Manganese(III)-mediated oxidative free-radical cyclisations of allenyl malonates

Article abstract of DOI:10.1016/j.tet.2009.09.112

The regioselective synthesis of alkenylcyclanones by the oxidative radical cyclisation of malonyl radicals onto both allenes and an allylsilane is reported, along with the diastereoselective formation of [3.3.0]-bicyclic γ-lactones from two of these alken

Full text of DOI:10.1016/j.tet.2009.09.112

Tetrahedron 65 (2009) 10882–10892
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Manganese(III)-mediated oxidative free-radical cyclisations of allenyl malonates
*
Lucy Curry, Michal S. Hallside, Luke H. Powell, Simon J. Sprague, Jonathan W. Burton
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 July 2009
Received in revised form 9 September 2009
Accepted 28 September 2009
Available online 1 October 2009
The regioselective synthesis of alkenylcyclanones by the oxidative radical cyclisation of malonyl radicals onto
both allenes and an allylsilane is reported, along with the diastereoselective formation of [3.3.0]-bicyclic g-
lactones from two of these alkenylcyclanones. Furthermore, the cyclisation of 3-, 4- and 5-allenyl malonates
on exposure to manganese(III) acetate under bothoxidative and reductive termination conditions is reported.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Extension of the methodology to non-terminal alkenes was also
possible; however, there was little control at the newly formed
We recently reported the diastereoselective formation of
lactone stereocentre. For example, cyclisation of the 4-pentenyl
[3.3.0]-bicyclic
g-lactones from the cyclisation of 4-pentenyl mal-
malonate 6 (R0¼OMe, R¼n-butyl) gave the desired [3.3.0]-bicyclic
g-
onates under oxidative radical conditions.1,2 Treatment of the 4-
pentenyl malonate 1 with manganese(III) acetate and copper(II)
triflate in acetonitrile under reflux delivered the [3.3.0]-bicyclic
lactone 7 in 58% yield but as a 2:1 mixture of lactone diastereomers
(Scheme 2).
g
-lactone 5 in 88% yield and with good diastereocontrol (>13:1 dr)
Mn(OAc)3,
Cu(OTf)2,
MeCN, reflux
O
(Scheme 1). The reaction most likely proceeds by generation of an
electrophilic C-centred radical from the interaction of the substrate
with manganese(III) acetate,3 which undergoes 5-exo-trig cyclisa-
tion, via a chair-like transition state 2,4 to deliver the adduct radical
3. Rapid reaction of the adduct radical with copper(II) gives a cop-
per(III) intermediate 4 from which the
formed. These reaction conditions were applicable to the synthesis
of a good number of substituted [3.3.0]-bicyclic
COR'
O
MeO2C
R' = OMe, R = nBu
Bu
MeO2C
R
6
H
58%
ref. 1
Mn(OAc)3, Cu(OAc)2
AcOH, R' = Me, R = Et
67%
7; 2:1 mixture
Mn(OAc)3
Cu(OAc)2
R' = OMe,
of diastereomers
g-lactone product 5 is
ref. 6
O
O
g
-lactones.1
MeO2C CO2Me
MeO2C COMe
I2
MeO2C
R
R
H
H
8
H
I
OTBDPS
OTBDPS
10
11
and
Mn(III)
MeO2C
MeO2C
MeO2C
•
MeO2C COMe
H
MeO2C
H
1
2
9
8:9, 7:3
Scheme 2. Cyclisations with non-terminal alkenes.
5-exo-trig
OTBDPS
OTBDPS
H
OTBDPS
Cu(III)
An indirect solution to the low diastereocontrol observed in the
above reaction would be to synthesise the corresponding alkenyl-
substituted cyclopentane e.g., 10, which should then undergo
a diastereocontrolled iodolactonisation, to give 11, with good con-
trol over the lactone stereocentre.5 The alkenyl-cyclopentane 10
would potentially be available by cyclisation of a 4-pentenyl
malonate in the presence of manganese(III) acetate and copper(II)
acetate3; however, Snider and co-workers have previously shown
that cyclisation of methyl acetoacetate 6 (R0¼Me, R¼Et) using
copper(II) acetate as the additive gave a 7:3 mixture of Hofmann–
Saytzev alkenes (8:9).6 We have similarly found that cyclisation of
- Cu(I)
Cu(II)
MeO2C
•
O
CO2Me
CO2Me
MeO2C
MeO2C
O
5
4
3
Scheme 1. Previous work on the synthesis of [3.3.0]-bicyclic g-lactones.
* Corresponding author. Tel.: þ44 1865 285119; fax: þ44 1865 285002.
E-mail address: jonathan.burton@chem.ox.ac.uk (J.W. Burton).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.112

L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
10883
5-pentenyl malonates in the presence of copper(II) acetate gives
(i)
HO
HO
mixtures of olefin regioisomers.7 The aim of this work was there-
fore to develop a regioselective synthesis of alkenyl-substituted
cyclopentanes by the treatment of the appropriate malonate sub-
strate with manganese(III) acetate. We envisaged two approaches
to achieve this goal (Scheme 3). First, oxidative radical cyclisation of
OH
20
CO2Me
21
SiMe3
SiMe3
(ii)
(iii)
MsO
MeO2C
a malonate such as 12 would deliver the
b-silyl adduct radical 14,
23
SiMe3
22
(iv)
which would be readily oxidised to a -silyl cation 15 in the pres-
b
ence of an appropriate metal oxidant. Electrofugal loss of the silyl
group would deliver the desired vinylcyclopentane 16 (Hofmann
alkene).8 Alternatively treatment of the appropriately substituted
allenyl malonate (e.g., 17) under oxidative radical conditions could
potentially yield the vinyl adduct radical 19, which could undergo
reduction by solvent to give the desired vinyl cyclopentane 16.9 In
this article we describe the successful application of both strategies
for the synthesis of alkenyl-cyclopentanes and more generally re-
port an investigation into the manganese(III)-mediated oxidative
free-radical cyclisations of allenyl malonates.
MeO2C CO2Me
24
Scheme 4. Allylsilane preparation and cyclisation. (i) Ref. 10, 18%; (ii) MsCl, Et3N,
CH2Cl2, 99%; (iii) dimethyl malonate, NaH, KI, DMF, THF, 80%; (iv) Mn(OAc)3, Cu(OTf)2,
MeCN, reflux, 96%.
2.2. Allenyl-substituted malonates
2.2.1. Introduction
CO2R
CO2R
The impetus for this research project was to develop a method for
the synthesis of alkenyl-cyclopentanes by the oxidative radical cyc-
lisation of appropriately substituted malonates. This presented us
with the opportunity to investigate the cyclisation of various allenyl
malonates under oxidative radical conditions. We elected to in-
vestigate the cyclisation of the six substrates 25–30 (Scheme 5)
under two separate reaction conditions: Conditions A 2 equiv of
manganese(III) acetate, 0.02 M substrate in ethanol conditions,
which favour reduction of adduct radicals (e.g., 19/16)1,9; Condi-
tions B 2 equiv of manganese(III) acetate and 1 equiv of copper(II)
triflate or acetate, 0.2 M substrate in acetonitrile conditions, which
favour the formation of products arising from oxidation of adduct
radicals.1,7,9,14 The regiochemistry of the radical cyclisations onto
allenes has been investigated both experimentally15 and theoreti-
cally.16 Guo et al.16 have shown that the regiochemistry in the cyc-
lisation of a range of allenyl-substituted alkyl radicals may be
explained using Marcus theory, which provides excellent agreement
with the experimental results of Crandall and co-workers.15 On the
basis of this prior art, cyclisation of the electrophilic C-centred rad-
icals 31 derived from the malonates 25–30 would be expected to give
the adduct radicals 32, 33 and 34 in varying proportions depending
on the value of n. The adduct radicals could then undergo various
termination pathways depending on the reaction conditions.9,14
RO2C
RO2C
SiR'3
SiR'3
RO2C
•
12
17
Mn(III)
Mn(III)
CO2R
•
CO2R
•
RO2C
•
5-exo-trig
5-exo-trig
13
18
CO2R
CO2R
RO2C
RO2C
•
•
SiR'3
[O]
14
19
H•, (solvent)
CO2R
RO2C CO2R
RO2C
SiR'3
15
16
Scheme 3. Synthetic strategy for the formation of alkenyl-cyclopentanes.
