Ru-Catalyzed Migratory Geminal Semihydrogenation of Internal Alkynes to Terminal Olefins

Article abstract of DOI:10.1021/jacs.9b09658

Semihydrogenation of alkynes to alkenes represents a fundamentally useful transformation. In addition to the well-known cis- and trans-semihydrogenation, herein a geminal semihydrogenation of internal alkynes featuring 1,2-migration is described, which pr

Full text of DOI:10.1021/jacs.9b09658

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Article
Ru-Catalyzed Migratory Geminal Semi-
Hydrogenation of Internal Alkynes to Terminal Olefins
Lijuan Song, Qiang Feng, Yong Wang, Shengtao Ding, Yun-
Dong Wu, Xinhao Zhang, Lung Wa Chung, and Jianwei Sun
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b09658 • Publication Date (Web): 09 Oct 2019
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Ru-Catalyzed Migratory Geminal Semi-Hydrogenation of Internal Alkynes to
Terminal Olefins
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⊥
‡
#
#
Lijuan Song,†, Qiang Feng,# ‡ Yong Wang, Shengtao Ding, Yun-Dong Wu,†,§,¶
,
,
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Xinhao Zhang,†,¶ Lung Wa Chung,‖,* and Jianwei Sun#,*
†
Lab of Computational Chemistry and Drug Design, State Key Laboratory of
Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen
518055, China
#
Department of Chemistry, The Hong Kong University of Science and Technology,
Clear Water Bay, Kowloon, Hong Kong SAR, China
‖
Department of Chemistry and Shenzhen Grubbs Institute, Southern University of
Science and Technology, Shenzhen 518055, China
¶
Shenzhen Bay Laboratory, Shenzhen 518055, China
§
College of Chemistry, Peking University, Beijing 100871, China
⊥
Institute of Organic Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17,
D-35392 Giessen, Germany
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Abstract
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Semi-hydrogenation of alkynes to alkenes represents a fundamentally useful
transformation. In addition to the well-known cis- and trans-semi-hydrogenation,
herein a geminal semi-hydrogenation of internal alkynes featuring 1,2-migration is
described, which provides new access to the useful terminal vinylsilanes. This process
also presents a new mode of reactivity of silyl alkynes. With the proper choice of the
cationic [CpRu(MeCN)3]PF6 catalyst and a suitable silyl group, both aryl- and alkyl-
substituted silyl alkynes can participate in this highly efficient gem-selective process.
Furthermore, dedicated condition optimization also allowed switching of selectivity
from gem to trans by using a combination of parameters, including the suitable silyl
group, additive and H2 pressure. A systematic DFT study on the reaction mechanism
revealed that the formation of the gem-H2 Ru-carbene might be the key intermediate
in both gem- and trans-addition reactions, rather than the Ru-vinylidene intermediate.
The DFT results were further supported by carefully designed control experiments.
This uncommon gem-addition combined with 1,2-silyl migration in the metal-carbene
intermediate should open up a new synthetic avenue for alkyne transformations.
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Introduction
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Semi-hydrogenation of alkynes to form alkenes represents a fundamentally important
transformation in organic synthesis.1 For internal alkynes, such transformations
involve stereoselectivity control, i.e. cis- or trans-hydrogenation (Scheme 1). As a
textbook reaction, syn-selective semi-hydrogenation to form Z-alkenes has been well-
established and found wide applications using various metal catalytic systems (both
homogeneous and heterogeneous), with the Lindlar catalyst being most widely used
(Scheme 1a).1,2 The syn-selectivity can be well-controlled by the intrinsically
stereodefined syn-hydrometallation and reductive elimination elementary steps. In
contrast to cis-hydrogenation, trans-hydrogenation to form E-alkenes has been less
straightforward.1,3 For a long time, the synthetic community has relied on the non-
catalytic approaches using dissolving metals, such as Birch reduction with NH3 or
amines, although they suffer limited functional group tolerance and low operational
benignity (Scheme 1b).1c Nevertheless, significant progress with different catalytic
systems has been achieved in the past two decades, including indirect approaches.3-5
Among them, an elegant two-step approach involving Ru-catalyzed trans-
hydrosilylation and mild protodesilylation, pioneered by Trost, has found wide
applications in complex molecule synthesis owing to its good functional group
compatibility and excellent E-selectivity.4 More recently, Fürstner and co-workers
have further extended this trans-addition system to the direct E-selective
hydrogenation using molecular hydrogen with equally excellent functional group
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compatibility and stereoselectivity, thus representing a revolution on this
transformation.5
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While both cis- and trans-semi-hydrogenations have been established, geminal
(gem-) semi-hydrogenation of internal alkynes, which delivers H2 to the same carbon
of the triple bond with concomitant 1,2-migration of the substituent on this carbon to
form terminal olefins, is an under-developed transformation (Scheme 1c).5d Herein,
we report a new example of this type as well as the detailed mechanistic studies.
