Cobalt-catalyzed conjugate addition of silylacetylenes to α,β-unsaturated ketones

Article abstract of DOI:10.1039/c1cc14098a

Catalytic addition of silylacetylenes to α,β-unsaturated ketones proceeded in the presence of a cobalt complex coordinated with a bisphosphine ligand to give high yields of β-alkynylketones. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1cc14098a

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COMMUNICATION
Cobalt-catalyzed conjugate addition of silylacetylenes to a,b-unsaturated
ketoneswz
Takahiro Nishimura,* Takahiro Sawano, Keiyu Ou and Tamio Hayashi*
Received 8th July 2011, Accepted 27th July 2011
DOI: 10.1039/c1cc14098a
Catalytic addition of silylacetylenes to a,b-unsaturated ketones
proceeded in the presence of a cobalt complex coordinated with a
bisphosphine ligand to give high yields of b-alkynylketones.
reductive coupling reactions. Based on their reports, we examined
the catalytic activity of cobalt(I) complexes in the addition of a
silylacetylene to an enone. It was found that the conjugate
alkynylation is catalyzed by cobalt complexes, where significant
effects of a solvent, a catalyst precursor, and a ligand were
observed (Table 1). Thus, treatment of 1-phenyl-2-buten-1-one
(1a) with 2 equiv.20 of (triisopropylsilyl)acetylene (2m) in the
presence of Co(OAc)2ꢀ4H2O (5 mol%), 1,2-bis(diphenylphos-
phino)ethane (dppe) (5 mol%), and zinc powder (50 mol%) in
dimethylsulfoxide (DMSO) at 80 1C for 10 h gave the alkynyl-
ation product 3am in 81% yield (Table 1, entry 1). The
reactions in polar solvents, N,N-dimethylformamide (DMF)
Catalytic conjugate addition of terminal alkynes to
a,b-unsaturated carbonyl compounds and related compounds
is one of the most straightforward methods to prepare functional-
ized internal alkynes.1 There have been several reports on
the metal-catalyzed conjugate addition of terminal alkynes to
a,b-unsaturated carbonyl compounds. The conjugate addition
to b-unsubstituted enones (vinyl ketones) or enoates (acrylates),
which are more reactive than b-substituted ones, has been
reported by use of Rh,2 Ru,3 and Pd4 catalysts. The asymmetric
conjugate alkynylation of b-substituted a,b-unsaturated carbonyl
compounds has also been recently developed: the asymmetric
alkynylation of Meldrum’s acid derived acceptors (Cu5 and Rh),6
oxazepanedione acceptors (Zn),7 and a,b-unsaturated thioamides
(Cu).8,9 In this context, we recently reported rhodium-catalyzed
reactions which realize the asymmetric conjugate addition of
silylacetylenes to enones,10 enals,11 and nitroalkenes.12,13
Cobalt-catalyzed reactions have received particular attention
in the area of carbon–carbon coupling reactions displaying
their unique reactivity and selectivity.14 Cobalt complexes
have also been reported to catalyze the conjugate addition of
malonate esters15 or alkyl and aryl halides under reductive
conditions.16,17 Recently, Li and co-workers reported that the
addition of terminal alkynes to iminium ions, in situ generated
from aldehydes and secondary amines, is efficiently catalyzed
by cobalt complex CoCl2(PPh3)2.18 Meanwhile, there have been
no reports on the cobalt-catalyzed conjugate alkynylation of
enones to the best of our knowledge. Here we report the cobalt-
catalyzed addition of silylacetylenes to a,b-unsaturated ketones
and some preliminary results of its asymmetric variant.
Table 1 Cobalt-catalyzed conjugate addition of alkyne 2m to enone 1aa
Entry
Catalyst
Ligand
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
Co(OAc)2
CoCl2
CoBr2
CoI2
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
—
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
Co(OAc)2ꢀ4H2O
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppm
dppp
dppb
rac-binap
dppe
—
DMSO
DMF
81
24
8
0
0
75
29
21
19
0
63
0
0
CH3CN
Toluene
1,4-Dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
9
10
11
12
13
14
15
16c
17d
Cheng and co-workers14e,19 have extensively studied a catalytic
system of CoX2/bisphosphine/Zn generating a Co(I) species in
0
0
0
97
Department of Chemistry, Graduate School of Science,
Kyoto University, Sakyo, Kyoto 606-8502, Japan.
E-mail: tnishi@kuchem.kyoto-u.ac.jp, thayashi@kuchem.kyoto-u.ac.jp;
Fax: +81 75 753 3988; Tel: +81 75 753 3983
w This article is part of the ChemComm ‘Advances in catalytic C–C
bond formation via late transition metals’ web themed issue.
z Electronic supplementary information (ESI) available: Experimental
procedures and compound characterization data. See DOI: 10.1039/
c1cc14098a
dppe
dppe
a
Reaction conditions: 1a (0.30 mmol), (triisopropylsilyl)acetylene
(2m) (0.60 mmol), cobalt catalyst (5 mol%), ligand (5 mol%), Zn
b
(50 mol%), solvent (0.5 mL) at 80 1C for 10 h. Yield of 3am
determined by H NMR. Performed without Zn. For 20 h. binap:
2,20-bis(diphenylphosphino)-1,10-binaphthyl.
1
c
d
c
10142 Chem. Commun., 2011, 47, 10142–10144
This journal is The Royal Society of Chemistry 2011

