Heterobimetallic control of regioselectivity in alkyne hydrostannylation: Divergent syntheses of α-A nd (E)-β-vinylstannanes via cooperative Sn-H bond activation

Article abstract of DOI:10.1021/jacs.9b00068

Cooperative Sn-H bond activation of hydrostannanes (Bu₃SnH) by tunable heterobimetallic (NHC)Cu-[M_CO] catalysts ([M_CO] = FeCp(CO)₂ or Mn(CO)₅) enables the catalytic hydrostannylation of terminal alkynes under mild conditions, with Markovnikov/anti-Markovnikov selectivity controlled by the Cu/M pairing. By using the ^MeIMesCu-FeCp(CO)₂ catalyst, a variety of α-vinylstannanes were produced from simple alkyl-substituted alkynes and Bu₃SnH in high yield and good regioselectivity; these products are challenging to access under mononuclear metal-catalyzed hydrostannylation conditions. In addition, reversed regioselectivity was observed for aryl-substituted alkynes under the Cu/Fe-catalyzed conditions, affording the (E)-β-vinylstannanes as major products. On the other hand, by using the IMesCu-Mn(CO)₅ catalyst, a variety of (E)-β-vinylstannanes were produced from primary, secondary, and tertiary alkyl-substituted alkynes, thus demonstrating divergent regioselectivity for alkyne hydrostannylation controlled by Cu/Fe vs Cu/Mn pairing. Both methods are amenable to gram-scale vinylstannane synthesis as well as late-stage hydrostannylation in a natural-product setting. Mechanistic experiments indicate the syn addition of Bu₃SnH to the alkynes and imply the involvement of Sn-H bond activation in the rate-determining step. Two distinct catalytic cycles were proposed for the Cu/Fe and Cu/Mn catalysis based on stoichiometric reactivity experiments.

Full text of DOI:10.1021/jacs.9b00068

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Article
Heterobimetallic Control of Regioselectivity in Alkyne
Hydrostannylation: Divergent Syntheses of #- and (E)-
#-Vinylstannanes via Cooperative Sn-H Bond Activation
Li-Jie Cheng, and Neal P. Mankad
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b00068 • Publication Date (Web): 31 Jan 2019
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Journal of the American Chemical Society
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Heterobimetallic Control of Regioselectivity in Alkyne
Hydrostannylation: Divergent Syntheses of α- and (E)-β-
Vinylstannanes via Cooperative Sn-H Bond Activation
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Li-Jie Cheng and Neal P. Mankad*
Department of Chemistry, University of Illinois at Chicago, 845 W. Taylor St., Chicago, IL 60607
Supporting Information Placeholder
ABSTRACT: Cooperative Sn-H bond activation of hydrostannanes (Bu SnH) by tunable heterobimetallic (NHC)Cu-
3
[
M ] catalysts ([M ] = FeCp(CO) or Mn(CO) ) enables catalytic hydrostannylation of terminal alkynes under mild
CO CO 2 5
Me
conditions, with Markovnikov/anti-Markovnikov selectivity controlled by the Cu/M pairing. By using the IMesCu-
FeCp(CO) catalyst, a variety of α-vinylstannanes were produced from simple alkyl-substituted alkynes and Bu SnH in
2
3
high yield and good regioselectivity; these products are challenging to access by mononuclear metal-catalyzed
hydrostannylation conditions. In addition, reversed regioselectivity was observed for aryl-substituted alkynes under the
Cu/Fe-catalyzed conditions, affording the (E)-β-vinylstannanes as major products. On the other hand, by using the
IMesCu-Mn(CO) catalyst, a variety of (E)-β-vinylstannanes were produced from primary, secondary, and tertiary alkyl-
5
substituted alkynes, thus demonstrating divergent regioselectivity for alkyne hydrostannylation controlled by Cu/Fe vs.
Cu/Mn pairing. Both methods are amenable to gram-scale vinylstannane synthesis as well as late-stage hydrostannylation
in a natural-product setting. Mechanistic experiments indicate syn-addition of Bu SnH to the alkynes and imply the
3
involvement Sn-H bond activation in the rate-determining step. Two distinct catalytic cycles were proposed for the Cu/Fe
and Cu/Mn catalysis based on the stoichiometric reactivity experiments.
regio- and stereoselective preparation of vinylstannanes
INTRODUCTION
has been a major area of focus. A variety of catalysts
Alkyne hydrofunctionalization represents a highly
based on e.g. Pd, Rh, and Mo have been employed in such
atom-economical approach for introducing synthetic
transformations and display obvious advantages over
functionality to a hydrocarbon functional group. The
radical-initiated processes in controlling regio- and
major challenge in alkyne hydrofunctionalization is the
control of product selectivity, both with regard to
Markovnikov vs. anti-Markovnikov regioselectivity and
towards over-reduction or dehydrogenative coupling
4
stereoselectivity. However, despite these advances,
major voids still exist and motivate further catalyst
development, particularly for controlling Markovnikov
vs. anti-Markovnikov selectivity to produce either α- or
(Scheme 1a). A typical approach for developing selective
5
β-vinylstananes selectively. Thus far, most of reported
hydrofunctionalization methods is to identify
mononuclear metal catalysts capable of mediating the
desired hydrofunctionalization, and then optimizing
methods lack generality by requiring alkynes bearing
bulky or coordinating groups to enhance the
6
regioselectivity. While hydrostannylation of simple
1
product selectivity through ligand design. For cases
alkynes to produce (E)-β-vinylstananes selectively has
been recently accomplished (Scheme 1b), corresponding
methods to provide α-vinylstananes selectively are
underdeveloped. Current successful methods to
synthesize α-vinylstananes from simple terminal alkynes
where this classical approach has proven ineffective, it is
worthwhile to consider alternative paradigms for catalyst
design that provide new synthetic parameters with which
to control selectivity.