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Scheme 1. Introduction to Semi-Hydrogenation of Alkynes
In 2013, we reported an unusual ligand-controlled regio- and stereodivergent
hydrosilylation process of silyl alkynes, in which the steric difference in the ligand of
the Ru-catalytic system (Cp* vs. Cp) dramatically influenced the H‒Si addition
mode.6a This remarkable selectivity divergence prompted us to explore the possibility
of extending this system to stereodivergent semi-hydrogenation of silyl alkynes. To
our surprise, an unprecedented gem-hydrogenation (Scheme 1c) was observed.
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Moreover, we were also able to control the selectivity between gem-hydrogenation
and trans-hydrogenation by different ligands. Mechanistically, both experimental and
computational studies have excluded the involvement of a metal vinylidene
intermediate, a typical pathway responsible for 1,2-migration of internal alkynes,
particularly for silyl alkynes. Instead, the geminal addition of H2 to the alkyne to form
a Ru-carbene intermediate followed by 1,2-migration is more consistent to our
observations (Scheme 2).
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Scheme 2. Potential Intermediates Responsible for Semi-Hydrogenation of
Alkynes
Results and Discussion
Silyl alkynes are versatile species in organic synthesis.7 The silyl group on the
triple bond not only serves as a convertible masking group, but also imposes unique
steric and electronic difference (from the other terminal of the alkyne) to benefit
selectivity control in the triple bond addition reactions.6a,7 Moreover, vinyl silanes
resulting from these addition reactions are useful molecules in organic synthesis and
materials science.8 Therefore, we used 1-trimethylsilylhexyne as the model substrate
for our hydrogenation reaction. Initial catalyst evaluation was focused on ruthenium-
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based complexes, a family of versatile catalysts for alkyne additions.4-6,8-11 In
particular, the cationic catalyst [Cp*Ru(MeCN)3]PF6 has been superior for a wide
range of alkyne additions. In many of them, particularly trans-hydrogenation, the Cp*
ligand was noted to be necessary for high reactivity and selectivity.5,6c,9 Unfortunately,
initial evaluation of this catalyst for the hydrogenation of 1 resulted in extremely low
reactivity, leading to the E-alkene in only 10% yield (Table 1, entry 1). A cationic Rh-
complex with the same ligands did not show any catalytic activity (entry 2), nor other
metal-based catalysts previously known for alkyne additions, such as [Ir(COD)Cl]2
(entry 3).6b Inspired by our previous experience in the hydrosilylation of silyl alkynes,
we believed that the severe steric repulsion might lead to the diminished reactivity
when the large silyl alkyne encounters the bulky Cp* ligand.6a Thus, its small sibling
[CpRu(MeCN)3]PF6 was evaluated.11 Gratifyingly, at 1 bar of H2 pressure, smooth
semi-hydrogenation in DCM proceeded almost quantitatively at room temperature.
Surprisingly, the reaction afforded both branched gem-hydrogenation product (2) and
linear trans-hydrogenation product (3), with the former being major (B/L = 3.3:1,
entry 4). While the size difference between Cp an Cp* seemed to be important, the
influence of their electronic difference should not be excluded.5f Nevertheless, these
observations foreshadowed the unusual reactivity of silyl alkynes.
