Ligand-Controlled Cobalt-Catalyzed Transfer Hydrogenation of Alkynes: Stereodivergent Synthesis of Z- and E-Alkenes

Article abstract of DOI:10.1021/jacs.6b04271

Herein, we report a novel cobalt-catalyzed stereodivergent transfer hydrogenation of alkynes to Z- and E-alkenes. Effective selectivity control is achieved based on a rational catalyst design. Moreover, this mild system allows for the transfer hydrogenation of alkynes bearing a wide range of functional groups in good yields using catalyst loadings as low as 0.2 mol %. The general applicability of this procedure is highlighted by the synthesis of more than 50 alkenes with good chemo- and stereoselectivity. A preliminary mechanistic study revealed that E-alkene product was generated via sequential alkyne hydrogenation to give Z-alkene intermediate, followed by a Z to E alkene isomerization process.

Full text of DOI:10.1021/jacs.6b04271

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Article
Ligand-Controlled Cobalt-Catalyzed Transfer Hydrogenation
of Alkynes: Stereodivergent Synthesis of Z- and E-Alkenes
Shaomin Fu, Nan-Yu Chen, Xufang Liu, Zhihui Shao, Shu-Ping Luo, and Qiang Liu
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b04271 • Publication Date (Web): 20 Jun 2016
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Ligand-Controlled Cobalt-Catalyzed Transfer Hydrogenation of Al-
kynes: Stereodivergent Synthesis of Z- and E-Alkenes
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Shaomin Fu,a† Nan-Yu Chen,a,b† Xufang Liu,a† Zhihui Shao,a Shu-Ping Luo,*b and Qiang Liu*a
aCenter of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 100084, China.
bState Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology,
Hangzhou 310014, China.
ABSTRACT: Herein, we report a novel cobalt-catalyzed stereodivergent transfer hydrogenation of alkynes to Z- and E-
alkenes. Effective selectivity control is achieved based on a rational catalyst design. Moreover, this mild system allows for
the transfer hydrogenation of alkynes bearing a wide range of functional groups in good yields using catalyst loadings as
low as 0.2 mol%. The general applicability of this procedure is highlighted by the synthesis of more than 50 alkenes with
good chemo-and stereo-selectivity. Preliminary mechanistic study revealed that E-alkene product was generated via se-
quential alkyne hydrogenation to give Z-alkene intermediate, followed by a Z to E alkene isomerization process.
ammonia borane (NH3-BH3, AB) as a practical hydrogen
INTRODUCTION
source17 has also been studied,18 however limited scope of
Catalytic hydrogenation of unsaturated compounds is
substrates was demonstrated along with variable E/Z rati-
os. To date, a base-metal catalyzed stereodivergent (trans-
one of the most impactful reactions in organic synthesis.1
For decades, these reactions relied on the use of rare and
fer) hydrogenation of alkynes to produce Z- and E-alkenes
expensive late transition metals. It is highly desirable to
with great selectivity and efficiency has not been estab-
replace noble-metal catalysts by non-precious base-
lished. Herein, we report the first example of cobalt-
metals in catalytic hydrogenation reactions. The unique
catalyzed transfer hydrogenation of alkynes to synthesize
properties of such base metals like cobalt not only offer
environmental and economic advantages but also provide
both Z-and E-alkenes selectively promoted by different
ligands (Scheme 1). These reactions uses a series of well-
new opportunities to uncover unusual reactivity and se-
defined cobalt catalysts with ammonia borane as the hy-
lectivity.2 In this context, although several remarkable
drogen donor under mild conditions.
homogeneous cobalt catalysts have been developed for
the hydrogenation of C=C,3 C=O3c,4, C=N3c,4a bonds, heter-
ocycles5 as well as nitriles6, a general cobalt catalyzed
semi-hydrogenation of alkynes has not been revealed.