7
either rely on the use of specialized tin hydride reagents
As a case study, one can consider catalytic
hydrostannylation of alkynes to produce vinylstannanes,
which are of great important in synthetic chemistry due to
8
(
e.g. Bu SnIH), or lose the desirable atom-efficiency of
2
hydrofuncationalization by employing distannane,
9
10
2
silylstannane, or stannylmetallic reagents. Known
methods for adding readily available hydrostannanes
their versatile transformations in many reactions,
especially the well-known Stille C-C cross-coupling
3
such as Bu SnH directly to alkynes with Markovnikov
3
reaction. The development of efficient methods for the
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selectivity rely on substrate rather than catalyst control
Scheme 1c), such as exploiting directing effects for
generated in situ through salt metathesis between two
readily-available pre-catalysts, (NHC)CuCl and Na[MCO]
1
2
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(
11
propargyl-functionalized alkynes
or aryl alkynes
or K[M ], which obviates additional steps for
CO
12
bearing ortho-substituents on the aromatic ring.
Therefore, the development of new strategies to enrich
the hydrostannylation reaction and overcome the
unsolved problem of approaching α-vinylstannanes from
heterobimetallic catalyst preparation and makes
optimization more efficient. 2) Both the α- and (E)-β-
vinylstannanes can be accessed from a conserved
heterobimetallic catalyst design. In particular, this has
enabled us to develop the first general synthetic method
to provide α-vinylstannanes from simple alkynes using
simple alkynes using R SnH reagents as the tin source is
3
13
highly desirable.
Bu SnH as the tin source. 3) The use of cooperative
3
Scheme 1. Hydrostannylation of Terminal Alkynes
0
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0
bimetallic catalysis for hydrofunctionalization is
conceptually novel and complements established
monometallic catalysis4 and recently reported metal-
ligand cooperativity in the dehydrogenative stannylation
(a) General problem of selectivity control in alkyne hydrofunctionalization
LnM
E
R
E
E
R
E
R
+
H
E
+
+
R
E
+
H
MLn
E
R
1
7
(Z/E)-
+ isomers
of alkynes. Moreover, two distinct Sn-H bond activation
modes are proposed to account for the divergent
selectivity exhibited by the Cu/Fe and Cu/Mn catalysts.
Classically:
via monometallic activation
(b) Anti-Markovnikov hydrostannylation of alkynes
[
Mo] or [Pd]
RESULTS AND DISCUSSION
+
Bu3SnH
SnBu3
E)-
R
R
(
We began our work by studying the reaction between
(c) Directed Markovnikov hydrostannylation of alkynes
1-decyne (1a) and Bu SnH using heterobimetallic
3
complexes (NHC)Cu-[M ] formed in situ through salt
CO
SnBu3
metathesis between (NHC)CuCl and Na[M ] or K[M ]
CO
CO
[
Mo] or [Pd]
DG
or
1
5
R
in toluene at room temperature. The initial investigation
DG = directing group
of Na[M ] in the presence of IPrCuCl suggest that
CO
DG
d) This work: Hydrostannylation of terminal alkynes using heterobimetallic catalysis
Ar
SnBu3
1
8
nucleophilicity of the metal carbonyl anion is a very
important parameter for this reaction. No product was
found when the less nucleophilic metal carbonyl anions
(
[Mco] = FeCp(CO)2
N
SnBu3
or
R
-
-
-
Cu [Mco]
R
such as [Co(CO) ] , [CrCp(CO) ] , [MoCp(CO) ] and
4 3 3
(E)-
R = aryl
N
Ar
o
o
-
R
R = 1 , 2 alkyl
[WCp(CO) ] were used (Table 1, entry 1-4). Trace α- and
3
+
-
Bu3SnH
(E)-훽-vinylstannanes were detected with [Mn(CO)
our delight, the use of more nucleophilic [RuCp(CO) ]
([Rp] ) and [FeCp(CO) ] ([Fp] ) anions gave the α-
5
] . To
[M] [M’]
Bu3Sn
via heterobimetallic activation
SnBu3
[
Mco] = Mn(CO)5
R
-
H
2
(
o
E)-
o
o
-
-
-
R = 1 , 2 , 3 alkyl
2
vinylstannane 2a selectively in 23% and 28%
respectively (Table 1, entry 6-7). Next, we optimized the
structure of NHC ligand to improve the reaction outcome:
the yield of 2a was largely enhanced when the IPr was
Bimetallic catalysis has emerged as an important
strategy in synthetic chemistry, in particular by enabling
different reactivity modes and/or selectivity patterns
compared to conventional monometallic catalysis.14 As
bimetallic catalysis matures, it can increasingly be viewed
as a tool to solve reactivity or selectivity problems that
are challenging to solve with monometallic catalysis by
harnessing these new bimetallic reactivity landscapes.
