Cobalt-catalyzed asymmetric 1,6-addition of (triisopropylsilyl)-acetylene to α,β,γ,δ-unsaturated carbonyl compounds

Article abstract of DOI:10.1021/ja309756k

Asymmetric addition of (triisopropylsilyl)acetylene to α,β, γ,δ-unsaturated carbonyl compounds took place in the presence of a cobalt/Duphos catalyst to give the 1,6-addition products in high yields with high regio- and enantioselectivity.

Full text of DOI:10.1021/ja309756k

Communication
pubs.acs.org/JACS
Cobalt-Catalyzed Asymmetric 1,6-Addition of (Triisopropylsilyl)-
acetylene to α,β,γ,δ-Unsaturated Carbonyl Compounds
Takahiro Sawano,† Akram Ashouri,† Takahiro Nishimura,*,† and Tamio Hayashi*,‡
†Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan
‡Institute of Materials Research and Engineering, A*STAR, 3 Research Link, Singapore 117602
S
* Supporting Information
alkynes to 1-aryl-1,3-butadienes was reported by Suginome,
ABSTRACT: Asymmetric addition of (triisopropylsilyl)-
acetylene to α,β,γ,δ-unsaturated carbonyl compounds took
place in the presence of a cobalt/Duphos catalyst to give
the 1,6-addition products in high yields with high regio-
and enantioselectivity.
where hydroalkynylation proceeds at the terminal alkene to
give 1-aryl-3-alkynyl-1-butene with high enantioselectivity
(Scheme 1b).11 Here we report the enantioselective 1,6-
addition of a terminal alkyne to linear α,β,γ,δ-unsaturated
carbonyl compounds with very high regioselectivity, which is
realized by use of a cobalt/chiral bisphosphine catalyst (Scheme
1c).
Recently, we reported that cobalt complexes can catalyze the
1,4-addition of silylacetylenes to conjugated enones, where
enoates and enamides were inert under the same reaction
conditions.5,12 In the course of our ongoing investigation into
cobalt-catalyzed alkynylation, we found that the addition of a
silylacetylene to conjugated dienoates proceeds with very high
1,6-selectivity in the presence of a cobalt catalyst (Table 1).
Thus, the reaction of ethyl (2E,4E)-2,4-octadienoate (1a) with
(triisopropylsilyl)acetylene (2) (2 equiv) in the presence of
Co(OAc)2·4H2O (5 mol %), dppe (5 mol %), and zinc powder
(50 mol %) in dimethyl sulfoxide (DMSO) at 80 °C for 20 h
gave δ-alkynylated α,β-unsaturated ester 3a in 83% yield (entry
1). This result prompted us to examine chiral bisphosphine
ligands to achieve the asymmetric variant of this reaction. The
reactions by use of chiral bisphosphine ligands, such as (S,S)-
chiraphos, (S,S)-bdpp, (R,R)-dipamp, and (R,R)-QuinoxP*,
proceeded to give the addition product 3a in moderate to good
yields, but they were ineffective in achieving high enantiose-
lectivity (entries 2−5). On the other hand, the Duphos ligands
L1 ((S,S)-Me-Duphos) and L2 ((S,S)-Et-Duphos) displayed
high enantioselectivity to give 3a with 88% and 96% ee,
respectively (entries 6 and 7). The yield was slightly improved
in a solvent system of DMSO/t-amyl alcohol (2:1) giving 3a in
86% yield (entry 8). The yield and enantioselectivity of 3a were
kept high (88% yield, 97% ee) in the reaction with a reduced
amount of zinc powder (10 mol %) (entry 9). The absolute
configuration of 3a obtained with (S,S)-Et-Duphos (L2) was
determined to be S by analogy with (S)-3c.13
ransition metal-catalyzed asymmetric 1,4-addition of
Tterminal alkynes to β-substituted α,β-unsaturated carbonyl
compounds and related compounds is one of the most efficient
