Regio-controllable Cobalt-Catalyzed Sequential Hydrosilylation/Hydroboration of Arylacetylenes

Article abstract of DOI:10.1002/anie.202109089

Regiodivergent addition reactions provide straightforward and atom-economic approaches to access different regioisomers. However, the regio-chemistry control to access all the possible results is still challenging especially for the reaction involving multiple addition steps. Herein, we reported regio-controllable cobalt-catalyzed sequential hydrosilylation/hydroboration of arylacetylenes, delivering all the possible regio-outcomes with high regioselectivities (up to >20/1 rr for all the cases). Each regioisomer of value-added silylboronates could be efficiently and regioselectively obtained from the same materials. The adjustment of the ligands of cobalt catalysts combined with dual catalysis relay strategy is the key to achieve regio-chemistry control. This regio-controllable research might inspire the exploration of the diversity-oriented synthesis that involves multiple additions and provide full sets of regioisomers of other synthetic useful molecules.

Full text of DOI:10.1002/anie.202109089

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
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International Edition
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Accepted Article
Title: Regio-controllable Cobalt-Catalyzed Sequential Hydrosilylation/
Hydroboration of Arylacetylenes
Authors: Zhaoyang Cheng, Jun Guo, Yufeng Sun, Yushan Zheng,
Zhehong Zhou, and Zhan Lu
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202109089
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10.1002/anie.202109089
Angewandte Chemie International Edition
RESEARCH ARTICLE
Regio-controllable Cobalt-Catalyzed Sequential Hydrosilylation/
Hydroboration of Arylacetylenes
Zhaoyang Cheng,[a] Jun Guo,[a] Yufeng Sun,[a] Yushan Zheng,[a] Zhehong Zhou,[a] Zhan Lu*[a]
In memory of Prof. Ei-ichi Negishi.
[a]
Z. Cheng, Dr. J. Guo, Y. Sun, Y. Zheng, Z. Zhou, Prof. Dr. Z. Lu
Department of Chemistry,
Zhejiang University
Hangzhou 310058, China
E-mail: luzhan@zju.edu.cn
Supporting information for this article is given via a link at the end of the document. ((Please delete this text if not appropriate))
Abstract: Regiodivergent addition reactions provide straightforward
and atom-economic approaches to access different regioisomers.
However, the regio-chemistry control to access all the possible results
is still challenging especially for the reaction involving multiple addition
steps. Herein, we reported regio-controllable cobalt-catalyzed
sequential hydrosilylation/hydroboration of arylacetylenes, delivering
all the possible regio-outcomes with high regioselectivities (up to
>20/1 rr for all the cases). Each regioisomer of value-added
silylboronates could be efficiently and regioselectively obtained from
the same materials. The adjustment of the ligands of cobalt catalysts
combined with dual catalysis relay strategy is the key to achieve regio-
chemistry control. This regio-controllable research might inspire the
exploration of the diversity-oriented synthesis that involves multiple
additions and provide full sets of regioisomers of other synthetic useful
molecules.
Introduction
Regiodivergent addition reactions provide straightforward and
atom-economic routes to access different regioisomers, which are
of great significance in organic chemistry and meet the need of
diversity-oriented synthesis (DOS).[1] With the rapid development
of metal catalysis, tremendous progress has been made in
regioselectivity control in recent years.[2] However, few examples
provide the complete set of regioisomeric products when the
reaction involves multiple addition processes. Due to the
serendipitous nature of most metal-catalyzed regiodivergent
reactions, the regio-chemistry switch is often difficult to predict or
manipulate.[2a,2c,2e] So far, completely regio-controllable
methodologies for multiple addition reactions remain elusive in
organic synthesis despite persistent interest.[2e,3]
Scheme 1. Metal-catalyzed sequential hydrosilylation/hydroboration of
arylacetylenes.
