Intermolecular rhodium catalyzed hydroacylation of allenes: the regioselective synthesis of β,γ-unsaturated ketones

Article abstract of DOI:10.1016/j.tet.2009.03.054

A variety of β-S-substituted aldehydes undergo efficient and regioselective rhodium catalyzed hydroacylation reactions with 1,3-disubstituted and 1,1,3-trisubstituted allenes, to deliver β,γ-unsaturated ketone products. Regioselectivites are controlled pr

Full text of DOI:10.1016/j.tet.2009.03.054

Tetrahedron 65 (2009) 5110–5117
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Intermolecular rhodium catalyzed hydroacylation of allenes: the regioselective
synthesis of b,g-unsaturated ketones
,
Helen E. Randell-Sly a, James D. Osborne b, Robert L. Woodward a, Gordon S. Currie c, Michael C. Willis b
*
a Department of Chemistry, University of Bath, Bath BA2 7AY, UK
b Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK
c AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of
b
-S-substituted aldehydes undergo efficient and regioselective rhodium catalyzed hydro-
-unsaturated
Received 4 February 2009
Received in revised form 18 March 2009
Accepted 19 March 2009
acylation reactions with 1,3-disubstituted and 1,1,3-trisubstituted allenes, to deliver
ketone products. Regioselectivites are controlled primarily by steric factors. The reactions are catalyzed
by the complex [Rh(dppe)]ClO4.
b,g
Available online 27 March 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
number of examples of di- or trisubstituted alkenes being
employed is small.
Transition metal catalyzed alkene hydroacylation, in which the
elements of an aldehyde are added across an alkene, is an attractive,
atom-economic, method for the preparation of ketone containing
products. The process was originally reported as an intramolecular
reaction,1 and it is in the preparation of cyclic ketones that the
reaction has received most attention.2 Competing metal catalyzed
decarbonylation limited early examples to the preparation of
cyclopentanone derivatives, although more recently methods for
the synthesis of larger ring systems have also been described.3
Enantioselective intramolecular reactions have also been de-
veloped.4 Intermolecular hydroacylation is similarly complicated
by decarbonylation processes; a number of strategies have been
developed to overcome this, including the use of elevated tem-
peratures and/or pressures of CO or ethene.5 Brookhart has shown
that Rh- and Co-cyclopentadienyl complexes can generate effective
catalysts,6 and recently a number of oxidative protocols have been
described.7 The Jun group has focused on the in situ generation of
picolyl-imines to achieve efficient hydroacylation reactions.8 The
use of substrates able to provide chelation-stabilization of the key
acyl-metal species, and thus limit decarbonylation, has also been
shown to deliver successful reactions.9 In spite of these advances,
a general limitation of intermolecular reactions is the relatively
narrow scope of the alkene components that can be employed,
which consequently limits the structures accessible using hydro-
acylation chemistry. Although alkenes bearing a variety of func-
tional groups have been employed in hydroacylation reactions, the
Allenes have emerged as useful C]C components in a variety of
transition metal catalyzed processes, often providing reactivity
contrasting to simple alkenes or alkynes.10 A number of asymmetric
processes based on selective additions to achiral allenes, or
exploiting the axially chiral nature of certain allenes, have also been
documented.11 Despite this proven utility, the use of allenes in
hydroacylation reactions is virtually unknown, with only a single
report describing the use of mono- and 1,1-disubstituted allenes in
combination with salicylaldehydes.12 In this manuscript we
establish that di- and trisubstituted allenes are effective substrates
in Rh-catalyzed hydroacylation reactions, providing access to syn-
thetically useful substituted
b,g-unsaturated ketone products in
good yields and with high regioselectivities (Scheme 1).13
2. Results and discussion
We have recently shown that when combined with cationic
Rh(I) catalysts, b-S-substituted aldehydes generate chelation sta-
bilized acylrhodium hydride intermediates, and are effective sub-
strates in intermolecular alkene and alkyne hydroacylation
reactions.14,15 To determine the compatibility of di- and tri-
substituted allenes in intermolecular hydroacylation chemistry we
O
O
R2
cat.
cat.
R3
R3
R1
R1
R1
R3
H
R2
O
O
R3
R2
R1
H
R2
* Corresponding author. Tel.: þ44 1865 285126; fax: þ44 1865 285002.
E-mail address: michael.willis@chem.ox.ac.uk (M.C. Willis).
Scheme 1. Alkene and allene hydroacylation.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.054

H.E. Randell-Sly et al. / Tetrahedron 65 (2009) 5110–5117
5111
MeS
MeS
addition across the least hindered C]C bond in a 1,3-dialkyl-
substituted allene (Pent vs i-Pr). Entries 18–23 show the good
yields and regioselectivities obtained when aldehyde 7 is combined
with a series of di- and trisubstituted allenes. Entries 24 and 25
demonstrate that simple hetero-aromatic aldehydes can also be
employed, with the adducts from the hexy,furyl- and hexyl,thienyl-
disubstituted allenes being isolated in excellent yields as single
regioisomers. The final two entries explore the effect of electroni-
cally differentiated 1,3-diaryl-substituted allenes; reaction with the
Ph,(4-CF3-Ph)-disubstituted allene resulted in a slight preference
for addition next to the more electron-poor arene (1.8:1). When the
Ph,(4-OMe-Ph)-disubstituted allene was employed, addition across
the PhC]C was favoured, albeit with similarly low selectivity
(1.6:1) and with only modest efficiency (32%).
O
Pent
Me
[Rh(dppe)]ClO4
MeS
MeS
O
4
Me
Pent
acetone
55 °C, 8 h
97%
Me
H
O
1
2
4:5, 1.25:1
5
Pent
Me
Me
MeS
O
[Rh(dppe)]ClO4
O
Me
acetone
55 °C, 16 h
80%
Et
H
1
3
6
Me
Et
Scheme 2. Hydroacylation of allenes 2 and 3.
first examined the reactions between
b
-MeS-propanal (1) and both
Scheme 3 illustrates the use of two further
dehydes in efficient, regioselective allene hydroacylation reactions.
-Dithiane-substituted propanal (8) underwent smooth reaction
with the Pent,i-Pr-disubstituted allene, with addition proceeding
across the Pent-substituted C]C bond. The second reaction fea-
tures the addition of 1-deuterated o-MeS-benzaldehyde (d-7) to
the Pent,Ph-disubstituted allene. Ketone 9 was obtained in good
yield, as a single regioisomer, and only featured deuterium in-
b-S-substituted al-
1,3-disubstituted allene 2, and 1,1,3-trisubstituted allene 3 (Scheme
2). The reactions were performed in acetone at 55 ꢀC, using
[Rh(dppe)]ClO4 as the catalyst, and pleasingly, both combinations
provided good yields of the hydroacylation products. The reaction
employing the Me-,Pent-disubstituted allene (2) delivered a mix-
ture of the two regioisomeric adducts 4 and 5 in a 1.25:1 ratio, with
a slight preference for the smaller Me-substituent next to the car-
bonyl. The transformation employing the trisubstituted allene (3)
took a longer time to reach completion (16 h vs 8 h), but provided
a single product (6), resulting from addition across the less-hin-
dered C]C bond of the allene.
b
corporation at the position
b to the carbonyl. Deuterium in-
corporation at this single position indicates that reversible addition
of the acylrhodium deuteride in the opposite regioselective sense,
i.e., formation of an intermediate corresponding to structure 10, is
not occurring, and that the reaction most likely proceeds through
an intermediate such as 11.
