Facile synthesis of trifluoromethyl-substituted enynes: Remarkable reactivity and stereoselectivity of tributyl(3,3,3-trifluoropropynyl)stannane in carbostannylation of alkynes

Article abstract of DOI:10.1246/cl.2005.1700

Carbostannylation of alkynes with tributyl(3,3,3-trifluoropropynyl)stannane is found to proceed at room temperature in a syn-manner, giving rise to the corresponding CF₃-substituted enynes as a single stereoisomer in good yields. Both terminal

Full text of DOI:10.1246/cl.2005.1700

1700
Chemistry Letters Vol.34, No.12 (2005)
Facile Synthesis of Trifluoromethyl-substituted Enynes:
Remarkable Reactivity and Stereoselectivity
of Tributyl(3,3,3-trifluoropropynyl)stannane in Carbostannylation of Alkynes
Masaki Shimizu,ꢀ Guofang Jiang, Masahito Murai, Youhei Takeda, Yoshiaki Nakao, Tamejiro Hiyama, and Eiji Shirakaway
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510
yDepartment of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 666-8502
(Received September 29, 2005; CL-051245)
Carbostannylation of alkynes with tributyl(3,3,3-trifluoro-
propynyl)stannane is found to proceed at room temperature in
a syn-manner, giving rise to the corresponding CF3-substituted
enynes as a single stereoisomer in good yields. Both terminal
and, CF3- or RO2C-substituted internal alkynes are applicable
to the addition reaction. Synthetic applications of the adduct
are also demonstrated.
stereochemically pure form in good yields (Entries 1–4),7 re-
spectively. Z-Stereochemistry of 3b determined by NOE data
of the vinyl hydrogen and protonolysis of the C–Sn bond8 indi-
cated that the reaction proceeded via syn-addition and the Bu3Sn
group that was bulkier than a CF3CC group added to the less hin-
dered sp carbon. Methyl propiolate (2e) and N,N-dimethyl pro-
piolamide (2f) also reacted with 1 to afford stereochemically
pure 3e and 3f, whose stereochemistries were deduced by proto-
nolysis, with the opposite regioselectivity (Entries 5 and 6).8
Since these stereochemical outcome is consistent with typical
carbostannylation, the present reaction is considered to proceed
via the well-accepted reaction mechanism,4 which involves ox-
idative addition of 1 to the Pd(0) complex and successive inser-
tion of an alkyne to the Pd–C bond followed by reductive elim-
ination, resulting in production of 3 and regeneration of the
Pd(0) complex.
Furthermore, the reaction of internal alkynes, which was
usually difficult to achieve in the typical alkynylstannylation
chemistry,4 was scrutinized. The results are shown in entries
7–17 in Table 1. To our delight, the addition to CF3-substituted
aryl acetylenes 2g–2n occurred also at room temperature under
the same conditions to give 3g–3n as a sole product (Entries 7–
14). Various functional groups were tolerant under the condi-
tions. Phenyl- and methyl-substituted propiolate derivatives 2o
and 2p as well as dimethyl acetylenic dicarboxylate (2q) reacted
Since carbon–carbon triple bonds can undergo various kinds
of transformations, 3,3,3-trifluoropropynyl-containing com-
pounds1 serve as versatile building blocks for the preparation
of trifluoromethylated molecules, to which much attention has
been paid in the fields of pharmaceuticals, agrochemicals, and
organic materials.2 Hence, generation and reactions of 3,3,3-tri-
fluoropropynyllithium, -magnesium, -silyl, and -zinc reagents
have been studied well.3 Meanwhile, transition metal-catalyzed
carbostannylation of alkynes with alkynylstannanes has emerged
as a powerful synthetic tool because an alkynyl and stannyl
groups are simultaneously incorporated into alkynes in a syn-
manner to afford stereodefined alkenyltins, which can further
be transformed into a variety of alkenes via stereospecific car-
bon–carbon and carbon–heteroatom bond formations with the
aid of the tin functionality.4 Therefore, carbostannylation of al-
kynes with 3,3,3-trifluoropropynylstannanes is highly attractive
for the preparation of diverse trifluoromethylated enynes. We re-
port here palladium-catalyzed carbostannylation of alkynes with
tributyl(3,3,3-trifluoropropynyl)stannane (1),5 which proceeds
smoothly at room temperature to give CF3-substituted enynes
3 as a single stereoisomer in good yields (Eq 1).
Table 1. Carbostannylation of alkynes 2 with 1a
Entry
2
R1
R2
3
Yield/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
