Reactive organoallyl species generated from aryl halides and allene: allylation of α,β-unsaturated aldehydes and cyclic ketones employing Pd/In transmetallation processes

Article abstract of DOI:10.1016/j.tet.2008.06.100

Allylation of α,β-unsaturated aldehydes and cyclic ketones promoted by Pd/In transmetallation processes has been studied. The unsaturated aldehydes underwent regioselective 1,2-addition to afford secondary homoally alcohols. The reactions have been performed using Pd(OAc)₂/PPh₃ as catalytic system and metallic indium affording the products in good yields. The same transformation with unsaturated ketones proved to be less efficient, while saturated cyclic ketones delivered generally excellent yields in the presence of CuI. In these latter processes the presence of a distal heteroatom influences the reaction rate.

Full text of DOI:10.1016/j.tet.2008.06.100

Tetrahedron 64 (2008) 8731–8737
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Reactive organoallyl species generated from aryl halides and allene:
allylation of a,b-unsaturated aldehydes and cyclic ketones employing
Pd/In transmetallation processes
,
b
,
b
Laura A.T. Cleghorn a, Ronald Grigg a , Vladimir Savic , Milena Simic
*
*
a Molecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, Department of Chemistry, Leeds University, Woodhouse Lane, Leeds LS29JT, UK
b Department of Organic Chemistry, Faculty of Pharmacy, Belgrade University, Vojvode Stepe 450, 11000 Belgrade, Serbia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 April 2008
Received in revised form 7 June 2008
Accepted 26 June 2008
Available online 28 June 2008
Allylation of a,b-unsaturated aldehydes and cyclic ketones promoted by Pd/In transmetallation processes
has been studied. The unsaturated aldehydes underwent regioselective 1,2-addition to afford secondary
homoally alcohols. The reactions have been performed using Pd(OAc)2/PPh3 as catalytic system and
metallic indium affording the products in good yields. The same transformation with unsaturated
ketones proved to be less efficient, while saturated cyclic ketones delivered generally excellent yields in
the presence of CuI. In these latter processes the presence of a distal heteroatom influences the reaction
rate.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
that they permit concomitant regioselective addition of further
functionality as illustrated by Scheme 1 for allene.
Synthetic methodologies based on palladium have become
indispensable for the preparation of a wide range of organic com-
R1
R1
In
pounds.1 The electrophilicity of
p
-allylpalladium species and the
[Pd]
[In]
Z
Pd
R1Y
•
ability to finely tune their reactivity has led to the development of a
plethora of very efficient synthetic procedures.2 Occasional reports
of
p-allylpalladium(II) species displaying nucleophilic properties
R3
R2
ZH
have appeared, which invariably involve intramolecular processes
and, which merit further study.3 In recent years, transmetallation
processes of Pd-intermediates have been intensively studied.4
Generally, these transformations provide an access to nucleophilic
organometallic species generated from electrophilic organo-
palladium intermediates. Various procedures have been developed
employing a range of metals/metal salts such as: Zn, Et2Zn, Et3B,
SnX2, Et2AlSnBu3, SmI2, In and InXn.4 Particularly appealing is the
use of indium in these processes5 as the metal has a low oxidation
potential, is not affected by water or alkali, does not form oxides
when exposed to air and is non-toxic.6 Consequently, it is being
increasingly used in transmetallation processes involving Pd.
R1
R2
R3
R1
[Pd]
Scheme 1.
The
p-allylpalladium(II) intermediates undergo a reductive
transmetallation in presence of indium, creating an allylindium and
regenerating the Pd(0)-catalyst.
The in situ formed organoindium intermediate reacts with an
electrophilic multiple bond to afford the final product. The process
outlined in Scheme 1 has proved to be very efficient and has been
p-Allylpalladium(II) intermediates can be generated in different
ways, most frequently from dienes, allenes and allyl acetates or
related compounds. The advantage of the former two protocols is
applied in stereoselective synthesis of amines7 and both
a
- and
b
-aminoacids.8 Recently we have shown that additives, such as
secondary amines, CuI or ascorbic acid have a beneficial effect on
cascades involving allene/ArX as allyl precursors by shortening the
reaction time for some less reactive electrophilic multiple bonds
and increasing the yields.9
* Corresponding authors. Tel./fax: þ44 1133436501 (R.G.); tel.: þ38 1113951243
(V.S.).
E-mail addresses: r.grigg@leeds.ac.uk (R. Grigg), vladimir.savic@pharmacy.bg.
ac.yu (V. Savic).
In this paper, we discuss further extensions of this methodology.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.06.100

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L.A.T. Cleghorn et al. / Tetrahedron 64 (2008) 8731–8737
Table 1
Allylation of
2. Results and discussion
a,b
-unsaturated aldehydesa
1,2-Allylation of
a,b-unsaturated aldehydes is synthetically
Entry Aldehyde 1 Aryl halide 2
Product
Yieldb
(%)
useful transformation, which generates unsaturated secondary al-
cohols, Scheme 2. It suffers, in particular, from a lack of readily
available allylating reagents with C(2) substituents. The allene/aryl
or vinyl halide strategy overcomes this difficulty. The 1,5-diene
products 3 potentially may undergo 3,3-sigmatropic rearrange-
OH
O
I
a
b
c
72
63
76
CF3
3a
ment to afford d-unsaturated aldehydes, providing further diversity
CF3
and synthetic oportunities.10
OH
Br
O
+
+
Ar
X
•
N
3b
1R
2
N
1
OH
Pd(OAc)2
PPh3
In
DMF
I
3c
OH
OH
I
1R
Ar
d
75
N
3
3d
Scheme 2.
N
The allylation processes, outlined in Scheme 2, were studied
under our typical conditions employing Pd(OAc)2/PPh3 as a cata-
lytic system and 1.5 mol equiv of In. Current evidence supports the
involvement of In(I) allyl species,11 which requires 2 equiv of In(0)
for the reduction of Pd(II) to Pd(0) and the detail of this process is
unclear.12 All reactions were carried out in a Schlenk flask, using
DMF as a solvent, at 85 ꢀC. After work-up the products were isolated
by flash chromatography on silica gel.