Our group recently developed heterobimetallic catalysts
consisting of copper carbene Lewis acids and metal
Me
replaced by IMes, and IMes turned out to be the optimal
NHC ligand for this reaction (Table 1, entry 8-10). The
-
-
use of [FeCp*(CO)2] ([Fp*] ) which has similar
,
-
nucleophilicity as [Fp] but increased steric hindrance,
gave a nearly same result (Table 1, entry 11). Control
experiments demonstrated that both of the copper and
iron partners were necessary for the reaction to occur
(Table 1, entry 12-13). Better selectivity and yield were
15
carbonyl anion Lewis bases, i.e. (NHC)Cu-[MCO],
o
o
observed after lowering the temperature to 0 C or -10 C
Table 1, entry 14-15). In addition, increasing the loading
of Bu SnH to 1.5 equivalents resulted in a slightly higher
wherein two metal sites within one catalyst could
cooperatively activate H-Bpin or H-H bonds in catalytic
(
16
3
scenarios through tunable bimetallic pairing. Herein, we
yield (Table 1, entry 16). Finally, we also found that use
report that the tunable heterobimetallic (NHC)Cu-[MCO]
catalysts ([M ] = FeCp(CO) or Mn(CO) ) enable
Me
of excess IMesCuCl relative to KFp provides higher
CO
2
5
yields compared to equimolar co-catalyst loadings or with
divergent syntheses of α- and (E)-β-vinylstannanes via
catalytic hydrostannylation of terminal alkynes under
mild conditions, with the selectivity being controlled by
the Cu/M heterobimetallic pairing (Scheme 1d). Several
aspects of this study make it both fundamentally
important and also amenable to complex molecule
synthesis. 1) The bimetallic catalyst can be easily
Me
the pre-prepared IMesCu-Fp complex (Table 1, entry
1
7). We reasoned this might be due to an unstable
organocopper intermediate during the catalytic cycle
necessitating supplemental copper loading for optimal
results.
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Journal of the American Chemical Society
Table 1. Optimizations for Synthesis of 훼-
well, providing potential synthetic handles for further
coupling reactions. Trace product and low yield was
found with the substrates bearing a remote aldehyde (2m)
or aryl ester group (2q). Under the same reaction
conditions, the substrate scope can be extended to cyclic
alkyl-substituted alkynes, although the corresponding
vinylstannanes (2p, 2q) were obtained in moderate yield.
Interestingly, reversed regioselectivity was observed
when tert-butylethyne was used as substrate, although the
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a
Vinylstannane
(E)-훽-vinylstannane (3t) was formed in poor yield. This
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behavior is possibly caused by the increased steric
hindrance of the tertiary-alkyl substituent. Internal
alkynes did not react under these conditions.
T
2a
3a
entry
[Cu]
[MCO]
(oC) (%) (%)
Table 2. Hydrostannylation of Alkyl-substituted
a
Alkynes Using [Cu-Fe] catalyst
1
2
3
4
5
6
7
8
9
IPrCuCl
IPrCuCl
NaCo(CO)
NaCrCp(CO)
NaMoCp(CO)
NaMn(CO)
4
rt
rt
0
0
0
0
3
IPrCuCl
3
rt
0
0
IPrCuCl
5
rt
<5
0
6
IPrCuCl
NaWCp(CO)
NaRp
KFp
3
rt
0
IPrCuCl
rt
23
28
63
47
67
67
0
5
IPrCuCl
rt
8
IMesCuCl
ClIMesCuCl
MeIMesCuCl
MeIMesCuCl
--
MeIMesCuCl
MeIMesCuCl
MeIMesCuCl
MeIMesCuCl
KFp
rt
11
28
14
15
0
KFp
rt
1
1
1
0
1
2
KFp
rt
NaFp*
KFp
rt
rt
13
--
rt
0
0
1
1
4
5
KFp
0
70
75
84
91
11
8
KFp
-10
-10
-10
1
6b
KFp
8
17b,c MeIMesCuCl
KFp
8
a
Reaction was performed on 0.1 mmol scale. Yields were
determined by H NMR integration of crude mixtures against
an internal standard. 1.5 equiv. Bu SnH was used. 12 mol%
3
1
b
c
Me
IMesCuCl and 8 mol% KFp were used.
With the optimal conditions in hand, we next
investigated the substrate scope of alkyl-substituted
alkynes (Table 2). We were delighted to find that a variety
of alkynes underwent hydrostannylation under our
catalytic conditions to furnish α-vinylstannanes in high
yields with good regioselectivity. Functional groups such
as indolyl (2c), silyl ether (2d), benzyl ether (2e), ester
aThe reaction was conducted on 0.2 mmol scale. All yields
are isolated yields unless otherwise noted. The α/β ratios were
(
2f) and phthalimide (2g) were generally well tolerated.