methods to construct a stereocenter at the propargylic
position.1 An ideal process is the reaction of terminal alkynes
in the presence of a truly catalytic amount of a catalyst without
using a stoichiometric amount of pre-prepared alkynylmetal
reagents in view of the atom efficiency. Since the first report of
such an alkynylation by Carreira and co-workers on copper-
catalyzed reactions of terminal alkynes with Meldrum’s acid
derivatives,2 several successful examples have been reported by
use of Cu,3 Rh,4 Co,5 and Pd6 catalysts.7 On the contrary, to
the best of our knowledge, the asymmetric addition of terminal
alkynes to extended conjugate systems such as α,β,γ,δ-
unsaturated carbonyl compounds has not been achieved to
date probably due to the difficulty of controlling the
regioselectivity as well as the enantioselectivity.8,9 Mitsudo
and Watanabe reported ruthenium-catalyzed addition of
terminal alkynes to 1,3-dienes, which includes the examples
of formal 1,6-addition to dienoates (Scheme 1a).10 On the
other hand, nickel-catalyzed asymmetric addition of terminal
Scheme 1. Catalytic Addition of Terminal Alkynes
The results obtained for the cobalt-catalyzed 1,6-addition of
(triisopropylsilyl)acetylene to dienoates and dienamides using
L2 or L1 are summarized in Table 2.14 The reaction of
i
dienoates 1a−1e bearing substituents (nPr, Et, Me, Pr,
CH2OCH2Ph) at the δ position gave the corresponding
addition products 3a−3e in good yields with high enantiose-
lectivity (95−97% ee, entries 1−5). The addition to tert-butyl
(1f) and phenyl (1g) esters proceeded well to give 3f and 3g
Received: October 2, 2012
Published: November 6, 2012
© 2012 American Chemical Society
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Journal of the American Chemical Society
Communication
α,β-unsaturated amides 3h−3j with high enantioselectivity
(88−99% ee, entries 8−10). It should be noted that the 1,6-
addition selectivity was very high, none of the 1,4-addition
products being observed for any of the α,β,γ,δ-unsaturated
carbonyl compound 1.
Table 1. Cobalt-Catalyzed Asymmetric Alkynylation of
α,β,γ,δ-Unsaturated Ester 1a
a
The reaction of 1,3-diene 4 with (triisopropylsilyl)acetylene
(2) in the presence of the Co/L1 (10 mol %) and Zn (20 mol
%) also proceeded with very high regioselectivity to give δ-
alkynylated α,β-unsaturated arene 5 in 68% yield with 88% ee
(eq 1).
b
c
entry
ligand
yield (%)
ee (%)
It is likely that the active catalytic species in the present
reaction is a monovalent cobalt in situ generated by reduction
of cobalt(II) acetate with zinc. Thus, no reaction was observed
in the reaction of 1a with 2 without zinc in a short reaction
time of 0.5 h, while the addition proceeded in the presence of
zinc to give 3a in 59% yield (eq 2). It was also found that a
1
2
3
4
5
6
7
dppe
83
90
−
(S,S)-chiraphos
26
39
19
75
88
96
96
97
d
(S,S)-bdpp
44
d
(R,R)-dipamp
80
d
(R,R)-QuinoxP*
63
(S,S)-Me-Duphos (L1)
(S,S)-Et-Duphos (L2)
(S,S)-Et-Duphos (L2)
(S,S)-Et-Duphos (L2)
92
81
86
88
e
8
e,f
9
a
Reaction conditions: 1a (0.20 mmol), 2 (0.40 mmol), Co-
(OAc)2·4H2O (5 mol %), ligand (5 mol %), Zn (50 mol %),
b
c
DMSO (0.3 mL) at 80 °C for 20 h. Isolated yield. Determined by
chiral HPLC analysis. Including other isomers (5−6%). In DMSO
(0.2 mL) and t-amyl alcohol (0.1 mL). Zn (10 mol %) was used.