Having established the feasibility of intermolecular hydro-
acylation reactions between allenes and
b-S-substituted alde-
hydes, we moved on to explore the scope of the process with
respect to the allene. Given the mixture of products obtained
from the combination of aldehyde 1 and Me-,Pent-disubstituted
allene (2), we were particularly keen to probe the effect of the
allene substituents on the regioselectivity of the reactions (Table
3. Conclusion
We have demonstrated that
b-S-substituted aldehydes un-
dergo high yielding, highly regioselective hydroacylation re-
actions with both 1,3-disubstituted and 1,1,3-trisubstituted
allenes. For di- or trialkylsubstituted allenes the regioselectivity
is controlled by steric factors, however, for aryl,alkyl-di-
substituted allenes, the low reactivity of the aryl-substituted
alkene results in addition across the alkyl-substituted C]C
bond. For allenes substituted with only alkyl- or aryl-sub-
stituents, or combinations of the two, only non-conjugated
enone products are obtained; the corresponding conjugated
enones are not observed. The described methodology represents
a significant addition to the substitution patterns that can be
accessed using hydroacylation chemistry, and provides a direct
1).
b-MeS-propanal (1) and o-MeS-benzaldehyde (7) were se-
lected as the standard aldehydes and used in combination with
[Rh(dppe)]ClO4 as the catalyst. The first 16 entries employ al-
dehyde 1. Entries 1–14 demonstrate the effective coupling of
aldehyde 1 with a variety of mono-, di- and trisubstituted
allenes, delivering the hydroacylation adducts in good to excel-
lent yields. For dialkyl-substituted allenes, provided that there is
a reasonable difference in the steric requirements of the two
substituents, reaction takes place across the least hindered C]C
bond with good regioselectivity. For example, in entry 4 the
Pent-,i-Pr-allene delivers the hydroacylation adducts with 15:1
selectivity favouring addition across the pentyl-substituted C]C
bond. For aryl-,alkyl-disubstituted allenes, reaction occurs
exclusively across the alkyl-substituted C]C bond; for example,
in entry 5 the Ph-,Pent-allene delivers the expected adduct
with >20:1 regioselectivity. When trisubstituted allenes are
employed addition again takes place exclusively across the least
hindered C]C bond; for example, in entry 10 1,1-dimethyl-3-Ph-
allene undergoes reaction selectively across the Ph–C]C bond.
Entries 15 and 16 feature ethyl ester substituted allenes; as
shown in entry 15 the Me-,CO2Et-substituted allene delivered
a single compound in 96% yield. Although the adduct results
from addition across the least hindered Me-substituted C]C
bond, the final product has the alkene conjugated with the ke-
tone carbonyl and not the ester carbonyl. This is attributed to
isomerization after the initial addition. Reaction with the
H-,CO2Et-substituted allene resulted in a 1:1 mixture of prod-
ucts, both originating from addition across the more accessible
C]C of the allene, but differing in the position of the conjugated
alkene (entry 16).
and efficient route to synthetically challenging b,g-unsaturated
ketones. Importantly, the majority of products obtained from
di- or trisubstituted allene hydroacylation reactions feature
a stereogenic centre, therefore presenting the possibility of
enantioselective catalysis.13,20
4. Experimental section
4.1. General information
All reactions were performed under an inert atmosphere of ni-
trogen, in oven or flame dried glassware. Aldehydes 1 and 7 were
purchased from Aldrich Chemical Company and distilled under
reduced pressure before use. The rhodium catalyst,16 allenes17 and
aldehydes 818 and 919 were prepared according to literature
procedures.
4.2. General procedure for the hydroacylation of allenes using
b-thio-substituted aldehydes
Entries 17–27 all employ aromatic aldehyde 7, and generally
confirm the same trends established using alkyl aldehyde 1. For
example, entry 17 again illustrates the selectivity of the process for
Acetone (2.0 mL) was added to pre-catalyst [Rh(nbd)(dppe)]ClO4
(10 mg, 0.015 mmol) under nitrogen. The catalyst was activated in

5112
H.E. Randell-Sly et al. / Tetrahedron 65 (2009) 5110–5117
Table 1
Variation of allene structure in combination with aldehydes 1 and 7a
MeS
O
R2
MeS
O
MeS
O
[Rh(dppe)]ClO4
R3
or
R1
R3
acetone
55 °C
H
H
R1
R2
1
7
Entry
1
Aldehyde
Allene
Time
(h)
Product
Regioselectivityb
Yieldc (%)
87
MeS
O
MeS
MeS
O
8
>20:1
Pent
Pent
H
H
O
O
MeS
MeS
MeS
MeS
O
Pent
Pent
2
3
4
5
8
8
8
8
1.25:1
97
70
92
89
Me
Pent
Me
MeS
MeS
O
O
O
d
Pent
Pent
Pent
H
H
H
Pent
Pent
O
Me
Me
15:1
>20:1
Me
Me
MeS
O
Pent
Ph
Pent
MeS
MeS
O
O
MeS
MeS
O
O
6
7
8
8
>20:1
>20:1
97
89
Me
Et
Ph
H
H
Me
Et
Ph
MeS
MeS
MeS
MeS
O
Me
MeS
MeS
MeS
MeS
O
O
O
O
Me
Me
Me
8
16
16
16
16
>20:1
>20:1
>20:1
>20:1
80
74
70
78
Et
Hex
Ph
Me
H
H
H
H
Et
Me
O
O
Me
9
Me
Hex Me
Me
10
11
Me
Ph
Me
O
Me
Me
MeS
MeS
O
O
MeS
MeS
O
O
12
13
16
16
>20:1
>20:1
81
89
H
H
Et
Et
Hex
Hex
MeS
MeS
O
MeS
MeS
MeS
O
O
O
14
15
16
16
16
16
>20:1
>20:1
1:1
62
96
81
H
H
H
Ph
Ph
O
O
O
OEt
Me
OEt
O
Me
OEt
MeS
O
O
OEt

H.E. Randell-Sly et al. / Tetrahedron 65 (2009) 5110–5117
5113
Table 1 (continued )
Entry
Aldehyde
Allene
Time
(h)
Product
Regioselectivityb
Yieldc (%)
MeS
MeS
MeS
MeS
MeS
MeS
MeS
O
O
O
O
O
O
O
MeS
O
Me
Me
Pent
17
8
8
>20:1
98
82
94
99
99
96
99
H
H
H
H
H
H
H
Me
Me
Pent
Me
MeS
O
Ph
18
19
20
21
22
23
>20:1
>20:1
>20:1
12:1
Me
Ph
MeS
MeS
O
Ph
Ph
8
Hex
Ph
Hex
O
Ph
8
Ph
Ph
MeS
O
Me
Ph
Ph
8
Ph
Me
Me
O
Me
MeS
MeS
Ph
16
16
>20:1
>20:1
Et
Ph
Et
Ph
O
Hex
Hex
MeS
MeS
O
O
MeS
O
O
O
S
24
25
8
8
>20:1
>20:1
99
99
Hex
H
H
O
Hex
Hex
MeS
Hex
S
MeS
O
Ph
MeS
MeS
O
O
F3C
26
16
1.8:1
97
H
Ph
Ph
CF3
OMe
MeS
O
MeO
27
16
1.6:1
32
H
Ph
a
Reaction conditions: aldehyde (1.0 equiv), allene (2.0 equiv), [Rh(dppe)]ClO4 (10 mol %), acetone, 55 ꢀC. Catalyst generated in situ from [Rh(nbd)(dppe)]ClO4 and H2.
