Gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with allylic alcohols

Article abstract of DOI:10.1016/j.tet.2008.11.102

A highly efficient gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with allylic alcohols has been developed. The reaction was shown to proceed expediently for a wide variety of 1,3-dicarbonyl compounds and allylic alcohols, including 1° and terminal ones, under very mild conditions at room temperature in good to excellent yields (55-96%).

Full text of DOI:10.1016/j.tet.2008.11.102

Tetrahedron 65 (2009) 1833–1838
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with
allylic alcohols
*
Prasath Kothandaraman, Weidong Rao, Xiaoxiang Zhang, Philip Wai Hong Chan
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 July 2008
Received in revised form 2 November 2008
Accepted 3 November 2008
Available online 24 December 2008
A highly efficient gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with allylic
alcohols has been developed. The reaction was shown to proceed expediently for a wide variety of 1,3-
dicarbonyl compounds and allylic alcohols, including 1ꢀ and terminal ones, under very mild conditions at
room temperature in good to excellent yields (55–96%).
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
works have focused on the interaction of the gold catalyst with the
p-bonds of alkenes, alkynes, and allenes, their applications to re-
Allylic alkylations of 1,3-dicarbonyl compounds are an impor-
tant type of carbon–carbon bond formation reaction that provide
a convenient strategy for the construction of complex molecular
structures from simple building blocks.1 Generally, the reactions
have relied on the use of preformed electrophiles such as allylic
halides, carbonates, acetates, triflates, and related compounds with
good leaving group ability. However, with the recent shift in green
chemistry toward developing new methods that make use of in-
expensive and readily available electrophiles that follow the prin-
ciples of atom-economy,2 the establishing of alternative allylic
alkylation strategies has been actively pursued.3–13 One such
strategy has been the use of allylic alcohols as the allylating reagent
in the presence of Pd, Co, and Cu salts as the catalyst.4 More re-
cently, Lewis and Brønsted acids such as BF3$OEt2,5 InCl3,6 FeCl3,7
LnOTf (Ln¼La, Yb, Sc, Hf),8 Bi(OTf)3,9 p-toluenesulfonic acid,10 mole-
cular iodine,11 and H-Montmorillonite12 have also been reported to
catalyze these reactions. Although shown to be efficient, producing
H2O as the only side product, catalytic systems that can mediate
allylic alkylation of 1,3-dicarbonyl compounds with a broad range
of allylic alcohols have remained sparse. In this regard, we envi-
sioned that gold catalysis would form the basis for developing
a new approach for allylic alkylations of 1,3-dicarbonyl compounds
with allylic alcohols irrespective of the nature of the pre-
electrophile.
actions with other functional groups have also gathered momen-
tum in recent years. A notable example is that by Campagne and
co-workers who reported the propargylation of allylsilanes with
propargylic alcohols in the presence of HAuCl4$2H2O as catalyst
could be accomplished in good to excellent yields and selectivity.14
Following this seminal work, we15 and the respective groups of
Beller16 and Dyker17 reported similar efficient approaches for
Friedel–Crafts allylic alkylations, benzylations, and propargylations
of aromatic compounds with allylic, propargylic, and benzylic alco-
hols. Methods for the allylic alkylation, benzylation and prop-
argylation of anilines, azides and sulfonamides with allylic, benzylic
and propargylic alcohols that make use of gold catalysis have also
been recently communicated.18 To our knowledge, however, a gold-
catalyzed protocol for the allylic alkylation of 1,3-dicarbonyl com-
pounds with allylic alcohols is not known. As part of an ongoing
program examining the utility of alcohols as building blocks in
organic synthesis,20 we report herein the allylic alkylation of 1,3-
dicarbonyl compounds with allylic alcohols catalyzed by AuCl3 with
AgSbF6 as a co-catalyst (Scheme 1). The reactions were shown to
proceed smoothly in good to excellent product yields up to 96% for
a wide variety of starting materials under mild conditions at room
temperature.
Gold complexes have emerged as an efficient and versatile class
of Lewis acid catalysts for a wide variety of stereoselective C–X
(X¼C, N, O, S) bond formations.13–19 While much of the current
O
O
R
AuCl (5 mol%)
3
OH
O
O
AgSbF (15 mol%)
1
2
6
+
R
R
4
1
2
3
CH NO , r.t.
R
R
R
R
3
2
3
4
30-45 min.
R
1
2
3
1
4
R -R = H, alkyl, aryl
* Corresponding author. Tel.: þ65 6316 8760; fax: þ65 6791 1961.
E-mail address: waihong@ntu.edu.sg (P.W.H. Chan).
Scheme 1.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.102

1834
P. Kothandaraman et al. / Tetrahedron 65 (2009) 1833–1838
Table 1
Notably, the low catalytic activity observed for the analogous
Optimization of the reaction conditionsa
AgSbF6-catalyzed reaction also provided evidence that the cationic
Au(III) complex was the active species (entry 13). In addition, the
only Lewis acid catalysts that were found to lead to no reaction on
the basis of TLC analysis was Ph3PAuCl or Ph3PAuCl in combination
with AgOTf (entries 9 and 12). In the case of a survey of reactions
catalyzed by Brønsted acids, only those mediated by p-TsOH$H2O,
TFA, or H2SO4 were found to give 3a in moderate to good yields of
45–68% (entries 17–19). In the latter two cases, however, extended
reaction times of 16 and 24 h were required. In contrast, much
lower product yields of 20–22% could only be accomplished for the
analogous reactions catalyzed by TfOH or HCl even after increasing
reaction times to 24 h (entries 20 and 21).