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Systematic optimizations were then performed in hope of improving the gem-
hydrogenation selectivity, as this represents a new reactivity. We initially studied the
influence of hydrogen pressure on selectivity. Unfortunately, at a higher pressure, the
gem-hydrogenation pathway was disfavored (Figure 1). Next, we studied the
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t
influence of the silyl group. Increasing its size to Et3Si (TES), BuMe2Si (TBS), and
BnMe2Si all led to lower reactivity and essentially no improvement on gem-selectivity
(entries 5-7). Changing the electronic property with triethoxysilyl group shut down
the reactivity completely (entry 8). However, ultimately we found that the use of
phenyldimethylsilyl group (PhMe2Si) led to exclusive formation of the desired
branched product 2a (B/L >30:1), albeit with low reactivity (entry 9). Then, different
solvents were screened (entries 10‒15), which indicated that polar and good-
coordinating solvents, such as MeCN, could inhibit the reactivity. Among them,
CHCl3 provided the highest reactivity (entry 11). Finally, in order to accelerate the
reaction, we found that the use of 10 bar hydrogen pressure resulted in excellent yield
while maintaining equally high gem-selectivity (entry 16). In contrast to the
significantly decreased gem-selectivity at high pressure observed with the TMS-
alkyne (Figure 1), the excellent gem-selectivity with PhMe2Si-alkyne at high H2
pressure is remarkable, which also implies that the phenyl group in the silyl group
(PhMe2Si-) plays an essential role in the selectivity and deserves special study (vide
infra). It is also worth noting that this phenyl group also makes the whole silyl group
more synthetically useful regarding subsequent conversions.12 Finally, no appreciable
over-reduction to the corresponding silyl alkane was observed.
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Table 1. Optimization of Reaction Conditions.a
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aReaction conditions: 1 (0.1 mmol), catalyst (10 mol%), H2 (1 bar), solvent (0.1 M), rt.
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bYield was determined by analysis of the H NMR spectrum of the crude product
using CH2Br2 as the internal standard. The unreacted substrate accounts for major
remainder of the mass balance. cRun at 10 bar pressure (H2) for 12 h.
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Figure 1. Dependence of B/L ratio on the hydrogen pressure. For accurate
determination of the B/L ratio, TMSC≡C(CH2)2OTHP was used as substrate.
With the optimized conditions, we examined the scope of this gem-semi-
hydrogenation (Table 2). A wide range of silyl alkynes participated in this mild
process to provide a diverse set of terminal vinyl silanes with good to excellent
efficiency and gem-selectivity. A wide variety of functional groups were tolerated,
including free alcohol, ether, ester, mesylate, silyl ether, acetal, halide, and
phthalimide. Electron-rich arenes, such as furan and thiophene, could also be
incorporated in the substrates. Substitution of a secondary alkyl substituent, such as
cyclopentyl and cyclohexyl groups, on the triple bond did not influence the high
reactivity. However, with bulky tBu-substitution, the reactivity was almost shut down.
A particularly notable example is the highly electron-deficient ynone 1t, which was
equally reactive to form the corresponding gem-hydrogenation product 2t with high
efficiency and respectable gem-selectivity. It is noteworthy that the ketone carbonyl
group remained intact under this reduction condition, demonstrating high
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chemoselectivity as well. While this protocol is generally selective for aliphatic silyl
alkynes, unfortunately, the aryl analogs failed to give high gem-selectivity (e.g., 2u-v),
although the reactivity remained high.
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Table 2. Substrate Scope. a
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aReaction conditions: 1 (0.2 mmol), [CpRu(MeCN)3]PF6 (10 mol%), CHCl3 (0.1 M),
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H2 (10 bar), rt, 12 h. Isolated yield is provided. The B/L selectivity was determined by
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analysis of the H NMR spectrum of the crude product. Catalyst loading: 5 mol%.
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cCatalyst loading: 20 mol%.
To improve the gem-selectivity of aryl alkynes, we employed phenyl silyl alkyne
1u as the model substrate for further condition optimization. Keeping in mind that the
gem-selectivity is reversely dependent on hydrogen pressure, we first decreased the
hydrogen pressure to 1 bar. As expected, the gem-selectivity was improved to 7:1,
though at the expense of reaction time and conversion (Table 2, entry 2). We next
evaluated the influence of additive. To our delight, the use of NaBArF could further
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improve the gem-selectivity to 10:1 (entry 3, see the SI for more details). Furthermore,
different solvents were compared, which identified DCM as the superior solvent,
leading to the formation of essentially the single gem-isomer 2u (B/L >30:1). The
effect of additive was then further confirmed in DCM solvent (entry 6). While the
origin of the additive effect is unknown, it might be related to the influence on the
cationic nature of the catalyst as well as the dielectric constant of the reaction medium.