b
c
Determined by 1H NMR spectroscopy.
Isolated yields.
situ by passing H2 through the solution for 2 min or until a colour
4.3. (E)-1-(Methylthio)undec-5-en-3-one (Table 1, entry 1)
change from orange to light yellow was observed. After this time the
hydrogen atmosphere was purged by passing nitrogen through the
solution for 0.5 min. To this was added the thio-aldehyde
(0.15 mmol) followed by the appropriate allene (0.3 mmol). The
resulting mixture was stirred and heated at 55 ꢀC for 8–16 h. After
this time the solution was filtered through a silica plug, reduced in
vacuo and purified by flash chromatography.
Flash chromatography (9:1 hexane/EtOAc) yielded the title
compound as a pale yellow oil (26 mg, 87%); nmax (film)/cmꢁ1 2955,
2927, 2858, 1715; dH (300 MHz, CDCl3) 5.65–5.45 (2H, m), 3.11 (2H,
d, J 5.2), 2.73 (4H, t, J 6.8), 2.12 (3H, s), 2.02 (2H, q, J 6.7), 1.40–1.20
(6H, m), 0.88 (3H, t, J 6.7); dC (75 MHz, CDCl3) 208.1, 134.6, 120.8,
47.4, 42.1, 32.9, 31.7, 29.2, 28.2, 22.9, 16.1, 14.4; m/z (CIþ, NH3) 232

5114
H.E. Randell-Sly et al. / Tetrahedron 65 (2009) 5110–5117
28.4, 27.2, 22.9, 22.7, 16.2, 14.4; m/z (EIþ) 256 (10%, [M]þ), 103 (60%,
[Mꢁ(CH3)2CHCHCH(CH2)4CH3]þ), 75 (100%, [Mꢁ(CH3)2CHCHCH-
S
O
Me
Me
Me
Me
S
O
a
a
Pent
Pent
S
(CH2)4CH3CO]þ); found [MþH]þ 257.1931, C15H29
S
requires
S
H
8
Pent
D
82%,10:1
257.1934.
MeS
O
MeS
O
4.7. (E)-1-(Methylthio)-4-styrylnonan-3-one (Table 1, entry 5)
Ph
Ph
D
Pent
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (39 mg, 89%); nmax (film)/cmꢁ1 2926,
1709, 1457, 908; dH (300 MHz, CDCl3) 7.32–7.14 (5H, m), 6.43 (1H, d,
J 15.8), 6.0 (1H, dd, J 15.8, 9.3), 3.17 (1H, dt, J 9.3, 6.8), 2.83–2.62 (4H,
m), 2.02 (3H, s), 1.78–1.68 (1H, m), 1.55–1.45 (1H, m), 1.27–1.16 (6H,
m), 0.82–0.67 (3H, m); dC (75 MHz, CDCl3) 209.8, 137.1, 133.6, 129.0,
128.1, 128.0, 126.7, 57.6, 41.8, 32.1, 31.6, 28.4, 27.3, 22.9, 16.2, 14.4; m/z
(EIþ) 290 (20%, [M]þ), 187 (40%, [MꢁCH3SCH2CH2CO]þ), 116 (100%,
[MꢁPhCHCHCH2CH2CH2CH2CH3]þ); found [MþH]þ 291.1783,
C18H27OS requires 291.1777.
d-7
9, 93%, >20:1
>97% D-incorporation
O
D
Ar [Rh]
D
Ar [Rh]
O
Ph
Ph
Pent
11
Pent
10
Scheme 3. Allene hydroacylations employing aldehydes 8 and d-7. (a) [Rh(dppe)]ClO4
(10 mol %), acetone, 55 ꢀC.
4.8. (E)-4-Methyl-1-(methylthio)-6-phenylhex-5-en-3-one
(Table 1, entry 6)
(100%, [MþNH4]þ), 215 (20%, [MþH]þ), 200 (30%, [MꢁCH2]þ), 184
(70%, [MꢁCH3CH3]þ); found [MþNH4]þ 232.1730, C12H26NOS re-
quires 232.1730.
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (34 mg, 97%); nmax (film)/cmꢁ1 2972,
1709, 1447, 898; dH (300 MHz, CDCl3) 7.31–7.14 (5H, m), 6.42 (1H, d,
J 15.8), 6.08 (1H, dd, J 15.8, 8.3), 3.36–3.25 (1H, m), 2.87–2.63 (4H,
m), 2.02 (3H, s), 1.21 (3H, d, J 6.8); dC (75 MHz, CDCl3) 209.9, 137.1,
132.8, 129.0, 128.9, 128.2, 126.6, 51.3, 41.0, 28.4, 16.5, 16.2; m/z (EIþ)
234 (30%, [M]þ), 130 (10%, [MꢁCH3SCH2CH2COH]þ), 91 (80%,
[MꢁPhCHCHCH CH3O]þ); found [MþH]þ 235.1152, C14H19OS re-
quires 235.1151.