To define the scope of the AuCl3/AgSbF6-catalyzed reactions,
we applied this process to a series of substituted 1,3-dicarbonyl
compounds 1a–e and allylic alcohols 2a–j (Table 2). This revealed
the allylic alkylation of 1a with primary allylic alcohols bearing
either an electron-withdrawing or electron-donating group pro-
ceeded in excellent yields (entries 1–3). Similarly, the analogous
reaction of other 1,3-dicarbonyl compounds with electron-rich
and electron-deficient 2ꢀ allylic alcohols afforded the corre-
sponding allylated adducts in yields of 55–93% (entries 4–11).
O
O
O
catalyst
solvent, r.t.
time
Ph
Ph
+ Ph
OH
Ph
Ph
O
3a
Ph
1a
2a
Entry
Catalyst
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
AuCl3/AgSbF6
AuCl3/AgSbF6
AuCl3/AgSbF6
AuCl3/AgSbF6
AuCl3/AgSbF6
AuCl3/AgSbF6
AuCl3/AgOTf
AuCl/AgOTf
Ph3PAuCl/AgOTf
AuCl3
AuCl
Ph3PAuCl
AgSbF6
Cu(OTf)2
In(OTf)3
ZnCl2
MeNO2
CH2Cl2
MeCN
1,4-Dioxane
C6H6
0.5
3
84
58
15
32
23
12
75
72
dc
28
26
dc
29
62
64
25
47
68
45
20
22
16
16
18
18
0.5
0.5
24
16
18
24
24
0.5
24
24
16
0.5
16
24
24
PhMe
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
9
10
11
12
13
14
15
16
17
18
19
20
21
TFA
p-TsOH$H2O
H2SO4
TfOH
HCl
Notably, this included the allylic alkylation of less acidic
b-
ketoesters 1c and 1d with 2f or 2g, which gave 3f–g and 3k–l in
excellent yields (entries 5 and 6 and 10 and 11). Likewise, we were
pleased to find allylic alkylations 1a with less reactive terminal
allylic alcohols 2h–j proceeded well and gave the corresponding
products 3m–o in excellent yields of 82–86% (entries 12–14). The
allylated products 3m and 3n were also obtained as single
regioisomers on the basis of NOE measurements of these adducts
(see Supplementary data for details). The present procedure was
also shown to work well for the allylic alkylation of cyclic 1,3-
diketone 1e with 2g, giving 3h in good yield as its enol ether
(entry 7). Similarly, 1,5-diene alcohol 2k was found to be good
allylating source, affording the product in 70% yield (entry 15).
However, poor regioselectivities were found for reactions with
allylic alcohols containing two different substituents such as an
aryl and alkyl group as in 2l and 2m (entries 16 and 18). In each of
these reactions, the corresponding allylated products were fur-
nished in good to excellent yields but also as inseparable mixture
of regioisomers. The allylic alkylation of 1b with 2l was the only
instance where product 3r was furnished as a single regioisomer
in 83% yield (entry 17), which is consistent with our earlier find-
ings for reactions with 1ꢀ and terminal allylic alcohols.
Although the above experimental results do not provide a clear
perspective on the mechanism of the present procedure, we ten-
tatively propose the reaction to proceed in a manner similar to that
put forward by us11 and Campagne.14 This could involve combina-
tion of the gold and silver catalyst to give a more electrophilic
Au(III) complex as postulated by Li and co-workers.19 This newly
formed active species subsequently activates the allylic alcohol
thereby making the hydroxyl group a better leaving group. The
regioselectivities obtained in these reactions may be due to sub-
sequent attack at the sterically less hindered carbon center of this
presumed activated intermediate.
a
All reactions were performed at room temperature with catalyst/1a/2a
ratio¼1:80:20.
b
c
Isolated yield.
No reaction.
2. Results and discussion
At the outset of this study, we purposely chose to focus our at-
tention to develop a catalytic system that would effect allylic al-
kylations of 1,3-dicarbonyl compounds with less reactive primary
allylic alcohols. With this in mind, we chose to examine the allylic
alkylation of 1,3-diphenylpropane-1,3-dione 1a with (E)-3-phe-
nylprop-2-en-1-ol 2a as the model substrates to establish the re-
action conditions (Table 1). This revealed treatment of 4 equiv of 1a
with 2a (1 equiv) and 5 mol % of AuCl3 and 15 mol % of AgSbF6 as
catalyst in CH3NO2 at room temperature for 0.5 h gave the best
result. Under these conditions, 2-cinnamyl-1,3-diphenylpropane-
1,3-dione 3a was furnished in 84% yield (entry 1) that was com-
parable to those obtained with other catalytic systems previously
reported for this reaction.21 Retention of trans-stereochemistry in
the allylated product, which was afforded as a single regioisomer,
was also confirmed by comparison with NOE spectroscopic data
obtained for closely related adducts (see below) and known liter-
ature data.11 A lower product yield of 58%, on the other hand, was
obtained when the reaction was repeated with CH2Cl2 instead of
MeNO2 as the solvent (entry 2). In contrast, the analogous reactions
conducted in other polar solvents such as MeCN and 1,4-dioxane
were less effective and gave markedly lower product yields of 15
and 32%, respectively (entries 3 and 4). Significantly lower product
yields of 12 and 23% were also found for the respective reactions in
non-polar solvents C6H6 and PhMe (entries 5 and 6). Examination
of other different gold and silver combinations revealed that
changing the silver source to AgOTf or switching the gold catalyst
from AuCl3 to AuCl gave 3a in lower yields of 72–75% (entries 7 and
8). A similar outcome was found when reactions employing other
single metal Lewis acid or Brønsted catalysts were examined. In our
hands, while reactions with either Cu(OTf)2 or In(OTf)3 as catalyst
gave low product yields of 62–64%, those mediated by AuCl, AuCl3,
AgSbF6 or ZnCl2 afforded 3a in yields of 29% or less (entries 10–16).
