Angewandte
Communications
Chemie
Table 1: Effect of NHC ligands on the semi-hydrogenation of alkynes.[a]
Complete control of the chemo-, regio-, and stereoselectivity
of the desired transformation is undoubtedly a challenge.
Herein, we report a relay catalytic process by combination
of base-catalyzed alkyne isomerization and cobalt-catalyzed
semi-hydrogenation of internal alkynes, which enables the
selective synthesis of (Z)-2-alkenes from terminal alkynes. In
addition, conjugated E alkene and terminal alkene products
can be also readily accessed by slightly changing the reaction
conditions. A divergent and selective synthesis of Z alkenes,
E alkenes, as well as terminal alkenes by the hydrogenation of
easily available terminal alkynes has therefore been realized.
The selective chain-walking reaction of alkynes has been
much less studied compared to that of alkenes.[9] Never-
theless, base-promoted alkyne isomerization was observed,[10]
but has not been widely applied in synthetic chemistry.
Accordingly, we began this study with an investigation of
Entry
x/mol%
Ligand
Conv. [%][b]
Yield [%][b]
2a
3a (Z/E)
1
2
10 mol%
10 mol%
10 mol%
16 mol%
16 mol%
16 mol%
16 mol%
16 mol%
16 mol%
16 mol%
16 mol%
16 mol%
16 mol%
L2c
L2d
L2d
L2c
L2c
L2c
L2a
L2b
L2d
L1a
L1b
L3
88
85
91
97
2
9
–
–
–
<1
–
–
–
1
1
100
100
77
3[c]
4
19 (33:1)
84 (30:1)
90 (22:1)
18 (31:1)
10 (17:1)
99 (>99:1)
25 (80:1)
40 (48:1)
2
5[d]
6[e]
7[e]
8[e]
9[e]
10[e]
11[e]
12[e]
13[f]
100
100
100
100
100
100
100
100
100
base-catalyzed isomerization of
a
terminal alkyne
–
<1
(Scheme 3). It was found that a 10 mol% of KOtBu allowed
complete conversion of pent-4-yn-1-ylbenzene (1a) into the
2-alkyne 1a’ in 99% yield. In contrast, other bases displayed
no reactivity at all. Encouraged by the high efficiency of this
base-catalyzed alkyne isomerization, we turned our attention
to develop the subsequent Z-selective hydrogenation of 2-
alkynes, which we hoped would be compatible with the
reaction conditions for the alkyne isomerization to ensure
relay catalysis.
L2d
99 (>99:1)
[a] Reaction conditions: 1a (0.5 mmol), CoCl2 (0.01 mmol), ligand
(0.01 mmol), and KOtBu (10–16 mol%) in 1.0 mL of THF, under 5 bar of
H2 at RT for 5 h. [b] The conversion, yield, and Z/E ratio were determined
by GC analysis. [c] The reaction time was 3 h. [d] 1-(Trimethylsilyl)-1-
propyne) (7 mol%) was added as an additive. [e] One-pot two-step
procedure: 1a (0.5 mmol) and KOtBu (0.08 mmol) in 0.5 mL of THF was
reacted at RT for 5 h. Then the reaction mixture was transferred into
a mixture of CoCl2 (0.01 mmol) and ligand (0.01 mmol) in 0.5 mL of
THF, which was reacted under 5 bar of H2 at RT for 5 h. [f] The reaction
time of the hydrogenation step was 16 h.
was produced in 19% yield as the amount of KOtBu was
increased to 16 mol%, along with the generation of the 2-
alkynes 1a’ and penta-3,4-dien-1-ylbenzene (1a’’; entry 4).
Surprisingly, adding a catalytic amount of (1-(trimethylsilyl)-
1-propyne) as the additive greatly enhanced the reactivity and
selectivity, leading to an 84% yield of (Z)-3a with 30:1 Z/E
selectivity (entry 5). Notably, a one-pot two-step procedure
further improved the selectivity to 90% without the presence
of any additive (entry 6). We examined a series of NHC
pincer ligands in this transformation. The lutidine-based
pincer ligand L2d,[13] bearing a Dipp substituent (Dipp =
C6H3-2,6-iPr2), turned out to be the best choice with 99%
yield and greater than 99:1 Z/E selectivity (entry 9). More-
over, it was also the optimal ligand for the direct hydro-
genation of 1a into 2a (entries 2 and 3). Increasing the steric
bulk of the NHC ligands by tuning the N-substituents
dramatically enhanced the reactivity and Z/E selectivity
(entries 6, 8, and 9). The corresponding bidentate ligand L3
exhibited almost no reactivity (entry 12), indicating that
a tridentate coordination mode is crucial. It is noteworthy
that (Z)-3a was not further isomerized or hydrogenated at all
with an extended reaction time from 5 to 16 hours (entries 9
and 13), highlighting the unique feature of this cobalt catalyst
Scheme 3. Base-catalyzed isomerization of terminal alkynes. [a] Reac-
tion conditions: 1a (0. 5 mmol), base (0.05 mmol) in 0.5 mL of THF at
RT for 5 h, the conversion and yield were determined by GC analysis
using biphenyl as an internal standard.
Cobalt-catalyzed hydrogenation reactions have attracted
considerable attention over recent years because of the
abundance, sustainability, and biological compatibility of
cobalt metal.[11] Very recently, we developed an in situ
formed, robust, and phosphine-free cobalt catalytic system
for the hydrogenation of carbonyl compounds, using KOtBu
as an additive for the activation of N-hetercyclic carbebe
(NHC) ligand precursors.[12] Therefore, a tandem catalytic
process involving KOtBu-catalyzed alkyne isomerization and
NHC-cobalt catalyzed hydrogenation would be feasible,
wherein the base would play a dual role. Based on this
consideration, we then performed the designed tandem relay
catalysis using 1a as the model substrate (Table 1). A new
catalytic system comprising CoCl2, L2c, and KOtBu
(10 mol%) resulted in the formation of the direct hydro-
genated product 2a in 85% yield under 5 bar of H2 at room
temperature (entry 1). To our delight, the (Z)-2-alkene 3a
2
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Angew. Chem. Int. Ed. 2020, 59, 1 – 7
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