4.4. (E)-4-Methyl-1-(methylthio)undec-5-en-3-one (5) and
(E)-1-(methylthio)-4-(prop-1-enyl)nonan-3-one (4) (Table 1,
entry 2)
Flash chromatography (1:9, Et2O/hexane) yielded the title
compounds 4 and 5 (1:1.25) as a pale yellow oil (1:1.25, 5/4, 33 mg,
97%); nmax (film)/cmꢁ1 3049, 1647, 1421, 1262; dH (300 MHz, CDCl3)
(4) 5.58–5.46 (1H, m), 5.28 (1H, ddt, J 16.5, 8.3, 1.4), 3.12–3.03 (1H,
m), 2.79–2.56 (4H, m), 2.16–1.92 (3H, m), 1.36–1.13 (8H, m), 1.08
(3H, d, J 6.9), 0.83–0.78 (3H, m); dH (300 MHz, CDCl3) (5) 5.58–5.46
(1H, m), 5.25 (1H, ddq, J 16.5, 9.0, 1.5), 3.12–3.03 (1H, m), 2.79–2.56
(4H, m), 2.16–1.92 (3H, m), 1.62 (3H, dd, J 6.4, 1.5), 1.36–1.13 (8H, m),
0.83–0.78 (3H, m); dC (75 MHz, CDCl3) (both) 207.2, 206.3, 134.4,
129.5, 129.3, 129.1, 57.2, 51.0, 41.3, 40.6, 32.9, 32.1, 32.0, 29.6, 29.5,
29.2, 28.4, 27.5, 23.1, 23.0, 18.4, 16.5, 16.3, 16.2, 14.5, 14.4; m/z (EIþ)
228 (20%, [M]þ), 102 (75%, [MꢁCH3CHCHCHCH2CH2CH2CH2CH3]þ),
75 (100%, [MꢁCH3CHCHCHCH2CH2CH2CH2CH3CO]þ); found
[MþH]þ 229.1621, C13H25OS requires 229.1621.
4.9. (E)-4-Ethyl-1-(methylthio)-6-phenylhex-5-en-3-one
(Table 1, entry 7)
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (33 mg, 89%); nmax (film)/cmꢁ1 2989,
1723, 1406, 917; dH (300 MHz, CDCl3) 7.31–7.12 (5H, m), 6.44 (1H, d,
J 15.8), 6.00 (1H, dd, J 15.8, 9.3), 3.13–3.05 (1H, m), 2.83–2.56 (4H,
m), 2.03 (3H, s), 1.87–1.73 (1H, m), 1.60–1.46 (1H, m), 0.84 (3H, t, J
7.4); dC (75 MHz, CDCl3) 209.7, 137.1, 133.8, 129.0, 128.1, 127.8, 126.7,
59.2, 41.8, 28.3, 24.8, 16.2, 12.2; m/z (EIþ) 248 (20%, [M]þ), 145
(100%, [MꢁCH3SCH2CH2CO]þ); found [MþH]þ 249.1309, C15H21OS
requires 249.1309.
4.5. (E)-1-(Methylthio)-4-pentylundec-5-en-3-one (Table 1,
entry 3)
4.10. 4-Ethyl-6-methyl-1-(methylthio)hept-5-en-3-one (6)
(Table 1, entry 8)
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (30 mg, 70%); nmax (film)/cmꢁ1 2926,
1699, 1457, 898, 718; dH (300 MHz, CDCl3) 5.58 (1H, dt, J 15.4, 6.8),
5.26 (1H, ddt, J 15.4, 9.1, 1.6), 3.01 (1H, dt, J 9.1, 7.0), 2.85–2.64 (4H,
m), 2.10 (3H, s), 2.06–1.97 (2H, m), 1.78–1.62 (2H, m), 1.43–1.19
(12H, m), 0.94–0.83 (6H, m); dC (75 MHz, CDCl3) 210.2, 134.9, 127.7,
56.9, 40.9, 32.5, 31.7, 31.6, 31.3, 30.9, 28.9, 28.0, 26.8, 22.5, 15.8, 14.1,
14.0; m/z (EIþ) 284 (3%, [M]þ), 103 (100%, [MꢁPentCHCHCHPent]þ);
found [MþH]þ 285.2247, C17H33OS requires 285.2247.
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (24 mg, 80%); nmax (film)/cmꢁ1 3020,1747,
1457, 1142; dH (300 MHz, CDCl3) 4.91–4.82 (1H, m), 3.23–3.15 (1H,
m), 2.71–2.57 (4H, m), 2.03 (3H, s), 1.68 (3H, d, J 1.3), 1.64 (3H, d, J
1.2), 1.32–1.05 (2H, m), 0.80 (3H, t, J 6.7); dC (75 MHz, CDCl3) 210.6,
136.1, 123.2, 53.1, 41.1, 32.1, 26.3, 23.0, 22.6, 18.8, 14.5; m/z (EIþ) 200
(2%, [M]þ) 97 (30%, [MꢁCH3SCH2CH2CO]þ), 55 (100%,
[MꢁCH3SCH2CH2COCHCH2CH3]þ); found [MþH]þ 201.1306,
C11H21OS requires 201.1308.
4.6. (E)-4-((3-Methylbut-1-enyl)-1-methylthio)nonan-3-one
(Table 1, entry 4)
4.11. 4-(2-Methylprop-1-enyl)-1-(methylthio)decan-3-one
(Table 1, entry 9)
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (35 mg, 92%); nmax (film)/cmꢁ1 2916,
1704, 1463, 903; dH (300 MHz, CDCl3) 5.48 (1H, dd, J 15.4, 6.7), 5.15
(1H, ddd, J 15.4, 9.0, 1.2), 2.92 (1H, m), 2.77–2.55 (4H, m), 2.29–2.16
(1H, m), 2.03 (3H, s), 1.70–1.56 (1H, m), 1.41–1.30 (1H, m), 1.27–1.09
(6H, m), 0.92 (3H, d, J 1.2), 0.90 (3H, d, J 1.2), 0.82–0.77 (3H, m); dC
(75 MHz, CDCl3) 210.6, 142.1, 125.2, 57.2, 41.3, 32.1, 32.0, 31.6, 31.3,
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (28 mg, 74%); nmax (film)/cmꢁ1 2936,
1699, 1452, 913; dH (300 MHz, CDCl3) 4.96 (1H, br d, J 9.8), 3.26 (1H,
ddd, J 9.8, 8.0, 6.2), 2.78–2.62 (4H, m), 2.10 (3H, s), 1.74 (3H, d, J 1.2),
1.69 (3H, d, J 1.3), 1.46–1.15 (10H, m), 0.87 (3H, t, J 6.7); dC (75 MHz,
CDCl3) 210.2, 135.7, 122.8, 52.7, 40.8, 31.7, 31.5, 29.3, 28.1, 27.1, 25.9,

H.E. Randell-Sly et al. / Tetrahedron 65 (2009) 5110–5117
5115
22.6, 18.4, 15.8, 14.1; m/z (EIþ) 256 (60%, [M]þ), 208 (50%,
[MꢁCH3SH]þ), 153 (100%, [MꢁCH3SCH2CH2CO]þ); found [MþH]þ
257.1938, C15H29OS requires 257.1934.
288 (10%, [M]þ), 185 (90%, [MꢁCH3SCH2CH2CO]þ), 117 (100%,
[MꢁCyCCPh]þ); found [MþH]þ 289.1622, C18H25OS requires
289.1621.