d
e
f
Table 2. Asymmetric Alkynylation of α,β,γ,δ-Unsaturated
a
Carbonyl Compounds
monovalent cobalt complex CoCl(PPh3)3 can be applied as a
catalyst precursor without use of zinc and the reaction in the
presence of L2 and KOAc for 20 h gave the addition product
3a in 88% yield with 97% ee, where an apparent induction
period was not observed: the reaction for 0.5 h gave 56% yield
of 3a (eq 3).15
yield
b
ee
c
entry
ligand
X
R
(%)
(%)
1
2
3
4
5
L2
L2
L2
L1
L2
L2
L2
L1
L1
L1
OEt
nPr (1a)
Et (1b)
Me (1c)
iPr (1d)
88 (3a)
98 (3b)
81 (3c)
83 (3d)
83 (3e)
93 (3f)
97
96
96
97
95
98
95
95
88
99
A geometrical structure of the starting dienoate was found to
affect both the absolute configuration of the product and
reactivity of the dienoate. Thus, the addition of 2 to (2E,4Z)-6
gave (R)-3a in 91% yield with 97% ee (eq 4), which is opposite
in the absolute configuration to that obtained for (2E,4E)-1a
(Table 2, entry 1). This result indicates that a mode of the
enantioface selection on a γ,δ-unsaturated double bond is the
same in both reactions of (2E,4E)-1a and (2E,4Z)-6. The
reaction of (2Z,4E)-7 gave (S)-(E)-3a in 49% yield with 83%
ee, which has also the same absolute configuration as that
obtained for (2E,4E)-1a (eq 5). The geometrical isomer (S)-
(Z)-8 was also formed in 27% yield with 27% ee. The
formation of (S)-(E)-3a implies that the cis−trans isomerization
of a π-allylcobalt intermediate takes place to give the stable
trans isomer during the catalytic cycle (vide infra). On the other
hand, the addition to (2Z,4Z)-9 was very slow and the reaction
gave only 4% yield of (R)-3a with 23% ee (eq 6). This low
reactivity of dienoate (2Z,4Z)-9, which is difficult to adopt a
cisoid conformation, may imply that η4-coordination of a cisoid
diene moiety to an alkynylcobalt species is involved in the
catalytic cycle.
OEt
OEt
OEt
OEt
CH2OCH2Ph (1e)
nPr (1f)
d
6
OtBu
OPh
NPh2
NPh2
NPh2
e
7
8
9
nPr (1g)
nPr (1h)
99 (3g)
83 (3h)
91 (3i)
65 (3j)
Me (1i)
iPr (1j)
f
10
a
Reaction conditions: 1 (0.20 mmol), 2 (0.40 mmol), Co-
(OAc)2·4H2O (5 mol %), ligand (5 mol %), Zn (10 mol %),
b
DMSO (0.2 mL), t-amyl alcohol (0.1 mL) at 80 °C for 20 h. Isolated
c
d
yield of 3. Determined by chiral HPLC analysis. Performed with
e
alkyne (0.60 mmol) for 40 h. Including 2% of an isomer.
Co(OAc)2·4H2O (10 mol %), L1 (10 mol %), Zn (20 mol %) for
f
40 h.
with 98% and 95% ee, respectively (entries 6 and 7). The
present cobalt-catalyzed reaction can also be applied to
dienamides 1h−1j to give the corresponding δ-alkynylated
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Communication
α,β,γ,δ-unsaturated carbonyl compounds, which is realized by
use of a cobalt/Duphos complex, giving δ-alkynylated α,β-
unsaturated carbonyl compounds in high yields with very high
regioselectivity and high enantioselectivity.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and compound characterization data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
tnishi@kuchem.kyoto-u.ac.jp; tamioh@imre.a-star.edu.sg
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work has been supported by a Grant-in-Aid for Scientific
Research from the MEXT, Japan. T.S. thanks the JSPS for a
Research Fellowship for Young Scientists.
A deuterium-labeling experiment gave us information on the
protonation step. Treatment of 1a with deuterated alkyne 2-d
in place of 2 gave the addition product 3a−d, which is
deuterated at γ-position selectively (eq 7).16
REFERENCES
■
(1) For reviews, see: (a) Trost, B. M.; Weiss, A. H. Adv. Synth. Catal.
