding substituents of allenes were changed to cyclohexyl and
alkene products resulted from the hydrogenation of allene isopropyl group (1e and 1f). Instead, the hydroboration of
substrates.
these two allenes yielded the alkenylboronates 3e and 3f in
The data in Figure 2 indicate that the electronic properties of high yields in the presence of Co(acac)2 and dppf (eq 1). The
aromatic substituents of the allenes have little influence on the results of these two reactions (eq 1) suggest that this Co/dppf-
yield and regioselectivity of these Co-catalyzed hydroboration catalyzed hydroboration reaction occur at the phenyl-activated
double bond when both double bonds in allenes become
Co(acac)2 (3 mol %)
dppf (3 mol %)
similarly accessible with respect to steric hindrance.
•
Bpin
Bpin
R
Ar
+
Ar
Ar
+
1
Bpin
Co(acac)2 (3 mol %)
dppf (3 mol %)
toluene, rt, 12 h
R
R
3 (minor)
HBpin
•
R
+
HBpin
2 (major)
(1)
R
toluene, rt, 12 h
Bpin
Bpin
Bpin
R = Cy, 1e
R = iPr, 1f
R = Cy, 3e, 77% (2e:3e = 9:91)
R = iPr, 3f, 63% (2f:3f = 13:87)
Me
Me
Me
2a, 81%
(2a:3a = 96:4)
2b, 70%
(2b:3b = 86:14)
2c, 68%
(2c:3c = 82:18)
This Co(acac)2/dppf-catalyzed hydroboration of allenes
tolerates a range of functionalities, including ether (2k), chloro
Bpin
Me
Bpin
Me
Bpin
(
2n), bromo (2o), iodo (2p), trimethylsilyl (2q), cyano (2r),
Me Me
2g, 81%
(2g:3g = 91:9)
boronic ester (2s), thioether (2t), and carboxylic ester (2u
)
2d, 74%
(2d:3d = 84:16)
2h, 76%
(2h:3h = 93:7)
moieties. In addition, sulfur- and oxygen-containing heteroaryl
substituted allenes also reacted with high yields and high
regioselectivity (2v and 2w).
Bpin
Bpin
Bpin
Me
Me
tBu
Me
MeO
Me
Figure 3 summarized the scope of allenes that undergo the
2i, 77%
(2i:3i = 95:5)
2j, 78%
(2j:3j = 93:7)
2k, 78%
(2k:3k = 94:6)
hydroboration to yield the alkenylboroante
3 in the presence
Bpin
of Co(acac)2 and xantphos (entry 12 in Table 1). In general, a
range of internal allenes underwent this Co-catalyzed
hydroboration in the presence of 3 mol % Co(acac)2/xantphos
at room temperature, yielding the corresponding (Z)-
Bpin
Bpin
F3C
Me
F
Me
Cl
Me
2l, 78%
(2l:3l = 94:6)
2m, 78%
(2m:3m = 96:4)
2n, 82%
(2n:3n = 93:7)
Bpin
Bpin
Me
2p, 75%
(2p:3p = 93:7)
Bpin
alkenylboronates in high yields (62
regioselectivity ( ratio up to 1:99). Different from the
Co(acac)2/dppf-catalyzed allene hydroboration, the
-86%) with good
2:3
Br
Me
I
TMS
Me
2o, 78%
2q, 84%
(2q:3q = 96:4)
(2o:3o = 93:7)
Bpin
Me
hydroboration of allene catalyzed by Co(acac)2 and xantphos
could not tolerate chloro-, bromo-, and iodo-substituted
aromatic groups, which underwent the Co-mediated C-X (X =
Cl, Br, or I) borylation under the reaction conditions.12 The GC-
MS analysis on the crude reaction mixtures of the
Bpin
Bpin
Bpin
Me
NC
MeS
Me
2r, 79%
(2r:3r = 95:5)
2s, 85%
(2s:3s = 97:3)
2t,b 55%
(2t:3t = 91:9)
Bpin
Bpin
Bpin
O
Co(acac)2/xantphos-catalzyed hydroboration of allenes 1n
-1p
MeO
S
MeO2C
Me
Me
2v,b 73%
(2v:3v = 95:5)
Me
indicated the formation of the alkenylboronate 3s
.