OH
I
e
65
74
S
3e
S
O
OH
I
f
The initial p-allylpalladium intermediate is formed via the oxi-
3f
dative addition of Pd(0) to the aryl halide followed by regioselective
reaction with allene. The following step, the reductive trans-
metallation involving indium, generates the allylindium species
and concomitantly regenerates Pd(0). The nucleophilic allylindium
OH
I
Cl
Cl
g
61
68
Cl
Cl
reacts by 1,2-addition to the a,b-unsaturated aldehyde to afford 3 in
61–76% yield (Table 1). The observed regioselectivity is in accor-
dance with the general reactivity of allylindium intermediates,
which favour 1,2- over 1,4-addition. The latter pathway has been
observed in the case of highly activated double bonds13a or when
tetraorganoindium ate complexes are employed as reactants.13b In
addition, formal 1,4-addition was observed when Me2S and TBSOTf
were used as coreactants.13c The reaction cascade depicted by
Scheme 2 and Table 1 does not seem to be significantly affected
3g
OH
I
h
COOMe
3h
COOMe
a
Reaction conditions: aldehyde 1 mol equiv, aryl iodide 1 mol equiv, Pd(OAc)2
10 mol %, PPh3 20 mol %, In 1.5 mol equiv, DMF, allene (Schlenk flask, 85 ꢀC, 12 h).
by the electronic properties of the reactants. Thus, both,
b-alkyl and
b-aryl enones react while electron rich and electron deficient aryl
b
Isolated yield.
halides afford products in comparable yields. The potential dehy-
dratation of diene to the conjugated triene did not significantly
interfere with the reaction.
The potential for 3 to undergo 3,3-sigmatropic rearrangement
was demonstrated using compound 3a, which upon heating in
N-methylpyrrolidinone (NMP) afforded unsaturated aldehyde 4 in
60% yield (Scheme 3).
rearrangement than 3a. While yields for both reactions are com-
parable, under the same conditions, the reaction time is shorter for
diene 6 (3 h vs 6 h, the reactions were monitored by TLC). This is
likely to be the result of the Thorpe–Ingold effect caused by the
additional methyl substituent.14
We have also attempted to use
a,b-unsaturated ketones in
place of aldehydes. Ketones have been used before in allylation
procedures employing indium, but generally the scope of Pd/In
transmetallation methodology in these processes was not fully
investigated. In our hands, the use of methyl vinylketone resulted in
very low conversion (Scheme 4), in the absence of additives.
Longer reaction time did not affect the yield significantly, nei-
ther did a range of different additives such as piperidine and CuI.
However, diene 6 was shown to be more reactive in 3,3-sigmatropic
OH
O
NMP
180 °C
60%
CF3
CF3
3a
4
Scheme 3.

L.A.T. Cleghorn et al. / Tetrahedron 64 (2008) 8731–8737
8733
Table 2
O
HO
Allylation of cyclic ketonesa
I
•
+
Entry Ketone 8
Aryl halide 9
Product
Yieldb
(%)
Pd(OAc)2
CF3
2a
PPh3
5
O
CF3
In
DMF
6
O
I
a
81
64
10a
~10%
OH
NMP
63%
O
180 °C
O
I
CF3
F3C
b
c
O
OH
10b
O
I
OMe
MeO
63
58
7
OH
CF3
10c
Scheme 4.
O
I
d
10d
OH
We have also investigated the reactivity of a group of six-
membered cyclic ketones to the Pd/In allylation cascade. Generally,
ketones have been used in related processes but the reactivity of
2-arylallyl indium species has been little studied.
A series of cyclic ketones 8 were successfully integrated into
the Pd/In cascade reaction affording tertiary alcohols in moderate
to good yields, Scheme 5, Table 2. Under optimised conditions, the
reaction employed Pd(OAc)2/TFP (trifurylphosphine) catalytic sys-
tem and CuI as an additive, which is essential to obtain the products
in good yields.
O
S
I
e
65
84
10e
OH
S
S
I
Cl
Cl
Cl
Cl
f
OH
10f
S
I
g
92
47
OH
O
X
•
OMe
10g
MeO
Ar
I
+
Ar
Pd(OAc)2
S
OH
I
X
9
TFP
In
CuI
DMF
h
10
8 a. X = O
OH
10h
b. X = S
c. X = NCOOEt
d. X = CH2
O
NCOOEt
I
77c
Scheme 5.
i
OH
10i
N
Cyclic ketones, such as cyclohexanone or heteroatom
substituted cyclohexanones, afforded the products in the reaction
with various aryl iodides in comparable yields.
COOEt
NCOOEt
I
j
61c
58c
72c
94d
10j
The pyran 8a and thiopyran 8b reacted much faster (3 h) than
cyclohexanone (19 h) or the N-substituted piperidone 8c (24 h).
This trend did not correlate with the IR stretching frequency or the
13C chemical shift of the C]O moiety of the ketone. It is not clear,
which step, Pd or In promoted, is influenced by the heteroatom. If
it is the latter one, the transition state may involve chelation of
allyl-In by the heteroatom via the boat or the twisted boat con-
formation of the six-membered ring (Fig. 1). This would increase
the polarisation of the carbonyl group making it more reactive as
well as providing a lower energy, structured, transition state. Some
ketones additionally activated by electron withdrawing sub-
stituents are known to be reactive in related processes.9 In case of
the piperidone derivative this transition state would involve the
carbamate oxygen rather than N-atom, creating the eight-mem-
bered chelate. Although known for many metals, these chelates are
generally considered less favoured than their five- or six-mem-
bered equivalents.15 The coordinating ability of DMF, used as a
solvent, may suppress formation of the eight-membered cyclic
transition state. In addition, inspection of molecular models sug-
gested that the keto and the carbamate oxygen are not ideally
positioned to allow formation of the chelate. Alternatively, the
heteroatom may help solubilising indium. This would suggest that
additives other than those already studied9 may be beneficial.16 The
observed effect remains to be studied in more detail.
OH
OMe
Me
MeO
NCOOEt
I
k
l
OH
10k
I
NCOOEt
OH
S
10l
S
O
I
m
10m
OH
I
OMe
88d
MeO
n
OH
10n
a
Reaction conditions: aryl iodide 1.5 mol equiv, ketone 1 mol equiv, Pd(OAc)2
10 mol %, TFP 20 mol %, CuI 40 mol %, In 1.5 mol equiv, DMF, allene (Schlenk flask,
85 ꢀC, 3 h).
b
Isolated yield.
c
Time: 24 h at 85 ꢀC.
d
Time: 19 h at 85 ꢀC.

8734
L.A.T. Cleghorn et al. / Tetrahedron 64 (2008) 8731–8737
142.63, 136.80, 133.88, 133.57, 127.77, 123.56, 117.24 (ArC, C],
CH2]), 71.24 (COH), 43.56 (CH2 allyl), 18.00 (vinyl–CH3). nmax
(film)/cmꢂ1: 3348 (OH), 1673, 1628, 1415, 1026, 720. HRMS (CI) m/z
calcd for C12H16NO 190.1226, found 190.1231.
O
In
R
X
Figure 1.
3.2.3. (E)-2-p-Tolylhepta-1,5-dien-4-ol (3c)
Isolated as a pale yellow oil (76%).