2009, 351, 963. (b) Fujimori, S.; Knopfel, T. F.; Zarotti, P.; Ichikawa,
T.; Boyall, D.; Carreira, E. M. Bull. Chem. Soc. Jpn. 2007, 80, 1635.
̈
(2) Knopfel, T. F.; Zarotti, P.; Ichikawa, T.; Carreira, E. M. J. Am.
̈
Chem. Soc. 2005, 127, 9682.
(3) (a) Yazaki, R.; Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc. 2010,
132, 10275. (b) Yazaki, R.; Kumagai, N.; Shibasaki, M. Org. Lett. 2011,
13, 952. (c) Yazaki, R.; Kumagai, N.; Shibasaki, M. Chem. Asian. J.
2011, 6, 1778.
(4) (a) Nishimura, T.; Guo, X.-X.; Uchiyama, N.; Katoh, T.; Hayashi,
T. J. Am. Chem. Soc. 2008, 130, 1576. (b) Nishimura, T.; Sawano, T.;
Hayashi, T. Angew. Chem., Int. Ed. 2009, 48, 8057. (c) Nishimura, T.;
Sawano, T.; Tokuji, S.; Hayashi, T. Chem. Commun. 2010, 46, 6837.
(d) Fillion, E.; Zorzitto, A. K. J. Am. Chem. Soc. 2009, 131, 14608.
(5) Nishimura, T.; Sawano, T.; Ou, K.; Hayashi, T. Chem. Commun.
2011, 47, 10142.
On the basis of the results obtained in eqs 2−7, a catalytic
cycle of the present reaction is proposed as illustrated in
Scheme 2. The catalytic reaction is initiated by the reduction of
Scheme 2. Proposed Catalytic Cycle for the Cobalt-
Catalyzed 1,6-Addition of 2 to 1a
(6) Villarino, L.; Garcia-Fandino, R.; Lopez, F.; Mascarenas, J. L. Org.
́
̃
̃
Lett. 2012, 14, 2996.
(7) For examples of asymmetric 1,4-addition of alkynylmetal
reagents, see: (a) Wu, T. R.; Chong, J. M. J. Am. Chem. Soc. 2005,
127, 3244. (b) Larionov, O. V.; Corey, E. J. Org. Lett. 2010, 12, 300.
(c) Cui, S.; Walker, S. D.; Woo, J. C. S.; Borths, C. J.; Mukherjee, H.;
Chen, M. J.; Faul, M. M. J. Am. Chem. Soc. 2010, 132, 436.
(8) For examples of transition metal-catalyzed asymmetric 1,6-
addition of arylmetal reagents to α,β,γ,δ-unsaturated carbonyl
compounds, see: (a) Hayashi, T.; Yamamoto, S.; Tokunaga, N.
Angew. Chem., Int. Ed. 2005, 44, 4224. (b) Nishimura, T.; Yasuhara, Y.;
Sawano, T.; Hayashi, T. J. Am. Chem. Soc. 2010, 132, 7872.
(c) Nishimura, T.; Noishiki, A.; Hayashi, T. Chem. Commun. 2012,
48, 973. For an example of diastereoselective 1,6-addition, see:
(d) Okada, S.; Arayama, K.; Murayama, R.; Ishizuka, T.; Hara, K.;
Hirone, N.; Hata, T.; Urabe, H. Angew. Chem., Int. Ed. 2008, 47, 6860.
(9) For examples of transition-metal catalyzed enantioselective 1,6-
addition of alkylmetal reagents to α,β,γ,δ-unsaturated carbonyl
compounds and related compounds, see: (a) Fillion, E.; Wilsily, A.;
Liao, E-T. Tetrahedron: Asymmetry 2006, 17, 2957. (b) den Hartog, T.;
Harutyunyan, S. R.; Font, D.; Minnaard, A. J.; Feringa, B. L. Angew.
cobalt(II) to cobalt(I) by zinc powder giving cobalt(I) acetate
A,17 which undergoes the reaction with a terminal alkyne to
form alkynylcobalt(I)18 B and acetic acid. Coordination of
dienoate 1a to alkynylcobalt B with a cisoid diene moiety
results in the formation of a (η4-diene)−cobalt complex C.