2u, 82%
(2u:3u = 96:4)
2w, 71%
(2w:3w = 97:3)
Figure 2. Co(acac)2/dppf-Catalyzed Hydroboration of Internal Allenesa
a Conditions: allene (0.400 mmol), HBpin (0.440 mmol), Co(acac)2 (12 µmol),
dppf (12 µmol), toluene (1 mL), room temperature, 12 h, and isolated yields
after column chromatography; b18 h.
This journal is © The Royal Society of Chemistry 20xx
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ARTICLE
Journal Name
Co(acac)2 (3 mol %)
xantphos (3 mol %)
View Article Online
Bpin
Bpin
•
R
Ar
DOI: 10.1039/C9SC06136C
+
A)
Co(acac)2 (1 mol %)
dppf (1 mol %)
Ar
Ar
+
Bpin
1
toluene, rt, 12 h
•
1m, 8.0 mmol
•
Me
R
R
+
HBpin
HBpin
2 (minor)
3 (major)
toluene, rt, 12 h
F
F
Me
2m, 1.81 g; 82%
2m:3m = 95:5
Bpin
Bpin
Bpin
B)
Co(acac)2 (1 mol %)
xantphos (1 mol %)
Bpin
Me
n-C3H7
n-C5H11
3c, 76%
iPr
+
HBpin
iPr
3a, 80%
(2a:3a = 6:94)
3b, 81%
(2b:3b = 5:95)
toluene, rt, 12 h
(2c:3c = 5:95)
1f, 8.0 mmol
3f, 1.99 g; 87%
2f:3f < 1:99
Bpin
Bpin
Bpin
Pd(PtBu3)2 (5 mol %)
PhI (1.5 equiv)
Ph
Me
Me
NaOH (aq, 3 M, 3 equiv)
toluene, 70 °C, 24h
MeO
Me
4, 92%
3d, 82%
3e, 86%
3f, 84%
(2d:3d = 5:95)
(2e:3e < 1:99)
(2f:3f < 1:99)
C)
MeO
BPin
H
Bpin
KHF2 (3.0 equiv)
CH3COOH, rt
Me
Bpin
Bpin
Me
MeO
Me
Me
2k
5, 84%
6, 77%
Me
Me
Me
Me
3g, 80%
(2g:3g = 6:94)
I
I2 (2 equiv)
3h, 81%
(2h:3h = 5:95)
3i, 75%
(2i:3i = 9:91)
NaOH (aq, 3 M, 3 equiv)
MeO
Me
Bpin
Bpin
Bpin
tBu
Me
F
Me
TMS
Me
Scheme 2 Gram-scale reactions and transformations of alkenylboronate 2k
3j, 73%
(2j:3j = 9:91)
3m, 63%
(2m:3m = 14:86)
3q, 82%
(2q:3q = 5:95)
xantphos yielded 3a-d1 with the deuterium atom located at the
benzylic carbon (Scheme 3B). Previous studies suggest that the
hydroboration reactions of unsaturated hydrocarbons proceed
through either a Co-H or Co-Bpin intermediate. However, the
results of these deuterium-labeling experiments could not
provide conclusive evidence on the identity of cobalt
intermediates in these allene hydroboration reactions.
Bpin
Bpin
Bpin
Bpin
Me MeS
Me
Me
S
3v, 66%
(2v:3v = 12:88)
3s, 80%
(2s:3s = 3:97)
3t, 72%
(2t:3t = 8:92)
Figure 3. Co(acac)2/xantphos-Catalyzed Hydroboration of Internal Allenesa
To reveal the cobalt intermediate in this Co-catalyzed allene
a Conditions: allene (0.400 mmol), HBpin (0.440 mmol), Co(acac)2 (12 µmol),
xantphos (12 µmol), toluene (1 mL), room temperature, 12 h, and isolated
yields after column chromatography.