3. Conclusion
In summary, we have demonstrated a practical and straight-
forward method for the allylic alkylation of 1,3-dicarbonyl com-
pounds under mild conditions at room temperature that proceeded
in good to excellent yields. The present protocol is applicable to
a variety of 1,3-dicarbonyl compounds and allylic alcohols con-
taining electron-withdrawing and electron-donating, and sterically
demanding substrate combinations. The reactivity of gold catalysis
to mediate this useful carbon–carbon bond formation was

P. Kothandaraman et al. / Tetrahedron 65 (2009) 1833–1838
1835
Table 2
AuCl3/AgSbF6-catalyzed allylic alkylation of 1,3-dicarbonyl compounds 1a–e with allylic alcohols 2a–ma
OH
O
O
Ph
OH
OH
R1
R2
O
O
Me
R
R1
R2
1b, R1 = R2 = Me
2e, R1 = R2 = H
2f, R1 = R2 = Br
2g, R1 = R2 = Me
1e
2b, R = Br
2c, R = Me
2d
1c, R1 = Me, R2 = OEt
1d, R1 = Ph, R2 = OEt
OH
OH
OH
R
OH
OH
Me
O
O
Me
Ph
Ph
Ph
Ph
Ph
Me
2h
2i, R = Me
2j, R = Ph
2k
2l
2m
Entry
Substrates
Time (h)
Product
Yieldb (%)
O
1
2
1aþ2b
1aþ2c
0.75
0.5
3b, R¼Br
3c, R¼Me
79
83
Ph
Ph
R
O
Ph
O
3
4
1aþ2d
1bþ2e
0.5
0.5
3d
3e
96
91
Ph
O
O
Ph
Me
O
Me
Me
Ph
Ph
O
O
R
OEt
5
6
1cþ2f
1dþ2f
0.75
0.75
3f, R¼Me
3g, R¼Ph
87c
87d
Br
Br
HO
O
7
1eþ2g
0.75
3h
82
Me
Me
Me
O
O
8
9
10
11
1aþ2g
1bþ2g
1cþ2g
1dþ2g
0.5
0.5
0.5
0.5
3i, R1¼R2¼Ph
91
93
R1
R2
3j, R1¼R2¼Me
3k, R1¼Me, R2¼OEt
3l, R1¼Ph, R2¼OEt
93c
91c
Me
O
12
1aþ2h
0.5
Ph
Ph
Ph
3m
86
Me
O
Ph
O
R
13
14
1aþ2i
1aþ2j
0.5
0.5
3n, R¼Me
3o, R¼Ph
82
86
Ph
O
Ph
O
O
15
16
1bþ2k
1aþ2l
0.5
0.5
3p
3q
70
Me
Ph
Me
Ph
O
O
O
O
Ph
Ph
Me
Ph
Ph
Me
87e
Ph
Ph
(continued on next page)

1836
P. Kothandaraman et al. / Tetrahedron 65 (2009) 1833–1838
Table 2 (continued )
Entry
Substrates
Time (h)
0.5
Product
Yieldb (%)
83
O
O
17
1bþ2l
3r
3s
Me
Ph
Me
Me
O
O
O
O
Me
Me
Me
Me
Me
Me
18
1bþ2m
0.5
55f
O
O
O
O
a
All reactions were performed at room temperature with AuCl3/AgSbF6/1a/2a ratio¼1:3:80:20.
Isolated yield.
b
c
d
e
f
Isolated as an inseparable mixture of diastereomers in a ratio¼1:1.
Isolated as an inseparable mixture of diastereomers in a ratio¼3:1.
Isolated as an inseparable mixture of regioisomers in a ratio¼3:1.
Isolated as an inseparable mixture of regioisomers, the ratio of which could not be determined by 1H NMR analysis due to overlapping peaks.
exemplified by short reaction times and high product yields
obtained for reactions with 1ꢀ and terminal allylic alcohols. The
superior catalytic activity exhibited by the present AuCl3/AgSbF6-
mediated method may also provide an explanation for the poor
regioselectivities observed.
(0.3 mmol), followed by the slow addition of 1 (1.2 mmol) dissolved
in MeNO2 (2 mL). The mixture was stirred at room temperature and
monitored by TLC analysis. On completion, the reaction mixture
was filtered through CeliteÒ and washed with EtOAc (15 mL). The
organic solvent was removed under reduced pressure and the re-
sultant residue obtained was subjected to purification by flash
column chromatography to give the title compound 3.
4. Experimental
4.3.1. 2-Cinnamyl-1,3-diphenylpropane-1,3-dione (3a)4e,9,22
4.1. General remarks
Yellow solid; yield: 84%; 1H NMR
d 7.98 (m, 4H), 7.54 (m, 2H),
7.43 (m, 4H), 7.23 (m, 5H), 6.48 (d, 1H, J¼15.6 Hz), 6.21 (m, 1H), 5.34
All reactions were performed under an argon atmosphere. Un-
less specified, all reagents and starting materials were purchased
from commercial sources and used as received. Solvents were pu-
rified following standard literature procedures. Analytical thin layer
chromatography (TLC) was performed using Merck 60 F254 pre-
coated silica gel plates. Visualization was achieved by UV light
(254 nm). Flash chromatography was performed using Merck silica
gel 60 and a gradient solvent system (EtOAc/n-hexane as eluant).
Unless otherwise stated, 1H and 13C NMR spectra were measured on
Bruker Avance 400 MHz spectrometer. Chemical shifts (ppm) were
recorded with tetramethylsilane (TMS) as the internal reference
standard. Infrared spectra were recorded on Shimadzu IR Prestige-
21 FTIR spectrometer. Solid samples were examined as a thin film
between NaCl salt plates. Low resolution mass spectra were de-
termined on a Finnigan LCQ XP MAX mass spectrometer. High
resolution mass spectra (HRMS) were obtained on a Finnigan
MAT95XP LC/HRMS mass spectrometer.