1
determined by H NMR from the isolated mixtures and are
Terminal alkene (2h) was also compatible with the
reaction conditions and the C=C double bond remains
intact. (Pseudo)halide groups such as alkyl tosylates and
chlorides were also found to be compatible (2i, 2j).
Remarkably, the reaction can also be conducted in the
presence of an unprotected alcohol group (2k). Strongly
coordinating alkyl nitriles (2l) and aryl nitriles (2n) had
little effect on the results. Substrates bearing remote aryl
bromide and aryl iodide linkages (2n, 2o) also worked
b
1
given in parentheses. Yields were determined by H NMR
integration of crude mixtures against an internal standard.
Ratio of β/α.
c
Next, aryl-substituted alkynes were tested under the
same reaction conditions (Table 3). Surprisingly, the (E)-
β-vinylstannanes were observed as the major products.
This outcome differs from that of previous Cu-catalyzed
hydrostannylation of aryl-substituted alkynes using
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hexamethyldistannane, where the 훼-vinylstannanes are
generated as the major products. We speculate the
substantial steric hindrance of the aryl-substitute renders
T
2a
3a
(%)
entry (NHC)CuCl
solvent
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3
4
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6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
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5
5
5
5
6
9
o
( C) (%)
1
2
3
4
IPrCuCl
IMesCuCl
ClIMesCuCl
MeIMesCuCl
IMesCuCl
IMesCuCl
IMesCuCl
IMesCuCl
IMesCuCl
IMesCuCl
toluene
toluene
toluene
toluene
toluene
toluene
benzene
1,4-dioxane
THF
rt
rt
<5
5
6
the -SnBu group more likely add to the 훽 position of the
3
79
79
72
86
90
88
89
89
93
alkynes, whereas in previous report the use of the
relative small -SnMe3 group did not alter the
regioselectivity. It is worthy to note similar reversed
rt
7
rt
6
regioselectivity
was
also
observed
in
the
5
6b
7b
8b
60
60
60
60
60
60
10
10
12
11
11
7
hydrostannylation of alkyl- or aryl-substituted alkynes
1
9
using stoichiometric stannylcopper reagents. Briefly
investigating the substrate scope revealed that an
electron-deficient aryl alkyne gave excellent yield and
regioselectivity (3v), while poor regioselectivity was
observed with an electron-rich aryl alkyne (3w).
0
1
2
3
4
5
6
7
8
9
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9
0
9b
0b
1
DCE
Table 3. Hydrostannylation of Aryl-substituted
a
Reaction was performed on 0.1 mmol scale. Yields were
determined by H NMR integration of crude mixtures against
a
Alkynes Using [Cu-Fe] catalyst
1
b
an internal standard. 1.2 equiv. Bu
reaction time is 4 h.
3
SnH was used and the
Under the optimal conditions, a range of alkynes
bearing different functional groups were investigated
Table 5). Almost all the alkynes tested in [Cu-Fe]
catalysis smoothly underwent anti-Markovnikov Bu SnH
addition under [Cu-Mn]-catalyzed conditions to afford
(
3
(
E)-훽-vinylstannanes in high yields with good
regioselectivity. The remote aldehyde (3m) and aryl ester
groups (3q) that were not tolerated in the [Cu-Fe] system
were found to be compatible with the [Cu-Mn] system.
While an arylcyano group (3n) has no effect on the
reaction, a remote alkylcyano group (2l) led to only trace
product. Under the same reaction conditions, the substrate
scope can be extended to include secondary and even
tertiary alkyl alkynes (3t), the latter of which was
unsuccessful in the [Cu-Fe] catalysis. Unfortunately,
moderated yield and selectivity were obtained with
phenyl acetylene (3u).
a
The reaction was conducted on 0.2 mmol scale. All yields
1
are isolated yields. The β/α ratios were determined by H NMR
from the isolated mixtures and are given in parentheses.
During the course of optimization, the (E)-β-
vinylstannanes 3a was observed in low yield as the major
product when NaMn(CO) instead of KFp was used as the
5
partner with IPrCuCl (Table 1, entry 4). This result
indicated that the reversed regioselectivity for
hydrostannylation of terminal alkyl alkynes might be
achieved by tuning one of the two metal sites within the
bimetallic complex. Thus, we directed our efforts towards
optimizing the formation of (E)-β-vinylstannanes 3a
Table 5. Hydrostannylation of Alkyl-substituted
a
Alkynes Using [Cu-Mn] catalyst
(Table 4). Further investigation of other NHC ligands
revealed the IMesCuCl greatly enhanced the yield and
selectivity (Table 4, entry 2-4). Performing the reaction at
o
higher temperature (60 C) could speed up the reaction
and led to a higher yield of 3a (Table 4, entry 5). In
addition, increasing the amount of Bu SnH to 1.2
3
equivalent resulted in a slightly increased yield (Table 4,
entry 6). While other solvents such as benzene, 1,4-
dioxane and THF gave similar result as toluene (Table 4,
entry 7-9), we were delighted to find use of DCE afforded
the (E)-β-vinylstannanes 3a in both higher yield and
better selectivity (Table 4, entry 10).