Moreover, reports pertaining to Co-catalyzed transfer
hydrogenation reactions are also scarce.7
Semi-hydrogenation of alkynes using the Lindlar cata-
lyst8 and various modern improvements of heterogeneous
catalysts9 have proven to be efficient ways to generate Z-
Scheme 1. Stereodivergent Cobalt-Catalyzed Transfer
Hydrogenation of Alkynes (AB = NH3-BH3).
alkenes. In contrast, few studies focusing on the corre-
sponding E-selective (transfer) hydrogenation of alkynes
have been reported. Most pioneering examples to actual-
ize this transformation used precious metal catalysts10,
such as Ru,11 bimetallic [Ag-Ru]12, Ir13 as well as Pd14 com-
plexes. Nevertheless, with respect to base metal catalysis,
very few catalytic systems have been developed for this
reaction. More specifically, Milstein and co-wokers devel-
oped a novel imino borohydride iron complex, which was
prepared using sodium borohydride, for the E-selective
alkyne hydrogenation in 2013.15 Very recently, a Ni-
catalyzed transfer hydrogenation of alkynes at elevated
temperature using high catalyst loadings along with stoi-
chiometric amounts of zinc and formic acid as reductants
was reported.16 Another nickel-catalyzed reaction utilizing
Z-selective alkyne hydrogenation is an intrinsic feature
for most transition metal catalysts through a cis-
hydrometalation of C≡C bond. In spite of this, the
unusual E-isomers is possible to be generated via a
sequential Z-selective alkyne hydrogenation, followed by
a Z to E alkene isomerization process (Scheme 2).12,15 The
isomerization process could be rationalized by the
insertion of the Z-alkene intermediate into metal hydride
bond and a following β-hydride elimination step. In
principle, the coordination and insertion of Z-alkene
intermediate require a less steric hindered metal center
with an open coordination site, which would also
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facilitate the following β-hydride elimination step.19 Thus
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this isomerization process should be promoted by less
bulky ligand, affording the E-alkene products. In this
case, a non-ignorable problem would be the undesired
over reduction of alkenes to alkanes due to the prerequi-
site interaction of Z-alkene intermediates with the metal
catalyst. Meanwhile, we proposed that this isomerization
process could be suppressed by using an appropriate
bulky ligand due to the sterically unfavored coordination
and insertion of Z-alkenes. As a result, Z-alkene products
would be selectively generated in this way. Therefore, a
ligand-controlled stereodivergent transfer hydrogenation
of alkynes is promising. Delightfully, the cobalt based
catalyst systems described here addressed these prob-
lems, providing access to both Z-and E-alkene products in
good chemo-and setereo-selectivity.
Scheme 3. Molecular Structures of Cobalt Complexes
I and III (The thermal ellipsoids set at 50% probability
and hydrogen atoms were omitted for clarity).
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conversion (30%) with the Z-isomer 2a as the major
product (Table 1, entry 1). When cobalt complex I was
employed as the catalyst, the Z-alkene product 2a was
produced in 94% yield with 18:1 Z/E ratio (Table 1, entry
2), which revealed the crucial role of the supporting pin-
cer ligand. Indeed, a slight change of PNP ligand structure
from tertbutyl to isopropyl substituted phosphine result-
ed in a completely different stereoselectivity. The reaction
catalyzed by complex II gave a high yield of the alkene
products with 12:1 E/Z selectivity (Table 1, entry 3). More-
over, the NNP cobalt catalyst III led to excellent yield of
E-isomer 3a with >99:1 E/Z selectivity highlighting the
beneficial effect of the pyridine coordination site on NNP
ligand (Table 1, entry 4). These results therefore support
our initial hypothesis that the E/Z selectivity is well con-
trolled by the levels of steric hindrance of cobalt catalysts.
Furthermore, no impact was found when adding mercury
to this reaction system, which suggests that the catalyst is
homogeneous in nature under these reaction conditions
(Table 1, entry 5). Notably, all of these cobalt catalyst pre-
cursors were readily activated in the presence of AB with-
out any additional sensitive additives.24 Moreover, no
over-reduced alkane byproduct was detected in the pres-
ence of these cobalt pincer catalysts. Control experiment
in the absence of cobalt gave no conversion. (Table 1, en-
try 6).
Scheme 2. Steric Effect Controlled Stereodivergent
Alkyne Reduction.