4.12. 6-Methyl-1-(methylthio)-4-phenylhept-5-en-3-one
(Table 1, entry 10)
4.17. (E)-Ethyl 4-methyl-7-(methylthio)-5-oxohept-3-enoate
(Table 1, entry 15)
Flash chromatography (1:9, Et2O/hexane) yielded the title com-
pound as a yellow oil (27 mg, 70%); nmax (film)/cmꢁ1 3049, 2680,1709,
1416, 1262; dH (300 MHz, CDCl3) 7.32–7.16 (5H, m), 5.59–5.54 (1H, m),
4.49 (1H, d, J 9.4), 2.75–2.54 (4H, m),1.95 (3H, s),1.71 (3H, d, J 1.2), 1.61
(3H, d, J 1.3); dC (75 MHz, CDCl3) 207.8, 139.3,136.0,129.3, 128.5, 127.5,
121.7, 58.7, 41.1, 28.6, 26.4, 18.7, 16.1; m/z (EIþ) 248 (10%, [M]þ), 145
(100%, [MꢁMeSCH2CH2CO]þ), 103 (20%, [MꢁMe2CCHCHPh]þ); found
[MþH]þ 249.1308, C15H21OS requires 249.1308.
Flash chromatography (1:8, Et2O/hexane) yielded the title
compound as a yellow oil (31 mg, 96%); nmax (film)/cmꢁ1 2978,
1735, 1663, 1365, 913; dH (300 MHz, CDCl3) 6.78–6.72 (1H, m), 4.13
(2H, q, J 7.2), 3.22 (2H, d, J 6.8), 2.95 (2H, t, J 7.3), 2.71 (2H, t, J 7.3),
2.06 (3H, s), 1.73 (3H, d, J 1.1), 1.22 (3H, t, J 7.2); dC (75 MHz, CDCl3)
199.9, 175.5, 139.7, 133.8, 61.6, 37.7, 34.8, 29.3, 16.2, 14.8, 12.1; m/z
(ESþ) 230 (100%, [M]þ), 182 (80%, [MꢁCH3SH]þ); found [MþH]þ
231.1048, C11H19O3S requires 231.1049.
4.13. 1-Cyclohexylidene-2-methyl-5-(methylthio)pentan-3-
one (Table 1, entry 11)
4.18. (E)-Ethyl 7-(methylthio)-5-oxohept-2-enoate and (E)-
ethyl 7-(methylthio)-5-oxohept-3-enoate (Table 1, entry 16)
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (26 mg, 78%); nmax (film)/cmꢁ1 3055,
1704, 1416, 1257; dH (300 MHz, CDCl3) 4.87 (1H, d, J 9.7), 3.36 (1H,
dq, J 9.7, 6.8), 2.76–2.54 (4H, m), 2.16–2.14 (2H, m), 2.05–1.98 (2H,
m), 2.03 (3H, s), 1.62–1.44 (6H, m), 1.05 (3H, d, J 6.8); dC (75 MHz,
CDCl3) 210.9, 143.3, 120.9, 46.1, 40.5, 37.6, 29.7, 28.8, 28.6, 28.2, 27.1,
16.9, 16.2; m/z (EIþ) 226 (5%, [M]þ), 123 (75%, [MꢁCH3SCH2CH2-
CO]þ), 82 (100%, [MꢁCy]þ); found [MþH]þ 227.1464, C13H23OS re-
quires 227.1462.
Flash chromatography (1:8, Et2O/hexane) yielded the title
compounds 16a and 16b as an inseparable mixture (1:1) as a yellow
oil (26 mg, 81%); nmax (film)/cmꢁ1 2983, 1791, 1719, 1440, 1375,
1160; dH (300 MHz, CDCl3) ((E)-ethyl 7-(methylthio)-5-oxohept-2-
enoate) 6.96 (1H, dt, J 15.7, 7.2), 5.84 (1H, dt, J 15.7, 1.5), 4.17–4.08
(2H, m), 3.31–3.28 (2H, m), 2.74–2.65 (4H, m), 2.05 (3H, s), 1.22 (3H,
t, J 6.0); dH (300 MHz, CDCl3) ((E)-ethyl 7-(methylthio)-5-oxohept-
3-enoate) 6.85 (1H, dt, J 16.1, 7.1), 6.13 (1H, dt, J 16.1, 1.5), 4.17–4.08
(2H, m), 3.19 (2H, dd, J 7.1 1.5), 2.83 (2H, t, J 8.5), 2.74–2.65 (2H, m),
2.06 (3H, s), 1.23 (3H, t, J 5.9); dC (75 MHz, CDCl3) (both) 205.2,
198.4, 170.2, 166.1, 139.8, 138.8, 135.0, 125.6, 61.7, 60.9, 46.2, 42.9,
40.2, 38.1, 30.1, 28.5, 28.1, 16.2, 14.6, 14.5; m/z (FIþ) found [M]þ
216.0830, C10H16O3S requires 216.0820.
4.14. 4-(Cyclohexylidenemethyl)-1-(methylthio)hexan-3-one
(Table 1, entry 12)
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (29 mg, 81%); nmax (film)/cmꢁ1 2972,
1653, 1473, 1365, 1160; dH (300 MHz, CDCl3) 4.81 (1H, d, J 9.8), 3.71
(1H, ddd, J 9.8, 8.2, 6.0), 2.73–2.55 (4H, m), 2.19–2.12 (2H, m), 2.08–
2.04 (2H, m), 2.03 (3H, s),1.74–1.60 (1H, m),1.53–1.46 (6H, m), 1.43–
1.28 (1H, m), 0.78 (3H, t, J 7.4); dC (75 MHz, CDCl3) 210.7, 144.5,
119.5, 53.7, 41.1, 37.7, 29.8, 29.0, 28.5, 28.2, 27.1, 24.8, 16.2, 12.1; m/z
(EIþ) 240 (5%, [M]þ), 137 (55%, [MꢁCH3SCH2CH2CO]þ), 95 (100%,
[MꢁCH3SCH2CH2COCHCH2CH3]þ); found [MþH]þ 241.1621,
C14H25OS requires 241.1621.
4.19. (E)-2-(3-Methylbut-1-enyl)-1-(2-(methylthio)-
phenyl)heptan-1-one (Table 1, entry 17)
Flash chromatography (1:20, EtOAc/hexane) yielded the title
compound (10:1) as a colourless oil (45 mg, 98%); nmax (film)/cmꢁ1
2957, 1672, 1585, 1434, 1270, 973, 740; dH (400 MHz, CDCl3); 7.78
(1H, dd, J 4.6, 1.3), 7.47–7.28 (2H, m), 7.25–7.13 (1H, m), 5.51 (1H, dd,
J 15.9, 6.3), 5.41 (1H, d, J 15.9, 8.6), 3.90–3.82 (1H, m), 2.42 (3H, s,
SCH3), 2.33–2.16 (1H, m), 1.93–1.77 (1H, m),1.63–1.49 (1H, m),1.45–
1.13 (6H, m), 1.04–0.77 (9H, m); dC (100 MHz, CDCl3) 203.4, 141.9,
141.0, 135.7, 131.7, 129.8, 125.8, 125.6, 123.6, 52.7, 32.5, 31.8, 31.3,
27.0, 22.6, 22.4, 16.4, 14.2; m/z (FIþ) found [M]þ 304.1871, C19H28OS
requires 304.1861.