In conclusion, it has been shown that a,b-unsaturated aldehydes
dH (500 MHz): 7.29 (d, 2H, ArH), 7.15 (d, 2H, ArH), 5.61 (m, 1H,
vinyl–H), 5.52 (m,1H, vinyl–H), 5.38 (s,1H, ]CH2), 5.13 (s,1H, ]CH2),
4.10 (m,1H, CH), 2.76 (m,1H, CH2 allyl), 2.65 (m,1H, CH2 allyl), 2.35 (s,
3H, CH3Ar), 1.56 (s, 3H, vinyl–CH3). dC (75 MHz): 145.20, 137.99,
137.87,133.68,129.51,127.30,126.47 (ArC, C]),115.05 (CH2]), 70.99
(COH), 44.29 (CH2 allyl), 21.49 (CH3Ar), 18.05 (vinyl–CH3). nmax
(film)/cmꢂ1: 3368 (OH), 3083 (ArH), 1625, 1513, 1447, 1030, 825.
HRMS (CI) m/z calcd for C14H18OþNa 225.1250, found 225.1252.
efficiently participate in the Pd/In promoted allylation processes
affording exclusively products of 1,2-addition. Related unsaturated
ketones are less reactive and afford the product but with a poor
conversion. On the other hand cyclic saturated ketones under
optimised conditions, in the presence of CuI, proved to be a good
substrates for these transformations yielding the products in good
yields.
3. Experimental
3.1. General
3.2.4. (E)-2-[4-(1H-Pyrrol-1-yl)phenyl]hepta-1,5-dien-4-ol (3d)
Isolated as a pale yellow oil (75%), which solidified upon
standing, mp 81–82 ꢀC.
dH (500 MHz): 7.47 (d, 2H, ArH), 7.37 (d, 2H, ArH), 7.10 (s, 2H,
ArH), 6.35 (s, 2H, ArH), 5.50 (m, 1H, vinyl–H), 5.45 (m, 1H, vinyl–H),
5.42 (s, 1H, ]CH2), 5.19 (s, 1H, ]CH2), 4.10 (m, 1H, CH), 2.76 (m, 2H,
CH2 allyl), 2.69 (m, 2H, CH2 allyl), 1.56 (s, 3H, vinyl–CH3). dC
(75 MHz): 144.04, 140.09, 137.93, 133.24, 127.41, 127.16, 120.27,
119.21, 115.36, 110.53 (ArC, C]C, CH2]), 70.79 (COH), 43.70 (CH2
allyl), 17.65 (vinyl–CH3). HRMS (CI) m/z calcd for C17H20NO
254.1539, found 254.1539.
Nuclear magnetic resonance spectra were recorded using
Bruker DPX300 and DRX500 MHz spectrometers. Chemical shifts
are reported in parts per million (d) relative to the internal refer-
ence tetramethylsilane. Unless otherwise specified, NMR spectra
were recorded in CDCl3 at room temperature. Mass spectra were
recorded using a micromass ZMD 2000 using electrospray ionisa-
tion. Infrared spectra were recorded using a Perkin–Elmer FTIR
spectrometer. Microanalysis was performed using a Carlo–Erba
1108 elemental analyser. Chromatography columns were prepared
3.2.5. (E)-2-(Thiophen-3-yl)hepta-1,5-dien-4-ol (3e)
using Fisher Chemicals 60A 35–70 mm silica gel. Unless otherwise
stated, all reagents were obtained from commercial suppliers and
used without further purification.
Isolated as a pale yellow oil (65%).
dH (500 MHz): 7.28 (m, 3H, ArH), 5.69 (m, 1H, vinyl–H), 5.55 (m,
1H, vinyl–H), 5.48 (s, 1H, ]CH2), 5.12 (s, 1H, ]CH2), 4.24 (m, 1H,
CH), 2.73 (m,1H, CH2 allyl), 2.59 (dd,1H, CH2 allyl, J 14.1 and 8.6 Hz),
1.56 (s, 3H, vinyl–CH3). dC (75 MHz): 141.95, 139.33, 133.29, 127.07,
126.62, 125.82, 120.78, 114.00 (ArC, C]C, CH2]), 70.84 (COH),
44.07 (CH2 allyl), 17.67 (vinyl–CH3). nmax (film)/cmꢂ1: 3390 (OH),
3103, 1625, 1446, 1028, 996. HRMS (CI) m/z calcd for C11H14OSþNa
217.0658, found 217.0667.
3.2. General procedure for Pd/In mediated allylation of
unsaturated aldehydes
Aryl iodide (1.4 mmol), aldehyde (1.4 mmol), indium powder
(100 mesh, 1.5 equiv), Pd(OAc)2 (0.14 mmol), PPh3 (0.28 mmol) and
DMF (10 mL) were added sequentially to a Schlenk tube, which was
then sealed, subjected to two freeze/pump/thaw cycles followed by
the addition of allene gas (w1 bar). The tube was allowed to warm
to room temperature and then heated at 85 ꢀC for 12 h before
cooling to room temperature and venting. Et2O (40 mL) and H2O
(10 mL) were added and the mixture was stirred for 20 min, the
aqueous layer separated and extracted with Et2O (3ꢁ15 mL).
The combined Et2O extracts were washed with H2O (4ꢁ20 mL), the
organic phase dried over MgSO4, filtered and the filtrate evaporated
under reduced pressure. The crude residue was purified by column
chromatography (SiO2, petrol ether/Et2O) to afford the product.
3.2.6. (E)-1-Phenyl-5-p-tolylhexa-1,5-dien-3-ol (3f)
Isolated as a pale yellow oil (74%).
dH (500 MHz): 7.34–7.25 (m, 9H, ArH), 6.54 (d, 1H, vinyl–H, J
15.9 Hz), 6.21 (dd, 1H, vinyl–H, J 15.9 and 6.4 Hz), 5.40 (s, 1H,
]CH2), 5.17 (s, 1H, ]CH2), 4.36 (m, 1H, CH), 2.90 (m, 1H, CH2 allyl),
2.78 (m, 1H, CH2 allyl), 2.35 (s, 3H, CH3Ar). dC (75 MHz): 144.56,
137.61, 137.53, 136.78, 131.61, 130.20, 129.21, 128.53, 127.59, 126.48,
126.21 (ArC, C]), 115.06 (CH2]), 70.66 (COH), 44.00 (CH2 allyl),
21.11 (CH3Ar). nmax (film)/cmꢂ1: 3368 (OH), 3082 (ArH), 3025, 1513,
1448, 966, 825. HRMS (CI) m/z calcd for C19H20OþNa 287.1406,
found 287.1400.
3.2.1. (E)-2-[4-(Trifluoromethyl)phenyl]hepta-1,5-dien-4-ol (3a)
Isolated as a pale yellow oil (72%).