2. Results and discussion
2.1. Allylsilane-substituted malonate
CO2Me
CO2Me
•
The allylsilane cyclisation substrate 23 was prepared from 1,4-
butane diol 20 via the known alcohol 21,10 and was readily trans-
formed into the desired cyclisation substrate 23 via the mesylate 2211
(Scheme 4). Treatment of the malonate 23 with 2 equiv of man-
ganese(III) acetate in acetonitrile at reflux led to formation of the
known desired vinylcyclopentane 2412 in only 30% yield. Copper(II)
salts3 are compatiblewith manganese(III)acetateandfrequentlygive
rise to higher yields of products arising from oxidation of adduct
radicals formed during manganese(III)-mediated cyclisations.
Treatment of the malonate 23 with 2 equiv of manganese(III) acetate
and 1 equiv of copper(II) triflate13 in acetonitrile at reflux returned
the vinylcyclopentane 24 in excellent yield (96%). The formation of
the vinylcyclopentane 24 most likely proceeds according to the
mechanism outlined in Scheme 3. Thus, the malonate is oxidised in
the presence of Mn(III) to give the corresponding educt radical 13
(R¼R0¼Me), which undergoes 5-exo-trig cyclisation to deliver the
( )n
( )n
MeO2C
•
R
MeO2C
31
•
R
25; n = 0, R = H
26; n = 0, R = Et
27; n = 1, R = H
28; n = 1, R = Et
29; n = 2, R = H
30; n = 2, R = Et
MeO2C CO2Me
R
CO2Me
•
CO2Me
•
MeO2C
MeO2C
R
•
( )n
( )n
( )n
R
32
33
34
Scheme 5. Cyclisation substrates and possible adduct radicals.
2.2.2. Cyclisation studies
2.2.2.1. Cyclisation of the allenyl malonate 25. Treatment of the
known allenyl malonate 2512 with 2 equiv of manganese(III) ace-
tate in ethanol at reflux (Conditions A) gave complete conversion of
the starting material as indicted by crude 1H NMR (Scheme 6).
Purification of the reaction mixture allowed the isolation of a mix-
ture of compounds, which were assigned as the isomeric cyclic
dimers 37 (90%) for the following reasons. Mass spectrometry in-
dicated that product had a molecular mass of 394 {ES m/z 395.1
[(MþH)þ, 61%], 412.2 [(MþNH4)þ, 100%], 417.1 [(MþNa)þ, 89%],
806.3 [(2MþNH4)þ, 60%] 811.3 [(2MþNa)þ, 63%]} demonstrating
b
-silyl adduct radical 14 (R¼R0¼Me). Oxidation of the
b-silyl radical
14 (R¼R0¼Me) with copper(II) yields the corresponding
b-silyl cation
15 (R¼R0¼Me), which gives the productonelectrofugalloss ofsilicon.
Although the cyclisation of the malonate 23 was efficient, the prep-
aration of the substrate was lengthy, and, in our hands, low yielding.
We therefore turned our attention to investigating the oxidative
radical cyclisation of allenyl-substituted malonates.

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L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
that the product resulted from two molecules of starting material
minus two hydrogen atoms. It was evident that cyclisation had
occurred due to the absence of the malonate proton and the allene
protons in the 1H NMR. Furthermore, the 1H NMR indicated the
presence of a number of resonances in the olefinic region consistent
with trisubstituted and 1,1-disubstituted alkenes. The fact that
4-allenyl radicals undergo cyclisation to form allyl adduct radi-
cals15,16 combined with the above data led us to assign the products
as the isomeric dimers 37. This assignment was confirmed by fur-
ther purification to give the dimer 37a in pure form, which was fully
characterised. The likely mechanism for the formation of the di-
mers 37 involves conversion of substrate 25 into the electrophilic
C-centred radical 35, which undergoes exclusive five-membered
ring formation to form the allyl radical 36 in accord with the work
of Guo16 and Crandall.15 Allyl radicals are only slowly oxidised by
manganese(III) acetate.3b The stability of the allyl radical results in
slow hydrogen atom abstraction from the solvent and hence radical
dimerisation occurs to give the products 37.
As before, these reactions most likely proceed by the formation of
an electrophilic C-centred radical 35, which undergoes exclusive
five-membered ring formation to give the allylic radical 36.15,16 In the
absence of a copper(II) salt, the adduct radical 36 undergoes
dimerisation giving 37. In the presence of a copper(II) salt the adduct
radical may be rapidly trapped at the primary carbon to give a cop-
per(III) intermediate 38, analogous to steps in the Kharasch–Sos-
novsky reaction.19 The copper(III) intermediate can then decompose
via a pericyclic mechanism, as proposed by Beckwith,20 to give the
1,1-disubstituted alkene 39 as the major regioisomeric product. Al-
ternatively, the adduct radical may be oxidised by copper(II) to give
the allylic cation 43, which is trapped by acetic acid preferentially at
the more electron deficient terminus, giving the same major product
39. The alcohols 40 and 42 either arise from in situ hydrolysis of the
acetates or from trapping of the allyl cation 43 with water.
2.2.2.2. Cyclisation of the allenyl malonate 26. Cyclisation of the
non-terminalallene 26underthetwosetsofreactionconditionsgave
products analogous tothoseformed in thecyclisation of the substrate
25 (Scheme 8). Analysis of the crude 1H NMR from cyclisation of the
allene 26 under reductive termination conditions (Conditions A)
indicated the presence of a number of compounds. Mass spectrom-
etry showed the presence of dimers 44 analogous to those formed in
the cyclisation of substrate 25; {ES m/z 451.25 [(MþH)þ, 23%], 468.3
[(MþNH4)þ, 65%], 473.18 [(MþNa)þ, 98%], 918.52 [(2MþNH4)þ,18%],
923.4 [(2MþNa)þ, 95%], found [MþNa]þ 437.2141; C24H34NaO8 re-
quires 473.2146}. However; it was not possible to isolate any of the
pure isomers from the mixture. Exposure of the malonate 26 to
manganese(III) acetate and copper(II) triflate (Conditions B) gave an
impure component, which was tentatively assigned as the secondary
allylic alcohols 48 and 46 as a 4:1 inseparable mixture of di-
astereomers (ca. 19%), and the corresponding acetates 47 and 45 as
a 1:1.5 mixture of endo:exo-cyclic alkenes (50%); the exo-cyclic al-
kenes were formed as a 3:1 mixture of (unassigned) geometric iso-
mers. In the presence of copper(II) acetate the acetates 47 and 45
were isolated in 76% yield as a 1.2:1 mixture of endo:exo-cyclic al-
kenes; the exo-cyclic alkenes were formed as a 1:1.5 mixture of un-
assigned geometric isomers. The formation of the products 44–48 is
again in keeping with theoretical16 and experimental work15, which
showed that hexa-4,5-dien-1-yl radicals undergo exclusive five-
membered ring formation to give allyl radicals.
(i)
MeO2C
MeO2C
•
•
•
CO2Me
25
CO2Me
35
MeO2C CO2Me
MeO2C CO2Me
MeO2C CO2Me
•
37a
36
MeO2C CO2Me
CO2Me
CO2Me
37b
CO2Me
CO2Me
MeO2C
MeO2C
37c
Scheme 6. Cyclisation of the allene 25 in EtOH. (i) Conditions A, 37, 90%.