Table 4. Optimizations for Synthesis of (E)-β-
a
Vinylstannane
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Next, some experiments were conducted to explore the
mechanism of bimetallic catalysis. Kinetic isotope effect
KIE) experiments were performed using Bu SnH and
(
3
Bu SnD in the [Cu-Fe] catalysis. In these experiments,
3
the reaction was quenched after 1 h by addition of Et N.
3
The KIE value was calculated to be 2.0 and 1.9 from
parallel and competition experiments, respectively
(Scheme 3a). In addition, a relative rate of 1.0 was found
in two parallel experiments using 1a and 1a-D with
a
Bu SnH (see Supporting Information). These results
The reaction was conducted on 0.2 mmol scale. All yields
3
1
are isolated yields. The β/α ratios were determined by H NMR
from the isolated mixtures and are given in parentheses. Yields
were determined by H NMR integration of crude mixtures
against an internal standard.
strongly suggest the involvement of Sn-H activation in
the rate-determining step during bimetallic catalysis. For
[Cu-Mn] catalysis, the selective formation of (E)-훽-
vinylstannanes clearly demonstrates the syn addition of
b
1
the Bu SnH to alkynes. For [Cu-Fe] catalysis, deuterated
alkyne 1a-D was synthesized and subjected to
hydrostannylation catalyzed (Scheme 3b). The E-isomer
3
To demonstrate the practical utility of this
methodology, we performed the reaction on large scale.
Under the standard reaction conditions established for
2
a-D was selectively formed, which demonstrates that
[
Cu-Fe] and [Cu-Mn] catalysis, use of 4 mmol of 1b
allowed for isolation of 1.7 g of α-vinylstannane 2b and
.6 g of (E)-훽-vinylstannane 3b, respectively, while
maintaining high reactivity and regioselectivity (Scheme
a). Moreover, the mild reaction conditions provide the
syn addition of Bu SnH to the alkyne also occurs under
3
the [Cu-Fe] catalytic conditions. This result also indicates
that formation of a copper acetylide intermediate is
unlikely because no occurrence of H/D exchange from
1
2
1
a-D and Bu SnH was observed. To further probe the
3
opportunity for late-stage hydrostannylation of natural
products or drugs. For example, when Mestranol, an
estrogen medication used in birth control pills, was
subjected to the two reaction conditions, the (E)-훽-
vinylstannane 4 was obtained as a single isomer in
excellent yield under the [Cu-Fe] catalytic conditions,
whereas moderate yield was observed under the [Cu-Mn]
catalytic conditions using the toluene as solvent (Scheme
activation modes by two different bimetallic catalysts, we
conducted stoichiometric experiments. For [Cu-Fe]
catalysis, according to the previous literatures involving
20
the stannylcupration of alkynes, we assume a [Cu]-
SnBu intermediate is generated upon the activation of
3
Bu SnH. However, our attempts to prepare (NHC)Cu-
3
SnBu via many methods failed, producing Bu Sn-SnBu
3
3
3
as a decomposition product in the absence of alkyne
substrate. Nevertheless, we found no reaction occurred
2
b).
Scheme 2. Synthetic Utility
between Bu Sn-Fp or Fp*-H and 1-decyne. These results
3
may exclude the [Fe] partner interacting with the alkynes
and necessity the role of [Cu]-SnBu . On the other hand,
3
we prepared the alkenylcopper 6 from the addition of the
[Cu]-H to 1-decyne. The alkenylcopper 6 readily reacted
with the Bu Sn-Mn(CO) at the room temperature to give
3
5
the β-vinylstannanes as a single product in 80% yield.
These results support the intermediacy of (NHC)Cu-H
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and Bu Sn-Mn(CO) in the activation of Bu SnH by the
alkyl-substituted alkynes using readily available Bu SnH
as the tin source. In addition, reversed regioselectivity
3
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[Cu-Mn] catalyst.
was found for aryl-substituted alkynes, affording the (E)-
β-vinylstannanes as major products. Further investigation
of heterobimetallic catalysts revealed IMesCu-Mn(CO)5
was an efficient catalyst for synthesis of (E)-β-
vinylstannanes. Primary, secondary and tertiary alkyl-
substituted alkynes are all applicable under the reaction
conditions. The utility of this method was demonstrated
by the large-scale synthesis of vinylstannanes and by late-
stage hydrostannylation of Mestranol. Mechanistic
Scheme 3. Mechanistic Studies
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experiments supported the syn addition of Bu SnH to the
3
alkynes and indicated the involvement Sn-H bond
activation in the rate-determining step. Two distinct Sn-
H bond activation modes were proposed based on the
stoichiometric experiments. In the [Cu-Fe] catalytic cycle,
[
Cu]-SnBu and protic [Fe]-H were likely formed upon
3
the activation of Bu SnH; however, the selectivity was
3
reversed in the [Cu-Mn] catalytic cycle, where [Cu]-H
and [Mn]-SnBu3 were likely generated as the key
intermediates. This divergent reactivity with Bu SnH is
3
the source of the heterobimetallic control of
regioselectivity.