Table 2 Cobalt-catalyzed conjugate alkynylation of enones 1a
Entry R1
R2 R3
SiR3
Yieldb (%)
1
2
3
4
5
6
Ph
H
H
H
H
Me (1a)
Si(i-Pr)3 (2m)
Si(i-Pr)3 (2m)
Si(i-Pr)3 (2m)
Si(i-Pr)3 (2m)
Si(i-Pr)3 (2m)
Si(i-Pr)3 (2m)
97 (3am)
92 (3bm)
74 (3cm)
93 (3dm)
80 (3em)
88 (3fm)
65 (3gm)
92 (3hm)
87 (3im)
67 (3jm)
73 (3km)
77 (3lm)
4-MeOC6H4
4-ClC6H4
2-furyl
(E)-PhCHQCH H Me (1e)
Ph
Ph
Me (1b)
Me (1c)
Me (1d)
Scheme 1 Asymmetric addition of alkyne 2m to enone 1a.
of the rhodium catalysis.10,23 The present cobalt-catalyzed
conjugate alkynylation can introduce bulky silylacetylenes
2m–2p (entries 1, 13–15), but the addition of phenylacetylene
or 1-octyne to 1a did not take place.24
H
H
H
H
H
Et (1f)
i-Pr (1g) Si(i-Pr)3 (2m)
Me (1h)
Me (1i)
C5H11 (1j) Si(i-Pr)3 (2m)
7c
8d,e
9d,e
Me
PhCH2CH2
Si(i-Pr)3 (2m)
Si(i-Pr)3 (2m)
10d,e Me
The asymmetric variant of the present alkynylation is
promising for the synthesis of chiral internal alkynes because
the catalytic system can be applied to the addition to
b-substituted enones, which can create stereogenic center at
the b-position by the alkynylation. The preliminary results of
the asymmetric alkynylation are shown in Scheme 1 and
Table 3. The chiral bisphosphine ligand (S,S)-chiraphos25
was attempted as a first choice, because dppe was a good
ligand for the cobalt-catalyzed alkynylation. Unfortunately,
however, the enantioselectivity of the asymmetric alkynylation
of enone 1a catalyzed by the cobalt/(S,S)-chiraphos catalyst
was very low giving 3am of 1% ee. The use of (S,S)-bdpp,26
which was successfully used in the cobalt-catalyzed asymmetric
arylation of aldehydes by Cheng and co-workers,27 displayed
high enantioselectivity (87% ee), where a higher catalyst
loading (10 mol%) was required to give 3am in high yield
(93%).28 As summarized in Table 3, the asymmetric addition
of alkyne 2m to enones 1a–1d and 1f gave the corresponding
b-alkynyl ketones in good yields, with enantioselectivities
ranging from 79 to 91% ee (Table 3, entries 1–5).
11e
12
Ph
Et
Ph
Ph
Ph
Me H (1k)
Si(i-Pr)3 (2m)
Si(i-Pr)3 (2m)
SiPh2(t-Bu) (2n) 95 (3an)
SiMe2(t-Bu) (2o) 70 (3ao)
H
H
H
H
H (1l)
13
Me (1a)
Me (1a)
Me (1a)
14f
15f
SiEt3 (2p)
40 (3ap)
a
Reaction conditions:
1
(0.30 mmol), alkyne
2
(0.60 mmol),
Co(OAc)2ꢀ4H2O (5 mol%), dppe (5 mol%), Zn (50 mol%), DMSO
b
c
(0.50 mL) at 80 1C for 20 h. Isolated yield of 3. Performed with 2m
d
e
(3 equiv.) at 60 1C for 60 h. Alkyne 2m (4 equiv.). For 40 h.
Alkyne 2 (5.0 equiv.).
f
and acetonitrile, took place to give 3am in 24% and 8% yield,
respectively (entries 2 and 3), whereas the addition product
was not formed at all in toluene or 1,4-dioxane (entries 4 and 5).
The use of anhydrous Co(OAc)2 gave 3am in 75% yield (entry
6), while cobalt(II) halides, which are often used as catalyst
precursors combined with zinc in the cobalt-catalyzed reac-
tions,14 were lower in their catalytic activity than Co(OAc)2
(entries 7–9). Of common bisphosphine ligands other than