Treatment of the malonate 25 with manganese(III) acetate in
acetonitrile (Scheme 7) using copper(II) acetate as a co-oxidant
(Conditions B) gave the acetates 3917 and 4117 (71%, 8:1 inseparable
mixture of 39:41) also isolated were the alcohols 4017 and 4217
(10%, 4.5:1 inseparable mixture 40:42). Using copper(II) triflate as
additive gave similar results.18
MeO2C
MeO2C
CO2Me
CO2Me
MeO2C
CO2Me
(i)
MeO2C
MeO2C
•
(i)
MeO2C
•
•
MeO2C
•
CO2Me
CO2Me
CO2Me
CO2Me
(ii), (iii)
25
35
26
CO2Me
CO2Me
MeO2C
MeO2C
MeO2C CO2Me
•
MeO2C CO2Me
Cu(OAc)
Cu(II)
AcOH
CO2Me
44
MeO2C CO2Me
OR
MeO2C
OR
O
O
38
36
Cu(II)
45; R = Ac
47; R = Ac
48; R = H
MeO2C CO2Me
MeO2C CO2Me
MeO2C CO2Me
OR
46; R = H
+
Scheme 8. Cyclisation of the allenyl malonate 26. (i) Conditions A; (ii) Conditions B,
copper(II) triflate 46 and 48, 1:4, 19 %, 45 and 47, 1.5:1, 50%; (iii) Conditions B, cop-
per(II) acetate, 47 and 45, 1.2:1, 76%.
or H2O
OR
39; R = Ac
40; R = H
43
41; R = Ac
42; R = H
2.2.2.3. Cyclisation of the allenyl malonate 27. Cyclisation of the
malonyl radical derived from the substrate 27 was expected, on the
Scheme 7. Cyclisation of the allene 25 in acetonitrile. (i) Conditions B, 39 and 41 (8:1
mixture), 71%, 40 and 42 (4.5:1 mixture), 10%.

L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
10885
basis of precedent15,16 to give rise predominantly to five-membered
ring products with products containing six-membered rings being
formed as minor components. To our delight, exposure of the
malonate 27 to 2 equiv of manganese(III) acetate in ethanol (Con-
ditions A) gave the desired known vinyl cyclopentane 2412 in 66%
(Z):(E)-diastereomers (56%) reflecting the configurational mobility
of the intermediate alkenyl radical 57.22 Further purification by flash
chromatography gave the allylic g-lactones 62 as a 1:3.5 mixture of
diastereomers (5%). These products arise by mechanisms analogous
to those discussed in relation to Scheme 9. Changing the solvent to
acetonitrile and addition of copper(II) triflate (Conditions B) again
reduced the products arising from reductive termination, although
a multitude of products were formed. The alkenes 58 were isolated
yield (Scheme 9). Additionally the g-lactones 53 and 54 were iso-
lated in 15% yield as an inseparable 7:1 mixture of isomers.21 All of
the products arise by cyclisation of the electrophilic C-centred ra-
dial 49 derived from the malonate 27 to give the five- and six-
membered adduct radicals. The five-membered ring vinyl radical
50 undergoes H-atom abstraction from ethanol to give the desired
vinylcyclopentane 24.9 The six-membered allylic radical 51 un-
dergoes slow oxidation to give the corresponding allyl cation from
in 25% yield along with the enol acetates 59, the g-lactones 62 and
the allylic acetates 61, which were formed as a 5.6:2:1 ratio in
a combined yield of ca. 43%. These oxidative substitution products
were partly separated by HPLC, which allowed characterisation and
their structures were assigned by standard techniques. As with
compound 27, the cyclisation of 28 gave rise predominantly to five-
membered ring products in keeping with the work of Guo16 and
Crandall.15
which the
g-lactones are formed. It is not clear why the allylic
radical 36 suffers dimerisation prior to oxidation whereas for the
allylic radical 51 the reverse is true. Analysis of the crude 1H NMR
spectrum from the corresponding reaction conducted in the pres-
ence of copper(II) triflate (Conditions B) indicated the presence of
two major products (55:24, 3:1 ratio) along with a trace amount of
starting material. Purification by flash chromatography gave the
vinylcyclopentane 24 (10%) and the vinyl acetate 55 (22%)dno
products from six-ring formation were seen although there were
a number of unidentifiable products in the crude 1H NMR. Similar
results were obtained using copper(II) acetate. The vinyl acetate 55
is derived from the vinyl radical 50. Vinyl radicals are not oxidised
by manganese(III)3; however, in the presence of copper(II) a vinyl
copper(III) species may be formed from which on reductive elimi-
nation gives the vinyl acetate 55. Alternatively, copper(II) may
oxidise the vinyl radical to the corresponding vinyl cation, which is
then trapped by acetic acid to give product 55. The yield of the vinyl
acetate 55 could be improved to 35% by slow addition (4 h) of the
substrate 27 to the mixture of manganese(III) acetate and copper(II)
triflate in acetonitrile at reflux. Keeping the substrate concentration
low by slow addition reduces reduction of the vinyl radical 50 by
H-atom abstraction from another molecule of starting material (27)
thus maximising the likelihood of oxidation to the vinyl acetate 55.
CO2Me
CO2Me
•
(i) or (ii)
MeO2C
•
MeO2C
•
28
56
CO2Me
•
MeO2C
MeO2C
MeO2C CO2Me
•
MeO2C
Cu(II)
OAc
57
61
60
Cu(II)
Cu(II)
EtOH
O
CO2Me
O
MeO2C CO2Me
MeO2C
MeO2C
OAc
62
59
58
Scheme 10. Cyclisation of the allenyl malonate 28. (i) Conditions A, 58, 56%, 62, 5%; (ii)
Conditions B, 58, 25%, 59, 62, 61, combined yield of 43%.
2.2.2.5. Cyclisation of the allenyl malonates 29 and 30. We were
delighted to find that treatment of the malonate 29 under conditions
A gave the known vinylcyclohexane 6323 (48%) and recovered start-
ing material 29 (24%) (Scheme 11). By increasing the amount of
manganese(III) acetate to 3 equiv and the reaction time to 45 h the
yield of vinylcyclohexane could be raised to 65%. Under oxidative
termination conditions using copper(II) triflate (Conditions B) the
vinyl acetate 64 was isolated in 35% yield along with 11% of the
vinylcyclohexane 63; similar results were obtained with copper(II)
acetate. With the non-terminal allene 30, cyclisation under condi-
tions A gave the alkylidene cyclohexane 65 (40%) along with
CO2Me
CO2Me
•
(i) or (ii)
MeO2C
•
MeO2C
•
27
49
MeO2C CO2Me
MeO2C CO2Me
•
MeO2C CO2Me
•
52
51 Cu(II)
50
EtOH
MeO2C
MeO2C
OAc
MeO2C CO2Me
O
CO2Me
O
CO2Me
MeO2C CO2Me
MeO2C
MeO2C
OAc
+
•
MeO2C
MeO2C
29
63
64
53
55
24
+
O
CO2Me
MeO2C CO2Me
O
•
MeO2C
54
30
65
Scheme 9. Cyclisation of the allenyl malonate 27. Conditions A, 24 66%, 53 and 54 (7:1
mixture) 15%; (ii) Conditions B, 24 10%, 55 22%.
+
MeO2C
MeO2C
OAc
2.2.2.4. Cyclisation of the allenyl malonate 28. Treatment of the
non-terminal allene 28 with manganese(III) acetate in ethanol at
reflux (Conditions A) resulted in complete conversion of the starting
material to olefin-containing products and minor amounts of other
products as judged bycrude 1H NMR (Scheme 10). Purification of the
crude reaction mixture gave the alkenes 58 as a 1:1.5 mixture of
66
Scheme 11. Cyclisation of the allenyl malonates 29 and 30. (i) Conditions A with
3 equiv of Mn(OAc)3, 63, 65%, 65, 61%; (ii) Conditions B with copper(II) triflate, 63, 11%,
64, 35%; 65, 9%, 66, 25%.