Based on the above experiments combined with our
previous work, two distinct mechanisms were proposed
for [Cu-Fe] and [Cu-Mn] catalysis (Scheme 4). For the
ASSOCIATED CONTENT
Supporting Information. The Supporting Information is
available free of charge on the ACS Publications website.
Experimental procedures & spectral data (PDF)
[
Cu-Fe] catalyst, Bu Sn-H activation forms protic [Fe]-H
3
B and Bu Sn-[Cu] C. Then, syn addition of C to alkyl-
3
substituted terminal alkynes affords the α-
20
stannylalkenylcopper D.
Finally, protonolysis of
AUTHOR INFORMATION
complex D by [Fe]-H B gives the α-vinylstannanes and
regenerates the bimetallic catalyst. For aryl-substituted
alkynes, we hypothesize that the formation of β-
stannylalkenylcopper D’ was favored due to the increased
steric hindrance of the aryl substituent, thus leading to the
β-vinylstannane product after protonolysis by B. For the
Corresponding Author
* npm@uic.edu
ACKNOWLEDGMENT
Funding was provided by the NSF (CHE-1664632). We
thank Prof. Vladimir Gevorgyan and his group for providing
access to a low temperature cooler.
[
Cu-Mn] system, we instead propose that Bu Sn-H
3
activation forms Bu Sn-[Mn]
F and [Cu]-H G
3
intermediates. The addition of the [Cu]-H G to the alkyne
gives alkenylcopper H, which reacts with the F to deliver
the (E)-β-vinylstannanes and regenerate the bimetallic
catalyst. At this time, we do not have a clear
understanding of the factors that control the divergent Sn-
H activation behavior of catalysts A and E, and further
experimental and computational studies probing this
issue are underway.
REFERENCES
1
(a) Yadav, J. S.; Antony, A.; Rao, T. S.; Reddy, B. V. S. Recent
progress in transition metal catalyzed hydrofunctionalization of less
activated olefins. J. Organomet. Chem. 2011, 696, 16. (b) Ananikov,
V. P.; Tanaka, T. Hydrofunctionalization, Springer, Heidelberg, 2013.
(c) Zheng, Y.; Zi, W. Transition-metal catalyzed enantioselective
hydrofunctionalization of alkynes. Tetrahedron Lett. 2018, 59, 2205.
(d) Chen, J.; Guo, J.; Lu, Z. Recent Advances in Hydrometallation of
Alkenes and Alkynes via the First Row Transition Metal Catalysis.
Chin. J. Chem. 2018, 36, 1075.
SUMMARY
In summary, we have developed an unprecedented
procedure for divergent synthesis of the α-vinylstannanes
and (E)-β-vinylstannanes via hydrostannyaltion of
2
(a) Pereyre, M. Quintard, J.-P. Rahm, A. Tin in Organic Synthesis;
Butterworths: London, 1987; (b) Main Group Metals in Organic
Synthesis, Vol. 1, 2 (Eds.: H. Yamamoto, K. Oshima), Wiley-VCH,
Weinheim, 2004.
terminal alkynes mediated by a tunable heterobimetallic
Me
catalysts. By using IMesCu-FeCp(CO) as a catalyst, a
3
2
Farina, V.; Krishnamurthy, V.; Scott, W. J. The Stille Reaction;
variety of α-vinylstannanes can be synthesized in high
yield and good selectivity under mild reaction conditions.
This protocol represents the first general synthetic
method for preparation of α-vinylstannanes from simple
Wiley: New York, 2004.
4
For reviews of hydrostannylation reactions, see (a) Yoshida, H.
Stannylation Reactions under Base Metal Catalysis: Some Recent
Advances. Synthesis 2016, 48, 2540. (b) Trost, B. M.; Ball, Z. T.
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Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Addition of Metalloid Hydrides to Alkynes: Hydrometallation with
Steps in the Synthesis of Functionalized Amino Alcohols and
Heterocycles. Eur. J. Org. Chem. 2007, 2839; (f) Jena, N.; Kazmaier,
Boron, Silicon, and Tin. Synthesis 2005, 853. (c) Smith, N. D.;
Mancuso, J.; Lautens, M. Metal-Catalyzed Hydrostannations. Chem.
Rev. 2000, 100, 3257.
U. Synthesis of Stannylated Allyl‐ and Vinylphosphonates via
Molybdenum‐Catalyzed Hydrostannations. Eur. J. Org. Chem. 2008,
5
See ref 3 and the follow example: Rice, M. B.; Whitehead, S. L.;
Horvath, C. M.; Muchnij, J. A.; Maleczka, R. E., Jr. The Regiochemical
Influence of Oxo-Substitution in Palladium-Mediated
3
852. (g) Lin, H.; Kazmaier, U. Molybdenum‐Catalyzed
α‐Hydrostannations of Propargylamines as the Key Step in the
Synthesis of N‐Heterocycles. Eur. J. Org. Chem. 2009, 1221.
Hydrostannations of 1-Alkynes. Synthesis 2001, 1495.