3.2.7. (E)-5-(3,4-Dichlorophenyl)-1-phenylhexa-1,5-dien-3-ol (3g)
Isolated as a pale yellow oil (61%).
dH (500 MHz): 7.59 (d, 2H, ArH), 7.52 (d, 2H, ArH), 5.62 (m, 1H,
vinyl–H), 5.50 (m, 1H, vinyl–H), 5.44 (s, 1H, ]CH2), 5.27 (s, 1H,
]CH2), 4.10 (m, 1H, H–COH), 2.75 (m, 2H, CH2 allyl), 1.56 (m, 3H,
vinyl–CH3). dC (75 MHz): 144.50, 144.13, 133.16, 127.41, 126.63,
125.44, 125.34, 125.29, 117.24 (ArC, C], CH2], CF3), 70.88 (COH),
43.51 (CH2), 34.39 (CH2 allyl), 17.24 (vinyl–CH3). HRMS (CI) m/z
calcd for C14H15F3OþNa 279.0967, found 279.096.
dH (500 MHz): 7.50 (s, 1H, ArH), 7.40 (d, 1H, ArH), 7.32 (m, 5H,
ArH), 7.23 (d, 1H, ArH), 6.52 (d, 1H, vinyl–H, J 15.9 Hz), 6.18 (dd, 1H,
vinyl–H, J 15.9 and 6.6 Hz), 5.41 (s, 1H, ]CH2), 5.26 (s, 1H, ]CH2),
4.34 (m, 1H, CH), 2.78 (m, 2H, CH2 allyl). dC (75 MHz): 142.83,
140.89, 136.45, 132.64, 131.64, 131.21, 130.75, 130.37, 128.61, 128.35,
127.82, 126.49, 125.68 (ArC, C]), 117.18 (CH2]), 70.91 (COH), 43.47
(CH2 allyl), 21.11 (CH3Ar). nmax (film)/cmꢂ1: 3368 (OH), 3083 (ArH),
35
3.2.2. (E)-2-(Pyridin-3-yl)hepta-1,5-dien-4-ol (3b)
1473, 1028, 966. HRMS (CI) m/z calcd for C
found 341.0465.
H
Cl2OþNa 341.0470,
18 16
Isolated as a pale yellow oil (63%).
dH (500 MHz): 8.65 (s, 1H, ArH), 8.52 (d, 1H, ArH), 7.70 (d, 1H,
ArH), 7.27 (t, 1H, ArH), 5.63 (m, 1H, vinyl–H), 5.50 (m, 1H, vinyl–H),
5.43 (s, 1H, ]CH2), 5.27 (s, 1H, ]CH2), 4.11 (m, 1H, CH), 2.73 (m, 2H,
CH2 allyl), 1.66 (m, 3H, vinyl–CH3). dC (75 MHz): 149.08, 148.10,
3.2.8. (E)-Methyl 4-(4-hydroxy-6-phenylhexa-1,5-dien-2-yl)-
benzoate (3h)
Isolated as a pale yellow oil (68%).

L.A.T. Cleghorn et al. / Tetrahedron 64 (2008) 8731–8737
8735
dH (500 MHz): 8.01 (d, 2H, ArH), 7.50 (d, 2H, ArH), 7.30 (m, 5H,
ArH), 6.52 (d, 1H, vinyl–H, J 15.9 Hz), 6.19 (dd, 1H, vinyl–H, J 15.9
and 6.6 Hz), 5.50 (s, 1H, ]CH2), 5.31 (s, 1H, ]CH2), 4.34 (m, 1H, CH),
3.92 (s, 3H, CH3), 2.87 (m, 2H, CH2 allyl). dC (75 MHz): 166.84 (C]O
ester), 145.26, 144.09, 136.55, 131.32, 130.62, 129.33, 128.57,
127.74, 126.48, 126.33 (ArC, C]), 117.53 (CH2]), 70.90 (COH), 52.12
(CH3–O), 43.61 (CH2 allyl). nmax (film)/cmꢂ1: 3424 (OH), 1720 (C]O
ester), 1607, 1435, 1281, 1118, 966. HRMS (CI) m/z calcd for
3.4.1. 4-(2-Phenylprop-2-en-1-yl)tetrahydro-2H-pyran-4-ol (10a)
Purified by column chromatography (EtOAc, SiO2) to afford the
product as a colourless oil (81%).
C14H18O2 found: C, 77.05; H, 8.5%. Required: C, 77.03; H, 8.3%. dH
(500 MHz): 7.42 (d, 2H, ArH, J 7.3 Hz), 7.34 (t, 2H, ArH, J 7.3 Hz), 7.29
(d, 1H, ArH, J 7.3 Hz), 5.42 (s, 1H, 1a-H), 5.17 (s, 1H, 1b-H), 3.68 (dd,
3H, 3,5-pyran–H, J 4.2 and 2.3 Hz), 3.66 (d, 1H, 5-pyran–H, J 2.3 Hz),
2.76 (s, 2H, 3-H), 1.61 (ddd, 2H, 2-pyran–H, J 14.0, 6.4 and 3.4 Hz),
1.42 (s, 1H, OH) and 1.36 (dd, 2H, 6-pyran–H, J 14.0 and 2.3 Hz). dC
(75 MHz): 144.81, 129.03, 128.21 and 126.84 (ArC), 118.20 (CH2),
C
20H20O3þNa 331.1305, found 331.1303.
3.2.9. 3-Methyl-5-[4-(trifluoromethyl)phenyl]hexa-1,5-dien-
3-ol (6)
69.16, 64.20 (CH2), 48.85 (CH2) and 38.53 (CH2). nmax (film)/cmꢂ1
:
3417 (OH), 3076 (ArH), 2951 and 2862 (CH), 1621 (Ar), 1599,
1572, 1492. m/z (ESþ, %): 242 ([MþNa], 93), 218 ([MþH], 8), 201
([MꢂOH], 100).
Isolated as a pale yellow oil (10%).
dH (500 MHz): 7.56 (d, 2H, ArH), 7.47 (d, 2H, ArH), 5.78 (dd, 1H,
vinyl–H, J 17.2 and 10 Hz), 5.43 (s, 1H, ]CH2), 5.25 (s, 1H, ]CH2),
5.12 (d, 1H, ]CH2, J 17.2 Hz), 4.89 (d, 1H, ]CH2, J 10 Hz), 2.81 (q, 2H,
CH2), 1.22 (s, 3H, CH3). HRMS (CI) m/z calcd for C14H15F3OþNa
279.0967, found 279.0949.
3.4.2. 4-[2-(3-Trifluoromethylphenyl)prop-2-en-1-yl] tetrahydro-
2H-pyran-4-ol (10b)
Purified by column chromatography (Et2O, SiO2) to afford the
product as colourless prisms (64%), mp 39–41 ꢀC.