Bis-organometallic reagents represent one of the most
versatile building blocks in organic synthesis, which could be
utilized for an array of downstream derivatizations to generate
molecule complexity efficiently.[4] Among them, silylboronates are
unique and useful ones due to their high stability and versatile
transformable manner (Scheme 1 a).[4d,4f] Accordingly, several
methods have been developed for the synthesis such as alkene
their further elaborations.[10] Besides, different regioisomers of
silylboronates from the same starting material are still difficult to
obtain.
Sequential double hydrofunctionalization of alkynes (SDHA)
offers a straightforward approach for efficiently introducing two
functional groups to readily available alkynes in high atom and pot
economy.[3,11] Thus, sequential hydrosilylation/hydroboration of
arylacetylenes could be another powerful strategy for the
synthesis of silylboronates (Scheme 1 b). Since there are two
addition transformations in this reaction, the possible regio-
silaboration,[5]
vinylsilane
hydroboration,[6]
vinylboronate
hydrosilylation,[7] Suzuki-Miyaura coupling,[8] etc.[4d,4f,9] Despite
the advances, most of these methodologies afford the products
bearing silyl groups without Si-H bond,[6c,6d] which would diminish
1
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10.1002/anie.202109089
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RESEARCH ARTICLE
Table 1. Condition optimizations for β,β- and β,α-regioselectivity.[a]
different outcomes as well as the requirements of regioselectivity
control, are multiplied. Although metal-catalyzed regiodivergent
hydrosilylation of arylacetylenes[6c,6d,10b,12] and some examples of
vinylsilane hydroboration[6b-f] have been reported, several
challenges remain in the regio-controllable sequential reactions
(Scheme 1 b): (1) precise regio-chemistry regulation of both steps,
particularly the regio-controllable hydroboration of styrylsilanes
has not been fully explored; (2) good chemoselectivity to avoid
the side reactions such as hydrogenation[13] and over-
hydrosilylation[14]; (3) good compatibility for hydroboration process
with the former hydrosilylation conditions to avoid the
deterioration of the reactivity and selectivity. Elegant works from
Hoveyda group have exhibited one example of sequential
protosilylation/protoboration to access a gem-silylboronate,[15]
although the use of silylboronic esters and diboron reagents leads
to a stoichiometric amount of undesired byproduct. Meanwhile,
the completely regio-controllable hydrosilylation/hydroboration of
arylacetylenes to obtain all the regioisomers from the same
materials is highly desirable but has not been systematically
investigated yet.
Yield of 1a+2a
Entry
[Co]2
Solvent
Ratio (1a:2a)
(%)[b]
For β-hydrosilylation/β-hydroboration[c]
1
2
/
/
/
/
/
/
toluene
THF
10:1
17:1
15:1
20:1
20:1
>20:1
26
31
3
dioxane
Et2O
18
4
44
5[d]
6[d,e]
Et2O
65
87[f]
Et2O
For β-hydrosilylation/α-hydroborationg[g]
Earth-abundant metals possess several advantages such as
high reserves, low toxicity, and affordable costs.[16] Our group’s
research interests focus on earth-abundant-metal catalysis.
Inspired by our previous studies[17] and others’ works,[2e] here, we
systematically developed a regio-controllable cobalt-catalyzed
sequential hydrosilylation/hydroboration of arylacetylenes
(Scheme 1 c).
7
8
La•CoCl2
Lb•CoCl2
Lc•CoCl2
Ld•CoCl2
Ld•CoBr2
Ld•CoBr2
toluene
toluene
toluene
toluene
toluene
toluene
/
n.d.
10
8
1:1
9
1:1
10
11
12[h]
1:18
1:>20
1:>20
78
86
86[f]
[a] Phenylacetylene (0.50 mmol), H2SiPh2 (1.0 equiv.), HBpin (2.0 equiv.), Ar.