A)
•
•
Me
Bpin
Co(acac)2 (3 mol %)
dppf (3 mol %)
1q
Subsequently, we conducted gram-scale reactions to
highlight the utility of these Co-catalzyed protocols for the
synthesis of (Z)-alkenylboronates. The hydroboration of allenes
1m and 1f on a 8.0 mmol scale proceeded well in the presence
of 1 mol % Co(acac)2/dppf and Co(acac)2/xantphos, yielding
the corresponding (Z)-alkenylboronate 2m (1.81 g, 82%,
Scheme 2A) and 3f (1.99 g, 87%, Scheme 2B) with similarly
high regioselectivity, respectively. In addition, we also showed
that the (Z)-alkenylboronate products could be utilized in
several organic transformations (Scheme 2C). For example, the
(Z)-alkenylboronate 2k could undergo Pd-catalyzed Suzuki-
Miyaura coupling with iodobenzene to give a trisubstituted (E)-
D
98% D
Bpin
+
Bpin
Me
toluene, rt, 12 h
H
DBpin
2q-d1, 83%
B)
Bpin
Me
Co(acac)2 (3 mol %)
xantphos (3 mol %)
Bpin
Me
1q
Bpin
D
+
toluene, rt, 12 h
98% D
H
3q-d1, 86%
DBpin
Scheme 3 Deuterium-labelling experiments
hydroboration, we conducted the hydroboration and
hydrosilylation reactions of the internal allene 1a in the
presence of Co(acac)2/dppf or Co(acac)2/xantphos and
compared the regioselectivity of the corresponding reactions
(Scheme 4). The hydrosilylation of 1a with Ph2SiH2 conducted
with both cobalt catalysts produced the allylsilanes 7a and 7b
with high regioselectivity for 7a (Scheme 4A and 4B). The
results of these hydrosilylation reactions of internal allenes are
consistent with our previous studies on cobalt-catalyzed
hydrosilylation of terminal allenes, which occurs through a Co-
H intermediate and produces allylsilanes as major products.13
If the hydroboration reaction of internal allenes occurs
through the same Co-H intermediate as in the corresponding
hydrosilylation reaction, the hydroboration reactions
conducted with both cobalt catalysts will selectively yield the
allylboronate products. However, the hydroboration of 1a with
HBpin by both cobalt catalysts produced the alkenylboronates
alkene
in 84% yield, and iodination with I2 to produce a (E)-alkenyl
iodide in 77% yield. Thus, this Co-catalyzed allene
4 in 92% yield, protodeboronation to yield a (Z)-alkene
5
6
hydroboration provides a practical method to prepare organic
compounds containing stereodefined alkene moiety.
To understand this Co-catalyzed hydroboration of internal
allenes, we conducted deuterium-labeling experiments in the
presence of both cobalt catalysts, and the results are
summarized in Scheme 3. The hydroboration of buta-1,2-dien-
1-ylbenzene (1a) with DBpin in the presence of Co(acac)2 and
dppf produced 2a-d1, and the deuterium atom of this
alkenylboronate was exclusively located at the allylic carbon
(Scheme 3A). The same reaction catalyzed by Co(acac)2 and
4 | J. Name., 2012, 00, 1-3
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2a and 3a as major products (Scheme 4C and 4D). These dppf ligand, steric control) or (II for xantphos ligand, electronic
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DOI: 10.1039/C9SC06136C
results suggest that this Co-catalyzed hydroboration of allenes control), which then turn over with HBpin to release the
occurs through a Co-Bpin intermediate.
alkenylboronate products 2a or 3a and regenerate the
catalytically active cobalt boryl intermediate ( )Co-Bpin.
