Gold-catalyzed stereoselective synthesis of Di- or trisubstituted olefins possessing a 1,4-diene framework via intramolecular allylation of alkynes

Article abstract of DOI:10.1055/s-0030-1259038

The cationic gold(I)-catalyzed reaction of 1-alkynyl-2-allylsilylbenzenes with water results in intramolecular allylation of the alkynes via 7-exo-dig cyclization to give 1,4-dienes in good yield with excellent stereoselectivities. Georg Thieme Verlag Stu

Full text of DOI:10.1055/s-0030-1259038

LETTER
2879
Gold-Catalyzed Stereoselective Synthesis of Di- or Trisubstituted Olefins
Possessing a 1,4-Diene Framework via Intramolecular Allylation of Alkynes
G
old-CatalyzedIn
o
tramolecular
s
A
llylation
h
of
A
lkynesikazu Horino,* Yuichi Nakashima, Ken Hashimoto, Shigeyasu Kuroda*
Department of Applied Chemistry, Graduate School of Science and Engineering, University of Toyama,
Gofuku 3190, Toyama, 930-8555, Japan
Fax +81(76)4456819; E-mail: horino@eng.u-toyama.ac.jp; E-mail: kuro@eng.u-toyama.ac.jp
Received 12 July 2010
Ph
SiMe3
R
Abstract: The cationic gold(I)-catalyzed reaction of 1-alkynyl-2-
HfCl4
[Au]+
(1)
(2)
+
+
+
Ph
R
allylsilylbenzenes with water results in intramolecular allylation of
the alkynes via 7-exo-dig cyclization to give 1,4-dienes in good
yield with excellent stereoselectivities.
SiMe3
Key words: catalysis, 1,4-dienes, allylation, allylsilanes, gold
Ph
OPh
Ph
Si
Si
PhOH
Ph
Ph
Ph
Ph
The efficient regio- and stereoselective synthesis of
trisubstituted olefins possessing a 1,4-diene framework,
which constitutes an important structural assembly in
many molecules of biological importance,1 is a particular
challenge in organic synthesis.2 The addition of active al-
lylmetal reagents to nonactivated alkynes is a well-recog-
nized and straightforward method for this purpose.3,4
However, although a number of transition-metal-cata-
lyzed allylmetalations of alkynes have been reported,
some of which allow for the regio- and stereoselective
construction of trisubstituted olefins possessing a 1,4-di-
ene framework, the allyl group is usually introduced in a
position vicinal to the aryl group due to steric or electronic
effects.
R2
R2
Si
R1
R1
[Au]+
Si OH
H2O
(3)
R
R
1
2
Scheme 1
In light of the reported acetylenic sila-Cope rearrange-
ment of alkynylallylsilane, we envisioned that a cationic
gold(I) complex induced 7-exo-dig cyclization of 1-alky-
nyl-2-allylsilylbenzenes 1 would initiate a related allyla-
tion and provide a method for the stereoselective synthesis
of trisubstituted E-olefins 2 possessing a 1,4-diene frame-
work, where the allyl group is installed at the geminal po-
sition to the aryl group (Scheme 1, equation 3). To this
end, we initially examined the intramolecular allylation of
alkynes using 1-(1-hexynyl)-2-allyldimethylsilylbenzene
(1a) in the presence of catalytic amounts of (PPh3)AuNTf2
and two equivalents of water in nitromethane as a solvent
(Table 1, entry 1).9,10 The reaction proceeded smoothly to
give the desired 1,4-diene 2a, which possesses a silanol
functional group, in 20% isolated yield along with a sig-
nificant amount of dimer 3. Although changing the dime-
thylsilyl group of 1a to a more sterically bulky group such
as methyl(phenyl)silyl and diphenylsilyl group caused a
noticeable elongation of reaction time,11 dimerization of
the resulting silanol was eliminated, and the desired prod-
ucts 2b and 2c were isolated in high yields, respectively
(entries 2 and 3).12 It was found that the use of ni-
tromethane, which is known to be a cation stabilizing and
Lewis acid activating solvent, was suitable for the present
reaction (entries 3 and 4).13 Among the several ligands
tested, triphenylphosphine showed the best catalytic ac-
tivity (entries 3–6). The use of AgSbF6 as the silver re-
agent exhibited similar results to AgNTf2 (entry 7),
whereas changing the silver additive from AgNTf2 to
AgBF4 resulted in prolonged reaction time and dimin-
ished yield of 2c (entry 8). The use of other transition-
In contrast, little attention has been paid to the transition-
metal-catalyzed allylsilylation of alkynes due to the rela-
tive stability of allylsilanes.4–6 Thus, Yamamoto and Asao
reported the aluminium- or hafnium-catalyzed trans-allyl-
silylation of nonactivated alkynes (Scheme 1, equation
1).4b–4f These methods allow the use of allylsilanes as the
nucleophile and lead to the corresponding 1,4-diene effi-
ciently in a different manner from the allylmetalation of
alkynes with other active allylmetal reagents, where the
allyl group is introduced at the geminal position to the aryl
group. Furthermore, the recently developed acetylenic
sila-Cope rearrangement7 catalyzed by cationic gold com-
plexes, which have emerged as powerful p-acids that are
capable of promoting a diverse range of unsaturated car-
bon–carbon bonds,8 has been also used to synthesize geo-
metrically pure trisubstituted olefins possessing a 1,4-
diene framework (Scheme 1, equation 2). However, the
former reaction has several limitations as regards the in-
troduction of functional groups, and stereoselectivity can
be problematic with some substrates in the latter case.
SYNLETT 2010, No. 19, pp 2879–2882
x
x
.x
x
.2
0
1
0
Advanced online publication: 10.11.2010
DOI: 10.1055/s-0030-1259038; Art ID: U06410ST
© Georg Thieme Verlag Stuttgart · New York