[b] Yield of the mixture of 1a and 2a, determined by 1H NMR using TMSPh as
the internal standard. [c] Xantphos•CoBr2 (2.0 mol%), NaBHEt3 (6.0 mol%),
solvent (1.0 M) at rt for 5 min (hydrosilylation); solvent (1.0 M) at 30 oC for 16 h
(hydroboration). [d] 40 oC for hydroboration. [e]Neat condition for hydroboration.
[f] Isolated yield. [g] Xantphos•CoBr2 (0.5 mol%), NaBHEt3 (1.5 mol%), toluene
(2.0 M) at rt for 2 h (hydrosilylation); [Co]2 (5.0 mol%), NaBHEt3 (15 mol%),
solvent (2.0 M) at 15 oC for 4 h (hydroboration). [h] 1.0 mmol scale.
Results and Discussion
Condition
optimizations
for
Co-catalyzed
sequential
of
regiodivergent
β-hydrosilylation/hydroboration
arylacetylenes. We performed the study of the sequential reaction
using phenylacetylene as the model substrate, diphenylsilane
(H2SiPh2), and pinacolborane (HBpin) as the hydrosilane reagent
and hydroboronate reagent, respectively. CoBr2•Xantphos was
selected as the precatalyst and NaBHEt3 was used as the
activator, which had been successfully employed for the (E)-anti-
Markovnikov hydrosilylation of terminal alkynes in our previous
works.[10a,10b] The results have been summarized in Table 1.
Surprisingly, Co-Xantphos/NaBHEt3 catalytic system was
competent not only for the hydrosilylation reaction but also
hydroboration of intermediate styrylsilane (see SI for control
experiments), which catalyzed these two steps sequentially to
afford silylboronate in 26% NMR yield with 10:1 rr (ratio of
regioisomers) with the preference of β,β-selectivity (1a) (Table 1,
entry 1). The major compound of the resulting mixture was the
intermediate (E)-β-styrylsilane, indicating the efficiency of the
hydroboration step was not enough. After the screening of solvent
(entries 2-4), diethyl ether was selected as the best choice. The
reaction gave silylboronate in 44% yield with a ratio of 1a:2a =
20:1 (entry 4). The yield and regioselectivity were further
improved by elevating the reaction temperature and removing
solvent for the hydroboration step (entries 5-6), giving 1a in 87%
isolated yield with >20:1 rr, and the conditions of entry 6 were
selected as the standard conditions (standard conditions A).
Next, we considered whether or not α-hydroboration of (E)-
β-styrylsilanes could be achieved by using a structurally different
ligand. It should be mentioned that, to the best of our knowledge,
this α-hydroboration of β-styrylsilanes to give corresponding (β-Si,
α-B)-silylboronates has not been realized yet. Bearing this in mind,
a bis(imino)pyridine (PDI) (La)-cobalt was tested for the reaction,
however, no desired product was detected (Table 1, entry 7), in
which only 74% intermediate (E)-β-styrylsilane and 10%
hydrogenation of the (E)-β-styrylsilane were observed. Then,
various oxazoline iminopyridine (OIP) ligands bearing different
oxazoline groups (Lb-Ld) were evaluated (entries 8-10).[18] When
Lb and Lc were applied, the reactions mainly afforded β-
styrylsilanes, indicating the reactivity of the hydroboration was
generally low. Interestingly, the reactivity was dramatically
improved when sterically bulky tertiary butyl group was applied
(entry 10), affording 2a as the major product in 78% NMR yield
with 18:1 rr. We suppose that the enhanced reactivity could be
attributed to the weak dispersion interaction.[19] Substitution of
chloride anion to bromide anion further improved the yield and
regioselectivity (entry 11). Finally, with 1 mmol scale, the reaction
gave 2a in 86% isolated yield with >20:1 rr (entry 12). The
conditions of entry 12 were selected as the standard conditions
for the β,α-regioselectivity (standard conditions B).