3.3. General procedure for 3,3-sigmatropic rearrangement
C15H16F3O2 found: C, 62.65; H, 5.9%. Required: C, 62.93; H, 5.9%.
dH (500 MHz): 7.66 (s, 1H, 2-ArH), 7.60 (d, 1H, 6-ArH, J 7.7 Hz), 7.54
(d,1H, 4-ArH, J 7.7 Hz), 7.45 (t,1H, 5-ArH, J 7.7 Hz), 5.49 (s,1H,1a-H),
5.27 (s, 1H, 1b-H), 3.67 (d, 4H, 3,5-pyran–H, J 7.7 Hz), 2.77 (s, 2H,
3-H), 1.64 (dt, 2H, 2,6-pyran–H, J 13.6 and 7.7 Hz), 1.38 (s, 1H, OH)
and 1.35 (s, 2H, 2,6-pyran–H). dC (75 MHz): 143.59 and 143.46
(ArC), 119.82 (CH2), 69.25, 64.06 (CH2), 48.77 (CH2), 38.44 (CH2).
nmax (film)/cmꢂ1: 3427 (OH), 3082 (ArH), 2953 and 2869 (CH), 1626
(Ar), 1489. m/z (ESþ, %): 310 ([MþNa], 93), 269 ([MꢂOH], 100).
Unsaturated alcohol (0.18 mmol) was dissolved in N-methyl-
pyrrolidinone (3 mL) and the mixture heated at 180 ꢀC (oil bath
temperature) under N2 atmosphere. The reaction was monitored
by TLC and when completed the mixture was allowed to cool to
room temperature. Et2O (20 mL) was then added and the mixture
washed with H2O (3ꢁ5mL). The ethereal layer was dried over
MgSO4, filtered and the filtrate evaporated under reduced pressure.
The crude residue was purified by column chromatography (SiO2,
petrol ether/Et2O) to afford the product.
3.4.3. 4-[2-(3-Methoxyphenyl)prop-2-en-1-yl]tetrahydro-2H-
pyran-4-ol (10c)
3.3.1. 3-Methyl-5-phenylhex-5-enal (4)
Purified by column chromatography (Et2O, SiO2) to afford the
product as a colourless oil (63%).
Isolated as a pale yellow oil (60%).
dH (500 MHz): 9.70 (s, 1H, H–CO), 7.59 (d, 2H, ArH), 7.50 (d, 2H,
ArH), 5.38 (s, 1H, ]CH2), 5.17 (s, 1H, ]CH2), 2.61 (m, 1H, CH), 2.43
(m, 2H, CH2–CO), 2.27 (m, 1H, CH2 allyl), 2.13 (m, 1H, CH2 allyl), 0.94
(d, 3H, CH3). HRMS (CI) m/z calcd for C14H15F3OþNa 279.0967,
found 279.0977.
C15H20O3 found: C, 72.25; H, 8.05%. Required: C, 72.55; H, 8.12%.
dH (500 MHz): 7.25 (t, 1H, 5-ArH, J 7.9 Hz), 6.99 (d, 1H, 6-ArH, J
7.9 Hz), 6.94 (s, 1H, 2-ArH), 6.82 (dd, 1H, 4-ArH, J 7.9 and 2.2 Hz),
5.43 (s, 1H, 1a-H), 5.16 (s, 1H, 1b-H), 3.82 (s, 3H, OCH3), 3.67 (s, 4H,
3,5-pyran–H), 2.73 (s, 2H, 3-H), 1.62 (dd, 1H, 2-pyran–H, J 10.2 and
3.4 Hz), 1.60 (dd, 1H, 6-pyran–H, J 6.6 and 3.4 Hz), 1.48 (s, 1H, OH)
and 1.37 (d, 2H, 2,6-pyran–H, J 13.5 Hz). dC (75 MHz): 160.10,144.69,
144.08, 130.03, 119.32 and 113.22 (ArC), 112.90 (CH2), 69.16, 64.19
3.3.2. 6-Phenylhept-6-en-2-one (7)
Isolated as a pale yellow oil (63%).
dH (500 MHz): 7.58 (d, 2H, ArH), 7.49 (d, 2H, ArH), 5.36 (s, 1H,
]CH2), 5.16 (s, 1H, ]CH2), 2.52 (m, 2H, CH2 CO), 2.45 (m, 1H, CH2
allyl), 2.12 (s, 3H, CH3), 1.58 (m, 2H, CH2). dC (75 MHz): 208.43
(C]O), 146.78, 144.50, 126.43, 125.36, 125.30, 125.25, 114.74 (ArC,
C], CH2], CF3), 42.71 (CH2CO), 34.39 (CH2 allyl), 29.99 (CH3–CO),
22.04 (CH2). HRMS (CI) m/z calcd for C14H15F3OþNa 279.0967,
found 279.0969.
(CH2), 55.65 (CH3), 48.94 (CH2) and 38.45 (CH2). nmax (film)/cmꢂ1
:
3425 (OH), 3081 (ArH), 2951 and 2866 (CH), 1598, 1579, 1487, 1465,
1427. m/z (ESþ, %): 349 ([MþH], 10), 231 ([MꢂOH], 35).
3.4.4. 4-[2-(4-Methylphenyl)prop-2-en-1-yl]tetrahydro-2H-pyran-
4-ol (10d)
Purified by column chromatography (Et2O, SiO2) to afford the
product as a colourless oil (55%).
3.4. General procedure for Pd/In mediated allylation
of cyclic ketones
C15H20O2 found: C, 77.55; H, 8.68%. Required: C, 77.15; H, 8.60%.
dH (500 MHz): 7.23 (d, 2H, 2,6-ArH, J 7.9 Hz), 7.06 (d, 2H, 3,5-ArH,
J 7.9 Hz), 5.32 (s, 1H, 1a-H), 5.04 (s, 1H, 1b-H), 3.60–3.58 (m, 4H,
3,5-pyran–H), 2.66 (s, 2H, 3-H), 2.27 (s, 3H, CH3), 1.52 (ddd, 2H, 2,6-
pyran–H, J 14.0, 10.3 and 6.5 Hz), 1.43 (s, 1H, OH) and 1.29 (d, 2H,
2,6-pyran–H, J 13.9 Hz). dC (75 MHz): 143.13, 138.12, 136.52, 128.24,
125.26, 115.96 (CH2), 67.64, 62.72 (CH2), 47.36 (CH2), 37.01 (CH2)
and 20.06. nmax (film)/cmꢂ1: 3428 (OH), 3084 (ArH), 2952 and 2868
(CH), 1622 (Ar), 1512, 1467. m/z (ESþ, %): 218 ([Mþ(HꢂMe)], 86), 177
([Mꢂ(MeþOH)], 100).
Aryl iodide (1.5 mol equiv), cyclic ketone (1 mol equiv), indium
powder (100 mesh, 1.5 mol equiv), Pd(OAc)2 (0.1 mol equiv), TFP
(0.2 mol equiv), CuI (0.4 mol equiv) and DMF (AR, 10 mL/mmol)
were added sequentially to a Schlenk tube, which was then sealed,
subjected to two freeze/pump/thaw cycles followed by the addition
of allene gas (w1 bar). The tube was allowed to warm to room
temperature and then heated at 85 ꢀC for 3–24 h (see Table 2) be-
fore cooling to room temperature and venting. Ether (20 mL) and
H2O (10 mL) were then added and the mixture stirred for 20 min,
the aqueous layer separated and extracted with ether (3ꢁ15 mL)
and the combined ether extracts washed with H2O (4ꢁ20 mL). The
organic phase was dried over MgSO4, filtered and the filtrate
evaporated to dryness. The crude residue was purified by column
chromatography to afford the alcohol.
