Rhodium-catalyzed oxidative alkynylation of acrylate esters with propargylic alcohols

Article abstract of DOI:10.1016/j.tetlet.2010.11.120

Oxidative alkynylation of acrylate esters with propargylic alcohols giving conjugated enyne esters was realized by use of a diene-rhodium catalyst. Propargylic alcohols were found to be useful alkynylating reagents in the present reaction to produce alkynylrhodium species via carbon-carbon bond cleavage. An excess of the acrylate ester worked as a hydride acceptor to reproduce the active rhodium species.

Full text of DOI:10.1016/j.tetlet.2010.11.120

Tetrahedron Letters 52 (2011) 2185–2187
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rhodium-catalyzed oxidative alkynylation of acrylate esters with
propargylic alcohols
⇑
⇑
Takahiro Nishimura , Makoto Nagaosa, Tamio Hayashi
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 28 November 2010
Oxidative alkynylation of acrylate esters with propargylic alcohols giving conjugated enyne esters was
realized by use of a diene–rhodium catalyst. Propargylic alcohols were found to be useful alkynylating
reagents in the present reaction to produce alkynylrhodium species via carbon–carbon bond cleavage.
An excess of the acrylate ester worked as a hydride acceptor to reproduce the active rhodium species.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Rhodium
Alkynylation
Acrylates
Alkynes
Enynes
Conjugated enynes are important building blocks in organic
synthesis1 and recent development of synthesis of conjugated eny-
nes has focused on the new catalytic approaches as well as classical
cross-coupling reactions of terminal alkynes with alkenyl halides
or pseudo-halides.2 Palladium-catalyzed addition of terminal al-
kynes to substituted propiolates has been reported by Trost,3
which is one of the most useful methods to prepare conjugated
enyne–carbonyl compounds (Eq. 1). Oxidative alkynylation of al-
kenes is another approach to the synthesis of conjugated enynes.
Palladium-catalyzed oxidative alkynylation of alkenes with prop-
argylic alcohols (Uemura)4 or terminal alkynes (Jung)5 under oxy-
gen atmosphere has been reported to date (Eq. 2). Here we report
rhodium-catalyzed oxidative alkynylation of acrylate esters with
propargylic alcohols giving conjugated enyne esters, where an ex-
cess of the acrylate works as a hydride acceptor to reproduce the
active rhodium species.
Propargylic alcohols have been used as synthetic equivalents to
terminal alkynes in palladium4,6 and rhodium-catalyzed7 alkynyla-
tions, where an alkynyl-metal species is formed by b-alkynyl elim-
ination from the metal alkoxide (Eq. 3).8 The use of propargylic
alcohols as alkynylating reagents displays higher selectivity than
the use of terminal alkynes in the metal-catalyzed alkynyla-
tions7c–e because propargylic alcohols are less reactive toward
the dimerization or the origomerization, which often causes seri-
ous problems in the use of terminal alkynes.
[M]
OH
R'
O
[M]–X
– HX
R
[M]
R'
R'
ð3Þ
R'
R
R
O
R'
R'
During our investigation of conjugate alkynylation of
a,b-unsat-
urated carbonyl compounds,9 we found that the reaction of a prop-
argylic alcohol with an acrylate ester gives a conjugated enyne in
the presence of a rhodium catalyst. Thus, propargylic alcohol 1a
was treated with 3 equiv of tert-butyl acrylate (2m) in the presence
of [Rh(OH)(cod)]2 (2 mol % of Rh) (cod = 1,5-cyclooctadiene) at
80 °C for 24 h. 1H NMR analysis of the crude reaction mixture
showed the formation of conjugated enyne 3am (95%, E/Z = 96/
4), addition product 4am (5%), and tert-butyl propanoate (76%)
(Table 1, entry 1). From the mixture (E)-3am was isolated in 87%
yield. The formation of tert-butyl propanoate indicates that tert-
butyl acrylate works as a hydride acceptor (vide infra). The rho-
dium complexes [RhCl(cod)]2 and [Rh(cod)2]PF6 also displayed
high catalytic activity in the presence of Na2CO3 (50 mol %) gave
3am in 91% and 86% yield, respectively (entries 2 and 3). On the
other hand, RhCl(PPh3)3 had little catalytic activity in the present
O
R2
O
Pd catalyst
toluene
R1
H
+
OR3
R2 ≠ H
OR3
ð1Þ
ð2Þ
R1
R2
OH
R'
R'
Pd catalyst
O2
R
R"
+
R"
or
R
H
R1
⇑
Corresponding authors. Tel.: +81 75 753 3987; fax: +81 75 753 3988 (T.N.); tel.:
+81 75 753 3983; fax: +81 75 753 3988 (T.H.).
E-mail addresses: tnishi@kuchem.kyoto-u.ac.jp (T. Nishimura), thayashi@ku-
chem.kyoto-u.ac.jp (T. Hayashi).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.120