(t, 1H, J¼6.7 Hz), 3.0 (t, 2H, J¼6.8 Hz); 13C NMR
d 195.6, 137.0, 136.0,
133.6, 132.5, 129.0, 128.6, 128.5, 127.4, 126.8, 126.2, 57.1, 33.0; MS
(ESI) m/z 363 [MþNa]þ, 341 [MþH]þ.
4.3.2. 2-(4-Bromocinnamyl)-1,3-diphenylpropane-1,3-dione (3b)
Colorless oil; yield: 79%; 1H NMR
d 7.98 (m, 4H), 7.58 (m, 2H),
7.46 (m, 4H), 7.38 (d, 2H, J¼8.4 Hz), 7.12 (d, 2H, J¼8.6 Hz), 6.39 (d,
1H, J¼16.0 Hz), 6.22 (m, 1H), 5.35 (t, 1H, J¼6.8 Hz), 3.0 (t, 2H,
J¼6.4 Hz); 13C NMR
d 195.5, 136.0, 135.9, 133.7, 131.5, 131.3, 129.0,
128.6, 127.7, 127.6, 121.0, 57.0, 32.9; IR (neat, cmꢁ1) 3062, 2926,
1694, 1668, 1596, 1486, 1447, 1271, 1071, 616; HRMS (ESI) calcd for
C24H19O2BrNa: 441.0466, found: 441.0484.
4.3.3. 2-(4-Methylcinnamyl)-1,3-diphenylpropane-1,3-dione (3c)
Colorless oil; yield: 83%; 1H NMR
d 7.99 (m, 4H), 7.57 (m, 2H),
7.46 (m, 4H), 7.17 (d, 2H, J¼8.0 Hz), 7.07 (d, 2H, J¼8.2 Hz), 6.44 (d,
1H, J¼15.6 Hz), 6.17 (m, 1H), 5.35 (t, 1H, J¼6.4 Hz), 3.01 (t, 2H,
J¼6.8 Hz), 2.32 (s, 3H); 13C NMR
d 195.5, 137.1, 135.9, 134.2, 133.6,
4.2. General procedure for optimizing the Lewis and Brønsted
acid-catalyzed allylic alkylation of 1a with 2a
132.3, 129.1, 128.94, 128.8, 128.6, 126.0, 125.7, 57.2, 33.02, 21.17; IR
(neat, cmꢁ1) 3024, 2921, 2855, 1685, 1597, 1513, 1448, 1201, 967,
689; HRMS (ESI) calcd for C25H22O2Na: 377.1517, found: 377.1509.
To a solution of MeNO2 (2 mL) containing the Lewis or Brønsted
acid catalyst (5 mol %) under an argon atmosphere was added 2a
(0.3 mmol), followed by the slow addition of 1a (1.2 mmol) dis-
solved in MeNO2 (2 mL). The mixture was stirred at room tem-
perature and monitored by TLC analysis. On completion, the
reaction mixture was filtered through CeliteÒ and washed with
EtOAc (15 mL). The organic solvent was removed under reduced
pressure and the resultant residue obtained was subjected to pu-
rification by flash column chromatography to give 3a.
4.3.4. (E)-2-(2-Benzylideneoctyl)-1,3-diphenylpropane-1,3-
dione (3d)
Colorless oil; yield: 96%; 1H NMR (300 MHz)
d 7.98 (m, 4H), 7.54
(m, 2H), 7.42 (m, 4H), 7.22 (m, 3H), 7.01 (d, 2H, J¼7.2 Hz), 6.24 (s,
1H), 5.46 (t, 1H, J¼6.6 Hz), 3.02 (d, 2H, J¼5.7 Hz), 2.16 (t, 2H,
J¼8.4 Hz), 1.42 (m, 2H), 1.22 (m, 6H), 0.82 (t, 3H, J¼6.3 Hz); 13C NMR
d
195.7, 162.3, 139.9, 137.7, 136.2, 133.5, 128.9, 128.6, 128.5, 128.0,
127.5, 126.2, 56.1, 36.2, 31.5, 30.9, 29.3, 28.2, 22.5, 14.0; IR (neat,
cmꢁ1) 3062, 2926, 1693,1676, 1447, 1268, 665; HRMS (ESI) calcd for
C30H32O2Na: 447.2300, found: 447.2287.
4.3. General procedure for AuCl3/AgSbF6-catalyzed allylic
alkylation of 1,3-dicarbonyl compounds 1a–e with allylic
alcohols 2a–m
4.3.5. (E)-3-(1,3-Diphenylallyl)pentane-2,4-dione (3e)23
White solid; yield: 91%; 1H NMR
d 7.20 (m, 10H), 6.40 (d, 1H,
To a solution of MeNO2 (2 mL) containing AuCl3 (5 mol %),
AgSbF6 (15 mol %) under an argon atmosphere was added 2
J¼15.8 Hz), 6.16 (m, 1H), 4.28 (m, 2H), 2.24 (s, 3H), 1.92 (s, 3H); 13C

P. Kothandaraman et al. / Tetrahedron 65 (2009) 1833–1838
1837
NMR
d
202.8, 202.7, 200.1, 136.5, 131.6, 129.2, 129.0, 128.5, 128.4,
126.2, 125.9, 65.7, 65.4, 61.5, 61.3, 48.7, 48.4, 40.5, 31.6, 29.9, 29.8,
21.1, 221.0, 14.2, 13.82; IR (neat, cmꢁ1) 3432, 2986, 2378, 1732, 1710,
1482, 1145, 1078, 966, 815; HRMS (ESI) calcd for C23H26O3Na:
373.1780, found: 373.1783.
128.4, 127.9, 127.7, 127.2, 126.3, 126.9, 74.5, 49.1, 30.0, 29.7; MS (ESI)
m/z 315 [MþNa]þ, 293 [MþH]þ.