Substrate scope of Co-catalyzed β-hydrosilylation/β-
hydroboration of arylacetylenes. After obtaining the optimized
reaction conditions, the substrate scope of this one-pot sequential
transformations for β,β-selectivity were investigated with standard
conditions A (Table 2). Various substituents including electron-
donating groups such as methoxyl group (1d), methyl group (1e,
1f, 1i, 1j), and electron-withdrawing groups such as fluorine (1b,
2
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10.1002/anie.202109089
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RESEARCH ARTICLE
Table 2. Substrate scope of β-hydrosilylation/β-hydroboration.[a]
Table 3. Substrate scope of β-hydrosilylation/α-hydroboration.[a]
[a] Standard conditions B: alkyne (1.0 mmol), H2SiPh2 (1.0 equiv.),
Xantphos•CoBr2 (0.50 mol%), NaBHEt3 (1.5 mol%), toluene (2.0 M), rt, Ar, 2 h
(hydrosilylation); HBpin (2.0 equiv.), Ld•CoBr2 (5 mol%), NaBHEt3 (15 mol%),
toluene (2.0 M), 15 oC, Ar, 4 h for hydroboration; The yields refer to isolated
yields, rr values were determined by 1H NMR of crude mixtures. [b] toluene (1.0
M). [c] 0.50 mmol scale, 20 min for hydrosilylation.
[a] Standard conditions A: alkyne (0.50 mmol), H2SiPh2 (1.0 equiv.),
Xantphos•CoBr2 (2.0 mol%), NaBHEt3 (6.0 mol%), Et2O (1.0 M), rt, Ar, 5 min
(hydrosilylation); HBpin (2.0 equiv.), neat, 40 oC, Ar, 16 h (hydroboration); The
yields refer to isolated yields, rr values were determined by 1H NMR of crude
mixtures. [b] Xantphos•CoBr2 (5.0 mol%), NaBHEt3 (15.0 mol%). [c] Et2O (0.50
M) for hydrosilylation. [d] 50 oC for hydroboration. [e] 60 oC for hydroboration.
[f]18 h for hydroboration. [g] H2SiAr2 instead of H2SiPh2.
with moderate regioselectivity (10:1 rr). The conversions of meta-
substituted substrates (2i-2l) resulted in moderate to good yields
(62-89%) with >20:1 rr. Disubstituted aryl substrates (2m-2o) and
2-naphthalene (2p) could also be well transformed. Functional
groups including fluorine (2h, 2j), chlorine (2d, 2k), alkoxyl groups
(2g, 2l), methylthio group (2f) were all compatible with the dual
cobalt catalysis. However, substrates bearing aryl bromide and
phenol hydroxyl group cannot be converted to corresponding
silylboronates in current reaction conditions.
1g), phenyl group (1c, 1h) could be well handled, delivering
corresponding (β-Si,β-B)-products in moderate to good yields with
excellent regioselectivities. Meanwhile, the steric hindrance at the
ortho- (1f-1h), para- (1b-1e), or meta- (1i-1j) position of aryl
alkynes has little effect on the regiocontrol, delivering
corresponding products with good to excellent regioselectivities
(17:1->20:1). The yields of substrates bearing 2-substituted
fluorine (1g) and phenyl group (1h) were slightly decreased even
with
5
mol% catalyst loading. Functional-group-tethered
Condition
optimizations
for
Co-catalyzed
sequential
of
arylacetylenes such as ether (1d), hydroxyl (1k), thioether (1l),
amino (1m) could be smoothly converted to corresponding
products, demonstrating good functional group tolerance.
Although the regioselectivities for alcohol (1k) and thioether (1l)
remained moderate (8:1-9:1 rr). Alkynes with heterocycle indole
(1n) and fused-ring naphthalenes (1o, 1p) could be also
transformed with 68-85% yields and 14:1->20:1 rr. Different
dihydrosilanes(1q-1r) were similarly feasible under the modified
conditions. However, for the reaction of 1-ethynyl-4-nitrobenzene,
neither intermediate vinylsilane or corresponding product could
be detected.