dppe such as dppm, dppp, dppb, and binap (entries 10–13),
only dppp displayed a catalytic activity to give 3am in 63%
yield (entry 11). The alkynylation in the absence of the cobalt
catalyst (entry 14), dppe (entry 15), or zinc (entry 16) did not
take place at all.21,22 The highest yield (97%) was obtained in
the reaction using Co(OAc)2ꢀ4H2O (5 mol%), dppe (5 mol%),
and zinc (50 mol%) for a prolonged reaction time (20 h)
(entry 17).
In summary, we have developed a cobalt-catalyzed addition
of silylacetylenes to a,b-unsaturated ketones giving b-alkynyl-
ketones in high yields. We have also demonstrated that the
Table 3 Cobalt-catalyzed asymmetric conjugate alkynylation of
enones 1a
Table 2 summarizes the results obtained for the reaction of
several enones 1 with alkynes 2. The reaction of 1-propenyl
ketones 1a–1e, substituted with aryl groups or a styryl group
on the carbonyl, proceeded well to give the corresponding
b-alkynylketones 3am–3em in high yields (entries 1–5). The
addition to linear enones bearing ethyl (1f) and isopropyl (1g)
at the b position gave the corresponding addition products 3fm
and 3gm in 88% and 65% yield, respectively (entries 6 and 7).
Alkyl alkenyl ketones 1h–1j are also good substrates to give
the corresponding addition products 3hm–3jm in 67–92%
yields, although their reactivities were lower than those of
aryl ketones (entries 8–10). It should be noted that the reaction
of a-substituted enone 1k gave the addition product 3km
in 73% yield (entry 11), whereas the formation of only 2%
of 3km was observed under the standard reaction conditions
Entry
R
R0
Time/h
Yieldb (%)
eec (%)
1
2
3
4
5
Ph
Me (1a)
Me (1b)
Me (1c)
Me (1d)
Et (1f)
20
40
40
20
40
93 (3am)
89 (3bm)
75 (3cm)
53 (3dm)
82 (3fm)
87
79
90
81
91
4-MeOC6H4
4-ClC6H4
2-Furyl
Ph
a
Reaction conditions: 1 (0.30 mmol), 2m (0.60 mmol), Co(OAc)2ꢀ4H2O
(10 mol%), (S,S)-bdpp (10 mol%), Zn (50 mol%), DMSO (0.50 mL) at
b
80 1C. Isolated yield. Determined by chiral HPLC analysis.
c
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 10142–10144 10143

asymmetric variant of the present catalysis is achieved by
use of a chiral bisphosphine ligand. Studies on development
of more efficient and stereoselective systems of the cobalt-
catalyzed alkynylation are underway.
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20 As a side reaction, the formation of the alkyne dimer (E)-1,4-
bis(triisopropylsilyl)-1-buten-3-yne was observed.
21 The formation of a cobalt(I) species by reduction of a cobalt(II)
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cobalt(II) halides as catalyst precursors with zinc, see ref. 14 and 16.
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28 The absolute configuration of 3am produced by use of (S,S)-bdpp
was determined to be (R)-(+) by comparison of its specific
rotation with the value reported previously (ref. 10).
c
10144 Chem. Commun., 2011, 47, 10142–10144
This journal is The Royal Society of Chemistry 2011