4.3.6. (E)-Ethyl-2-acetyl-3,5-bis(4-bromophenyl)pent-4-
enoate (3f)
4.3.12. (E)-Ethyl-2-benzoyl-3,5-di-p-tolylpent-4-enoate (3l)
White solid; yield 87%; mp 79–81 ꢀC; 1H NMR
d
7.42 (m, 8H),
White solid; yield: 91%; mp 97–103 ꢀC; 1H NMR (300 MHz)
7.13 (m, 8H), 6.38–6.14 (m, 4H), 4.22 (q, 2H, J¼8.2 Hz), 4.16 (q, 2H,
J¼7.15 Hz), 4.05 (q, 2H, J¼6.04 Hz), 3.93 (q, 4H, J¼7.12 Hz), 2.27 (s,
3H), 2.06 (s, 3H), 1.18 (t, 3H, J¼7.1 Hz), 1.0 (t, 3H, J¼7.1 Hz); 13C NMR
d 8.08 (m, 2H), 7.91 (m, 2H), 7.40 (m, 6H), 6.96 (m, 16H), 6.45 (d, 1H,
J¼15.6 Hz), 6.32 (m, 2H), 6.15 (dd, 1H, J¼15.2, 7.5 Hz), 4.93 (q, 2H,
J¼6.3 Hz), 4.50 (q, 2H, J¼7.6 Hz), 4.11 (m, 2H), 3.86 (m, 2H), 2.30 (s,
6H), 2.21 (s, 6H), 1.10 (t, 3H, J¼6.9 Hz), 0.91 (t, 3H, J¼7.2 Hz); 13C
d
201.1, 200.7, 167.6, 167.2, 139.1, 139.1, 135.5, 135.3, 132.0, 131.8,
131.6, 131.1, 130.8, 129.7, 129.6, 129.5, 127.9, 127.8, 121.5, 121.1, 121.0,
NMR d 193.3, 192.6, 168.0, 167.6, 138.0, 137.4, 137.2, 137.0, 136.6,
65.0, 64.9, 61.8, 61.6, 48.0, 47.8, 30.0, 29.9, 14.1, 13.8; IR (neat, cmꢁ1
)
136.6, 136.2, 134.2, 13.1, 133.5, 133.4, 131.3, 131.2, 129.3, 129.2, 129.1,
129.0, 128.8, 128.7, 128.6, 128.5, 128.2, 127.7, 126.2, 126.1, 61.6, 61.4,
59.9, 59.7, 48.5, 48.4, 21.1, 21.0, 20.9, 14.1, 13.7; IR (neat, cmꢁ1) 3065,
2985, 1720, 1675, 1487, 1445, 1300, 1155, 1072, 977, 806; HRMS (ESI)
calcd for C28H28O3Na: 435.1936, found: 435.1937.
2981, 1741, 1710, 1487, 1246, 1010; HRMS (ESI) calcd for
C21H20O3Br2Na: 500.9677, found: 500.9682.
4.3.7. (E)-Ethyl-2-benzoyl-3,5-bis(4-bromophenyl)pent-4-
enoate (3g)
White solid; yield 87%; mp 118–121 ꢀC; 1H NMR
d
7.93 (m, 2H),
4.3.13. 2-(2-Methyl-3-phenylallyl)-1,3-diphenylpropane-1,3-
7.91 (m, 1H), 7.50 (m, 6H), 7.33 (m, 6H), 6.99 (m, 2H), 6.12 (m, 2H),
dione (3m)
4.93 (d, 1H, J¼10.8 Hz), 4.52 (m, 1H), 4.10 (m, 1H), 3.89 (m, 2H), 1.11
Colorless oil; yield: 86%; 1H NMR
d 7.91 (m, 4H), 7.57 (m, 2H),
(t, 1H, J¼6.9 Hz), 0.93 (t, 3H, J¼6.9 Hz); 13C NMR
d
192.8, 192.1, 167.7,
7.43 (m, 4H), 7.25 (m, 3H), 7.02 (m, 2H), 6.27 (s, 1H), 5.47 (t, 3H,
167.2, 139.7, 139.1, 136.6, 136.3, 135.6, 135.5, 133.8, 133.7, 131.8, 131.8,
131.6,131.4,131.0,130.9,130.1,130.0,129.8,129.6,128.8,128.7,128.5,
127.8, 121.4, 121.3, 121.1, 120.8, 61.8, 61.6, 59.5, 59.3, 48.2, 48.1, 14.1,
13.7; IR (neat, cmꢁ1) 3064, 2980, 1720, 1678, 1487, 1259, 1010;
HRMS (ESI) calcd for C26H22O3Br2Na: 562.9833, found: 562.9830.
J¼6.8 Hz), 3.01 (d, 2H, J¼6.8 Hz), 1.87 (s, 3H); 13C NMR
d 195.7, 137.7,
136.2, 135.1, 133.5, 128.9, 128.7, 128.6, 127.9, 127.8, 126.2, 56.1, 39.7,
18.2; IR (neat, cmꢁ1) 3084, 3060, 2930, 1700, 1696, 1663, 1596, 1447,
1269, 781, 743, 699; HRMS (ESI) calcd for C25H22O2Na: 377.1517,
found: 377.1509.