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Table 3. Condition Optimization for Aryl Alkyne 1u.a
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aReaction conditions: 1u (0.05 mmol), [CpRu(MeCN)3]PF6 (20 mol%), CHCl3 (0.1
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M), rt. Yield and B/L selectivity were determined by analysis of the H NMR
spectrum of the crude product using CH2Br2 as the internal standard. The unreacted
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substrate accounts for major remainder of the mass balance. The conditions and data
for entry 1 were taken from Table 2. dRun in DCM solvent at 0.05 M concentration.
With the above slightly modified conditions, we then examined the generality of
this new protocol for a range of aryl alkynes. As shown in Table 4, both electron-
donating and electron-deficient substituents on the para-position of the aryl group all
led to excellent gem-selectivity. Unfortunately, ortho-substituted aryl alkynes showed
extremely low reactivity, presumably due to increased steric hindrance. For electron-
deficient cases, the reaction efficiency is reasonably good, although these aryl alkynes
are in general less reactive than alkyl ones. In particular, the electron-rich one showed
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much lower reactivity (2aa). We reasoned that the electron-rich arene has strong π-
interaction with the cationic catalyst, thereby deactivating its catalytic activity.13b This
is also consistent with the general observation with this type of Ru-based cationic
system.5
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Table 4. Substrate Scope on Aryl Silyl Alkynes with Improved Conditions.a
aReaction conditions: 1 (0.2 mmol), [CpRu(MeCN)3]PF6 (20 mol%), NaBArF (20
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mol%), DCM (4 mL), H2 (1 bar), rt. Isolated yield is provided. The B/L selectivity
was determined by analysis of the 1H NMR spectrum of the crude product.
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During the study of the influence of additive on gem-selectivity, we found that the
use of strongly coordinating ligand could reverse the selectivity. Among all the
evaluated coordinative additives, we found that DABCO imposed the highest
influence (see the SI for more details). After further optimization of other reaction
parameters, we identified that both good yield and trans-hydrogenation selectivity
could be obtained when the reaction of 1u was run in CHCl3 (0.05 M) at 15 bar of
hydrogen pressure.
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With this modification, we were able to achieve highly divergent trans-addition of
aryl silyl alkynes (Table 5). These linear E-olefins were all obtained with good
efficiency and selectivity, except the electron-rich ones (3aa), presumably due to the
same aforementioned reason (i.e., electron-rich arene interaction with the
catalyst).5,13b An aliphatic alkyne was also evaluated (entry 7). While only trans-
addition was observed, the reaction showed moderate E/Z selectivity.
Table 5. Trans-Hydrogenation of Aryl-Substituted Silyl Alkynesa
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aReaction conditions: 1 (0.2 mmol), [CpRu(MeCN)3]PF6 (20 mol%), DABCO (20
mol%), CHCl3 (0.1 M), H2 (15 bar), rt, 5 h. Isolated yield is provided. The L/B ratio
was determined by 1HNMR analysis of the crude reaction mixture. b NMR yield.
Mechanistic Studies
DFT Calculations. To understand the reaction mechanism of the novel gem-
hydrogenation catalyzed by the cationic Ru(II) catalyst, systematic DFT (the SMD
M06 method) calculations on several possible pathways were performed. Instead of
the common metal-vinylidene mechanism (Scheme 2), our computational results
suggest that the initial gem-hydrogenation process in the most favorable pathway
follows the mechanism proposed for the related hydrosilylation and other
hydrofunctionalizations by us6,13 as well as by the Fürstner and Thiel groups.5 First,
the exchange of two MeCN ligands by H2 and the alkyne substrate forms -H2 Ru(II)
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complex A2 (Figure 2), followed by the rate-determining concerted oxidative
hydrogen migration via A3a-TS with the barrier of ~25.3 kcal/mol in solution to
afford -vinyl Ru(IV) intermediate A4a (ΔGsoln = 20.5 kcal/mol).14 A very facile
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rotation along the Cα−Cβ bond of A4a preferentially takes place to form a more stable
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ruthenacyclopropene intermediate A6atrans (ΔGsoln = 13.3 kcal/mol) via A5a-TStrans
.