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L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
recovered starting material 30 (22%). Again, changing the reaction
conditions to 3 equiv of manganese(III) acetate and extending the
reaction time to 45 h gave the desired product in an increased yield of
61% along with recovered starting material (8%); the olefins 65 were
isolated as an inseparable 1:1.4 mixture of (Z):(E)-geometric isomers.
Using conditions B with copper(II) triflate as additive gave the alky-
lidiene cyclohexane 65 (9%). It was clear that other components were
present in the crude reaction mixture; however, complete purifica-
tion was not possible. Nevertheless partial purification gave an im-
pure oil, which appeared to be the enol acetate 66 in ca. 25% {ES m/z
330.20 [(MþNH4)þ, 25%], 335.14 [(MþNa)þ, 80%], 647.24 [(2MþNa)þ,
100%], found [MþNa]þ 335.1463; C16H24NaO6 requires 335.1465}.
Using copper(II) acetate did not give anyof theenol acetate but rather
the alkylidene cyclohexane 65 (27%). The exclusive formation of six-
membered ring products fromthe cyclisationof the allenes 29 and 30
is in keeping with the experimental work of Crandall.15
diastereomer 68a showed no such NOE, and instead an NOE was
observed between H-5 and the proton on the iodine-bearing carbon
atom. The relative configuration of the iodine-bearing stereocentre
in 68c was established using X-ray crystallography (Fig. 1).24 In-
terestingly, the racemic iodolactone 68c crystallises with both en-
antiomers in the asymmetric unit forming a chiral racemate where
the conformations of the two enantiomers in the unit cell are not
related by a crystallographic inversion centre. This is a rare example
of a racemic crystal, which belongs to an enantiomorphous class.25
2.3. Iodolactonisation
The studies reported above indicate that it is indeed possible to
form alkenylcyclonanes in synthetically useful yields by the cyclisa-
tion of electrophilic C-centred radicals onto allenes followed by re-
duction of the so-formed alkenyl radicals. The next step was to
demonstrate a diastereoselective iodolactonisation for the formation
of [3.3.0]-bicyclic
with iodine in dichloromethane according to the procedure of Bian5
gave the desired [3.3.0]-bicyclic -lactone 67 as a 7:1 mixture of di-
g-lactones. Treatment of the vinyl cyclopentane 24
g
astereomers in 83% combined yield (Scheme 12). The relative con-
figurationof the diastereomers wasassignedonthebasis ofa 1H NMR
NOESYexperiment. For the major diastereomer a diagnostic NOE was
observed between the lactone proton H-1 and the ring protons H-5
and H-6. By contrast, in the minor diastereomer no NOEs were ob-
served between H-1 and the cyclopentane protons; instead, one of
the iodomethyl protons had an NOE to the cyclopentane protons.
Figure 1. X-ray crystal structure of the iodolactone 68c showing both enantiomers
present in the asymmetric unit. Atomic displacement ellipsoids drawn at 50% proba-
bility; disorder omitted for clarity.
The final step in our proposed diastereoselective synthesis of
[3.3.0]-bicyclic
g-lactones required removal of the iodine atom, this
also served to verify that the
g-lactones 68b and 68c varied only in
the configuration of the iodine-bearing stereocentre. Compounds
O
O
68b and 68c were individually reduced using tributyltin hydride
I
MeO2C CO2Me
O
O
MeO2C
MeO2C
giving the same bicyclic
g-lactone 69 (Scheme 14). This confirmed
H
(i)
+
1
I
6a
that iodolactonisation of disubstituted vinyl cyclopentanes had
H
H
H
5
6
indeed given bicyclic
g-lactones with high diastereocontrol.
24
H
H
nOe
O
67a
67b
H
O
H
MeO2C
I
Scheme 12. Iodocyclisation of the vinyl cyclopentane 24. (i) I2, CH2Cl2, 0 ꢀC, 67, (7:1
O
(i)
(i)
mixture) 83%.
H
O
H
MeO2C
68c
Iodolactonisation of a 1.6:1 (E):(Z) mixtureof alkenes 58 occurred
analogously to give three separable iodolactone products with a di-
astereomeric ratio of 13:1 at the lactone stereocentre (Scheme 13).
The relative configuration of the lactone stereocentre, C-1, was
assigned on the basis of 1H NMR NOESY experiments. A diagnostic
NOE observed between H-1 and H-5 for both compounds 68b and
68c confirmed the lactone configuration. By contrast, the minor
H
O
H
O
H
MeO2C
I
69
H
68b
Scheme 14. Reduction of the iodolactones 68b,c. (i) Bu3SnH, AIBN, MeCN, reflux, 97%
from 68c, 63% from 68b.
MeO2C
CO2Me
3. Conclusions
In conclusion, we have developed methodology for the regio-
selective synthesis of alkenylcyclanones by the oxidative radical
cyclisation of malonyl radicals onto both allenes, and an allylsilane.
Furthermore, we have demonstrated the diastereoselective forma-
58
(i)
nOe
O
O
O
tion of [3.3.0]-bicyclic g-lactones from two of these alkenylcycla-
H
H
H
O
H
O
O
MeO2C
MeO2C
MeO2C
I
I
I
1
1
none products. The cyclisation of 3-, 4- and 5-allenyl malonates on
exposure to manganese(III) acetate under both oxidative and re-
ductive termination conditions has also been studied. In keeping
with previous theoretical and experimental work, the cyclisation of
radicals derived from substrates 25 and 26 gives exclusively five-
membered ring products. Under reductive termination conditions
H
H
H
5
5
5
H
H
68a
68b
68c
H
H
H
nOe
nOe
Scheme 13. Iodocyclisation of the alkenyl-cyclopentane 58. (i) I2, CH2Cl2, 0 ꢀC, 68a 7%,
68b 54%, 68c 38%.

L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
10887
(ethanol as solvent) the allylic adduct radicals dimerise, whereas
under oxidative termination conditions (in the presence of a cop-
per(II) additive) good yields of allylic acetates are formed. The
substrates 27 and 28 gave predominantly five-membered ring
products again in keeping with previous work, and the substrates 29
and 30 gave exclusively six-membered ring products. Under re-
ductive termination conditions synthetically useful yields of alke-
nylcyclanones were formed from substrates 27–30. Under oxidative
termination conditions product yields were far lower, reflecting the
difficulty in oxidising an alkenyl radical.
cmꢁ1 1739; dH (400 MHz, CDCl3) 5.45–5.31 (1H, m, H-50), 5.26–5.12
(1H, m, H-40), 3.71 (6H, s, 2ꢂOMe), 3.34 (1H, t, J¼7.5, H-2),1.99 (2H, q,
J¼7.3, H-30, H-300),1.89(2H, q, J¼7.6, H-10, H-100),1.43(2H, d,J¼8.7, H-60,
H-600),1.39–1.28 (2H, m, H-20, H-200), ꢁ0.03 (9H, s, SiMe3); dC (50 MHz,
CDCl3) 171.6 (C-1),128.2 (C-40),128.0 (C-50), 54.2 (2ꢂOMe), 53.4 (C-2),
30.1 (C-10), 29.2 (C-20), 28.4 (C-30), 20.3 (C-60), 0.0 (CH3, SiMe3); LRMS
m/z (ESIþ) 350.3 (MþNaþMeCNþ, 100%); HRMS m/z (ESIþ) found
[MþNa]þ, 309.1493; C14H26O4SiNa requires 309.1493.