L
According to the proposed mechanism, it is anticipated that
this Co-catalyzed regiodivergent hydroboration will not be
achieved for alkyl,alkyl-1,3-disubstituted allenes because the
two double bonds in these allenes are only different in terms
of steric hindrance. Indeed, hydroboration of n-hexyl,methyl-
1,3-disubstituted allene 1x yielded alkenylboronates 2x and 3x
with similar regioselectivity for both cobalt catalysts (Scheme
6A). Furthermore, increasing the steric difference between the
two alkyl substituents allows this hydroboration to proceed
selectively on the less hindered double bond of allenes. For
example, hydroboration of cyclohexyl,methyl-1,3-disubstituted
allene 1y took place in the presence of Co(acac)2/xantphos to
afford alkenylboronate 2y with 98% regioselectivity (Scheme
6B). In addition, we also tested a terminal allene for this Co-
catalyzed hydroboration. Similarly, hydroboration of terminal
allene 1z also occurred to the sterically more accessible bond,
yielding alkenylboronate 2z as the major product for both
cobalt catalysts (Scheme 6C).
A)
SiHPh2
Co(acac)2 (3 mol %)
dppf (3 mol %)
Ph
Me
Ph
+
+ H2SiPh2
Me
•
Ph
THF, 80 °C, 24 h
SiHPh2
Me
7b
7a
yield: 76% (7a + 7b)
7a:7b = 97:3
B)
SiHPh2
Co(acac)2 (3 mol %)
xantphos (3 mol %)
Ph
Me
Ph
+
+
H2SiPh2
•
Ph
Me
THF, rt, 18 h
SiHPh2
1a
Me
7b
7a
yield: 86% (7a + 7b)
7a:7b = 89:11
C)
Co(acac)2 (3 mol %)
dppf (3 mol %)
Bpin
Ph
+
Bpin
Ph
Me
+
Me
•
HBpin
Ph
THF, rt, 18 h
Me
1a
2a
3a
yield: 80%
2a:3a = 96:4
D)
Co(acac)2 (3 mol %)
xantphos (3 mol %)
Bpin
Bpin
Ph
Me
Ph
+
+
Me
•
HBpin
Ph
THF, rt, 18 h
Me
1a
2a
3a
yield: 81%
2a:3a = 6:94
Scheme
hydroboration of allene 1a
4 Comparison of regioselectivity in hydrosilylation and
A)
Bpin
Me
n-Hex
Co(acac)2 (1 mol %)
2x
3x
L (1 mol %)
+
•
+ HBpin
Me
n-Hex
Based on the results of control experiments and ligand
effects on the observed regioselectivity, a plausible catalytic
pathway was depicted in Scheme 5 for this Co-catalyzed
stereoselective regiodivergent hydrosilylation of aryl,alkyl-1,3-
disubstituted allenes. The activation of Co(acac)2 with HBpin in
the presence of a bisphsophine ligand generates a cobalt
toluene, rt, 12 h
Bpin
1x
full conversion of 1x
n-Hex
Me
L = dppf; 2x:3x = 59:41
L = xantphos; 2x:3x = 58:42
B)
Bpin
Cy
Co(acac)2 (1 mol %)
2y
L (1 mol %)
Me
+
•
+ HBpin
Me
Cy
hydride species (
L
)Co-H,5c which is then converted to a (
L)Co-
toluene, rt, 12 h
Bpin
1y
3y
full conversion of 1y
Bpin species by the reaction of the allene 1a and HBpin with
the concomitant hydrogenation of the allene.10a Accordingly,
the products from the hydrogenation of 1a were detected by
the GC-MS analysis. Subsequently, the migratory insertion of
allenes (for the demonstration purpose, only the insertion of
one enantiomer of allene 1a was shown in Scheme 5) into this
Cy
Me
L = dppf; 2y:3y = 76:24
L = xantphos; 2y:3y = 98:2
C)
Ph
Ph
Bpin
Bpin
Co(acac)2 (1 mol %)
2z
3z
L (1 mol %)
Ph
Me
+ HBpin
•
+
toluene, rt, 12 h
1z
full conversion of 1z
(L)Co-Bpin species produces the allylcobalt intermediates (I for
L = dppf; 2z:3z = 88:12
L = xantphos; 2z:3z = 80:20
Me
Scheme
terminal allene.