4.3.8. (E)-2-(1,3-Di-p-tolylallyl)-3-hydroxycyclohex-2-enone (3h)
4.3.14. 2-(3-Methyl-3-phenylallyl)-1,3-diphenylpropane-1,3-
Colorless oil; yield 82%; 1H NMR (300 MHz)
d
7.28 (m, 3H), 7.11
dione (3n)
(m, 5H), 6.54 (dd, 1H, J¼16.2, 6.3 Hz), 6.32 (d, 1H, J¼14.4 Hz), 5.29
Colorless oil; yield 82%; 1H NMR
d 7.99 (m, 4H), 7.54 (m, 2H), 7.43
(d, 1H, J¼6.3 Hz), 2.53 (t, 2H, J¼6.3 Hz), 2.44 (t, 2H, J¼6.9 Hz), 2.38
(m, 4H), 7.23 (m, 4H), 5.74 (t, 1H, J¼7.2 Hz), 5.32 (t, 1H, J¼6.8 Hz),
(s, 6H), 2.02 (m, 2H); 13C NMR
d
197.2, 172.3, 162.3, 137.9, 137.5,
3.01 (t, 2H, J¼7.2 Hz), 2.0 (s, 3H); 13C NMR
d 195.8, 143.4, 137.4,
136.6,133.8, 132.3, 129.7,129.4, 129.2,129.1, 129.0, 127.9, 126.3, 117.1,
40.8, 36.5, 29.4, 21.1, 21.0, 20.6; IR (neat, cmꢁ1) 3023, 2947, 2922,
2871, 1605, 1378, 1268, 1178; HRMS (ESI) calcd for C23H25O2:
333.1855, found: 333.1842.
136.0, 133.5, 128.9, 128.7, 128.6, 128.1, 126.8, 125.7, 124.3, 56.9, 28.9,
16.0; IR (neat, cmꢁ1) 3058, 2919, 1693, 1669, 1596, 1447, 1322, 1263,
1180; HRMS (ESI) calcd for C25H22O2Na: 377.1517, found: 377.1506.
4.3.15. 2-(3,3-Diphenylallyl)-1,3-diphenylpropane-1,3-dione (3o)
4.3.9. (E)-2-(1,3-Di-p-tolylallyl)-1,3-diphenylpropane-1,3-
dione (3i)
White solid; yield: 86%; mp 162–165 ꢀC; 1H NMR
d 7.82 (m, 4H),
7.52 (m, 2H), 7.36 (m, 6H), 7.20 (m, 3H), 7.10 (m, 5H), 6.25 (t, 1H,
White solid; yield: 91%; mp 159–163 ꢀC; 1H NMR (300 MHz)
J¼7.6 Hz), 5.19 (t, 1H, J¼6.8 Hz), 2.91 (t, 2H, J¼7.2 Hz); 13C NMR
d
7.98 (m, 2H), 7.82 (m, 2H), 7.52 (m, 1H), 7.46 (m, 3H), 7.32 (m, 2H),
d 195.7, 143.9, 141.8, 139.6, 135.8, 133.5, 129.9, 129.8, 129.5, 129.0,
7.20 (d, 2H, J¼10.8 Hz), 7.01 (d, 2H, J¼10.4 Hz), 6.96 (m, 4H), 6.19 (m,
128.9, 128.7, 128.6, 128.5, 128.4, 128.2, 128.1, 127.7, 127.4, 127.2, 127.1,
127.0, 125.6, 125.3, 124.9, 57.2, 29.2; IR (neat, cmꢁ1) 3057, 2926,
1694, 1672, 1596, 1494, 1447, 1268, 1180, 1073, 766, 693; HRMS (ESI)
calcd for C30H24O2Na: 439.1674, found: 439.1662.
2H), 5.89 (d, 1H, J¼6.8 Hz), 4.77 (m, 1H), 2.25 (s, 3H), 2.23 (s, 3H);
13C NMR
d 194.6, 193.8, 138.0, 137.3, 137.0, 136.9, 136.3, 134.1, 133.3,
133.1, 131.5, 129.3, 129.0, 128.9, 128.8, 128.82, 128.5, 128.1, 126.1,
62.8, 49.6, 21.1, 20.9; IR (neat, cmꢁ1) 3052, 2976, 2867, 1603, 1367,
1256, 1167; HRMS (ESI) calcd for C32H28O2Na: 467.1987, found:
467.1985.
4.3.16. 3-((2E,4E)-1,5-Diphenylpent-2,4-dienyl)pentane-2,4-
dione (3p)
Colorless oil; yield: 70%; 1H NMR
d 7.20 (m, 10H), 6.61 (dd, 1H,
4.3.10. (E)-3-(1,3-Di-p-tolylallyl)pentane-2,4-dione (3j)
J¼15.6, 10.3 Hz), 6.55 (d, 1H, J¼15.6 Hz), 6.20 (m, 1H), 5.76 (dd, 1H,
White solid; yield: 93%; mp 77–80 ꢀC; 1H NMR (300 MHz)
d 7.30
J¼15.1, 6.6 Hz), 4.23 (m, 2H), 2.25 (s, 3H), 1.90 (s, 3H); 13C NMR
(m, 4H), 7.05 (m, 4H), 6.34 (d, 1H, J¼15.9 Hz), 6.1 (dd, 1H, J¼15.3,
d 202.8, 202.6, 140.0, 137.0, 133.2, 132.7, 132.2, 129.0, 128.6, 128.1,
7.8 Hz), 4.27 (m, 2H), 2.30 (s, 6H), 2.23 (s, 3H), 1.92 (s, 3H); 13C NMR
127.9, 127.6, 127.5, 127.2, 126.3, 49.0, 30.0, 29.7; IR (neat, cmꢁ1
)
d
203.0, 202.9, 137.5, 137.2, 136.8, 133.8, 131.3, 129.7, 129.4, 129.3,
3052, 2935, 1687, 1665, 1439, 1265, 976, 695; HRMS (ESI) calcd for
C22H22O2Na: 341.1517, found: 341.1512.
129.2, 129.0, 128.5, 128.3, 127.8, 127.2, 126.3, 67.1, 48.9, 30.0, 29.8,
21.1, 21.0; IR (neat, cmꢁ1) 3042, 2985, 1690, 1682, 1437, 935; HRMS
(ESI) calcd for C22H24O2Na: 343.1674, found: 343.1675.