6
For selected examples, see: (a) Ichinose, Y. Oda, H. Oshima, K.
Utimoto, K. Palladium Catalyzed Hydrostannylation and
Hydrogermylation of Acetylenes. Bull. Chem. Soc. Jpn. 1987, 60,
1
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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Hamze, A.; Veau, D.; Provot, O.; Brion, J.-D.; Alami, M. Palladium-
Catalyzed Markovnikov Terminal Arylalkynes Hydrostannation:
Application to the Synthesis of 1,1-Diarylethylenes. J. Org. Chem.
3
468. (b) Zhang, H. X. Guibÿ, F. Balavoine, G. Palladium Catalyzed
Hydrostannation of Alkynes and Palladium-Catalyzed
2
009, 74, 1337.
Hydrostannolysis of Propargyl or Propargyloxycarbonyl Derivatives of
Various Functional Groups. Tetrahedron Lett. 1988, 29, 619. (c)
Zhang, H. X.; Guibe, F.; Balavoine, G. Palladium- and Molybdenum-
Catalyzed Hydrostannation of Alkynes. A Novel Access to Regio- and
Stereodefined Vinylstannanes. J. Org. Chem. 1990, 55, 1857. (d)
Maleczka, R. E. Jr.; Ghosh, B.; Gallagher, W. P.; Baker, A. J.; Muchnij,
J. A.; Szymanski, A. L. Non-Pd Transition Metal-catalyzed
13
For a relevant report with only 3 demonstrated examples, see:
Rummelt, S. M.; Fürstner, A. Ruthenium-Catalyzed trans-Selective
Hydrostannation of Alkynes. Angew. Chem. Int. Ed. 2014, 53, 3626.
1
4
(
a) Kamijo, S.; Yamamoto, Y. In Multimetallic Catalysts in Organic
Synthesis; Shibasaki, M., Yamamoto, Y., Eds.; Wiley-VCH: New York,
004; Chapter 1. (b) D. C. Powers, T. Ritter, Bimetallic Redox Synergy
2
in Oxidative Palladium Catalysis. Acc. Chem. Res. 2012, 45, 840. (c)
N. P. Mankad, Selectivity Effects in Bimetallic Catalysis. Chem. Eur.
J. 2016, 22, 5822; (d) D. R. Pye, N. P. Mankad, Bimetallic catalysis for
C–C and C–X coupling reactions. Chem. Sci. 2017, 8, 1705; (e) I. G.
Powers, C. Uyeda, Metal−Metal Bonds in Catalysis. ACS Catal. 2017,
3
Hydrostannations: Bu SnF/PMHS as a Tin Hydride Source.
Tetrahedron 2013, 69, 4000.
7
(a) Darwish, A.; Lang, A.; Kim, T.; Chong, J. M. The Use of
Phosphine Ligands to Control the Regiochemistry of Pd-Catalyzed
Hydrostannations of 1-Alkynes: Synthesis of (E)-1-Tributylstannyl-1-
alkenes. Org. Lett, 2008, 10, 861. (b) Oderinde, M. S.; Froese, R. D. J.;
Organ, M. G. 2,2’-Azobis(2-methylpropionitrile)-Mediated Alkyne
Hydrostannylation: Reaction Mechanism. Angew. Chem. Int. Ed. 2013,
52, 11334. (c) Gupta, S.; Do, Y.; Lee, J. H.; Lee, M.; Han, J.; Rhee, Y.
H.; Park, J. Novel Catalyst System for Hydrostannation of Alkynes.
Chem. Eur. J. 2014, 20, 1267. (d) Mandla, K. A. Moore, C. E.
Rheingold, A. L. Figueroa, J. S. Regioselective Formation of (E)-β-
Vinylstannanes with a Topologically Controlled Molybdenum-Based
Alkyne Hydrostannation Catalyst. Angew. Chem. Int. Ed. 2018, 57,
6853.
7
, 936.
1
5
Banerjee, S.; Karunananda, M. K.; Bagherzadeh, S.; Jayarathne, U.;
Parmelee, S. R.; Waldhart, G. W.; Mankad, N. P. Synthesis and
Characterization of Heterobimetallic Complexes with Direct Cu–M
Bonds (M = Cr, Mn, Co, Mo, Ru, W) Supported by N-Heterocyclic
Carbene Ligands: A Toolkit for Catalytic Reaction Discovery. Inorg.
Chem. 2014, 53, 11307.
1
6
For our group’s work on heterobimetallic catalysis, see: (a)
Mazzacano, T. J.; Mankad, N. P. Base Metal Catalysts for
Photochemical C-H Borylation That Utilize Metal-Metal
Cooperativity. J. Am. Chem. Soc. 2013, 135, 17258. (b) Karunananda,
M. K.; Mankad, N. P. E-Selective Semi-Hydrogenation of Alkynes by
Heterobimetallic Catalysis. J. Am. Chem. Soc. 2015, 137, 14598. (c)
8
Shibata, I.; Suwa, T.; Ryu, K.; Baba, A. Selective α-Stannylated
Addition of Di-n-butyliodotin Hydride Ate Complex to Simple
Aliphatic Alkynes. J. Am. Chem. Soc. 2001, 123, 4101.