4.1.3. Dimethyl 2-vinylcyclopentane-1,1-dicarboxylate 2412. Man-
ganese(III) acetate (107.2 mg, 0.40 mmol) and copper(II) triflate
(72.3 mg, 0.2 mmol) were added to a solution of the malonate 23
(57.2 mg, 1.0 mmol) in dry sparged acetonitrile (2 mL). The result-
ing suspension was heated to 80 ꢀC for 24 h. Water (20 mL) and
diethyl ether (20 mL) were added and the mixture was filtered and
extracted with diethyl ether (3ꢂ100 mL). The combined organic
layers were then dried (MgSO4), filtered and then concentrated
under vacuum. The resultant oil was purified by flash column
chromatography (gradient elution 5–20% diethyl ether/petroleum
ether) to yield the vinyl cyclopentane 2412 (40.8 mg, 96%) as a col-
ourless oil; Rf¼0.56 (diethyl ether/hexane, 1:1); dH (400 MHz,
CDCl3) 5.78 (1H, ddd, J¼17.2, 10.3, 8.0, CH]CH2), 5.12–5.06 (1H, m,
CH]CHH), 5.03–4.99 (1H, m, CH]CHH), 3.73 (3H, s, OMe), 3.65
(3H, s, OMe), 3.24 (1H, q, J¼7.7, H-2), 2.46 (1H, ddd, J¼13.8, 8.4, 8.1,
H-5), 2.08 (1H, ddd, J¼13.5, 8.5, 4.9, H-50), 1.99–1.91 (1H, m, H-3),
1.91–1.81 (1H, m, H-4), 1.73–1.55 (2H, m, H-30, H-40); dC (100 MHz,
CDCl3) 172.7, 171.2, 137.5 (CH]CH2), 115.9 (CH]CH2), 64.3 (C-1),
52.5 (OMe), 52.1 (OMe), 50.0 (C-2), 33.9 (C-5), 30.7 (C-3), 23.1 (C-4);
nmax (CH2Cl2/cmꢁ1) 2955, 1732, 1638; LRMS m/z (ESIþ) 235.1
(MþNaþ, 100%), 447.2 (2MþNaþ, 97%), 213.1 (MþHþ, 94%), 276.1
(MþNaþMeCNþ, 70%); HRMS m/z (ESIþ) found [MþNa]þ 235.0944;
C11H16NaO4 requires 235.094; data consistent with literature.12
4. Experimental
4.1. General experimental
1H and 13C NMR spectra were recorded on Bruker DPX-400,
Bruker DQX-200, Bruker DRX-500, or Avance AVC-500 spectrome-
ters, using CDCl3 as reference or internal deuterium lock. Chemical
shifts are quoted in parts per million relative to tetramethylsilane
(d¼0 ppm) and referenced to the solvent residual. Multiplicities
were assigned using DEPTQ or DEPT-135 sequence. The following
abbreviations were used; s-singlet, dddoublet, tdtriplet, qdquar-
tet, mdmultiplet, brdbroad, ddddoublet of doublets (etc.). Cou-
pling constants (J) are quoted in hertz. Infrared spectra were
recorded on a Bruker Tensor 27 Fourier Transform spectrophotom-
eter on a NaCl plate using a solution in the solvent indicated. The
characteristic peaks are quoted in wavenumbers (cmꢁ1). Mass
spectra were recorded by the Mass Spectrometry Service of the
Chemistry Research Laboratory, Oxford. Melting points were recor-
ded on a Kofler hot block and are uncorrected. Flash chromatography
was carried out using Merck Kieselgel 60 (230–400 mesh). Thin layer
chromatography was carried out on Merck aluminium backed sheets
coated with 60 F254 silica gel. Visualisation of the silica plates was
achieved using a UV lamp (lmax¼254 or 365 nm), potassium per-
manganate or vanillin. High performance liquid chromatography
was carried out using a Zorbax RX-SIL column with a pressure of
5 mL/min. Solvents were either used as commercially supplied, or as
purified by standard techniques. Petroleum ether refers to the frac-
tion boiling at 40–60 ꢀC. Brine refers to a saturated aqueous solution
of sodium chloride. Unless otherwise stated, reactions were carried
out in oven-dried flasks under an atmosphere of dry nitrogen. Sol-
vents were purified by standard techniques. The cyclisation sub-
strates 25–30 were synthesised from the corresponding known
allenyl mesylates, or from the known allenyl alcohols via the corre-
sponding mesylates (vide infra).
4.1.4. Generalproceduresformanganese(III) acetatemediated reactions
4.1.4.1. Conditions A: reactions in ethanol. To a mixture of allenyl
malonate (1 equiv) and manganese(III) acetate (2 equiv) was added
degassed ethanol (50 mL/mmol of malonate). The reaction mixture
was heated under reflux for 18 h before the solvent was removed in
vacuo. The resulting mixture was diluted with water (60 mL/mmol of
malonate), and extracted with ethyl acetate (3ꢂ80 mL/mmol of
malonate). The combined organic layers were washed with brine
(3ꢂ60 mL/mmol of malonate), dried (MgSO4), filtered and the solvent
removed in vacuo. The residue was purified by flash chromatography.
4.1.4.2. Conditions B: reactions in acetonitrile with copper(II)
salt. To a mixture of allenyl malonate (1 equiv), manganese(III)
acetate (2 equiv) and a copper additive (1 equiv) was added
degassed acetonitrile (5 mL/mmol of malonate). The reaction mix-
ture was heated under reflux for 18 h. The cooled reaction mixture
was diluted with water (200 mL/mmol of malonate), and extracted
with ethyl acetate (3ꢂ140 mL/mmol of malonate). The combined
organic extracts were washed with brine (3ꢂ100 mL/mmol of
malonate), dried (MgSO4), filtered and the solvent removed in
vacuo. The residue was purified by flash chromatography.
4.1.1. General procedure for the preparation of the malonate cycli-
sation substrates. Sodium hydride (3 equiv of a 60% dispersion in
mineral oil) was suspended in DMF (4 mL/mmol of mesylate) and
cooled to 0 ꢀC. Dimethyl malonate (3 equiv) was added over 10 min
and the resulting mixture allowed to warm to room temperature.
A solution of the primary mesylate (1 equiv) in THF (2 mL/mmol of
mesylate) was added dropwise. Potassium iodide (1.5 equiv) was
added and the reaction mixture was heated under reflux for 18 h
and then allowed to cool. Water (5 mL/mmol mesylate) was added
and the mixture extracted with diethyl ether (3ꢂ5 mL/mmol of
mesylate). The combined organic layers were washed with brine
(3ꢂ5 mL/mmol of mesylate), dried (MgSO4) and the solvent re-
moved in vacuo. Purificationwas achieved by flash chromatography.
4.1.5. Tetramethyl
2,20-(ethane-1,2-diyl)dicyclopent-2-ene-1,1-di-
carboxylate 37a. Synthesised from the known malonate 2512
(0.100 g, 0.505 mmol) using Conditions A. Purified by flash column
chromatography (diethyl ether/petroleum ether, 1:2) to give
a mixture of dimers 37 (0.457 mmol, 90%) from which 37a could be
isolated as a white crystalline solid after further chromatography
4.1.2. (Z)-Dimethyl 2-(6-(trimethylsilyl)hex-4-enyl)malonate 23. Pre-
pared according to the general procedure from (Z)-6-(trimethyl-
silyl)hex-4-enyl methanesulfonate 2211 (187.5 mg, 0.75 mmol).
Purificationby flashcolumn chromatography(gradientelution5–10%
diethyl ether/petroleum ether) to give the malonate 23as a colourless
oil (178.3 mg, 83%); Rf¼0.56 (diethyl ether/hexane, 1:1); nmax (film)/
(ethyl acetate/petroleum ether, 1:3) (16.8 mg, 42.6 mmol, 8%).