4.3.17. (E)-1,3-Diphenyl-2-(4-phenylbut-3-en-2-yl)propane-1,3-
dione (3q)
4.3.11. (E)-Ethyl-2-acetyl-3,5-di-p-tolylpent-4-enoate (3k)
Colorless oil; yield 87%; 1H NMR
d 8.01 (m, 3H), 7.96 (m, 2H),
Yellow oil; Yield: 93%; 1H NMR
d
7.04 (m, 16H), 6.35 (t, 2H,
7.77 (m, 1H), 7.48 (m, 8H), 7.30 (m, 3H), 7.11 (m, 7H), 6.39 (d, 1H,
J¼16.0 Hz), 6.09 (dd, 1H, J¼15.6, 8.4 Hz), 5.34 (d, 1H, J¼8.8 Hz), 4.56
(t, 1H, J¼9.5 Hz), 3.59 (q, 1H, J¼8.0 Hz), 1.44 (d, 2H, J¼6.1 Hz), 1.21
J¼15.2 Hz), 6.13 (m, 2H), 4.23 (q, 2H, J¼8.8 Hz), 4.11 (q, 2H,
J¼7.2 Hz), 4.03 (q, 2H, J¼7.6 Hz), 3.90 (q, 2H, J¼7.2 Hz), 2.27 (s, 15H),
2.02 (s, 3H), 1.17 (t, 3H, J¼6.8 Hz), 0.97 (t, 3H, J¼7.2 Hz); 13C NMR
(d, 3H, J¼6.4 Hz); 13C NMR
d 195.1, 194.9, 194.6, 194.0, 141.6, 137.3,
137.1, 137.0, 136.9, 136.9, 133.5, 133.4, 133.3, 133.1, 132.3, 131.0, 128.9,
128.8, 128.8, 128.7, 128.5, 128.4, 128.1, 127.7, 127.2, 126.6, 126.1, 63.0,
d
201.9, 201.7, 168.0, 167.7, 137.4, 137.2, 136.7, 136.6, 134.1, 133.9,
131.5,131.1,129.6,129.3,129.1,129.0,128.7,128.4,128.3,127.8,126.3,

1838
P. Kothandaraman et al. / Tetrahedron 65 (2009) 1833–1838
62.6, 50.0, 38.6, 18.9, 17.8; IR (neat cmꢁ1) 3059, 3026, 2966, 1697,
1664, 1593, 1446, 1278, 1197; HRMS (ESI) calcd for C25H22O2Na:
377.1517, found: 377.1503.
Tamaru, Y. Eur. J. Org. Chem. 2005, 2647; For selected examples, see: (e) Kayaki,
Y.; Koda, T.; Ikariya, T. J. Org. Chem. 2004, 69, 2595; (f) Kinoshita, H.; Shinokubo,
H.; Oshima, K. Org. Lett. 2004, 6, 4085; (g) Manabe, K.; Kobayashi, S. Org. Lett.
2003, 5, 3241; (h) Kimura, M.; Mukai, R.; Tanigawa, N.; Tanaka, S.; Tamaru, Y.
Tetrahedron 2003, 59, 7767; (i) Ozawa, F.; Okamoto, H.; Kawagishi, S.; Yama-
moto, S.; Minami, T.; Yoshifuji, M. J. Am. Chem. Soc. 2002, 124, 10968; (j) Mu-
khopadhyay, M.; Iqbal, J. Tetrahedron Lett. 1995, 36, 6761; (k) Baruah, J. B.;
Samuelson, A. G. J. Organomet. Chem. 1989, 361, C57.
4.3.18. (E)-3-(4-Phenylbut-3-en-2-yl)pentane-2,4-dione (3r)24
Colorless oil; yield: 83%; 1H NMR
d 7.26 (m, 5H), 6.41 (d, 1H,
5. Bisaro, F.; Pretat, G.; Vitale, M.; Poli, G. Synlett 2002, 1823.
J¼16 Hz), 5.96 (dd, 1H, J¼16.1, 8.4 Hz), 3.70 (d, 1H, J¼10.4 Hz), 3.17
(m, 1H), 2.22 (s, 3H), 2.12 (s, 3H), 1.08 (d, 3H, J¼6.8 Hz); 13C NMR
6. Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem., Int. Ed. 2006, 45, 793.
7. (a) Jana, U.; Biswas, S.; Maiti, S. Tetrahedron Lett. 2007, 48, 4065; (b) Salehi, P.;
Iranpoor, N.; Behbahani, F. K. Tetrahedron 1998, 54, 943.
8. (a) Noji, M.; Konno, Y.; Ishii, K. J. Org. Chem. 2007, 72, 5161; (b) Huang, W.;
Wang, J.; Shen, Q.; Zhou, X. Tetrahedron Lett. 2007, 48, 3969.
d
203.6, 203.5, 136.7, 130.9, 130.9, 128.5, 127.5, 126.2, 37.9, 30.0, 29.7,
18.8; MS (ESI) m/z 253 [MþNa]þ, 231 [MþH]þ.
9. Reping, M.; Nahtsheim, B. J.; Kuenkel, A. Org. Lett. 2007, 9, 825.
4.3.19. (E)-3-(4-(Benzo[d][1,3]dioxol-5-yl)but-3-en-2-yl)pentane-
`
´
´
´
10. Sanz, R.; Martınez, A.; Miguel, D.; Alvarez-Gutierrez, J. M.; Rodrıguez, F. Adv.
Synth. Catal. 2006, 348, 1841.
2,4-dione (3s)
Yellow liquid; yield 55%; 1H NMR
d 6.83 (s, 1H), 6.72 (d, 2H,
11. Rao, W.; Tay, A. H. L.; Goh, P. J.; Choy, J. M. L.; Ke, J. K.; Chan, P. W. H. Tetrahedron
Lett. 2008, 49, 122; Tetrahedron Lett. 2008, 49, 5112.