Interestingly, different from the hydrosilylation and other hydrofunctionalizations,13a
this critical ruthenacyclopropene intermediate does not prefer a direct reductive
hydrogen migration to the Cα atom to give the trans-addition product B1 due to a
higher-energy transition state B1-TS (ΔGsoln = 20.2 kcal/mol, Scheme 3). Instead, as
proposed by Fürstner and Thiel groups,5c the ruthenacyclopropene intermediate
A6atrans or A6acis preferentially undergoes another novel reductive hydrogen
migration to the Cβ atom to give the key and quite stable Ru(II)-carbene intermediate
C2 (ΔGsoln = 1.6 kcal/mol) via C2-TS1 (ΔGsoln = 15.5 kcal/mol), along with an
isomerization step via C1-TS (ΔGsoln = 15.8 kcal/mol)) or via C2-TS2 (ΔGsoln = 15.4
kcal/mol). Therefore, these results show that the formation of the Ru(II)-carbene
intermediate C2 is kinetically more preferable than direct reductive migration to yield
the final trans-addition product B1.
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Figure 2. Energetic profiles of the most favorable pathway for the initial stage of the
gem-hydrogenation in solution computed by the SMD M06 method.15d
Scheme 3. Energetic Profiles (kcal/mol) for Different Reductive Hydrogen
Migration Pathways from the Two Ruthenacyclopropene Intermediates in
Solution Computed by the SMD M06 Method.
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Cp
Ru
DGsoln(DEsoln
kcal/mol
)
MeCN
H
Me
6
7
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9
Cp
Ru
TMS
H
B1-TS
20.2(17.8)
MeCN
TMS
H
H
Me
B1
Reductive hydrogen migration
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-14.0(-15.7)
Cp
Ru
MeCN
Me
H
TMS
H
Cp
Cp
Ru
Ru
C1-TS
15.8(14.4)
MeCN
MeCN
Me
H
TMS
H
TMS
Me
Isomerization
H
H
A6atrans
C1
Cp
Ru
15.4(13.2)
13.3(12.2)
Cp
H
MeCN
Me
Ru
H
TMS
MeCN
Me
H
C2-TS1
15.5(13.6)
H migration
H
Cp
Ru
Cp
Ru
TMS
C2-TS2
15.4(13.2)
MeCN
MeCN
Me
H
H
H migration
Me
C2
H
H
TMS
TMS
A6acis
13.2(11.2)
1.6(-1.3)
Next, the five-coordinate Ru(II)-carbene intermediate C2 can bifurcate into two
pathways (Figure 3). One possibility is the coordination of a MeCN ligand to form a
stable six-coordinate Ru(II)-carbene C3 (ΔGsoln = -6.2 kcal/mol), followed by an
unusual 1,2-silyl migration from the Cβ atom to the Cα atom (via C3-TSa; ΔGsoln
=
10.7 kcal/mol) to form the desired gem-addition product C4a. Another competitive
pathway, as suggested by the Fürstner and Thiel groups,5c-d involves coordination of
another hydrogen molecule to C2. Subsequent oxidative addition via D1-TS proceeds
to give a Ru(IV)-carbene dihydride intermediate D2 (ΔGsoln = 10.6 kcal/mol).15e Next,
one hydride migrates to the Cα atom of the carbene via D2-TS (ΔGsoln = 11.4 kcal/mol)
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to afford the α-H agostic ruthenium(IV)-alkyl hydride intermediate D3 and,
subsequently, its β-H agostic isomer D4 (Figure 3). Finally, β-H elimination of D4
gives the trans-addition product D5. Moreover, other pathways involving 1,2-
hydrogen migration to the Cα atom via C3-TSb (ΔGsoln = 28.0 kcal/mol) or β-hydride
elimination via C4-TSa (21.9 kcal/mol) or C4-TS2a (17.6 kcal/mol) should be
excluded due to their higher barriers. Furthermore, other possible mechanisms for the
gem-addition, such as (1) the formation of metal-vinylidene intermediate (Scheme
4)16 and (2) hydrogenation followed by β-Si elimination and hydrosilylation (see
Figure S1 in the SI for details), were also found to have much higher reaction barriers
(32.6 and 34.3 kcal/mol, respectively), and should be excluded. Overall, the gem-
addition pathway depicted in Figure 3 was computed to be the most kinetically
favorable pathway and had a slightly lower barrier than the trans-addition pathway by
about 0.7 kcal/mol. This is qualitatively consistent with the observed low gem-
selectivity when TMS-alkyne was used (Table 1, entry 4).