Dimer 37a; Rf¼0.26 (petroleum ether/ethyl acetate, 3:1); mp
93 ꢀC; dH (500 MHz, CDCl3) 5.73 (2H, br s, 2ꢂH-3), 3.75 (12H, s,

10888
L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
OCH3), 2.51 (4H, dd, J¼7.1, 5.7, 2ꢂH-5, 2ꢂH-50), 2.42–2.38 (8H, m,
2ꢂH-4, 2ꢂH-40, CH2CH2); dC (125 MHz, CDCl3) 171.8, 141.0 (C-2),
130.1 (C-3), 68.2 (C-1), 52.5 (OMe), 34.2 (C-5), 30.5 (C-4), 26.4
(CH2CH2); nmax (CH2Cl2/cmꢁ1) 1731, 1646; LRMS m/z (ESIþ) 412.2
(MþNHþ4 , 100%), 417.1 (MþNaþ, 89%), 811.3 (2MþNaþ, 63%), 395.1
(MþHþ, 61%); HRMS m/z (ESIþ) found [MþNa]þ 417.1514;
C20H26NaO8 requires 417.1520.
was added and the reaction allowed to warm to room temperature
and was stirred for 1.5 h. The reaction was quenched with 0.5 M
aqueous HCl and extracted with DCM (3ꢂ50 mL). The organic layers
were combined, dried (Na2SO4) and the solvent removed in vacuo to
give crude hepta-3,4-dienyl methanesulfonate (2.07 g, 10.8 mmol,
96%) as an orange oil, which was used in the next reaction without
further purification; dH (500 MHz, CDCl3) 5.27–5.26 (1H, m, H-3 or
H-5), 5.15–5.09 (1H, m, H-3 or H-5), 4.27 (2H, t, J¼6.9, H-1, H-10), 3.02
(3H, s, CH3SO2), 2.44 (2H, dq, J¼3.0, 6.9, H-2, H-20), 2.02 (2H, ddq,
J¼3.3, 6.2, 7.5, H-6, H-60), 1.03 (3H, t, J¼7.4, CH2CH3); dC (125 MHz,
CDCl3) 204.4 (C-4), 94.2, 86.1, 69.2 (C-1), 37.5 (CH3SO2), 28.8 (C-2),
21.7 (C-6), 9.3 (C-7); nmax (film/cmꢁ1) 2967, 1965; HRMS m/z found
4.1.6. Dimethyl 3-acetoxy-2-methylenecyclopentane-1,1-dicarboxylate
39, dimethyl 2-(acetoxymethyl)cyclopent-2-ene-1,1-dicarboxylate 41,
dimethyl 3-hydroxy-2-methylenecyclopentane-1,1-dicarboxylate 40
and dimethyl 2-(hydroxymethyl)cyclopent-2-ene-1,1-dicarboxylate
42. Synthesised from the known malonate 2512 (0.100 g,
0.505 mmol) using Conditions B with copper(II) acetate. Purified by
flash column chromatography (petroleum ether/ethyl acetate, 2:1)
to give 39 and 41 as an inseparable 8:1 mixture of isomers as
a colourless oil (94.6 mg, 0.369 mmol, 71%); characterisation is on
the mixture of compounds. Further elution of the column gave the
alcohols 40 and 42 as an inseparable 4.5:1 mixture (11 mg,
0.051 mmol, 10%); partial separation could be obtained by further
chromatography.
Cyclopentane 39; Rf¼0.20 (petroleum ether/ethyl acetate, 3:1);
dH (500 MHz, CDCl3) 5.62 (1H, d, J¼1.7, C]CHH), 5.61 (1H, d, J¼1.7,
C]CHH), 5.55 (1H, dddd, J¼6.2, 4.9, 1.6, 1.6, H-3), 3.77 (3H, s, OMe),
3.75 (3H, s, OMe), 2.52 (1H, ddd, J¼13.5, 8.0, 7.3, H-5), 2.34 (1H, ddd,
J¼13.5, 6.9, 6.5, H-50), 2.10 (1H, dddd, J¼13.2, 8.0, 6.9, 6.2, H-4), 2.06
(3H, s, C(O)CH3), 1.81 (1H, dddd, J¼13.2, 7.3, 6.5, 4.9, H-40); dC
(125 MHz, CDCl3) 170.61, 170.59, 170.4, 145.7 (C-2), 118.3 (C]CH2),
76.2 (C-3), 61.4 (C-1), 53.0 (OMe), 52.98 (OMe), 32.1 (C-5), 30.7 (C-
4), 21.2 (C(O)CH3); nmax (CH2Cl2/cmꢁ1) 1735, 1659; LRMS m/z (ESIþ)
279.1 (MþNaþ, 100%), 274.1 (MþNHþ4 , 54%); HRMS m/z (ESIþ) found
[MþNa]þ 279.0841; C12H16NaO6 requires 279.0839; Found C, 56.31;
H, 6.22%; C12H16O6 requires: C, 56.24; H, 6.29%.
Cyclopentane 41, selected data; Rf¼0.20 (petroleum ether/ethyl
acetate, 3:1); dH (500 MHz, CDCl3) 6.06–6.04 (1H, m, H-3), 4.82 (2H,
q, J¼1.8, CH2O), 3.75 (6H, s, OMe), 2.59–2.56 (2H, m, H-5, H-50),
2.48–2.44 (2H, m, H-4, H-40), 2.05 (3H, s, C(O)CH3); dC (125 MHz,
CDCl3) 171.1, 170.5, 136.1 (C-2), 135.3 (C-3), 61.9 (C-1), 61.4 (CH2O),
33.8 (C-5), 305 (C-4), 20.9 (C(O)CH3).
Alcohol 40; Rf¼0.37 (CH2Cl2/ethyl acetate, 5:1þ1% IPA); dH
(500 MHz, CDCl3) 5.58 (1H, d, J¼1.6, C]CHH), 5.54 (1H, d, J¼1.6,
C]CHH), 4.53 (1H, ddd, J¼6.4, 5.8, 5.7, H-3), 3.77 (3H, s, OMe), 3.75
(3H, s, OMe), 2.50 (1H, dd, J¼13.7, 6.9, H-5), 2.30 (1H, ddd, J¼13.7,
7.4, 7.1, H-50), 2.04 (1H, dddd, J¼13.1, 7.1, 6.9, 6.4, H-4), 1.84 (1H, d,
J¼5.7, OH), 1.73 (1H, dddd, J¼13.1, 7.4, 7.4, 5.8, H-40); dC (125 MHz,
CDCl3) 171.2, 170.6, 150.4 (C-2), 115.3 (C]CH2), 75.2 (C-3), 59.8 (C-
1), 53.0 (OMe), 52.9 (OMe), 33.4 (C-4), 31.6 (C-5); nmax (CH2Cl2/
cmꢁ1) 3468, 1733, 1657; LRMS m/z (ESIþ) 451.1 (2MþNaþ, 100%),
237.1 (MþNaþ, 76%); HRMS m/z (ESIþ) found [MþNa]þ 237.0733;
C10H14NaO5 requires 237.0733; Found C, 56.18; H, 6.56%; C10H14O5
requires: C, 56.07; H, 6.59%.
M
þ 190.0661; C8H14O3S requires 190.0664.