3.4.5. 4-(2-Phenylprop-2-en-1-yl)tetrahydro-2H-thiopyran-
4-ol (10e)
Purified by column chromatography (9:1 v/v hexane/EtOAc,
SiO2) to afford the product as a colourless oil (65%).
C14H18OS found: C, 72.00; H, 7.65; S, 13.75%. Required: C, 71.75;
H, 7.74; S, 13.68%. dH (500 MHz): 7.39 (d, 2H, ArH, J 7.5 Hz), 7.33

8736
L.A.T. Cleghorn et al. / Tetrahedron 64 (2008) 8731–8737
(t, 2H, ArH, J 7.5 Hz), 7.28 (d, 1H, ArH, J 7.5 Hz), 5.41 (d, 1H, 1a-H, J
1.1 Hz), 5.14 (s, 1H, 1b-H), 2.93 (td, 2H, 3,5-thiopyran–H, Jaxax
18.8 Hz, Jgem 13.7 Hz and Jaxeq 1.8 Hz), 2.70 (s, 2H, 3-H), 2.35 (d, 2H,
3,5-thiopyran–H, Jgem 13.7 Hz), 1.77 (d, 2H, 2,6-thiopyran–H, Jgem
14.0 Hz), 1.65 (td, 2H, 2,6-thiopyran–H, Jgem 14.0 Hz, Jaxax 11.7 Hz
and Jaxeq 3.4 Hz) and 1.32 (s, 1H, OH). dC (75 MHz): 143.18, 141.02,
127.76 and 125.36 (ArC), 117.02 (CH2), 68.65, 47.68 (CH2), 37.62
(CH2) and 23.50 (CH2). nmax (film)/cmꢂ1: 3444 (OH), 3079 and 3049
(ArH), 3021, 2929 and 2851 (CH), 1709, 1602 (Ar), 1596, 1573, 1493.
m/z (EI, %): 234 ([M], 100).
C17H23NO3 found: C, 70.30; H, 7.90; N, 4.85%. Required: C, 70.56;
H, 8.01; N, 4.84%. dH (500 MHz): 7.39 (d, 2H, 2,6-PhH, J 7.1 Hz), 7.33
(t, 2H, 3,5-PhH, J 7.1 Hz), 7.27 (t, 1H, 4-PhH, J 7.1 Hz), 5.42 (d, 1H,
1a-H, J 1.5 Hz), 5.15 (s, 1H, 1b-H), 4.08 (q, 2H, CH2CH3, J 7.1 Hz),
3.77 (br s rotamer, 2H, 2-piperidine–H), 3.08 (br s rotamer, 2H,
6-piperidine–H), 2.73 (s, 2H, 3-H), 1.53 (s, 1H, OH), 1.43 (s, 4H, 3,5-
piperidine–H) and 1.22 (t, 3H, CH2CH3, J 7.1 Hz). dC (75 MHz): 155.87
(C]O), 144.78, 142.48, 129.00, 128.15 and 126.79 (ArC), 118.25
(CH2), 69.87, 48.59 (CH2), 40.17 (CH3), 37.46 (CH2) and 15.10 (CH2).
nmax (film)/cmꢂ1: 3435 (OH), 3076 and 3054 (ArH), 2978, 2949,
2917 and 2873 (CH), 1674 (C]O), 1624, 1572, 1472. m/z (ESþ, %): 580
(dimer), 290 ([MꢂH], 76), 272 ([MꢂOH], 100).
3.4.6. 4-[2-(3,4-Dichlorophenyl)prop-2-en-1-yl]tetrahydro-2H-
thiopyran-4-ol (10f)
Purified by column chromatography (1:1 v/v hexane/Et2O, SiO2)
to afford the product as yellow prisms (84%), mp 44–45 ꢀC.
3.4.10. Ethyl 4-hydroxy-4-[2-(4-methoxyphenyl)prop-2-en-1-
yl]piperidine-1-carboxylate (10j)
C
14H16Cl2OS found: C, 55.35; H, 5.15; S, 10.30%. Required: C,
Purified by column chromatography (Et2O, SiO2) to afford the
product as a yellow oil (61%).
55.45; H, 5.32; S, 10.57%. dH (500 MHz): 7.49 (d, 1H, 2-ArH, J 2.0 Hz),
7.40 (t, 1H, 5-ArH, J 8.3 Hz), 7.24 (dd, 1H, 6-ArH, J 8.3 and 2.0 Hz),
5.44 (d, 1H, 1a-H, J 1.1 Hz), 5.20 (s, 1H, 1b-H), 2.92 (td, 2H, 3,5-
thiopyran–H, Jgem 13.9 Hz, Jaxax 11.9 Hz and Jaxeq 2.4 Hz), 2.66 (s, 2H,
3-H), 2.33 (d, 2H, 3,5-thiopyran–H, Jgem 13.9 Hz), 1.76 (d, 2H, 2,6-
thiopyran–H, Jgem 13.9 Hz), 1.64 (td, 2H, 2,6-thiopyran–H, Jgem
13.9 Hz, Jaxax 11.8 Hz and Jaxeq 3.4 Hz) and 1.22 (s, 1H, OH). dC
(75 MHz): 142.70, 142.59, 130.87, 128.67 and 126.08 (ArC), 119.89
(CH2), 70.28 (CH2), 49.07 (CH2), 39.11 (CH2) and 24.49. nmax (film)/
cmꢂ1: 3429 (OH), 3082 (ArH), 2929 and 2846 (CH), 1648, 1618,
1602, 1547, 1474. m/z (EI, %): 306 ([(37Cl)M], 14), 304 ([(35Cl)þ(37Cl)
M], 73), 302 ([(35Cl)M], 100).
C
18H25NO4 found: C, 67.55; H, 7.70; N, 4.50%. Required: C, 67.69;
H, 7.89; N, 4.39%. dH (500 MHz): 7.39 (d, 2H, 2,6-ArH, J 7.1 Hz),
7.33 (t, 2H, 3,5-ArH, J 7.1 Hz), 5.42 (d, 1H, 1a-H, J 1.5 Hz), 5.15 (s, 1H,
1b-H), 4.09 (q, 2H, CH2CH3, J 7.1 Hz), 3.81 (s, 3H, OCH3 and 2H, 2,6-
piperidine–H), 3.08 (br s rotamer, 2H, 2,6–piperidine–H), 2.70 (s,
2H, 3-H), 1.50 (s, 1H, OH), 1.43 (s, 4H, 3,5-piperidine–H) and 1.22 (t,
3H, CH2CH3, J 7.1 Hz). dC (75 MHz): 159.71, 155.88 (C]O), 144.02,
134.68, 127.95 and 116.68 (ArC), 114.34 (CH2), 69.83, 61.56 (CH2),
55.67, 48.54 (CH2), 43.42, 40.20, 37.56 (CH2) and 15.10. nmax (film)/
cmꢂ1: 3443 (OH), 3082 (ArH), 2983, 2953 and 2838 (CH), 1678
(C]O), 1607 (Ar), 1573, 1467, 1440, 1352. m/z (ESþ, %): 320 ([MþH],
53), 302 ([MꢂOH], 54).