RESULTS AND DISCUSSION
Catalysts Development
Our study commenced with preparing the NH-based
PNP and NNP20 cobalt pincer complexes I-III (Scheme 1).
These cobalt complexes were easily accessible by the
treatment of CoCl2 with 1.1 equivalent of the correspond-
ing ligands. The preparation and crystal structure of
Complex II were reported.21 The structures of the other
two cobalt complexes I22 and III were characterized by X-
ray diffraction analysis in this study (Scheme 3). The neu-
tral pincer ligands coordinate to the Co center in a triden-
tate mode. Moreover, these complexes show a paramag-
netic behavior and effective magnetic moments between
4.2 and 4.5 μB, which are consistent with a high spin state
consisting of three unpaired electrons. P-tertbutyl and P-
isopropyl PNP ligands could lead to different levels of
steric hindrance in the resulting cobalt pincer complexes
I and II. Besides, it was envisioned that the modification
of PNP to an NNP pincer ligand would give rise to a
hemilabile cobalt catalyst III.23 We considered it as an
advantage over other catalysts to ultimately facilitate the
formation of E-alkene product since the labile pyridine
coordination would create a less steric hindered metal
center (vide supra).
Table 1. Co-catalyzed transfer hydrogenation of 1aa.
aReaction conditions: Diphenylethyne 1a (0.5 mmol), AB
(0.5 mmol) and 1.0 mol% Co catalyst in 2 mL of MeOH at
o
b
50 C for 16 h. Yields were determined by GC analysis
using biphenyl as the internal standard. ND means “Not
c
d
The catalytic activities of these cobalt pincer complexes
were then investigated in the transfer hydrogenation of di
phenylethyne 1a with 1 equivalent of AB in methanol (Ta-
ble 1). The use of solely CoCl2 as a catalyst afforded low
Detected”. AB (0.6 mmol) was used. One drop of mer-
cury was added.
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In addition, the effects of several key reaction
as methoxyl, fluoro, trifluoromethyl, chloro, cyano, ester,
amino, heterocycles and hydroxyl groups were all well
tolerated. However, the subtrates bearing amino and
pyridine substitued groups, 1m and 1o, afforded lower Z/E
selectivity probably due to the coordination of such
functional groups. The reaction of dialkyl acetylene 1u
also proceeded smoothly in 99% yield with >99:1 Z/E
selectivity.
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parameters (e.g. solvents and borohyrides effects) were
investigated with cobalt complex III as the catalyst (Table
S2). Among the solvents examined, only primary and
secondary alcohols gave high yields for 3a with high
selectivity. In addition, no reaction occurred in the
absence of AB, which shows that methanol alone is not
able to act as a reductant in this reaction.
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Table 3. Cobalt Complex III Catalyzed E-Selective
Substrate Scope
Transfer Hydrogenation of Alkynes 1.a
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Table 2. Cobalt Complex I Catalyzed Z-Selective
Transfer Hydrogenation of Alkynes 1.a
aReaction conditions: 1 (0.5 mmol), AB (0.75 mmol) and
2.0 mol% Co catalyst I in 1 mL of MeOH at 50 oC for 20 h.
Isolated yields of 2 along with Z/E ratios were shown. bAB
(0.6 mmol) and 1.0 mol% Co catalyst I. cReaction
o
d
e
temperature is 60 C. GC yields of 2. AB (1.3 mmol), 75
aReaction conditions: 1 (0.5 mmol), AB (0.5 mmol) and 1.0
f
g
o
oC. AB (1.2 mmol), 3.0 mol% Co catalyst. AB (0.5 mmol),
mol% Co catalyst III in 2 mL of MeOH at 50 C for 16 h.
h
o
i
b
1.5 mol% Co catalyst I. AB (1.2 mmol), 60 C. AB (0.5
mmol). Isolated yield for a 76:13:11 mixture of 2s, 3s and
Isolated yields of 3 along with E/Z ratios were shown. 1a
j
(5 mmol), AB (5 mmol) and 0.2 mol% Co catalyst III in 5
mL of MeOH at 50 oC for 16 h. cAB (0.35 mmol). dGC yield.
eAB (0.4 mmol) and 3.0 mol% Co catalyst III in 1.5 mL of
over reduced alkane by-product.