12. Motokura, K.; Fujita, N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew.
Chem., Int. Ed. 2006, 45, 2605.
13. For recent reviews on gold-catalyzed reactions, see: (a) Lipshutz, B. H., Yama-
moto, Y., Eds. Coinage Metals in Organic Synthesis. Chem. Rev. 2008, 108, 2793;
(b) Shen, H. C. Tetrahedron 2008, 64, 3885; (c) Yamamoto, Y. J. Org. Chem. 2007,
72, 7817; (d) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395; (e) Hashmi, A. S. K.;
Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896; (f) Hashmi, A. S. K. Chem.
Rev. 2007, 107, 3180; (g) Jime´nez-Nu´ ne˜z, E.; Echavarren, A. M. Chem. Commun.
2007, 333; (h) Fu¨rstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 2; (i)
Asao, N. Synlett 2006, 1645; (j) Hoffmann-Ro¨der, A.; Krause, N. Org. Biomol.
Chem. 2005, 3, 387.
J¼9.2 Hz), 6.31 (d, 1H, J¼15.7 Hz), 5.92 (s, 2H), 5.76 (dd, 1H, J¼15.7,
8.6 Hz), 3.67 (d, 1H, J¼10.4 Hz), 3.10 (m, 1H), 2.20 (s, 3H), 2.11 (s,
3H), 1.04 (d, 3H, J¼6.6 Hz); 13C NMR
d 203.6, 203.5, 148.0, 147.1,
131.2, 130.5, 129.1, 120.8, 108.2, 105.5, 101.0, 37.8, 30.0, 29.7, 18.9; IR
(neat, cmꢁ1) 2966, 1697, 1489, 1444, 1355, 1249,1037; HRMS (ESI)
calcd for C16H18O4Na: 297.1103, found: 297.1102.
Acknowledgements
14. Georgy, M.; Boucard, V.; Campagne, J.-M. J. Am. Chem. Soc. 2005, 127, 14180.
15. Rao, W.; Chan, P. W. H. Org. Biomol. Chem. 2008, 6, 2426.
16. Mertins, K.; Lovel, I.; Kischel, J.; Zapf, A.; Beller, M. Adv. Synth. Catal. 2006, 348,
691.
This work was supported by a College of Science Start-Up Grant
from Nanyang Technological University.
17. Liu, J.; Muth, E.; Florke, U.; Henkel, G.; Merz, K.; Sauvageau, J.; Schwake, E.;
Dyker, G. Adv. Synth. Catal. 2006, 348, 456.
Supplementary data
18. (a) Shu, X.-Z.; Liu, X.-Y.; Xiao, H.-Q.; Ji, K.-G.; Guo, L.-N.; Liang, Y.-M. Adv. Synth.
Catal. 2008, 350, 243; (b) Guo, S.; Song, F.; Liu, Y. Synlett 2007, 964; (c)
Terrasson, V.; Marque, S.; Georgy, M.; Campagne, J.-M.; Prim, D. Adv. Synth.
Catal. 2006, 348, 2063.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.11.102.
19. Nguyen, R.-V.; Yao, X.-Q.; Bohle, D. S.; Li, C.-J. Org. Lett. 2005, 7, 673.
20. Please refer to Refs. 11, 15 and (a) Rao, W.; Zhang, X.; Sze, W. M. L.; Chan,
P. W. H. J. Org. Chem. 2009, doi: 10.1021/jo8024626; (b) Rao, W.; Chan, P. W. H.
Chem.dEur. J. 2008, 14, 10486; (c) Zhang, X.; Rao, W.; Chan, P. W. H. Synlett
2008, Special Issue, 2204; (d) Wu, W.; Rao, W.; Er, Y. Q.; Loh, K. J.; Poh, C. Y.;
Chan, P. W. H. Tetrahedron Lett. 2008, 49, 2620; Tetrahedron Lett. 2008, 49, 4981;
(e) Chang, J. W. W.; Chee, S.; Mak, S.; Buranaprasertsuk, P.; Chavasiri, W.;
Chan, P. W. H. Tetrahedron Lett. 2008, 49, 2018.
References and notes
1. (a) Larock, R. C. ComprehensiveOrganic Transformations; VCH: New York, NY,1999;
(b) Palladium Reagents and Catalysts; Tsuji, J., Ed.; Wiley: Chichester, UK,1995; (c)
Godleski, S. A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford,1991; Vol. 4, Chapter 3.3; (d) Tsuji, J.; Minami, I. Acc. Chem. Res.
1987, 20, 140; (e) Trost, B. M. Acc. Chem. Res. 1980, 13, 385.
2. (a) Trost, B. M. Acc. Chem. Res. 2002, 35, 695; (b) Trost, B. M. Science 1991, 254,1471.
3. (a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921; (b) Trost, B. M.; Van
Vranken, D. L. Chem. Rev. 1996, 91, 395.
21. For a comparison of product yields obtained from reactions with 1ꢀ allylic
alcohols catalyzed by other Lewis acids, please refer to Refs. 7a, 8 and 9.
22. Patil, N. T.; Pahadi, N. K.; Yamamoto, Y. Synthesis 2004, 2186.
23. Ross, J.; Chen, W.; Xu, L.; Xiao, J. Organometallics 2001, 20, 138.
24. Hayashi, T.; Yamamoto, A.; Hagihara, T. J. Org. Chem. 1986, 51, 723.
4. For recent reviews, see: (a) Muzart, J. Tetrahedron 2008, 64, 5815; (b) Muzart, J.
Eur. J. Org. Chem. 2007, 3077; (c) Muzart, J. Tetrahedron 2005, 61, 4179; (d)