Substrate scope of Co-catalyzed β-hydrosilylation/α-
hydroboration of arylacetylenes. For β-hydrosilylation/α-
hydroboration (Table 3), similarly, various electron-poor (2c-2e,
2h, 2j, 2k) and electron-rich (2b, 2g, 2m-2n) aryl substrates could
react well under standard conditions B. Para-substituted aromatic
alkynes (2b-2f) could be transformed into corresponding
regiodivergent
α-hydrosilylation/hydroboration
arylacetylenes. Next, α,β-regioselectivity and α,α-regioselectivity
were explored. Based on our previous studies,[6d] we tested the
sequential α-hydrosilylation/β-hydroboration in one pot by the
previously used precatalyst Ld•CoBr2 (Table 4, entry 1). However,
only 39% NMR yield of 3a was generated with 39% of α-
styrylsilanes and an undetectable amount of 4a regioisomer,
indicating the reactivity of hydroboration was interfered by the
former hydrosilylation conditions. Then, sterically less hindered Lf
was applied to afford better yield (entry 2). And the yield was
further improved by employing electron-rich imidazoline
iminopyridine (IIP)[20] Lg as the ligand (entry 3). Lowering the
catalyst loading and increasing the concentration gave 86%
isolated yield of 3a (entry 4). The conditions of entry 4 were
selected as standard conditions (standard conditions C).
For α-hydrosilylation/α-hydroboration of alkynes, we
supposed that the hydroboration could be catalyzed by other
catalytic species rather than cobalt species considering that the
α-hydroboration would be sterically unfavorable for the insertion
of α-styrylsilanes into metal-hydride species.[18a,21] Taking the α-
stabilizing effect of the aryl and silyl group into account, we
silylboronates
2 in good yields (73-92%) with excellent
regioselectivities (>20:1 rr). The benzyloxy-substituted one could
be converted as well (2g). The reaction of sterically hindered
ortho-substituted substrate gave the corresponding product 2h
3
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10.1002/anie.202109089
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RESEARCH ARTICLE
chromatography. For this substrate scope, various arylacetylenes
were investigated under standard conditions C. Substrates with
aryl bearing electron-donating (3b, 3e, 3f) and electron-
withdrawing groups (3c-3d) could be transformed smoothly,
affording α,β-silylboronates in good yields (80-86%) with 15:1-
>20:1 rr. The reaction of 3,4-dimethyl-substituted aryl alkynes
gave moderate regioselectivity (10:1 rr). A series of functional
groups were well-compatible in these reaction conditions:
halogen atoms (3c, 3i, 3j), and ether (3e), ester (3h), thioether
(3m), alcohol (3n), amino (3o), indole (3p) could be tolerated.
Although the regioselectivities of the substances with chlorine (3i)
and bromine (3j) remained moderate. Sterically hindered 1-
naphthyl (3k) as well as ortho-substituted (3f) substrates required
5 mol% of catalyst loading for the hydroboration step. For
unsuccessful cases, the reactions of 3-ethynylpyridine and 3-
ethynylbenzonitrile failed to afford corresponding products and
only corresponding vinylsilane intermediates were detected.
Table 4. Condition optimizations for α,β-regioselectivity and α,α-
regioselectivity.[a]
Table 5. Substrate Scope of α-Hydrosilylation/β-Hydroboration.[a]
Yield of 3a
or 4a (%)[b]
Entry
[Co]4
For α-hydrosilylation/β-hydroboration[c]
Ratio (3a:4a)
1
2
Ld•CoBr2
Lf•CoBr2
Lg•CoBr2
Lg•CoBr2
>20:1
>20:1
>20:1
>20:1
39
58
3
4[d]
79
86[e]
For α-hydrosilylation/α-hydroboration[f]
5
/
/
/
/
1:>20
1:>20
1:>20
1:>20
87
80
6[g]
7[h]
8[i]
78
91[e]
[a] Phenylacetylene (0.50 mmol), H2SiPh2 (1.0 equiv.), HBpin (1.2 equiv.), Ar.