4.1.8. Dimethyl 2-(hepta-3,4-dienyl)malonate 26. Synthesised from
hepta-3,4-dienyl methanesulfonate (2.05 g, 10.7 mmol) according
to the general procedure. Purification by flash column chromato-
graphy (gradient petroleum ether/ethyl acetate, 20:1/6:1) gave
the malonate 26 (1.87 g, 8.27 mmol, 76%); Rf¼0.58 (petroleum
ether/ethyl acetate, 3:1); dH (500 MHz, CDCl3) 5.20–5.15 (1H, m, H-
30 or H-50), 5.08 (1H, tdt, J¼6.1, 6.1, 3.3, H-30 or H-50), 3.74 (6H, s,
2ꢂOMe), 3.49–3.40 (1H, m, H-1), 2.05–1.96 (6H, m, 2ꢂH-10, 2ꢂH-20,
2ꢂH-60), 1.00 (3H, t, J¼7.4, CH2CH3); dC (125 MHz, CDCl3) 203.7 (C-
40), 169.8, 93.6 (C-50), 89.8 (C-30), 52.4 (OMe), 52.4 (C-1), 50.7 (CH2),
28.1 (CH2), 26.5 (CH2), 21.9 (C-60),13.4 (C-70); nmax (film)/cmꢁ1 2962,
1963, 1754, 1738; LRMS m/z (ESIþ) 475.2 (2MþNaþ, 100%), 249.1
(MþNaþ, 62%); HRMS m/z (ESIþ) found [MþNa]þ 249.1091;
C12H18NaO4 requires 249.1097.
4.1.9. Dimethyl 3-acetoxy-2-propylidenecyclopentane-1,1-dicarboxy-
late 45 and dimethyl 2-(1-acetoxypropyl)cyclopent-2-ene-1,1-di-
carboxylate 47. Synthesised from the allene 26 (114 mg, 0.5 mmol)
using Conditions B with copper(II) acetate. Purification by flash
chromatography (gradient elution 30:1 petroleum ether/ethyl ac-
etate/ethyl acetate) gave the acetates 45 and 47 as an inseparable
1:1.2 mixture (108 mg, 0.38 mmol, 76%); the exo-cyclic alkenes 45
were formed as a 1:1.5 mixture of geometric isomers and charac-
terisation is on the mixture of compounds.
Acetates 45 and 47; Rf¼0.57 (petroleum ether/ethyl acetate,
3:1); dH (500 MHz, CDCl3) 6.09–6.08 (1H, br, H-347) 5.98 (1H, dt, J
1.6, 7.7, CH]C45d1), 5.92 (1H, t, J¼7.6, CH]C45d2), 5.78 (1H, br d,
J¼5.6, H-345d1), 5.56 (1H, t, J¼7.4, H-347), 5.52 (1H, t, J¼4.2, H-345d2),
3.77 (3H, s, OMe45d1), 3.77 (3H, s, OMe47), 3.74 (3H, s, OMe47), 3.737
(3H, s, OMe45d2), 3.731 (3H, s, OMe45d1), 3.72 (3H, s, OMe45d2),
2.65–2.34 (6H, m, H-545d1, H-5045d1, H-545d2, H-5045d2, H-447, H-
4047), 2.24–2.08 (4H, m, allylicCH245d1, allylicCH245d2), 2.06–1.98
(3H, m, CH2OAc45d2, CHHOAc45d1), 2.04 (3H, s, OAc45d2), 2.03 and
2.02 (2ꢂ3H, s, OAc45d1, OAc47), 1.88–1.81 (2H, m, CHHOAc45d1
,
CHHCH347), 1.78–1.69 (1H, m, CHHCH347), 1.01 (3H, t, J¼7.7,
CH2CH345d1), 0.96 (3H, t, J¼7.7, CH2CH345d2), 0.91 (3H, t, J¼7.7,
CH2CH347); dC (125 MHz, CDCl3) 171.6,171.5,171.3,171.2,171.2,171.0,
170.8, 170.5, 170.1, 140.5, 137.9, 136.3, 135.9, 134.8, 78.3, 73.6, 71.6,
67.0, 62.7, 61.0, 52.9, 52.8, 52.8, 52.6, 52.5, 34.6, 34.1, 32.9, 31.8, 31.1,
30.5, 27.4, 23.2, 23.2, 21.4, 21.3, 21.1, 13.6, 12.6, 9.9; nmax (CH2Cl2)/
cmꢁ1 2956, 1735; LRMS m/z (ESIþ) 307.1 (MþNaþ, 80%), 591.2
(2MþNaþ, 100%); HRMS m/z (ESIþ) found [MþNa]þ 307.1151;
C14H20NaO6 requires 307.1152.
Alcohol 42; Rf¼0.09 (CH2Cl2/ethyl acetate, 20:1); dH (500 MHz,
CDCl3) 6.06 (1H, tt, J¼2.5, 1.3, H-3), 4.29 (2H, dtd, J¼6.2, 1.5, 1.3,
CH2OH), 3.77 (6H, s, 2ꢂOMe), 2.70 (1H, t, J¼6.2, OH), 2.58–2.54 (2H,
m, H-5, H-50), 2.46 (2H, dddt, J¼5.1, 3.5, 2.5, 1.5, H-4, H-40); dC
(125 MHz, CDCl3) 172.0, 140.8 (C-2), 135.1 (C-3), 67.1 (C-1), 59.8
(CH2OH), 52.9 (OMe), 34.2 (C-5), 30.4 (C-4); nmax (CH2Cl2/cmꢁ1
)
3458, 1731, 1651; LRMS m/z (ESIþ) 197.1 (MꢁOHþ, 100%), 237.1
(MþNaþ, 96%), 451.1 (2MþNaþ, 93%), 278.1 (MþNaþMeCNþ, 83%);
HRMS m/z (ESIþ) found [MþNa]þ 237.0745; C10H14NaO5 requires
237.0733.
4.1.10. Dimethyl 2-vinylcyclopentane-1,1-dicarboxylate 24, methyl
3-oxo-1,3,3a,4,5,6-hexahydroisobenzofuran-3a-carboxylate 53 and
(1S
*
,5R )-methyl 8-methylene-7-oxo-6-oxabicyclo[3.2.1]octane-1-
*
carboxylate 54. Synthesised from the known allene 2729,30
(106 mg, 0.5 mmol) using Conditions A. Purification by flash chro-
matography (petroleum ether/diethyl ether, 3:1) gave the vinyl-
cyclopentane 2412 (70 mg, 0.33 mmol, 66%). Further elution of the
column gave the lactones 53 and 54 as 7:1 inseparable mixture
4.1.7. Hepta-3,4-dienyl methanesulfonate. To the known alcohol
hepta-3,4-dien-1-ol26–28 (1.27 g, 11.3 mmol) in DCM (30 mL) was
added triethylamine (2.3 mL, 16.5 mmol) and the mixture was
cooled to 0 ꢀC. Methanesulfonyl chloride (1.05 mL, 13.5 mmol)

L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
10889
(15 mg, 0.077 mmol, 15%); characterisation is on the mixture of
compounds.
Lactone 53; Rf¼0.27 (CH2Cl2/IPA, 20:1); dH (500 MHz, CDCl3)
diastereoisomers of the lactones 62 (5 mg, 22.3
terisation is on the mixture.
m
mol, 5%); charac-
(Z)-Dimethyl 2-(but-1-enyl)cyclopentane-1,1-dicarboxylate (Z)-
58; Rf¼0.16 (petroleum ether/ethyl acetate, 20:1); dH (500 MHz,
CDCl3) 5.40 (1H, dtd, J¼10.8, 7.4, 0.8, ]CHCH2), 5.15 (1H, ddt,
J¼10.8,10.7,1.6, CHCH]), 3.72 (3H, s, OMe), 3.66 (3H, s, OMe), 3.65–
3.64 (1H, m, H-2), 2.21–2.03 (4H, m, CH2CH3, H-4, H-40), 2.02–1.94
(1H, m, H-3), 1.89–1.80 (1H, m, H-5), 1.63–1.48 (2H, m, H-30, H-50),
0.96 (3H, t, J¼7.5 z, CH2CH3); dC (125 MHz, CDCl3) 172.8, 171.3, 133.3,
128.3, 64.6 (C-1), 52.5 (OMe), 52.1 (OMe), 43.3 (C-2), 34.1 (C-4), 32.9
5.90–5.87 (1H, m, H-7), 5.07 (1H, dddd, J¼10.8, 3.3, 3.3, 2.0, H-1),
4.73 (1H, dddd, J¼10.8,1.5,1.3,1.3, H-10), 3.78 (3H, s, OMe), 2.63 (1H,
dt, J¼13.2, 3.4, H-4), 2.22 (1H, dddd, J¼6.7, 5.1, 3.3, 1.5, H-6), 2.16–
2.06 (1H, m, H-60), 1.95–1.82 (1H, m, H-5), 1.82–1.69 (1H, m, H-50),
1.37 (1H, ddd, J¼13.5, 13.2, 3.7, H-40); dC (125 MHz, CDCl3) 173.4,
168.3, 131.1 (C-7a), 125.2 (C-7), 72.1 (C-1), 62.3 (C-3a), 53.1 (OMe),
26.0 (C-4), 23.5 (C-6), 18.3 (C-5); nmax (CH2Cl2/cmꢁ1) 2957, 1780,
1738; LRMS m/z (ESIþ) 415.1 (2MþNaþ, 100%), 219.0 (MþNaþ, 88%),
260.1 (MþNaþMeCNþ, 75%), 214.1 (MþNHþ4 , 63%); HRMS m/z
(ESIþ) found [MþNa]þ 219.0627; C10H12NaO4 requires 219.0628.