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Cp
Ru
Cp
Ru
Cp
Ru
H
H
H
H
NCMe
TMS
DGsoln(DEsoln): kcal/mol
MeCN
MeCN
H
H
MeCN
Me
D2-TS
H
H
H
Me
Me
TMS
H
TMS
D1-TS
C3-TSa
Cp
H
Ru
C3-TSa
10.7
(-2.2)
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H
MeCN
H
D2-TS
Me
H
D2
Cp
Ru
TMS
11.4
(1.9)
10.6
(1.8)
10.1
(1.3)
D1-TS
H
H
D3
6.7
H
D1
H2
MeCN
Cp
6.2
H
H
TMS
Me
C2
(-3.4)
Ru
(-2.0)
H
MeCN
Me
H
H
NCMe
1.6
Cp
D4-TS
-0.7
(-10.1)
D5
H
H
(-1.3)
D4
Ru
TMS
H
C3
MeCN
-6.5
(-15.6)
-6.7
(-15.9)
H
Cp
Ru
Me
-6.2
(-18.7)
TMS
Cp
Cp
Ru
Cp
H
H
Cp
Ru
H
MeCN
H
Ru
H
NCMe
Ru
H
NCCH3
H
H
MeCN
MeCN
C4a
Me
H
MeCN
H
H
H
MeCN
TMS
Me
TMS
TMS
Me
TMS
Me
-17.0
(-30.5)
H
H
TMS
Me
Cp
Ru
Cp
Cp
Ru
Cp
Ru
Cp
Ru
NCMe
H
NCMe
H
Ru
NCMe
TMS
NCMe
TMS
MeCN
MeCN
MeCN
H
H
H
H
H
H
TMS
H
Me
Me
Me
H
TMS
H
TMS
H
H
H
H
H
C3-TSb
C3-TS2a
C3-TS2b
C4-TSa
C4-TS2a
17.6(14.6)
28.0(15.6)
14.7(11.2)
31.7(30.8)
21.9(10.3)
Figure 3. Energetic profiles of the most favorable pathway for the gem- and trans-addition hydrogenation in solution computed by the
SMD M06 method.15e
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Scheme 4. Energetic Profiles for the Metal Vinylidene Mechanism in Solution Computed
by the SMD M06 Method.
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Cp
Ru
Cp
Ru
Cp
Ru
18.4
(12.6)
NCMe
TMS
+H2
NCMe
Me
-MeCN
N
C
e
M
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N
N
C
TMS
C
e
M
e
E1-TS
M
TMS
Me
Me
E1
5.8
(0.4)
E2
11.2
(7.2)
E3
20.2
(26.3)
Cp
Ru
Cp
Ru
Cp
Ru
32.6
(30.0)
25.7
(23.0)
TMS
Me
H
H
N
Me
MeCN
TMS
MeCN
C
e
M
H
E4-TSb
E5-TSb
H
H
E5b
H
TMS
Me
E6b
E4b
23.9
(22.9)
28.7
(26.6)
-13.4
(-15.8)
The important role of the phenyl group in PhMe2Si- on the gem-addition was further examined
by DFT calculations. When the PhMe2Si-alkyne substrate was used, the higher computed
selectivity (4.1 kcal/mol) towards gem-addition over trans-addition was also observed, compared
to TMS-alkyne (0.7 kcal/mol, see Table 6 and Figure 4). In the key and favorable silyl migration
step via C3-TSa(SiPhMe2), dissociation of one CH3CN ligand and η2-Ph coordination from
PhMe2Si to the ruthenium center are involved, which has a lower barrier than the silyl migration
step without the CH3CN dissociation and phenyl coordination (via C3-TS(SiPhMe2), Figure 4)
by about 4.9 kcal/mol. Hence, such phenyl coordination enhances gem-addition selectivity. On
the other hand, when one small MeCN ligand was replaced by a bulkier DABCO ligand, the
computed selectivity was reversed to prefer trans-addition by 4.0 kcal/mol (Table 6). Our results
showed that the silyl migration step, in which the silyl group approached M=Cα site and the
phenyl coordination to the metal was involved, was found to experience considerable steric
repulsion with the bulky DABCO ligand and thus considerably raise the reaction barrier (Figure
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4). These computational results are qualitatively consistent with the higher gem-selectivity by
5
6
using the PhMe2Si-substituted alkyne and with the reverse selectivity by the DABCO additive.