4.15. 4-(Cyclohexylidenemethyl)-1-(methylthio)decan-3-one
(Table 1, entry 13)
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (40 mg, 89%); nmax (film)/cmꢁ1 2936,
1709, 1468, 903; dH (300 MHz, CDCl3) 4.82 (1H, d, J 9.8), 3.24 (1H,
ddd, J 9.8, 8.2, 5.9), 2.74–2.55 (4H, m), 2.18–2.12 (2H, m), 2.07–2.05
(2H, m), 2.03 (3H, s), 1.68–1.58 (1H, m), 1.52–1.48 (6H, m), 1.39–1.28
(1H, m), 1.24–1.08 (8H, m), 0.80 (3H, t, J 6.7); dC (75 MHz, CDCl3)
210.7, 144.2, 119.8, 52.0, 41.1, 37.7, 32.1, 31.7, 29.8, 29.6, 29.0, 28.9,
28.5, 27.5, 27.1, 23.0, 16.2, 14.5; m/z (EI) 296 (5%, [M]þ), 193 (40%,
[MꢁCH3SCH2CH2CO]þ), 109 (100%, [MꢁCH3(CH2)5C2]þ); found
[MþH]þ 296.2169, C18H33OS requires 296.2168.
4.20. (E)-2-Methyl-1-(2-(methylthio)phenyl)-4-phenylbut-3-
en-1-one (Table 1, entry 18)
Flash chromatography (1:20, EtOAc/hexane) yielded the title
compound as a colourless oil (34 mg, 82%); nmax (film)/cmꢁ1 2976,
2972, 1669, 1586, 1433, 972, 741, 694; dH (400 MHz, CDCl3) 7.84 (1H,
dd, J 7.8, 1.5), 7.51–7.41 (1H, m), 7.38–7.18 (7H, m), 6.51 (1H, d, J
16.0), 6.29 (1H, dd, J 16.0, 8.3), 4.30–4.23 (1H, m), 2.45 (3H, s), 1.44
(3H, d); dC (100 MHz, CDCl3) 202.6, 142.0, 136.9, 135.0, 131.8, 131.6,
129.8, 129.6, 128.5, 127.4, 126.2, 125.7, 123.7, 46.7, 17.6, 16.3; m/z
(ESIþ) found [MþNa]þ 305.0971, C18H18OSNa requires 305.0976.
4.16. 1-Cyclohexylidene-5-(methylthio)-2-phenylpentan-3-
one (Table 1, entry 14)
4.21. (E)-1-(2-(Methylthio)phenyl)-2-styryloctan-1-one (Table
Flash chromatography (1:9, Et2O/hexane) yielded the title
compound as a yellow oil (27 mg, 62%); nmax (film)/cmꢁ1 3044,
1714, 1427, 1263; dH (300 MHz, CDCl3) 7.31–7.15 (5H, m), 5.49 (1H,
dt, J 9.3, 1.0), 4.58 (1H, d, J 9.3), 2.71–2.54 (4H, m), 2.14–1.94 (7H, m),
1.51–1.36 (6H, m); dC (75 MHz, CDCl3) 207.9, 144.0, 139.6, 129.2,
128.5, 127.4, 118.3, 57.7, 37.7, 29.8, 28.8, 27.9, 27.0, 23.1; m/z (EIþ)
1, entry 19)
Flash chromatography (1:20, EtOAc/hexane) yielded the title
compound as a colourless oil (49 mg, 94%); nmax (film)/cmꢁ1 3026,
2926, 2855, 1668, 1460, 1433, 969, 742; dH (400 MHz, CDCl3) 7.83
(1H, dd, J 7.8, 1.3), 7.48–7.44 (1H, m), 7.37–7.20 (7H, m), 6.49 (1H, d, J

5116
H.E. Randell-Sly et al. / Tetrahedron 65 (2009) 5110–5117
15.9), 6.30 (1H, dd, J 15.9, 8.8), 4.15–4.09 (1H, m), 2.44 (3H, s), 2.01–
1.95 (1H, m), 1.74–1.69 (1H, m), 1.43–1.22 (8H, br m), 0.92–0.83 (3H,
m); dC (100 MHz, CDCl3) 202.4, 142.2, 137.0, 135.3, 132.3, 131.9,
129.3, 128.8, 128.5, 127.4, 126.3, 125.6, 123.6, 52.8, 32.7, 31.7, 29.2,
27.3, 22.6, 16.2, 14.0; m/z (ESIþ) found [MþH]þ 353.1934, C23H29OS
requires 353.1939.
2857, 1781, 1669, 1587, 1435, 1245, 993, 751; dH (400 MHz, CDCl3)
7.82 (1H, dd, J 7.8, 1.0), 7.49–7.41 (1H, m), 7.33 (2H, t, J 8.2), 7.20 (1H,
t, J 7.5), 6.40–6.10 (4H, m), 4.06 (1H, q, J 7.8), 2.43 (3H, s), 2.04–1.86
(1H, m), 1.46–1.12 (1H, m), 0.98–0.78 (8H, m), 0.97–0.75 (3H, m); dC
(100 MHz, CDCl3) 202.2,152.6,142.4,141.9,135.3,132.0,129.9,127.6,
125.7, 123.7, 120.9, 111.3, 107.6, 52.4, 32.7, 31.8, 29.4, 27.5, 22.7, 16.3,
14.2; m/z (ESIþ) found [MþH]þ 343.1731, C21H27O2S requires
343.1732.
4.22. (E)-2-Benzyl-1-(2-(methylthio)phenyl)-4-phenylbut-3-
en-1-one (Table 1, entry 20)
4.27. (E)-1-(2-(Methylthio)phenyl)-2-(2-(thiophen-2-
Flash chromatography (1:20, EtOAc/hexane) yielded the title
compound as a colourless oil (52 mg, 99%); nmax (film)/cmꢁ1 3026,
2921, 1668, 1586, 1558, 1495, 1433, 1269, 1075, 968, 743, 697; dH
(400 MHz, CDCl3) 7.73 (1H, dd, J 7.8, 1.5), 7.52–7.38 (1H, m), 7.35–
7.02 (12H, m), 6.38 (1H, d, J 15.9), 6.30 (1H, dd, J 15.9, 8.1), 4.52–4.05
(1H, m), 3.40 (1H, dd, J 13.6, 6.8), 3.02 (1H, dd, J 13.6, 7.6), 2.43 (3H,
s); dC (100 MHz, CDCl3) 201.0, 142.0, 139.0, 136.5, 134.7, 132.8, 131.6,
129.5, 129.0, 128.1, 127.9, 127.4, 127.2, 125.9, 125.9, 125.2, 123.2, 54.3,
38.3, 15.9; m/z (ESIþ) found [MþNa]þ 381.1284, C24H22OSNa re-
quires 381.1289.