H
H
H
C6H5
p-MeO-C6H4
p-C6H5-C6H4
p-CF3-C6H4
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
79
73
82
79
78
58
76
52
67
62
68
57
58
67
87
77
71
CF3
Bu3Sn
CF3
Pd2(dba)3 (1 mol %)
1
t-Bu3P (2 mol %)
H
Bu3Sn
R1
(1)
+
CO2Me
CONMe2
CF3
toluene, rt
R2
R1
R2
H
Ph
3
2
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CO2Et
CO2Et
CO2Me
p-Me-C6H4
p-MeO-C6H4
p-Cl-C6H4
p-Ac-C6H4
p-EtO2C-C6H4
p-O2N-C6H4
p-CF3-C6H4
Ph
In the course of our synthetic study utilizing 1, we attempted
cross-coupling reaction of 1 with iodobenzene to prepare 3,3,3-
trifluoro-1-phenylpropyne. Thus, a toluene solution of 1 and io-
dobenzene in the presence of Pd2(dba)3 (1 mol %) and t-Bu3P
(2 mol %) was stirred at room temperature.6 The isolated product
unexpectedly turned out to be alkenylstannane 3 (R1 = CF3,
R2 = Ph) as a single stereoisomer in 40% yield, which was
considered to form via carbostannylation of the cross-coupled
product with 1. This result prompted us to investigate generality
of the carbostannylation with 1. The results are summarized in
Table 1. Under the same conditions, aryl acetylenes 2a–2d were
carbostannylated with 1 at room temperature to give 3a–3d as a
Me
CO2Me
aReagents and conditions: 1 (0.6 mmol), 2 (0.9 mmol), Pd2-
(dba)3 (6.0 mmol), t-Bu3P (12 mmol), toluene (1.6 mL), and rt.
Copyright ꢀ 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.12 (2005)
1701
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p-Ac-C6H4−I
Pd2(dba)3 (5 mol %)
t-Bu3P (20 mol %)
CF3
p-Ac-C6H4
CsF (1.2 equiv.), toluene
H
Ph
Ph
100 °C
4 (76%)
(E)-EtO2CCH=CHI
CF3
Pd2(dba)3 (5 mol%)
t-Bu3P (20 mol %)
EtO2C
3a
2
CuI (10 mol %)
CsF (1.2 equiv.)
toluene, 70 °C
H
5 (68%)
CF3
I2
I
THF
H
Ph
0 °C
6 (76%)
Scheme 1. Synthetic application of 3a.
in a Michael fashion to afford 3o–3q as a single stereoisomer in
good yields, respectively (Entries 15–17). Since diphenylacety-
lene and 4-octyne did not react with 1 at all, the presence of such
an electron-withdrawing group as CF3 and CO2R appears to be
essential for the realization.
The fact that all the reactions took place at room tempera-
ture definitely shows remarkably higher reactivity of 1 than
those of common alkynyltins which require heating at 50 or
90 ꢁC to effect the carbostannylation reaction.4 Strong elec-
tron-withdrawing effect by a CF3 group may induce acceleration
of the oxidative addition step to undergo the reaction at room
temperature, which lead to perfect stereoselectivity.9
Alkenyltin functionality of 3 can be readily utilized for
further transformation.10 Representative examples with 3a are
demonstrated in Scheme 1. Pd-catalyzed cross-coupling reac-
tion with aryl and alkenyl iodides gave CF3-substituted enyne
4 and dienyne 5, while iodinated enyne 6 was prepared in good
yield by treatment with I2 in THF.
In summary, we have demonstrated that carbostannylation
of alkynes with tributyl(3,3,3-trifluoropropynyl)stannane consti-
tutes facile and stereoselective synthesis of 1-tributylstannyl-
5,5,5-trifluoropent-1-en-3-ynes. Both terminal and internal al-
kynes are applicable to the reaction. Synthetic application of
the CF3-substituted enynes is in progress in our laboratory.
3
4
This work was supported by Grant-in-Aid for Creative
Scientific Research, No. 16GS0209, from Ministry of Education,
Culture, Sports, Science and Technology, Japan.
5
6
T. Hanamoto, Y. Hakoshima, and M. Egashira, Tetrahedron
Lett., 45, 7573 (2004).
References and Notes
No carbostannylated product formed when N-[2-(diphenylphos-
phino)benzylidene]cyclohexylamine, which was essential for
conventional carbostannylation of alkynes, or PPh3 was em-
ployed as a phosphine ligand with Pd2(dba)3 complex.
Reaction of alkyl acetylenes with 1 failed to give the carbostan-
nylation products under the conditions.
1
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7
8
9
See Supporting Information.
In marked contrast, no reaction took place with tributylpro-
pynylstannane under the same conditions, suggesting that the
fluorine atoms played a crucial role in the reaction of 1.
10 a) M. Pereyre, J.-P. Quintard, and A. Rahm, ‘‘Tin in Organic
Synthesis,’’ Butterworth, London (1987). b) A. G. Davies, ‘‘Or-
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Published on the web (Advance View) November 19, 2005; DOI 10.1246/cl.2005.1700