2880
Y. Horino et al.
LETTER
Table 1 Optimization of Reaction Conditions
Me
Me
R1 R2
Si
R1 R2
Si
Si
LAuCl (5 mol%)
AgX (5 mol%)
O
OH
+
H2O (2 equiv)
MeNO2, r.t.
n-Bu
2
n-Bu
n-Bu
1
2
3
Entry
L
X
1
R1
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
R2
Time
10 min
30 min
1 h
Yield of 2 (%)
2a 20
Yield of 3 (%)
1
Ph3P
Ph3P
Ph3P
Ph3P
t-Bu3P
IPrc
NTf2
NTf2
NTf2
NTf2
NTf2
NTf2
SbF6
BF4
1a
1b
1c
1c
1c
1c
1c
1c
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
69
2
2b 71
3
2c 88
4a
5
10 h
1 h
2c trace
2c 70
6b
7
3 h
2c 63
Ph3P
Ph3P
1 h
2c 81
8
10 h
2c 70
a MeCN was used as a solvent.
b Run at 60 °C.
c IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene.
metal catalysts proved unsuccessful.14 In all cases, the ste-
reochemistry of 2a–c was determined to be E by NOE ex-
periments.
Table 2 Gold-Catalyzed Intramolecular Allylation of Alkynes 1
Ph
Ph
Ph
Ph
Si
Si
OR2
(PPh3)AuCl (5 mol%)
AgNTf2 (5 mol%)
R2OH
+
Next, the substrate scope for this gold(I)-catalyzed in-
tramolecular allylation of alkynes was examined
(Table 2). We are pleased to find that the reaction is gen-
eral for a variety of substituent R1 on the acetylenic moi-
ety of 1, thus providing opportunities for further
elaboration of the 1,4-diene 2. Among them, the gold(I)-
catalyzed allylation of alkynes possessing electron-with-
drawing groups produced the desired 1,4-dienes 2 in bet-
ter yield than when using terminal or alkyl-substituted
alkynes as the electorophile (entries 1–5). It should be not-
ed that homoallyl-substituted 1g, which possesses a 1,5-
enyne skeleton, gave selective formation of the desired
1,4-diene 2g rather than the product of the competing 1,5-
enyne cycloisomerization (entry 4).15 As for the scope of
the aryl containing substrate, both electron-donating and
electron-withdrawing groups are also supported (entries
6–10). Furthermore, bromoalkyne moieties could be in-
stalled in the substituent to produce 2n in moderate yield
(entry 11).
MeNO2, r.t.
(2 equiv)
R1
1
2
R1
Entry
1
R1
R2
H
Time
1 h
Yield of 2 (%)
2d 83
2e 76
1
2
1d
1e
1f
1g
1h
1i
H
Me
All
H
30 min
3 h
3
H
2f 75
4
3-butenyl
CO2Me
H
3 h
2g 75
5
H
3 h
2h 93
2i 70
6
Ph
H
5 h
7
1j
1k
1l
4-MeO2CC6H4
4-BrC6H4
2-BrC6H4
2-MeOC6H4
Br
H
30 min
3 h
2j 95
8a
9
H
2k 69
2l 70
H
3 h
10a
11
1m
1n
H
1 h
2m 84
2n 42
The aryl group on the molecular backbone is not essential
for this reaction. For instance, switching the backbone
from an aromatic skeleton to an aliphatic one does not af-
fect the reaction notably. Indeed, treatment of 1o and 1p
afforded the desired a-alkylidene cyclic ketones 4a and
4b, respectively, as a single isomer after treatment under
Tamao–Fleming oxidation conditions (Scheme 2).16 The
stereochemistry of 4a and 4b was determined to be Z by
NOE experiments.
Me
3 h
a Run at 60 °C.
Synlett 2010, No. 19, 2879–2882 © Thieme Stuttgart · New York