6 Hydroboration of alkyl,alkyl-1,3-disubstituted allenes and a
Co(L)
Bpin
Ph
Bpin
•
Co(L)
Me
Ph
HBpin
Me
H
Co(acac)2/L
+
HBpin
Ph
Conclusions
H
Bpin
Co(L)
L = dppf
Bpin
In summary, we have developed an effective protocol for the
synthesis of (Z)-alkenylboronates through a ligand-controlled
Co-catalyzed stereoselective and regioselective hydroboration
of internal allenes. The cobalt catalysts are generated in situ
from bench stable Co(acac)2 and dppf or xantphos ligands, and
are activated by the reaction with HBpin. A variety of internal
aryl,alkyl-substituted allenes underwent this hydroboration
with HBpin added to the alkyl-substituted or aryl-substituted
carbon-carbon double bond in the presence of Co(acac)2/dppf
and Co(acac)2/xantphos, respectively. Preliminary mechanistic
studies suggest that this Co-catalyzed allene hydroboration
2a
•
•
Ph
Me
Me
•
1a
+ HBpin
Me
Ph
(L)
Co−H
(L)
Co−Bpin
alkene isomers from
hydrogenation of 1a
Ph
H
Me
L = xantphos
(L)Co
H
Bpin
Ph
Me
Bpin
•
3a
(L)
Co Me
Bpin
Ph
H
HBpin
(L)Co Bpin
Ph
Scheme
5 The proposed catalytic cycle for this Cobalt-catalyzed
regiodivergent hydroboration of aryl,alkyl-1,3-disubstituted allenes
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6
For selected examples of cobalt-catalyzed hydroboration
proceeds through a cobalt-boryl intermediate and that the
regioselectivity of this allene hydroboration is controlled by
the synergy between substrates and cobalt catalysts. This Co-
catalyzed allene hydroboration provides a useful approach to
access synthetically versatile trisubstituted alkenylboronates
with commercially available cobalt catalysts.
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Catal. 2019, 9, 4025-4029.
Experimental Details
General procedures for this cobalt-catalyzed stereoselective
regiodivergent hydroboration of internal allenes
In an Ar-filled glovebox, Co(acac)2 (12.0 µmol), dppf or
xantphos (12 µmol), allene (0.400 mmol), HBpin (0.440 mmol),
and toluene (1 mL) was added into a 4 mL screw-capped vial
containing a magnetic stirring bar. The vial was sealed with a
cap containing a PTFE septum and removed from the dry box.
The reaction mixture was stirred at room temperature for 12
h, and the crude product was purified by column
chromatography on silica gel with a mixture of hexane and
ethyl acetate as eluent. The conditions for flash
chromatography and data for characterization of the products
are listed in the ESI.
7
For selected examples of cobalt-catalyzed hydrosilylation
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Chem. Soc. 2014, 136, 17414-17417; (b) C. Chen, M. B.
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Acknowledgement
This work was supported by the Ministry of Singapore (R-143-
000-A07-112).
Notes and references
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9
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3
4
5
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View Article Online
DOI: 10.1039/C9SC06136C
Journal Name
ARTICLE
Ligand-controlled cobalt-catalyzed regiodivergent hydroboration
of aryl,alkyl-disubstituted internal allenes
Caizhi Wu and Shaozhong Ge*
Received 00th January 20xx,
Accepted 00th January 20xx
The first cobalt-catalyzed stereoselective regiodivergent hydroboration of internal allenes to access synthetically versatile
DOI: 10.1039/x0xx00000x
(Z)-alkenylboronate compounds was effectively achieved with two cobalt catalysts through ligand control.
www.rsc.org/
Co(acac)2
dppf
Co(acac)2
xantphos
•
R
Bpin
Bpin
R
Ar
Ar
Ar
+
R
HBpin
21 examples
77% ave. yeild
selectivity up to 97:3
15 examples
78% ave. yeild
selectivity up to 99:1
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