yl)vinyl)octan-1-one (Table 1, entry 25)
Flash chromatography (1:10, Et2O/hexane) yielded the title
compound as a colourless oil (54 mg, 99%); nmax (film)/cmꢁ1 2925,
2855, 1667, 1586, 1460, 1433, 1269, 1217, 1078, 957, 740, 696; dH
(400 MHz, CDCl3) 7.90–7.75 (1H, m), 7.50–7.42 (1H, m), 7.35 (1H, d, J
8.1), 7.20 (1H, t, J 7.5), 7.12 (1H, d J 4.8), 6.97–6.88 (2H, m), 6.62 (1H,
d, J 15.7), 6.14 (1H, dd, J 15.7, 8.9), 4.16–3.97 (1H, m), 2.44 (3H, s),
2.08–1.87 (1H, m), 1.80–1.59 (1H, m), 1.50–1.15 (8H, m), 0.97–0.75
(3H, m); dC (75 MHz, CDCl3) 202.1, 142.2, 142.1, 135.1, 131.9, 129.7,
128.3, 127.2, 125.6, 125.4, 125.3, 124.0, 123.6, 52.5, 32.6, 31.6, 29.2,
27.3, 22.5, 16.2, 14.0; m/z (ESIþ) found [MþH]þ 359.1505, C21H27OS2
requires 359.1498.
4.23. (E)-2-Isopropyl-1-(2-(methylthio)phenyl)-4-phenylbut-
3-en-1-one (Table 1, entry 21)
Flash chromatography (1:10, EtOAc/hexane) yielded the title
compound (12:1) as a colourless oil (47 mg, 99%); nmax (film)/cmꢁ1
2959, 1669, 1433, 970, 742, 691; dH (400 MHz, CDCl3) 7.88 (1H, dd, J
7.8, 1.3), 7.49–7.43 (1H, m), 7.41–7.17 (7H, m), 6.51 (1H, d, J 15.9),
6.33 (1H, dd, J 15.9, 9.4), 3.90–3.75 (1H, m), 2.42 (3H, s), 2.40–2.30
(1H, m), 0.99 (6H, t, J 7.0); dC (100 MHz, CDCl3) 202.6, 142.4, 137.0,
135.5, 133.2, 132.0, 129.8, 128.3, 128.0, 127.5, 126.4, 125.4, 123.5,
60.2, 31.5, 21.5, 20.1, 16.1; m/z (FIþ) found [M]þ 310.1391, C20H22OS
requires 310.1404.
4.28. (E)-1-(2-(Methylthio)phenyl)-2-phenyl-4-(4-
(trifluoromethyl)phenyl)but-3-en-1-one and (E)-1-(2-
(methylthio)phenyl)-2-phenyl-4-(4-(trifluoromethyl)-
phenyl)but-3-en-1-one (Table 1, entry 26)
Flash chromatography (1:5, EtOAc/hexane) yielded the title
compounds as an inseparable mixture (1.8:1) as a colourless oil
(60 mg, 97%); nmax (film)/cmꢁ1 3061, 2977, 2923, 1666, 1616, 1587,
1434, 1325, 1122, 733, 698; dH (400 MHz, CDCl3) 7.88–7.81 (1H, m),
7.65–7.58 (1H, m), 7.57–7.08 (11H, m), 6.93 (0.36H, dd, J 15.9, 7.8),
6.74 (0.64H, dd, J 15.9, 8.1), 6.51 (0.64H, d, J 15.9), 6.48 (0.36H, d, J
15.9), 5.53 (0.64H, d, J 8.1), 5.45 (0.36H, d, J 7.8), 2.44 (3H, s) dC
(100 MHz, CDCl3) 199.3, 199.0, 143.1, 142.8, 136.5, 134.1, 133.1, 132.4,
132.2, 131.8, 130.6, 130.5, 129.2, 128.9, 128.6, 128.4, 127.9, 127.7,
127.5, 126.6, 126.5, 125.9, 125.7, 125.6, 125.4, 123.7, 123.6, 114.2, 58.5,
58.1, 16.2; m/z (FIþ) found [M]þ 412.1106, C24H19F3OS requires
412.1106.
4.24. 2-Ethyl-1-(2-(methylthio)phenyl)-4,4-diphenylbut-3-
en-1-one (Table 1, entry 22)
Flash chromatography (1:20, EtOAc/hexane) yielded the title
compound as a colourless oil (54 mg, 96%); nmax (film)/cmꢁ1 3058,
2963, 2855, 1668, 1586, 1494, 1434, 1202, 1074, 895, 764, 702; dH
(400 MHz, CDCl3) 7.54–7.14 (11H, m), 7.13–6.90 (3H, m), 6.15 (1H, d,
J 10.4), 4.13 (1H, dt, J 10.4, 8.0), 2.39 (3H, s), 2.09–1.92 (1H, m), 1.87–
1.70 (1H, m), 0.95 (3H, t, J 7.3); dC (100 MHz, CDCl3) 203.1, 144.1,
141.6, 141.4, 139.7, 135.8, 131.6, 129.7, 129.5, 128.3, 128.1, 127.7, 127.4,
127.3, 127.2, 125.6, 123.5, 51.1, 26.1, 16.2, 12.0; m/z (ESIþ) found
[MþNa]þ 395.1440, C25H24NaOS requires 395.1440.
4.29. (E)-4-(4-Methoxyphenyl)-1-(2-(methylthio)phenyl)-2-
phenylbut-3-en-1-one and (E)-2-(4-methoxyphenyl)-1-(2-
(methylthio)phenyl)-4-phenylbut-3-en-1-one (Table 1,
entry 27)
4.25. 2-(Cyclohexylidenemethyl)-1-(2-(methylthio)-
phenyl)octan-1-one (Table 1, entry 23)
Flash chromatography (1:5, EtOAc/hexane) yielded the title
compounds as an inseparable mixture (1.6:1) as a colourless oil
(18 mg, 32%); nmax (film)/cmꢁ1 2926, 2855, 1668, 1607,1511, 1461,
1433, 1250, 1175, 1035, 741; dH (400 MHz, CDCl3) 7.88–7.78 (1H, m),
7.51–7.15 (10H, m), 7.13 (2H, t, J 7.6), 6.87 (0.38H, d, J 8.8), 6.83
(0.62H, d, J 8.8), 6.76 (0.38H, dd, J 15.9, 8.0), 6.63 (0.62H, dd, J 15.9,
8.1), 6.43 (0.38H, d, J 15.9), 6.40 (0.62H, d, J 15.9), 5.39 (0.62H, d, J
8.1), 5.36 (0.38H, d, J 8.0), 3.80 (1.86H, s), 3.78 (1.14H, s), 2.43 (3H, s);
dC (100 MHz, CDCl3) 200.0, 142.8, 139.4, 132.0, 131.8, 131.5, 130.8,
130.4, 129.7, 129.5, 129.1, 129.0, 128.5, 128.4, 127.7, 127.5, 127.2,
126.6, 126.5, 125.6, 125.4, 123.6, 114.4, 113.9, 58.6, 57.7, 55.3, 54.8,
16.3; m/z (FIþ) found [M]þ 374.1344, C24H22O2S requires 374.1341.