LETTER
Gold-Catalyzed Intramolecular Allylation of Alkynes
2881
Ph
Ph
Ph
Ph
Ph
Me
O
Si
Si
Si
(PPh3)AuCl (5 mol%)
AgNTf2 (5 mol%)
H2O2, KF
KHCO3
OH
[Au]+
LAu
H2O (2 equiv)
MeNO2
r.t., 15 min
n
n
R
R
1o (n = 1)
1p (n = 2)
(Z)-4a (n = 1): 56%
(Z)-4b (n = 2): 62%
2
1
[Au]+ or H+
Ph
Scheme 2
Ph
Ph
Ph
Si
Si
A deuterium labeling study was performed with 1c to con-
firm the reaction mechanism (Scheme 3). Under the con-
ditions shown above, the gold(I)-catalyzed reaction of 1c
with D2O (2 equiv) afforded (E)-2c-d in 83% isolated
yield, which strongly supported the existence of vinylgold
intermediate.17
OH
R
+[Au]
6
R
Ph
Ph
Ph
Si+
Si
[Au]+
Ph
+
H2O
– [Au]+
H2O
2
Ph
Ph
Ph
Ph
Si
Si
(PPh3)AuCl (5 mol%)
AgNTf2 (5 mol%)
[Au]
OH
R
5
[Au]
R
D2O (2 equiv)
MeNO2, r.t.
7
n-Bu
(70%-d)
D
n-Bu
Scheme 5 Proposed catalytic cycle
1c
(E)-2c-d: 83%
Scheme 3
In conclusion, we have developed a cationic gold(I)-cata-
lyzed intramolecular allylation of alkynes for the stereose-
lective synthesis of di- or trisubstituted olefins possessing
a 1,4-diene framework. Moreover, contrast to other meth-
ods, the present reaction enables the introduction of an al-
lyl group at the position geminal to the aryl group in a
regioselective manner. Further studies of this methodolo-
gy in organic synthesis are under way.
Furthermore, no crossover products were detected by 1H
NMR spectroscopy in a crossover experiment performed
under standard conditions with a 1:1 mixture of 1h and
(Z)-1q (Scheme 4), whereas the concerted products 2h
and 2q were obtained in 60% and 61% isolated yield, re-
spectively. This result strongly suggests that the present
reaction proceeds intramolecularly.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Ph
Ph
Ph
Ph
Si
Si
OH
Acknowledgment
CO2Et
1h
(PPh3)AuCl (5 mol%)
AgNTf2 (5 mol%)
2h
CO2Et
This work was supported by a Grant-in-Aid Scientific Research for
Young Scientist (B) (No. 19750071) from the Ministry of Educati-
on, Culture, Sports, Science and Technology, Japan.
Ph
H2O (2 equiv)
MeNO2, r.t.
Ph
Ph
Ph
Si
Si
OH
References and Notes
(Z)-1q
2q
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Scheme 4
A mechanism proposed on the basis of these experiments
is outlined in Scheme 5. Initial complexation of the cat-
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sponding desired product 2.18,19
Synlett 2010, No. 19, 2879–2882 © Thieme Stuttgart · New York

2882
Y. Horino et al.
LETTER
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Supporting Information for further details). Nevertheless,
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Synlett 2010, No. 19, 2879–2882 © Thieme Stuttgart · New York