3.4.7. 4-[2-(4-Methoxyphenyl)prop-2-en-1-yl]tetrahydro-2H-
thiopyran-4-ol (10g)
Purified by column chromatography (1:1 v/v hexane/Et2O, SiO2)
to afford the product as a yellow oil (92%).
3.4.11. Ethyl 4-hydroxy-4-[2-(2-thienyl)prop-2-en-1-yl]piperidine-
1-carboxylate (10l)
Purified by column chromatography (Et2O, SiO2) to afford the
product as a yellow oil (72%).
C15H20O2S found: C, 68.15; H, 7.70; S, 12.90%. Required: C, 68.14;
H, 7.62; S, 12.13%. dH (500 MHz): 7.34 (d, 2H, 2,6-ArH, J 8.7 Hz), 6.86
(d, 2H, 3,5-ArH, J 8.7 Hz), 5.35 (d, 1H, 1a-H, J 1.1 Hz), 5.06 (s, 1H, 1b-
H), 3.82 (s, 3H, OCH3), 2.91 (td, 2H, 3,5-thiopyran–H, Jgem 13.7 Hz,
Jaxax 11.9 Hz and Jaxeq 2.1 Hz), 2.68 (s, 2H, 3-H), 2.32 (d, 2H, 3,5-
thiopyran–H, Jgem 13.7 Hz), 1.78 (d, 2H, 2,6-thiopyran–H, Jgem
13.9 Hz), 1.63 (td, 2H, 2,6-thiopyran–H, Jgem 13.9 Hz, Jaxax 11.8 Hz
and Jaxeq 3.3 Hz) and 1.38 (s, 1H, OH). dC (75 MHz): 159.72, 143.93,
134.76 and 116.85 (ArC), 114.36 (CH2), 70.09, 55.70 (CH3), 49.12
(CH2), 39.18 (CH2) and 24.62 (CH2). nmax (film)/cmꢂ1: 3450 (OH),
3076 (ArH), 2932 and 2835 (CH), 1607 (Ar), 1572, 1511, 1441. m/z
(ESþ, %): 265 ([MþH], 100), 249 ([MꢂOH], 43).
C15H21NO4S found: C, 61.2; H, 7.0; N, 4.6%. Required: C, 61.0; H,
7.2; N, 4.7%. dH (500 MHz): 7.18 (d, 1H, thienyl 5-H, J 5.1 Hz), 7.06 (d,
1H, thienyl 3-H, J 3.7 Hz), 6.96 (t, 1H, thienyl 4-H, J 5.1 and 3.7 Hz),
5.57 (s, 1H, 1a-H), 5.02 (s, 1H, 1b-H), 4.08 (q, 2H, CH2CH3, J 7.1 Hz),
3.86 (br s rotamer, 2H, 2-piperidine–H), 3.11 (br s rotamer, 2H,
piperidine 6-H), 2.67 (s, 2H, 3-H), 1.66 (s, 1H, OH), 1.53 (s, 4H, 3,5-
piperidine–H) and 1.24 (t, 3H, CH2CH3, J 7.1 Hz). dC (75 MHz): 155.90
(C]O), 146.20, 137.36, 127.96, 125.35 and 124.98, 116.20 (CH2),
69.69 (CH2), 61.62, 48.94 (CH2), 43.41, 40.18, 37.38 (CH2), 15.10. nmax
(film)/cmꢂ1: 3433 (OH), 3104 and 3082 (ArH), 2978, 2923 and 2873
(CH), 2241, 1674 (C]O), 1613, 1472, 1385, 1352. m/z (ESþ, %): 296
([MþH], 86), 278 ([MꢂOH], 46).
3.4.8. 4-[2-(4-Methylphenyl)prop-2-en-1-yl]tetrahydro-2H-
thiopyran-4-ol (10h)
Purified by column chromatography (1:1 v/v hexane/Et2O, SiO2)
to afford the product as a yellow oil (47%).
3.4.12. Ethyl 4-hydroxy-4-[2-(4-methylphenyl)prop-2-en-1-
yl]piperidine-1-carboxylate (10k)
Purified by column chromatography (Et2O, SiO2) to afford the
product as a yellow oil (58%).
C15H20OS found: C, 72.5; H, 8.1; S, 12.75%. Required: C, 72.5; H,
8.1; S, 12.91%. dH (500 MHz): 7.29 (d, 2H, 2,6-ArH, J 8.0 Hz), 7.14 (d,
2H, 3,5-ArH, J 8.0 Hz), 5.38 (d, 1H, 1a-H, J 1.1 Hz), 5.09 (s, 1H, 1b-H),
2.90 (td, 3,5-thiopyran–H, Jgem 14.3 Hz, Jaxax 11.4 Hz and Jaxeq
2.4 Hz), 2.69 (s, 2H, 3-H), 2.34 (s, 3H, CH3), 2.30 (d, 2H, 3,5-H, Jgem
14.3 Hz), 1.77 (d, 2H, 2,6-H, Jgem 14.0 Hz), 1.63 (td, 2H, 2,6-H, Jgem
14.0 Hz, Jaxax 11.7 Hz and Jaxeq 3.3 Hz) and 1.36 (s, 1H, OH). dC
(75 MHz): 144.10, 139.14, 137.65, 129.33 and 126.29 (ArC), 117.18
(CH2), 69.69, 48.71 (CH3), 38.77 (CH2), 24.26 (CH2) and 21.06 (CH2).
nmax (film)/cmꢂ1: 3453 (OH), 3082 and 3021 (ArH), 2920 and 2851
(CH), 1709, 1651, 1620, 1563. m/z (ESþ, %): 249 ([MþH], 71).