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Table 6. Computed Relative Free Energies (kcal/mol) of the Key Transition States for the
trans-addition and gem-addition Pathways with Different Alkynes (MeC≡C-Si) or Ligand
(L) of the Catalyst in solution by the SMD M06 Method.
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gem-
trans-addition
Selectivity
addition
C3-TS
10.7
ΔΔGa
0.7
4.1
−4.0
Si/L
B1-TS
20.2
D1-TS
10.1
10.1
‒
D2-TS
11.4
10.7
15.6c
Si = TMS
21.8
26.4
6.6
19.6
Si = PhMe2Si
L = DABCOb
b
aΔΔG = ΔGtrans-add − ΔGgem-add. The relative free energies are with respect to the
[CpRu(MeCN)2(DABCO)]+ complex and isolated reactants. cOxidative addition of H2 concerted
with hydrogen migration.
C3-TSa(SiPhMe2)
C3-TS(SiPhMe2)
6.6(2.6)
11.5(-2.5)
C3-TSa(dabco)
D2-TS(dabco)
19.6 (16.8)
15.6 (5.9)
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Figure 4. Computed geometries and relative free energies and electronic energies (in parenthesis)
of the critical silyl migration step for the gem-addition with the MeC≡C-SiPhMe2 substrate in
solution by the SMD M06 method.
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On the basis of the above DFT study, the overall mechanistic details of the unusual gem- and
trans-hydrogenation are summarized in Scheme 5. The Ru(II)-carbene was found to be the key
intermediate in these reactions. Depending on the ligand environment, the migration propensity
of the silyl (vs. H) and H2 pressure, this carbene intermediate can undergo either the unusual 1,2-
silyl migration to give the gem-addition product (pathway B) or a cascade process involving
oxidative addition of another H2 followed by 1,2-hydrogen migration and β-H elimination to
give the trans-addition product (pathway A). The gem-addition can be enhanced by a phenyl
substituent on the silyl group through coordination to the ruthenium center in the key silyl
migration step. The pathway A is consistent with Fürstner’s observation.5 In retrospect, the
observed inverse dependence of the B/L ratio on hydrogen pressure was also consistent with the
proposed pathways, as pathway A should be more favored at high pressure due to the
involvement of another hydrogen molecule.
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Scheme 5. Proposed Mechanisms for Ru-Catalyzed gem- and trans-Hydrogenation.
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Control Experiments. More experiments were designed to further substantiate the proposed
mechanism for the unusual gem-hydrogenation, particularly to differentiate the Ru-carbene
pathway (C3 in Scheme 5) from the silyl-migrated Ru-vinylidene pathway (B3 in Scheme 4), as
the latter intermediate has been widely known with Ru-catalytic systems for internal alkynes.16
Thus, we designed two alkynes bearing two different silyl groups (4 and 5). If the Ru-vinylidene
intermediate is involved, alkyne 4 will proceed to form VD-4 only, while alkyne 5 will form VD-
5 only (Scheme 6). These two different vinylidene intermediates should proceed separately to
form the two corresponding hydrogenation products 6 and 7, respectively. However, if the gem-
H2 Ru-carbene intermediate is operative, these two alkynes should proceed to form the same
intermediate CB. Subsequent silyl migration would lead to a mixture of two products (both 6 and
7) resulting from silyl migrations from both sides, and theoretically, the ratios of the two
products from the two alkynes should be equal as a result of the common intermediate. In fact,
when the two alkynes were subjected separately to the standard gem-hydrogenation conditions,
both 6 and 7 were formed as a mixture. The ratios between 6 and 7 from both alkynes were
essentially the same (Scheme 6). Therefore, these observations provided a concrete
discrimination of the two mechanisms and excluded the involvement of the Ru-vinylidene
intermediate. They are also consistent with our DFT calculations (Scheme 5) as well as the
observations by Fürstner.5
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Scheme 6. Experimental Differentiation between Ru-Vinylidene and gem-H2 Ru-Carbene
5
6
Intermediates.