After establishing the optimized reaction conditions for
the stereodivergent transfer hydrogenation of 1a, the
substrate scope of this transformation was studied. In
Table 2 we have summarized the Z-selective semi-
reduction of various alkynes 1 using Co complex I as the
catalyst. Tested substrates in different steric and
electronic natures all provided the corresponding Z-
alkene products in good isolated yields with satisfying Z/E
selectivity, revealing the general applicability of this
protocol. Specifically, this reaction proceeded chemo-
selectively towards substituted diarylethynes bearing a
range of electron-donating as well as electron-
withdrawing substituents, 1e-1m. Functional groups such
f
MeOH and 0.5 mL of THF for 36 h. AB (0.75 mmol), 2.0
g
h
mol% Co catalyst III, 36 h. AB (0.35 mmol), 36 h. 2.0
i
mol% Co catalyst II. AB (0.75 mmol), 2.0 mol% Co cata-
lyst II in 1 mL of MeOH for 20 h. Isolated yield for a
81:5:14 mixture of 2s, 3s and over reduced alkane by-
j
k
product. AB (0.25 mmol), 2.0 mol% Co catalyst III. AB
(0.25 mmol), 4.0 mol% Co catalyst II in 1 mL of MeOH for
40 h. Isolated yield for a 45:45:10 mixture of 2s, 3s and
over reduced by-product.
As mentioned above, E-selective semi-reduction of
alkynes is more challenging. A survey of the substrate
scope was performed to demonstrate the versatility of this
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Co-catalyzed transfer hydrogenation of alkynes for the of alkyne impurities. The development of an efficient
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synthesis of E-alkenes using catalyst III (Table 3). The E-
alkene products were obtained in good yields with high
E/Z selectivty for most tested substrates. A wide range of
funtional groups were also well tolerated. In addition,
catalyst II was found to be more reactive for the tranfer
hydrogenation of dialkyl acetylenes. The N,N-dibenzyl
propargyl amine and propargyl sulfamide 1r and 1s
underwent this transfer hydrogenation reaction smoothly
using catalyst II, however, Z-alkenes were isolated as the
major products. The semi-redution of non-functionlized
dialkyl acetylene 1u also proceeded in the presence of
catalyst II in high yield, albeit low E/Z selectivity was
obtained. The reaction of phenyltrimethylsilyl acetylene
1w gave a 90% yield of the corresponding E-alkene 3w.
Unlike the known transfer hydrogenation of alkynes using
formic acid as a reducing agent,14 the near neutral
reaction conditions used in the current study allowed for
the tolerance of a trimethylsilyl group. A gram scale
synthesis of trans-stilbene 3a was performed in the
presence of 0.2 mol% cobalt catalyst III, which gave a
92% yield of 3a in high purity after a simple filtration. The
turnover number (TON) of cobalt catalyst for this
transformation reached as high as 460.
method for the selective reduction of the alkyne
impurities to alkenes is therefore significant, which would
benifit the subsequent alkene functionalization processes.
To demonstrate the feasibility, a 1:100 mixture of alkyne 1a
and cis-alkene 2a was exposed to the optimized reaction
conditions with 0.5 mol% cobalt catalyst III (Scheme 4).
Notably, 1a was selectively hydrogenated to trans-alkene
3a along with the efficient Z/E isomerization of 2a with
100% conversion.
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Scheme 4. Selective Semi-reduction and Isomeriza-
tion of a 1:100 Mixture of 1a and 2a.
Mechanistic Studies
To gain mechanistic insights, the kinetic behavior of
this reaction was investigated using in-situ IR (Figure 1).