[b] Yield of 3a or 4a determined by 1H NMR using TMSPh as the internal
standard. [c] Le•CoBr2 (2.0 mol%), NaBHEt3 (6.0 mol%), THF (0.50 M) at rt for
5 min (hydrosilylation); [Co]4 (5.0 mol%), NaBHEt3 (5.0 mol%), toluene (0.50 M)
at rt for 6 h (hydroboration). [d] Lg•CoBr2 (2.0 mol%), NaBHEt3 (2.0 mol%),
toluene (1.0 M). [e] Isolated yield. [f] Le•CoBr2 (2.0 mol%), NaBHEt3 (6.0 mol%),
THF (0.50 M) under Ar at rt for 5 min (hydrosilylation); NaBHEt3 (10 mol%), THF
(0.50 M) at rt for 10 h (hydroboration). [g] NaBHEt3 (5 mol%) (hydroboration).
[h] NaBHEt3 (15 mol%) (hydroboration). [i] 40 oC, 3 h (hydroboration).
hypothesized that the α-hydroboration could be catalyzed by
NaBHEt3.[22] To test this hypothesis, the experiment was
conducted by adding 1.2 equivalent of HBpin and 10 mol% of
NaBHEt3 to the α-styrylsilane in THF without cobalt complex (eq.
2). Excitingly, 98% yield of α,α-silylboronate 4a was detected.
With this finding, we added additional 10 mol% NaBHEt3 in one
pot for the hydroboration step of the sequential reaction, giving a
better yield (Table 4, entry 5) compared with previous result (60%
yield, eq. 1). An increase or decrease of the amount of NaBHEt3
did not give a better yield (entries 6-7). And the standard
conditions were chosen after elevating the reaction temperature
and decreasing the reaction time, giving 91% isolated yield of 4a
with exclusive regioselectivity (entry 8). The conditions of entry 8
was selected as standard conditions D.
Substrate scope of Co-Catalyzed α-hydrosilylation/β-
hydroboration of arylacetylenes. The substrate scope was next
evaluated for α-hydrosilylation/β-hydroboration (Table 5). It
should be mentioned that (β-Si,α-B)-regioisomer was generated
as the minor product in this reaction since OIP-Co could also
catalyze α-hydroboration of β-styrylsilanes (Table 5). However,
most of these regioisomers could be removed through column
[a] Standard conditions C: alkyne (0.50 mmol), H2SiPh2 (1.0 equiv.), Le•CoBr2
(2.0 mol%), NaBHEt3 (6.0 mol%), THF (0.50 M), rt, Ar, 5 min (hydrosilylation);
Lg•CoBr2 (2.0 mol%), NaBHEt3 (2.0 mol%), HBpin (1.2 equiv.), toluene (1.0 M),
rt, Ar, 6 h (hydroboration); The yields refer to isolated yields, rr values were
determined by 1H NMR of crude mixtures. [b] Lg•CoBr2 (5.0 mol%), NaBHEt3
(5.0 mol%), 16 h at rt for hydroboration. [c] 30 min at rt for hydrosilylation. [d]
Lg•CoBr2 (3.0 mol%) NaBHEt3 (3.0 mol%),16 h at rt for hydroboration.