Insertion of the diene into the alkynyl cobalt bond then gives π-
allylcobalt D.19 Protonation of D at γ-position with the terminal
alkyne 2 leads to the alkynylation product 3a and regenerates
the alkynylcobalt intermediate B.
Chem., Int. Ed. 2008, 47, 398. (c) Hen
Angew. Chem., Int. Ed. 2008, 47, 9122. (d) Wencel-Delord, J.; Alexakis,
A.; Crevisy, C.; Mauduit, M. Org. Lett. 2010, 12, 4335. (e) den Hartog,
T.; van Dijken, D. J.; Minnaard, A. J.; Feringa, B. L. Tetrahedron:
́
on, H.; Mauduit, M.; Alexakis, A.
́
In summary, we have developed a cobalt-catalyzed
asymmetric 1,6-addition of (triisopropylsilyl)acetylene to
Asymmetry 2010, 21, 1574. (f) Tissot, M.; Muller, D.; Belot, S.;
Alexakis, A. Org. Lett. 2010, 12, 2770. (g) Magrez, M.; Wencel-Delord,
̈
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Communication
J.; Alexakis, A.; Crev
(h) Tissot, M.; Poggiali, D.; Hen
́
isy, C.; Mauduit, M. Org. Lett. 2012, 14, 3576.
on, H.; Muller, D.; Guenee, L.;
́
́
́
̈
Mauduit, M.; Alexakis, A. Chem.Eur. J. 2012, 18, 8731.
(10) (a) Mitsudo, T.; Nakagawa, Y.; Watanabe, K.; Hori, Y.; Misawa,
H.; Watanabe, H.; Watanabe, Y. J. Org. Chem. 1985, 50, 565.
(b) Mitsudo, T.; Hori, Y.; Watanabe, Y. Bull. Chem. Soc. Jpn. 1986, 59,
3201.
(11) Shirakura, M.; Suginome, M. Angew. Chem., Int. Ed. 2010, 49,
3827.
(12) For an example of cobalt-catalyzed asymmetric addition of
silylacetylenes to oxa- and azabenzonorbornadienes, see: (a) Sawano,
T.; Ou, K.; Nishimura, T.; Hayashi, T. Chem. Commun. 2012, 48,
6106. For an example of cobalt-catalyzed addition of terminal alkynes
to iminium salts, see: (b) Chen, W.-W.; Bi, H.-P.; Li, C.-J. Synlett 2010,
475.
(13) See the Supporting Information for details.
(14) In the reaction of phenylacetylene or 1-octyne, the addition
products were not formed due to the alkyne oligomerization.
(15) The reaction in the absence of KOAc or L2 did not proceed at
all.
(16) The reaction was carried out with anhydrous Co(OAc)2 in the
absence of t-amyl alcohol to avoid the incorporation of protons. The
use of anhydrous Co(OAc)2 for the reaction of 1a with 2 gave
essentially the same yield and ee as that with Co(OAc)2·4H2O (3a in
90% yield with 97% ee).
(17) The formation of a cobalt(I) species by reduction of a cobalt(II)
complex with zinc is proposed in the cobalt-catalyzed reactions using
cobalt(II) halides as catalyst precursors with zinc, see: (a) Jeganmohan,
M.; Cheng, C.-H. Chem.Eur. J. 2008, 14, 10876. (b) Gosmini, C.;
́
Begouin, J.-M.; Moncomble, A. Chem. Commun. 2008, 3221.
(18) Albertin, G.; Antoniutti, S.; Bacchi, A.; Bordignon, E.; Pelizzi, G.
Organometallics 1995, 14, 4126.
(19) For examples of π-allylcobalt(I) complexes, see: (a) Jonas, K.
Angew. Chem., Int. Ed. Engl. 1985, 24, 295. (b) Jonas, K. J. Organomet.
Chem. 1990, 400, 165. (c) Bleeke, J. R.; Lutes, B. L.; Lipschutz, M.;
Sakellariou-Thompson, D.; Lee, J. S.; Rath, N. P. Organometallics 2010,
29, 5057.
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