The E-selective semi-reduction of 1c using catalyst III was
selected as a model reaction. The kinetic profile of this
reaction clearly showed that the Z-alkene intermediate 2c
was generated in the first 3 hours and that 2c was further
converted to the E-alkene 3c via a Z to E isomerization
process. It is noteworthy that a reduction in the
concentration of 1c led to a dramatic increase in the rate
of the isomerization step illustrated by a sudden change
at around 180 minutes on this kinetic profile. This result
indicated that the isomerization process was inhibited by
the alkyne substrate due to the higher affinity of alkyne
with the cobalt catalyst compared with Z-alkene
intermediate.
Table 4. Cobalt Complex II Catalyzed Transfer Hy-
drogenation of Terminal Alkynes 4.a
aReaction conditions: 4 (0.5 mmol), AB (0.25 mmol) and
o
2.0 mol% Co catalyst II in 2 mL of EtOH at 25 C for 1 h.
Yields 5/6 were determined by GC analysis using biphenyl
b
as the internal standard. 1.0 mol% Co catalyst I, 42%
c
conversion. 1.0 mol% Co catalyst III, 58% conversion.
dThe reaction time was 5 h.
The semi-reduction of terminal alkynes 4 was also
studied using these cobalt catalysts, and complex II was
found to be more effective than cobalt catalysts I and III
(Table 4). The desired terminal alkenes 5 were formed in
good yields with high chemo-selectivity utilizing cobalt
catalyst II. Very small amounts of the over-reduced by-
products 6 were detected in these cases.
Encouraged by high chemo-selectivity for this cobalt
catalyzed semi-reduction of alkynes to alkenes, we believe
the selective hydrogenation of a small fraction of alkyne
impurities to alkenes is promising. As we know, steam
cracking is a large scale process that provides access to a
mixture of important light alkenes. However, this process
also leads to the formation of small fraction (around 2%)
Figure 1. Kinetic Profile of the E-Selective Semi-
Reduction of 1c.
To further probe this isomerization process, cis-stilbene
2a was exposed to the catalytic conditions (Table 5). It
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was isomerized to trans-stilbene 3a within 30 minutes at
5, Eq 3). It indicates that the vinylidene-type11b and al-
25 oC with 1 mol% catalyst III and 1 or 0.1 equivalent of AB
(Table 5, entries 1 and 2). However, this isomerization
process did not take place in the absence of AB, thereby
highlighting the importance of AB for activating the co-
balt catalyst precursors (Table 5, entry 3). The isomeriza-
tion reaction was clearly inhibited by the addition of 1
equivalent of alkyne 1a into this reaction (Table 5, entry
4). This observation was in accordance with the results of
the kinetic study described above. In contrast, the expo-
sure of the trans-stilbene 3a to the catalytic conditions
resulted in no reaction. All taken together, these results
indicate that the E-selectivity could be attributed to the
transfer hydrogenation of alkyne to give Z-alkene inter-
mediate followed by a fast Z to E isomerization process,
which is accorded with our initial hypothesis.
kynyl-type mechanisms25 are also possible minor reaction
routes for the reaction of terminal alkynes.
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The dehydrogenation product of the hydrogen donor
AB was investigated (Scheme 6). Under the standard
reaction conditions, AB was completely converted to
B(OMe)3 which was the only boron containing compound
identified by 11B NMR analysis, together with the
formation of the hydrogenated product of 1a and H2 gas
(Scheme 6, eq 1).26 Two control experiments were then
conducted without alkyne 1a as a hydrogen acceptor.
Under the optimized conditions, the dehydrogenation of
AB delivered B(OMe)3 and H2 gas in full conversion
(Scheme 6, eq 2). Moreover, AB is thermally stable in
methanol at 50 oC, which revealed that the
dehydrogenation of AB is a catalytic process (Scheme 6,
eq 3).27
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Table 5. Cobalt Complex III Catalyzed Isomerization
of cis-Stilbene 2a to trans-Stilbene 3a.a
Scheme 6. Determination of the Dehydrogenation
Product of AB.
aReaction conditions: 1a (0.5 mmol), AB and 1.0 mol% Co
o
catalyst III in 2 mL of MeOH at 25 C for 16 h. bGC yields.