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Furthermore, silyl migration sometimes occurs by dissociation to form a silyl cation followed
by recombination. In order to probe this possibility, a cross-over experiment was designed
(Scheme 7). Under the standard conditions, a mixture of alkynes 1q and 8 reacted to form the
corresponding products 2q and 9 in high yields. The cross-over products 9 and 10 were not
observed, which excluded the possibility of fragmentation to form silyl cations in this process.
Scheme 7. A Cross-over Experiment to Probe Possible Involvement of Silyl Cations
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Furthermore, based on our computational conclusion, the two hydrogen atoms for the gem-
hydrogenation should originate from the same H2 molecule, while they can come from two
different H2 molecules for the trans-hydrogenation. We then carried out cross-over experiments
using a mixture of H2/D2 (Scheme 8). When alkyne 1h was subjected to the gem-hydrogenation
conditions, the corresponding products 2h-d2 and 2h were formed, but no cross-over product 2h-
d1 (with H‒D scrambling) was observed. However, when the trans-hydrogenation conditions
were employed, the reaction of 1y in mixed H2/D2 atmosphere formed not only 3y and 3y-d2, but
also the cross-over product 3y-d1. These experimental results further supported our calculated
favorable pathways for both gem- and trans-hydrogenation summarized in Scheme 5.17
Scheme 8. Cross-over Experiments with H2/D2.
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Conclusion
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We have developed the first migratory geminal semi-hydrogenation of silyl alkynes. This
process not only provides new access to the useful terminal vinylsilanes, but also presents a new
mode of reactivity of silyl alkynes, which is complementary to the established cis- and trans-
semi-hydrogenation. Different from the previously preferred [Cp*Ru]-based system for trans-
hydrogenation of alkynes, the use of [CpRu]-based system was found to be superior in this
unusual hydrogenation reaction. With the proper choice of a silyl group and suitable tuning of
the cationic nature of the catalyst, both aryl- and alkyl-substituted silyl alkynes can participate in
this highly efficient and gem-selective process. With a suitable additive (i.e., DABCO), we were
also able to alter the selectivity to favor trans-hydrogenation for aryl alkynes with good
selectivity. DFT computations provided important insights into the mechanisms for both gem-
and trans-selectivity. The superior role of the phenyldimethylsilyl group in the uncommon silyl
migration was also rationalized. Moreover, the gem-H2 Ru-carbene intermediate was proposed to
be the key intermediate for both gem- and trans-hydrogenation, rather than the Ru-vinylidene
intermediate, which was also substantiated by experimental results. The delicate design of two
disilyl alkynes provided concrete evidence for the differentiation of these two pathways. The
uncommon gem-addition5 and/or silyl migration from Cβ in the metal-carbene intermediate
should open up a new synthetic avenue for alkyne transformations.
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ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge via the Internet at http://pubs.acs.org at
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DOI: .
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Experimental and computational details and NMR data (PDF).
AUTHOR INFORMATION
Corresponding Author
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*J.S.: sunjw@ust.hk
*L.W.C.: oscarchung@sustech.edu.cn
ORCID
Jianwei Sun: 0000-0002-2470-1077
Lung Wa Chung: 0000-0001-9460-7812
Xinhao Zhang: 0000-0002-8210-2531
Yun-Dong Wu: 0000-0003-4477-7332
Author Contributions
‡ L.S. and Q.F. contributed equally to the work. L.S. contributed to the computational part,
and Q.F. contributed to the experimental part.
Notes
The authors declare no competing financial interest.
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