Flash chromatography (1:20, EtOAc/hexane) yielded the title
compound as a colourless oil (52 mg, 99%); nmax (film)/cmꢁ1 2927,
2854, 1675, 1587, 1434, 1212, 1078, 979, 852, 738; dH (400 MHz,
CDCl3) 7.68 (1H, dd, J 7.7, 1.9), 7.46–7.38 (1H, m), 7.35–7.29 (1H, m),
7.20–7.13 (1H, m), 5.04 (1H, d, J 9.9), 4.16 (1H, ddd, J 9.9, 8.1, 5.9),
2.43 (3H, s), 2.22–2.00 (4H, m), 1.94–1.77 (1H, m), 1.62–1.18 (15H,
m), 0.94–0.81 (3H, m); dC (100 MHz, CDCl3) 203.8, 162.4, 141.1,
136.3, 131.3, 129.3, 125.7, 123.6, 120.2, 48.1, 37.2, 32.2, 31.7, 29.5,
29.3, 28.4, 27.5, 27.1, 26.7, 22.6, 16.3, 14.1; m/z (ESIþ) found [MþH]þ
345.2251, C22H33OS requires 345.2252.
4.30. (E)-1-(1,3-Dithian-2-yl)-3-(3-methylbut-1-enyl)-octan-
4.26. (E)-2-(2-(Furan-2-yl)vinyl)-1-(2-(methylthio)-
2-one (Scheme 3)
phenyl)octan-1-one (Table 1, entry 24)
Flash chromatography (1:4, Et2O/hexane) yielded the title
compound (10:1) as a yellow oil (39 mg, 82%); nmax (film)/cmꢁ1
3060, 1714, 1416, 1267; dH (300 MHz, CDCl3) 5.50 (1H, ddd, J 15.4,
Flash chromatography (1:10, EtOAc/hexane) yielded the title
compound as a colourless oil (51 mg, 99%); nmax (film)/cmꢁ1 2928,

H.E. Randell-Sly et al. / Tetrahedron 65 (2009) 5110–5117
5117
Denise, B.; Sneeden, R. P. A.; Cognio, J. M.; Dural, P. J. Organomet. Chem. 1982,
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Milstein, D. Organometallics 1988, 7, 1451; (f) Kondo, T.; Tsuji, Y.; Watanabe, Y.
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6.7, 0.5), 5.12 (1H, ddd, J 15.4, 9.0, 1.2), 4.45 (1H, t, J 6.8), 2.97–2.82
(4H, m), 2.79–2.70 (4H, m), 2.27–2.16 and 2.09–1.99 (2H, m), 1.84–
1.57 (2H, m), 1.41–1.11 (6H, m), 0.91 (6H, d, J 6.8), 0.80 (3H, t, J 6.5);
dC (75 MHz, CDCl3) 207.3, 142.7, 124.6, 57.5, 46.5, 41.6, 32.0, 31.6,
31.0, 30.8, 27.1, 25.7, 22.9, 22.7, 14.4; m/z (EIþ) (both) 314 (10%,
[M]þ), 271 (20%, [MꢁCH(CH2)3]þ), 119 (100%, [MꢁCH2COCH(Pent)-
CHCHCH(CH3)2]þ); found [MþH]þ 315.1813, C17H31OS2 requires
315.1811.
7. (a) Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14120; (b)
Omura, S.; Fukuyama, T.; Horiguchi, J.; Murakami, Y.; Ryu, I. J. Am. Chem. Soc.
2008, 130, 14094.
4.31. (E)-1-(2-(Methylthio)phenyl)-2-(1-D-styryl)heptan-1-
one (9, Scheme 3)
8. (a) Jun, C. H.; Lee, D. Y.; Lee, H.; Hong, J. B. Angew. Chem., Int. Ed. 2000, 39, 3070;
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Chem. Soc. 1979, 101, 489; (c) Imai, M.; Tanaka, M.; Tanaka, K.; Yamamoto, Y.;
Imai-Ogata, N.; Shimowatari, M.; Nagumo, S.; Kawahara, N.; Suemune, H. J. Org.
Chem. 2004, 69, 1144; (d) Tanaka, T.; Tanaka, M.; Suemune, H. Tetrahedron Lett.
2005, 46, 6053; (e) Tanaka, K.; Shibata, Y.; Suda, T.; Hagiwara, Y.; Hirano, M. Org.
Lett. 2007, 9, 1215.
10. Allene general: (a) Modern Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.;
Wiley-VCH: Weinheim, 2004; (b) Ma, S. Chem. Rev. 2005, 105, 2829.
11. (a) Zhang, Z.; Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc. 2007, 129, 14148;
(b) Burks, H. E.; Liu, S.; Morken, J. P. J. Am. Chem. Soc. 2007, 129, 8766; (c)
LaLonde, R. L.; Sherry, B. D.; Kang, E. J.; Toste, F. D. J. Am. Chem. Soc. 2007, 129,
2452; (d) Trost, B. M.; Simas, A. B. C.; Plietker, B.; Ja¨kel, C.; Xie, J. Chem.dEur. J.
2005, 11, 7075.
Flash chromatography (1:9 Et2O/hexane) yielded the title
compound as a yellow oil (47 mg, 93%); nmax (film)/cmꢁ1 2911, 1678,
1463, 1365; dH (200 MHz, CDCl3) 7.78 (1H, dd, J 7.9, 1.4), 7.41–7.10
(8H, m), 6.41 (1H, br s), 4.11 (1H, t, J 7.0), 2.36 (3H, s), 1.95–1.84 (1H,
m), 1.69–1.54 (1H, m), 1.39–1.89 (6H, m), 0.79 (3H, t, J 7.0); dD
(77 MHz, CHCl3) 6.34 (br s); dC (125 MHz, CDCl3) 202.5, 142.1, 137.0,
135.3, 132.3, 131.9, 129.7, 128.5, 127.4, 126.3, 125.6, 123.6, 52.8, 32.6,
31.8, 27.0, 22.5, 16.2, 14.0; m/z (FIþ) 339; found [M]þ 339.1769,
C22H25DOS requires 339.1767.
12. Kokubo, K.; Matsumasa, K.; Nishinaka, Y.; Miura, M.; Nomura, M. Bull. Chem.
Soc. Jpn. 1999, 72, 303.
Acknowledgements
13. A communication detailing an enantioselective version of this process has re-
cently been reported: Osborne, J. D.; Randell-Sly, H. E.; Currie, G. S.; Cowley, A.
R.; Willis, M. C. J. Am. Chem. Soc. 2008, 130, 17232.
14. Bendorf, H. D.; Colella, C. M.; Dixon, E. C.; Marchetti, M.; Matukonis, A. N.;
Musselman, J. D.; Tiley, T. A. Tetrahedron Lett. 2002, 43, 7031.
This work was supported by the EPSRC and AstraZeneca.
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