Based on the above observations, a plausible reaction
mechanism for this transformation was proposed (Figure
2). It was hypothesized that cobalt dichloride complexes
I-III would be reduced by AB to generate catalytically
active cobalt hydride complex A. Such species was
c 1a (0.5 mmol) was added.
previously
hydrogenation reactions
proposed
for
the
cobalt-catalyzed
3d,6
as well as being reported for
the hydroboration of alkenes.28 Indeed, Chirik and co-
workers recently have proved that the treatment of
(PNP)CoCl2 complex with NaHBEt3 furnished the
[(PNP)CoH] complex.29 Catalytic cycle
1 would be
responsible for the Z-selective hydrogenation of the
alkynes. The coordination of alkyne substrate 1 to
complex A followed by the insertion of the alkyne into the
Co-H bond would lead to the formation of alkenyl cobalt
complex C. The subsequent protonation of Co-C bond by
methanol would afford the Z-alkene intermediate 2 and
methoxyl cobalt complex D verified by the deuterium
labelling experiments. Intermediate D would react with
AB to regenerate complex A along with the production of
B(OMe)3 detected by 11B NMR. The Z/E alkene
isomerization process would then be accomplished by
catalytic cycle 2. Specifically, the insertion of the Z-alkene
intermediate into the Co-H bond, followed by a β-hydride
elimination finally would lead to the generation of
thermodynamically more stable E-alkene product 3.30 The
isomerization process could be promoted by the less
steric hindered cobalt complexes II and III to generated
E-alkene products. In contrast, the more bulky cobalt
Scheme 5. Deuterium Labelling Experiments.
Deuterium labelling experiments were conducted to
verify the hydrogen source of the alkene product. When
CD3OH was used as the solvent, the cis-reduction product
was not deuterated in the presence of cobalt catalyst I
(Scheme 5, eq 1). Conversely, the mono-deuterated trans-
product 2a’ was isolated when the reaction was carried
out in the solvent of CD3OD (Scheme 5, Eq 2). These
results therefore demonstrated that methanol mediates
the protonation of the alkenyl cobalt intermediate. More-
over, 19% deuterium incorporation was observed at the
C2 position of the deuterated product 6a’ for the transfer
hydrogenation of deuterated phenylacetylene 5a’ (Scheme
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catalyst I effectively prevented the occurrence of this
isomerization process and afford the Z-alkene products.
The high chemoselectivity for the E-selective semi-
reduction is caused by the much faster β-hydride elimina-
tion of the alkyl cobalt intermediate F compared with its
protonation by methanol.31
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AUTHOR INFORMATION
5
Corresponding Author
6
7
qiang_liu@mail.tsinghua.edu.cn
8
luoshuping@zjut.edu.cn
9
Author Contributions
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†These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful for the financial supports of National Pro-
gram for Thousand Young Talents of China. We also thank
Prof. Lei Jiao, Prof. Bi-Jie Li, Prof. Ming-Tian Zhang, Prof.
Zheng Yin and Prof. Jin-Pei Cheng all form CBMS, for the
helpful discussions as well as the analytic center of CBMS.
REFERENCES
(1) de Vries, J. G.; Elsevier, C. J.; Editors Handbook of
Homogeneous Hydrogenation; WILEYꢀVCH, 2007.
(2) (a) Chirik, P. J. Acc. Chem. Res. 2015, 48, 1687; (b) Morris, R.
H. Acc. Chem. Res. 2015, 48, 1494; (c) Zell, T.; Milstein, D. Acc.
Chem. Res. 2015, 48, 1979.
(3) (a) Yu, R. P.; Darmon, J. M.; Milsmann, C.; Margulieux, G. W.;
Stieber, S. C. E.; DeBeer, S.; Chirik, P. J. J. Am. Chem. Soc. 2013,
135, 13168; (b) Friedfeld, M. R.; Shevlin, M.; Hoyt, J. M.; Krska, S.