C18H25NO3 found: C, 71.1; H, 8.2; N, 4.45%. Required: C, 71.2; H,
8.3; N, 4.62%. dH (500 MHz): 7.22 (d, 2H, 2,6-ArH, J 8.0 Hz), 7.06 (d,
2H, 3,5-ArH, J 8.0 Hz), 5.31 (s, 1H, 1a-H), 5.03 (s, 1H, 1b-H), 4.01 (q,
2H, CH2CH3, J 7.1 Hz), 3.71 (br s rotamer, 2H, 2-piperidine–H), 3.00
(br s rotamer, 2H, 6-piperidine–H), 2.64 (s, 2H, 3-H), 2.27 (s, 3H,
CH3), 1.45 (s, 1H, OH), 1.36 (s, 4H, 3,5-piperidine–H) and 1.15 (t, 3H,
CH2CH3, J 7.1 Hz). dC (75 MHz): 155.90 (C]O),146.20,137.36,127.96,
125.35 and 124.98 (ArC), 116.20 (CH2), 69.69, 61.62 (CH2), 48.94
(CH2), 43.41, 40.18, 37.38 (CH2) and 15.10. nmax (film)/cmꢂ1: 3433
(OH), 3104, 3082 (ArH), 2978, 2923 and 2873 (CH), 1674 (C]O),
1613, 1472, 1385. m/z (ES, %): 304 ([MþH], 33), 286 ([MꢂOH], 100).
3.4.9. Ethyl 4-hydroxy-4-(2-phenylprop-2-en-1-yl)piperidine-1-
carboxylate (10i)
Purified by column chromatography (1:1 v/v hexane/Et2O, SiO2)
to afford the product as a yellow oil (77%).
3.4.13. 1-(2-Phenylprop-2-en-1-yl)cyclohexanol (10m)
Purified by column chromatography (8:2 v/v hexane/EtOAc,
SiO2) to give the product as a yellow oil (88%).

L.A.T. Cleghorn et al. / Tetrahedron 64 (2008) 8731–8737
8737
Chem. Soc. 1999, 121, 3238–3239; Quan, L. G.; Gevorgyan, V.; Yamamoto, Y.
J. Am. Chem. Soc. 1999, 121, 3545–3546.
C15H20O found: C, 83.05; H, 9.6%. Required: C, 83.29; H, 9.3%. dH
(300 MHz): 7.43–7.27 (m, 5H, PhH), 5.38 (d, 1H, 1a-H, J 1.8 Hz),
5.14 (d, 1H, 1b-H, J 0.8 Hz), 2.73 (s, 2H, 3-H) and 1.58–1.13 (m, 11H,
cyclohexane–H and OH). dC (75 MHz): 145.74,143.03,128.83,127.89
and 126.91, 117.76 (CH2), 71.76 (CH), 48.13 (CH2), 38.26 (CH2), 26.12
(CH2), 22.55 (CH2). nmax (film)/cmꢂ1: 3434 (OH), 2931 and 2857
(CH), 1623, 1598 and 1576 (ArC), 1429, 1446. m/z (ESþ, %): 199
([MꢂOH], 56%).
4. For some recent reviews see: Zanoni, G.; Pontiroli, A.; Marchetti, A.; Vidari, G.
Eur. J. Org. Chem. 2007, 3599–3611; Marshall, J. Chem. Rev. 2000, 100, 3163–
3185; Tamaru, Y. J. Organomet. Chem. 1999, 576, 215–231; For recent papers,
see: Kimura, M.; Mukai, R.; Tamaki, T.; Horino, Y.; Tamaru, Y. J. Am. Chem. Soc.
2007, 129, 4122–4123; Hopkins, C. D.; Malinakova, H. C. Org. Lett. 2006, 8, 5971–
5974; Howell, G. P.; Minnaard, A. J.; Feringa, B. L. Org. Biomol. Chem. 2006, 4,
1278–1283; Zanoni, G.; Gladiali, S.; Marchetti, A.; Piccinini, P.; Tredici, I.; Vidari,
G. Angew. Chem., Int. Ed. 2004, 43, 846–849; Gomez, A. M.; Barrio, A.; Pedregosa,
A.; Valverde, S.; Lopez, J. C. Tetrahedron Lett. 2003, 44, 8433–8435; Araki, S.;
Kambe, S.; Kameda, K.; Hirashita, T. Synthesis 2003, 751–754.
3.4.14. 1-(2-(3-Methoxyphenyl)-prop-2-en-1-yl)cyclohexanol
(10n)
Purified by column chromatography (9:1 v/v hexane/EtOAc,
SiO2) to give the product as a yellow oil (216 mg, 94%).
5. Norsikian, S.; Lubineau, A. Org. Biomol. Chem. 2005, 3, 4089–4094; Miyabe, H.;
Yamaoka, Y.; Naito, T.; Takemoto, Y. J. Org. Chem. 2004, 69, 1415–1418; Hirashita,
T.; Kamei, T.; Satake, M.; Horie, T.; Shimizu, H.; Araki, S. Org. Biomol. Chem.
2003, 1, 3799–3803; Tang, T.; Keum, G.; Kang, S. B.; Chung, B. Y.; Kim, Y. Syn-
thesis 2003, 775–779; Cooper, I. R.; Grigg, R.; MacLachlan, W. S.; Sridharan, V.;
Thornton-Pett, M. Tetrahedron Lett. 2003, 44, 403–405; Kang, S.; Lee, S.; Jung, J.;
Lim, Y. J. Org. Chem. 2002, 67, 4376–4379; Araki, S.; Kameda, K.; Tanaka, J.;
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Kilner, C.; McCaffrey, S.; Savic, V.; Sridharan, V. Tetrahedron, submitted for
publication.
9. Cleghorn, L. A. T.; Cooper, I. R.; Fishwick, C. W. G.; Grigg, R.; MacLachlan, W. S.;
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C
16H22O2 found: C, 77.8; H, 9.0%. Required: C, 78.0; H, 9.0%. dH
(500 MHz): 7.24 (t, 1H, 5-ArH, J 7.9 Hz), 7.00 (d, 1H, 6-ArH, J 7.9 Hz),
6.95 (t, 1H, 2-ArH, J 2.2 Hz), 6.81 (dd, 1H, 4-ArH, J 7.9 and 2.2 Hz),
5.38 (d, 1H, 1a-H, J 1.7 Hz), 5.14 (s, 1H, 1b-H), 3.81 (s, 3H, CH3), 2.70
(s, 2H, 3-H), 1.54–1.33 (m, 9H, cyclohexane–H), 1.39 (s, 1H, OH) and
1.28 (d, 1H, cyclohexanol–H, J 10.3 Hz). dC (75 MHz): 159.98, 145.62,
144.61 and 129.81 (ArC), 119.44 (CH2), 117.88, 113.00 and 112.92
(ArC), 71.75 (CH), 55.64 (CH3), 48.24 (CH2), 38.21 (CH2), 26.12 (CH2)
and 22.56 (CH2). nmax (film)/cmꢂ1: 3435 (OH), 2935 and 2858 (CH),
1598, 1576, 1489, 1449, 1238. m/z (ESþ, %): 230 ([MꢂOH]þ, 22), 278
([MꢂOH], 97).
Acknowledgements
We thank Leeds University and the Serbian Ministry of Science
(grant no. 142071 and 142072) for support.
10. Miles, R. B.; Davis, C. E.; Coates, R. M. J. Org. Chem. 2006, 71, 1493–1501; Han, X.;
Widenhoefer, R. A. Organometallics 2007, 26, 4061–4065.
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