Bagherzadeh, S.; Mankad, N. P. Catalyst Control of Selectivity in CO
2
9
Yoshida, H.; Shinke, A.; Kawanoa Y.; Takakia, K. Copper-Catalyzed
Reduction Using a Tunable Heterobimetallic Effect. J. Am. Chem.
Soc. 2015, 137, 10898. (d) Pye, D. R.; Mankad, N. P. Cu/Mn Bimetallic
Catalysis Enables Carbonylative Suzuki-Miyaura Coupling with
Unactivated Alkyl Electrophiles. Chem. Sci. 2017, 8, 4750. For a recent
account, see: (e) Mankad, N. P. Selectivity Effects in Bimetallic
Catalysis. Chem. Commun. 2018, 54, 1291.
α-Selective Hydrostannylation of Alkynes for the Synthesis of
Branched Alkenylstannanes. Chem. Commun. 2015, 51, 10616.
1
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(a) Hibino, J.; Matsubara, S.; Morizawa, Y.; Oshima, K.; Nozaki, H.
Regioselective Stannylmetalation of Acetylenes in the Presence of
Transition-metal Catalyst. Tetrahedron Lett. 1984, 25, 2151; (b)
Matsubara, S.; Hibino, J.; Morizawa, Y.; Oshima, K.; Nozaki, H.
Regio- and Stereo-selective Synthesis of Vinylstannanes. Transition-
metal Catalyzed Stannylmetalation of Acetylenes and Conversion of
Enol Triflates and Vinyl Iodides into Vinylstannanes. J. Organomet.
Chem. 1985, 285, 163; (c) Sharma, S.; Oehlschlager, A. C. Control of
Regiochemistry in Bismetallation of 1-Decyne. Tetrahedron Lett.
1986, 27, 6161; (d) Sharma, S.; Oehlschlager, A. C. Regioselective
Synthesis and Cross Coupling Reactions of 1,2-Borostannyl-1-alkenes.
Tetrahedron Lett. 1988, 29, 261; (e) Sharma, S.; Oehlschlager, A. C.
Scope and Mechanism of Stannylalumination of 1-Alkynes. J. Org.
Chem. 1989, 54, 5064.
1
7
Forster, F.; Lopez, V. M. R.; Oestreich, M. Catalytic
Dehydrogenative Stannylation of C(sp)–H Bonds Involving
Cooperative Sn–H Bond Activation of Hydrostannanes. J. Am. Chem.
Soc. 2018, 140, 1259.
1
8
King, R. B. Some Applications of Metal Carbonyl Anions in the
Synthesis of Unusual Organometallic Compounds. Acc. Chem. Res.
970, 3, 417.
1
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(a) Barbero, A.; Cuadrado, P.; Fleming, I.; González, A. M.; Pulido, F.
J. The Stannyl-Cupration of Acetylenes and the Reaction of the
Intermediate Cuprates with Electrophiles as a Synthesis of Substituted
Vinylstannanes. J. Chem. Soc., Chem. Commun. 1992, 351. (b) Barbero, A.;
Cuadrado, P.;Fleming, I.; González, A. M.; Pulido, F. J.; Rubio, R. Stannyl-
cupration of Acetylenes and the Reaction of the Intermediate Cuprates with
Electrophiles as a Synthesis of Substituted Vinylstannanes. J. Chem. Soc.,
Perkin Trans.1, 1993, 1657. (c) Barbero A.; Pulido, F. J. Allylstannanes
and Vinylstannanes from Stannylcupration of C–C Multiple Bonds.
Recent Advances and Applications in Organic Synthesis. Chem. Soc.
Rev. 2005, 34, 913.
1
1
(a) Kazmaier, U.; Schauss, D.; Pohlman, M. Mo(CO)
3
(CN-t-
Bu) (MoBI ), New Efficient Catalyst for Regioselective
3
3
a
Hydrostannations. Org. Lett. 1999, 1, 1017; (b) Kazmaier, U.;
Pohlman, M.; Schauß, D. Regioselective Hydrostannations with
t
Mo(CO)
3
(CN Bu)
3
(MoBI
3
) as a New, Efficient Catalyst. Eur. J. Org.
Chem. 2000, 2761; (c) Braune, S.; Kazmaier, U. Regioselective
Hydrostannations Catalyzed by Molybdenum Isonitrile Complexes. J.
Organomet. Chem. 2002, 641, 26; (d) Braune, S.; Pohlman, M.;
Kazmaier, U. Molybdenum-Catalyzed Stannylations as Key Steps in
Heterocyclic Synthesis. J. Org. Chem. 2004, 69, 468; (e) Lin, H.;
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Singer, R. D.; Hutzzinger, M. W.; Oehlschlager, A. C. Additions of
CuCN-Derived Stannylcuprates to Terminal Alkynes: A Comparative
Spectroscopic and Chemical Study. J. Org. Chem. 1991, 56, 4933.
Kazmaier, U. Regioselective Mo‐Catalyzed Hydrostannations as Key
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Scheme 4. Proposed mechanisms for heterobimetallic alkyne hydrostannylation.
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