2186
T. Nishimura et al. / Tetrahedron Letters 52 (2011) 2185–2187
Table 1
H
O
Rhodium-catalyzed oxidative alkynylation of tert-butyl acrylatea
[Rh]
[Rh]
A
1/2
O
O
H
1a
OtBu
OtBu
OH
H2O
Rh catalyst
iPr3Si
O
O
(2 mol % Rh)
+
3am
[Rh]
O
OtBu
OtBu
iPr3Si
toluene
iPr3Si
O
80 ºC, 24 h
OH
1a
2m
O
iPr3Si
B
iPr3Si
4am
1a
[Rh]
O
Entry
Catalyst
Base
—
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
—
3amb (%) (E/Z)
4amb (%)
iPr3Si
[Rh]
OtBu
1
2
3
4
5
6
7f
[Rh(OH)(cod)]2
[RhCl(cod)]2
[Rh(cod)2]PF6
RhCl(PPh3)3
[Rh(OH)((R)-binap)]2
[Rh(OH)(cod)]2/dppbe
[Rh(OH)(cod)]2
95 (96/4) [87]c
91 (95/5)
86 (95/5)
2
0
1
5
3
2
0
0
C
F
[Rh] = [Rh(cod)]
d
O
d
O
OtBu
d
OtBu
2m
d
O
2m
d
H–[Rh]
0
OtBu
E
52 (91/9)
10
iPr3Si
[Rh]
a
Reaction conditions: 1a (0.5 mmol), 2m (1.5 mmol), Rh catalyst (2 mol % of Rh),
D
toluene (0.5 mL), 80 °C for 24 h.
O
b
Yields determined by 1H NMR.
c
OtBu
Isolated yield of (E)-3am.
50 mol %.
Rh/dppb = 1.0/1.2.
d
iPr3Si
e
3am
Scheme 1. Proposed catalytic cycle.
f
The reaction of (triisopropylsilyl)acetylene (0.5 mmol) in place of 1a.
Table 2
methylsilyl (1c), and triethylsilyl (1d) can be used as well, the reac-
tion with tert-butyl acrylate (2m) giving the corresponding enynes
3bm–dm (entries 7–9), although propargylic alcohols 1d with a
less bulky triethylsilyl group gave a lower yield of enynes 3dm (en-
try 9). The reaction of propargylic alcohols substituted with bulky
alkyl groups (iPr3SiO)Me2C (1e) and (tBuMe2SiO)iPr2C (1f) also pro-
ceeded to give 3em and 3fm in 53% and 93% yield, respectively
(entries 10 and 11).11
Rhodium-catalyzed oxidative alkynylation of acrylatesa
[Rh(OH)(cod)]2
(2 mol % Rh)
OH
O
O
+
OR'
OR'
toluene
R
80 ºC, 24 h
R
1
2
3
Entry
R
R’
3b (%) (E/Z)
(E)-3c (%)
1
2d
3
4
5
iPr3Si (1a)
iPr3Si (1a)
iPr3Si (1a)
iPr3Si (1a)
iPr3Si (1a)
iPr3Si (1a)
tBuPh2Si (1b)
tBuMe2Si (1c)
Et3Si (1d)
tBu (2m)
tBu (2m)
Me (2n)
Et (2o)
Bu (2p)
Ph (2q)
95 (96/4) (3am)
—e(3am)
87
82
83
86
85
76
70
59
52
52
92
A catalytic cycle proposed for the reaction producing enyne
3am from propargylic alcohol 1a and tert-butyl acrylate (2m) is
shown in Scheme 1. An alkoxorhodium species B generated from
hydroxorhodium A and 1a undergoes b-alkynyl elimination to give
an alkynylrhodium species C releasing acetone. The addition of the
alkynylrhodium to 2m, followed by b-hydrogen elimination gives
enyne 3am and a rhodium hydride E.12 The reaction of the species
89 (93/7) (3an)
91 (96/4) (3ao)
89 (96/4) (3ap)
84 (94/6) (3aq)
77 (95/5) (3bm)
70 (96/4) (3cm)
55 (96/4) (3dm)
53 (99/1) (3em)
93 (99/1) (3fm)
6
7f
tBu (2m)
tBu (2m)
tBu (2m)
tBu (2m)
tBu (2m)
8f,g
9f,g
10f
11
E with 2m gives oxa-p-allylrhodium F, which reacts with the alco-
(iPr3SiO)Me2C (1e)
(tBuMe2SiO)iPr2C (1f)
hol 1a to reproduce the alkoxorhodium B.12b,c
In summary, we developed a rhodium-catalyzed oxidative alk-
ynylation of acrylate esters giving conjugated enyne esters, which
was realized by use of a diene–rhodium catalyst.
a
Reaction conditions: 1 (0.5 mmol), 2 (1.5 mmol), [Rh(OH)(cod)]2 (2 mol % of
Rh), toluene (0.5 mL), 80 °C for 24 h.
b
c
d
e
f
Yields determined by 1H NMR.
Isolated yield of (E)-3.
The reaction of 1a (5 mmol) with 2m (15 mmol) in toluene (5 mL) for 48 h.
Not determined.
Compound 2m (2.5 mmol).
5 mol % of Rh.
Acknowledgments
This work was supported by a Grant-in-Aid for Scientific Re-
search (S) (19105002) from the MEXT, Japan. M.N. thanks the JSPS
for a Research Fellowship for Young Scientists.
g
reaction (entry 4). The rhodium catalysts coordinated with bis-
phosphine ligands, binap and dppb,10 did not catalyze the present
reaction (entries 5 and 6). The reaction of 2m with (triisopropylsi-
lyl)acetylene in place of propargylic alcohol 1a gave 3am in 52%
yield with the formation of 10% of 4am, although the terminal al-
kyne was completely consumed (entry 7).
Table 2 summarizes the results obtained for the reactions of
several acrylate esters 2 with propargylic alcohols 1. The reaction
of 1a in 5 mmol scale successfully proceeded, and (E)-3am was iso-
lated in 82% yield (entry 2). The reaction of 1a with methyl (2n),
ethyl (2o), butyl (2p), and phenyl (2q) acrylate all gave the corre-
sponding enynes 3an–aq in high yields (entries 3–6). Propargylic
alcohols substituted with tert-butyldiphenylsilyl (1b), tert-butyldi-
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.11.120.
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