W.; Tudge, M. T.; Chirik, P. J. Science 2013, 342, 1076; (c)
Gärtner, D.; Welther, A.; Rad, B. R.; Wolf, R.; Jacobi von Wangelin,
A. Angew. Chem. Int. Ed. 2014, 53, 3722; (d) Srimani, D.;
Mukherjee, A.; Goldberg, A. F. G.; Leitus, G.; DiskinꢀPosner, Y.;
Shimon, L. J. W.; Ben David, Y.; Milstein, D. Angew. Chem. Int. Ed.
2015, 54, 12357; (e) Friedfeld, M. R.; Shevlin, M.; Margulieux, G.
W.; Campeau, L.ꢀC.; Chirik, P. J. J. Am. Chem. Soc. 2016, 138,
3314.
(4) (a) Zhang, G.; Scott, B. L.; Hanson, S. K. Angew. Chem. Int. Ed.
2012, 51, 12102; (b) Rösler, S.; Obenauf, J.; Kempe, R. J. Am.
Chem. Soc. 2015, 137, 7998; (c) Korstanje, T. J.; Ivar van der
Vlugt, J.; Elsevier, C. J.; de Bruin, B. Science 2015, 350, 298.
(5) Xu, R.; Chakraborty, S.; Yuan, H.; Jones, W. D. ACS Catalysis
2015, 5, 6350.
Figure 2. Plausible Reaction Mechanism.
CONCLUSIONS
(6) Mukherjee, A.; Srimani, D.; Chakraborty, S.; BenꢀDavid, Y.;
Milstein, D. J. Am. Chem. Soc. 2015, 137, 8888.
(7) (a) Zhang, G.; Hanson, S. K. Chem. Commun. 2013, 49, 10151;
(b) King, S. M.; Ma, X.; Herzon, S. B. J. Am. Chem. Soc. 2014, 136,
6884; (c) Pagano, J. K.; Stelmach, J. P. W.; Waterman, R. Dalton
Trans. 2015, 44, 12074.
We have demonstrated a ligand controlled stereodiver-
gent transfer hydrogenation of alkynes to E-and Z-alkenes
using cobalt catalysts. Ammonia borane was used as a
bench stable and practical hydrogen source17 as well as a
mild reagent for the activation of a series of readily acces-
sible cobalt dichloride pincer catalysts. The current sys-
tem operates under mild conditions and allows for the
semi-reduction of various internal and terminal alkynes
with good yields and selectivity in the absence of any sen-
sitive additives. Notably, this Co-catalyzed reaction pro-
ceeds with high efficiency, and up to 460 turnovers has
been realized. We believe this strategy for the selectivity
control via rational catalyst design would provide useful
insights for the development of other base metal catalysis
processes.
(8) Lindlar, H.; Dubuis, R. Org. Synth. 1966, 46, 89.
(9) (a) Gieshoff, T. N.; Welther, A.; Kessler, M. T.; Prechtl, M. H. G.;
Jacobi von Wangelin, A. Chem. Commun. 2014, 50, 2261; (b)
Mitsudome, T.; Yamamoto, M.; Maeno, Z.; Mizugaki, T.; Jitsukawa,
K.; Kaneda, K. J. Am. Chem. Soc. 2015, 137, 13452.
(10) Liu, Y.; Hu, L.; Chen, H.; Du, H. Chem. Eur. J. 2015, 21, 3495.
(11) (a) Radkowski, K.; Sundararaju, B.; Fürstner, A. Angew.
Chem. Int. Ed. 2013, 52, 355; (b) Leutzsch, M.; Wolf, L. M.; Gupta,
P.; Fuchs, M.; Thiel, W.; Farès, C.; Fürstner, A. Angew. Chem. Int.
Ed. 2015, 54, 12431.
(12) Karunananda, M. K.; Mankad, N. P. J. Am. Chem. Soc. 2015,
137, 14598.
(13) Tani, K.; Iseki, A.; Yamagata, T. Chem. Commun. 1999, 1821.
(14) Shen, R.; Chen, T.; Zhao, Y.; Qiu, R.; Zhou, Y.; Yin, S.; Wang,
X.; Goto, M.; Han, L.ꢀB. J. Am. Chem. Soc. 2011, 133, 17037.
(15) Srimani, D.; DiskinꢀPosner, Y.; BenꢀDavid, Y.; Milstein, D.