Substrate scope of Co-catalyzed α-hydrosilylation/α-
hydroboration of arylacetylenes. The substrate scope of α-
hydrosilylation/α-hydroboration was next evaluated under
standard conditions D (Table 6). A variety of para- (4b-4g), meta-
(4h-4i), ortho- (4j) substituted substrates reacted smoothly to
corresponding molecules in good to excellent yields (85-95%) as
the single regioisomers. Meanwhile, disubstituted aryl alkynes
(4k-4n) could be transformed similarly. And, fused rings (4o-4p)
were feasible as well. The hydroboration of sterically hindered 1-
naphthyl (4o) substrate needed higher temperature and longer
4
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10.1002/anie.202109089
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RESEARCH ARTICLE
Table 6. Substrate scope of α-hydrosilylation/α-hydroboration.[a]
Downstream derivatizations of the silylboronates. The
synthetic applications of these Si-H containing silylboronates
were exhibited (Table 7). Firstly, the silyl or boryl group could be
individually converted: the Si-H bonds of -SiHPh2 group could be
easily transformed to Si-OMe (1a-1, 3a-1, 4a-1), Si-Me (1a-4),[6f]
Si-F (2a-1, 3a-4)[24] with Bpin group untouched. Meanwhile, the
Bpin group could be easily oxidized to hydroxyl group without
conversions of -SiHPh2 group (1a-2, 2a-2, 3a-2, 4a-2).
Furthermore, the Si-H could be converted to Si-C bond by iridium-
catalyzed intramolecular dehydrogenative cyclization[25] to afford
dihydrobenzosiloles (1a-3, 2a-3). Bpin group could also be
converted to vinyl group with SiHPh2 intact (3a-3). And 4a could
be utilized for transition-metal-free cross-coupling to prepare
tertiary benzylic silane (4a-3),[26] although, the yield was low due
to the side reactions (deboration and desilylation). Meanwhile,
Bpin group and Si-H bond could also be both converted in one-
pot reaction (2a-4). In addition, Bpin group and silyl group can be
both converted to hydroxyl group in one-pot reaction via Brown
oxidation and Fleming-Tamao oxidation, respectively (2a-5).
Table 7. Downstream derivatization of the silylboronates.
[a] Standard conditions D: alkyne (0.50 mmol), H2SiPh2 (1.0 equiv.), Le•CoBr2
(2.0 mol%), NaBHEt3 (6.0 mol%), THF (0.50 M), rt, Ar, 5 min (hydrosilylation);
HBpin (1.2 equiv.), additional NaBHEt3 (10 mol%), THF (0.50 M), 40 oC, Ar, 3 h
(hydroboration); >20:1 rr in all cases; The yields refer to isolated yields, rr values
were determined by 1H NMR of crude mixtures. [b] 6 h at 60 oC for hydroboration.
[c] 16 h at 60 oC for hydroboration. [d] 30 min for hydrosilylation. [e] HBpin (2.0
equiv.), additional NaBHEt3 (30 mol%) for hydroboration. [f] Additional NaBHEt3
(3.0 mol%), 9 h at rt for hydroboration. [g] H2SiAr2 (1.0 equiv.) instead of H2SiPh2.
[h] 4,4'-dimethyl-2,2'-bipyridine•CoBr2 (2 mol%), H3SiR (1.2 equiv.) instead of
H2SiPh2.
(a) cat. Pd/C, MeOH, 35 oC, 13-36 h. (b) aq. H2O2, aq. NaOH, Et2O, rt, 2-4 h.
(c) cat. [Ir(OMe)(cod)]2 (3-5 mol%), dtbpy (6-10 mol%), norbornene (1.2 equiv.),
THF, 18-24 h. (d) CH2I2 (10 equiv.), ZnEt2 (6.0 equiv.), DCE, rt, overnight. (e)
MeLi (1.28 equiv.), toluene, rt, 3 h. (f) cat. CuI (10 mol%), CuCl2 (2.0 equiv.), KF
(1.5 equiv.), THF, 30 oC, 24 h. (g) KF (4.0 equiv.), KHCO3 (4.0 equiv.), aq. H2O2
(30% wt), aq. NaOH (3.0 M), MeOH/THF (1/1), 65 oC, 12 h. (h) CH2=CHMgBr
(4.0 equiv.), THF, -78 oC, 30 min, then I2/MeOH, -78 oC, 40 min. (i) 2-
chloropropane (2.0 equiv.), KOtBu (1.0 equiv.), dioxane, 100 oC, 3 h.
reaction times. A variety of functional groups could be tolerated.