Angew. Chem. Int. Ed. 2013, 52, 14131.
ASSOCIATED CONTENT
Supporting Information.
(16) Richmond, E.; Moran, J. J. Org. Chem. 2015, 80, 6922.
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(17) Ammonia borane, as a benchꢀstable solid compound with high
(27) (a) Staubitz, A.; Robertson, A. P. M.; Manners, I. Chem. Rev.
2010, 110, 4079; (b) Denney, M. C.; Pons, V.; Hebden, T. J.;
Heinekey, D. M.; Goldberg, K. I. J. Am. Chem. Soc. 2006, 128,
12048; (c) Keaton, R. J.; Blacquiere, J. M.; Baker, R. T. J. Am.
Chem. Soc. 2007, 129, 1844; (d) Kaess, M.; Friedrich, A.; Drees,
M.; Schneider, S. Angew. Chem. Int. Ed. 2009, 48, 905; (e)
Bhattacharya, P.; Krause, J. A.; Guan, H. J. Am. Chem. Soc. 2014,
136, 11153.
(28) (a) Zhang, L.; Zuo, Z.; Leng, X.; Huang, Z. Angew. Chem. Int.
Ed. 2014, 53, 2696; (b) Zhang, L.; Huang, Z. J. Am. Chem. Soc.
2015, 137, 15600.
(29) Semproni, S. P.; Milsmann, C.; Chirik, P. J. J. Am. Chem. Soc.
2014, 136, 9211.
gravimetric hydrogen capacity, is available on tonꢀscale and easily
accessible from chemical industries with a low price, e.g. Shanghai
Forxine Pharmaceutical Co., Ltd., Catalog# 300161, $75 per 50 g.
(18) BarriosꢀFrancisco, R.; García, J. J. Appl. Catal. A-Gen 2010,
385, 108.
(19) Hartwig, J. F. Organotransition metal chemistry : from bonding
to catalysis; University Science Books: Sausalito, Calif., 2010.
(20) Spasyuk, D.; Smith, S.; Gusev, D. G. Angew. Chem. Int. Ed.
2012, 51, 2772.
(21) Rozenel, S. S.; Kerr, J. B.; Arnold, J. Dalton Trans. 2011, 40,
10397.
(22) During the submission of this manuscript, this complex was
reported by Schneider's group: Lagaditis, P. O.; Schluschaß, B.;
Demeshko, S.; Würtele, C.; Schneider, S. Inorg. Chem. 2016, 55,
4529.
(23) Choualeb, A.; Lough, A. J.; Gusev, D. G. Organometallics
2007, 26, 5224.
(24) In most above mentioned cobalt catalyzed hydrogenation
reactions, a sensitive acid, a strong base and/or an active reductant
was required as additive for the activation or preparation of cobalt
catalyst precursors. See references (3ꢀ6).
(25) Obligacion, J. V.; Neely, J. M.; Yazdani, A. N.; Pappas, I.;
Chirik, P. J. J. Am. Chem. Soc. 2015, 137, 5855.
(26) Couturier, M.; Tucker, J. L.; Andresen, B. M.; Dubé, P.; Negri,
J. T. Org. Lett. 2001, 3, 465.
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(30) Chen, C.; Dugan, T. R.; Brennessel, W. W.; Weix, D. J.;
Holland, P. L. J. Am. Chem. Soc. 2014, 136, 945.
(31) βꢀhydride elimination step could be facilitated by less stericꢀ
hindered cobalt catalysts with an open coordination site used in the
catalytic cycle 2. On the other hand, the protonation of this alkyl
cobalt complex F is more difficult than that of vinyl cobalt complex
C owing to the lack of secondary orbital interaction. This interaction
could exist in vinyl cobalt species C and lower the activation energy
of the protonation process via the interaction between vertical π
orbital of the vinyl group and the proton of methanol. See:
Wannere, C. S.; Paul, A.; Herges, R.; Houk, K. N.; Schaefer, H. F.;
Von Ragué Schleyer, P. J. Comput. Chem. 2007, 28, 344.
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