For instance, terminal aryl alkynes bearing acetal (4q), amide (4r)
and ester (4s) underwent this transformations smoothly. And,
halogen atoms such as fluorine (4c, 4i), chlorine (4d, 4l, 4n) and
bromine (4e, 4m) could be well tolerated without reduction. 2-
thienyl substrate (4t) could also be converted to corresponding
product. Furthermore, various hydrosilanes (4u-4y) were also
suitable, giving corresponding α,α-silylboronates in 55-92% yields.
The reactions using trihydrosilanes (4x, 4y) could be achieved by
using 4,4'-dimethyl-2,2'-bipyridine•CoBr2 as the precatalyst.[23]
Evaluation of the gram-scale reactions. To evaluate the
scalability of these procedures, all the reactions were conducted
on a 3 mmol-scale (Scheme 2). The cobalt-catalyzed sequential
hydrosilylation/hydrobation of alkynes could be easily scaled up
to gram-scale reactions, delivering corresponding silylboronates
(1a-4a) in 82-92% yields.
Mechanistic studies. Some preliminary mechanistic studies
were conducted to get insights into the hydroboration steps. A
phenylacetylene or styrylsilanes were used as the substrates
under the hydroboration conditions of each methods using DBpin
as the reagent. For the deuterium experiments (eq. 3-5),
scrambling deuterium-incorporation between α-carbon and β-
carbon of was detected, which could be caused by Co-H(D)
through reversible insertion/β-H elimination processes indicating
the existence of a cobalt-hydride species. Based on these results
and our previous studies,[13b,21] the cobalt-hydride could more
likely be the catalytic species. However, a cobalt-boryl-catalyzed
pathway and a direct H-D exchange pathway could not be fully
ruled out.[16b,16d] Meanwhile, the α-hydroboration of α-styrylsilane
catalyzed NaBHEt3 was proposed through carbanion
intermediate. The deuterium experiment using DBpin (eq. 6)
delivered the product only with deuterium-incorporation of β-
carbon. And the reaction of α-styrylsilane (eq. 7) using equivalent
of NaBHEt3 as the reagent and 2-chloropropane as the substrate
delivered a nucleophilic attack product 4a-3, indicating that
carbanion intermediate could be the catalytic species. The
primary mechanism has been discussed in SI and further
mechanistic studies will be conducted to explore the detail of
these transformations.
Scheme 2. Gram-scale reactions. [a] 20 min for hydrosilylation; 8 h for
hydroboration. [b] Le•CoBr2 (0.50 mol%), NaBHEt3 (1.5 mol%), THF (2.0 M), 20
min for hydrosilylation; 8 h for hydroboration.
5
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RESEARCH ARTICLE
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In conclusion, we have developed a cobalt-catalyzed regio-
controllable
sequential
hydrosilylation/hydroboration
of
arylacetylenes, affording complete outcomes of the four different
silylboronate regioisomers from the same starting materials. The
regioselectivities are regulated by sequential catalysis and
applying different cobalt catalysts and different mechanisms. The
regioselective α-hydroboration of (E)-β-styrylsilanes was first
achieved via sequential β-hydrosilylation/α-hydroboration of
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transformations possess good regioselectivities and functional
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We thank NSFC (21922107 and 21772171), Zhejiang Provincial
Natural Science Foundation of China (LR19B020001), and
Center of Chemistry for Frontier Technologies for generous
financial support.
Keywords: regiodivergent synthesis
hydrosilylation  hydroboration  alkynes
 cobalt catalysis 
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7
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Entry for the Table of Contents
A cobalt-catalyzed regio-controllable sequential hydrosilylation/hydroboration of alkynes has been developed with complete control of
all the possible regioselectivities for the double addition processes (up to >20/1 rr for all the cases). Various silylboronate regioisomers
can be efficiently obtained from the same materials, with good functional group tolerance, regioselectivities as well as atom- and pot-
economy.
8
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