Lactone 54; Rf¼0.27 (CH2Cl2:IPA, 20:1); dH (500 MHz, CDCl3)
5.10–5.06 (2H, m, CHH]C, H-5), 4.87 (1H, t, J¼1.0, CHH]C), 3.83
(3H, s, OMe), 2.39 (1H, ddt, J¼12.6, 5.3,1.4), 2.09 (1H, dt, J¼5.8,12.6),
2.24–2.18 (1H, m), 1.94–1.90 (2H, m), 1.76–1.68 (1H, m); dC
(125 MHz, CDCl3) 168.3, 168.0, 149.1 (C-8), 104.0 (CH2]C), 81.3 (C-
5), 72.9 (C-3a), 52.8 (OMe), 33.3, 31.4, 17.9.
(C-3), 23.4 (C-5), 20.7 (CH2CH3), 14.3 (CH2CH3); nmax (CH2Cl2/cmꢁ1
)
2958 (]CH), 1733 (C]O ester); LRMS m/z (ESIþ) 241.1 (MþHþ,
100%), 263.1 (MþNaþ, 94%), 503.2 (2MþNaþ, 93%); HRMS m/z
(ESIþ) found [MþNa]þ 263.1253; C13H20NaO4 requires 263.1254.
(E)-Dimethyl 2-(but-1-enyl)cyclopentane-1,1-dicarboxylate (E)-
58; Rf¼0.16 (petroleum ether/ethyl acetate, 20:1); dH (500 MHz,
CDCl3) 5.55 (1H, dtd, J¼15.3, 6.4, 1.0, ]CHCH2), 5.34 (1H, ddt,
J¼15.3, 8.0, 1.5, CHCH]), 3.73 (3H, s, OMe), 3.64 (3H, s, OMe), 3.23
(1H, br dt, J¼8.0, 7.6, H-2), 2.51–2.43 (2H, m, H-4, H-40), 2.21–2.14
(2H, m, H-5, H-50), 2.02–1.90 (3H, m, CH2CH3, H-3), 1.67–1.60 (1H,
m, H-30), 0.94 (3H, t, J¼7.5, CH2CH3); dC (125 MHz, CDCl3) 172.9,
171.33, 133.8, 128.0, 64.5 (C-1), 52.4 (OMe), 51.9 (OMe), 48.9 (C-2),
33.8 (C-4), 31.3 (C-3), 25.5 (CH2CH3), 23.2 (C-5), 13.8 (CH2CH3).
Lactones 62; Rf¼0.13 (petroleum ether/CH2Cl2, 1:3 with 1% IPA);
dH (500 MHz, CDCl3) 5.86–5.83 (1H, m, H-7d1), 5.82 (1H, ddd, J¼3.7,
3.5, 2.1, H-7d2), 5.19–5.15 (1H, m, H-1d2), 4.77 (1H, ttd, J¼7.7, 1.5, 1.4,
H-1d1), 3.78 (6H, s, OMed1 and d2), 2.61 (1H, dt, J¼13.2, 3.4, H-4d2),
2.52 (1H, dt, J¼13.0, 3.4, H-4d1), 2.31–2.27 (1H, m, H-6d1), 2.23 (1H,
ddddd, J¼19.1, 6.9, 3.5, 3.4, 1.4, H-6d2), 2.15–2.05 (2H, m, H-60d1 and
d2), 2.05–1.96 (1H, m, CHHCH3d2), 1.94–1.80 (4H, m, H-5d1 and d2, H-
50, CHHCH3d1), 1.78–1.70 (1H, m, H-50d2), 1.70–1.63 (1H, 0 m,
CHHCH3d1), 1.69–1.62 (1H, m, CHHCH3d2), 1.50–1.43 (1H, m, H-4 d1),
1.38 (1H, ddd, J¼13.5, 13.2, 3.7, H-40d2), 1.09 (3H, t, J¼7.4, CH2CH3d2),
1.02 (3H, t, J¼7.4, CH2CH3d1); dC (125 MHz, CDCl3) 173.0,168.5,134.9
(C-7ad1 and d2), 125.9 (C-7d1), 123.2 (C-7d2), 85.5 (C-1d1), 84.0 (C-
4.1.11. Dimethyl 2-(1-acetoxyvinyl)cyclopentane-1,1,-dicarboxylate
55. Synthesised from the known allene 2729,30 (106 mg, 0.5 mmol)
using Conditions B with copper(II) triflate. Purification by flash
chromatography (petroleum ether/diethyl ether, 3:1) gave the
vinylcyclopentane 2412 (11 mg, 0.05 mmol, 10%) and the enol ace-
tate 55 (30 mg, 0.11 mmol, 22%).
Enol acetate 55; Rf¼0.14 (petroleum ether/ethyl acetate, 5:1); dH
(500 MHz, CDCl3) 4.89 (1H, dd, J¼1.8, 0.8, C]CHH), 4.86 (1H, d,
J¼1.8, ]CHH), 3.73 (3H, s, OMe), 3.68 (3H, s, OMe), 3.53 (1H, ddd,
J¼9.9, 7.2, 0.8, H-2), 2.55 (1H, ddd, J¼13.8, 8.8, 8.6, H-5), 2.10 (3H, s,
C(O)CH3), 2.08–1.99 (2H, m, H-50, H-3), 1.91–1.83 (1H, m, H-4), 1.74
(1H, dddd, J¼12.8,10.0, 9.9, 8.1, H-30),1.58 (1H, dtdd, J¼12.5, 9.0, 8.8,
8.1, H-40); dC (125 MHz, CDCl3) 172.4, 170.9, 169.0, 154.4 (C]CH2),
103.3 (C]CH2), 63.3 (C-1), 52.7 (OMe), 52.4 (OMe), 49.7 (C-2), 34.9
(C-5), 29.4 (C-3), 23.1 (C-4), 21.1 (C(O)CH3); nmax (CH2Cl2/cmꢁ1
)
2955, 1761, 1732, 1663; LRMS m/z (ESIþ) 288.1 (MþNH4þ, 100%),
563.2 (2MþNaþ, 82%), 276.1 (MþNaþ, 81%); HRMS m/z (ESIþ) found
[MþNa]þ 293.0997; C13H18NaO6 requires 293.0996. Found C, 57.81;
H, 6.63%; C13H18O6 requires: C, 57.77; H, 6.71%.
1d2), 62.32 (C-3ad1
d2), 60.4 (C-3ad1
d2), 53.2 (OMed1), 53.1
or
or
(OMed2), 27.9 (C-4d1), 27.6 (CH2CH3d1), 26.3 (C-4d2), 25.3
(CH2CH3d2), 23.6 (C-6d2), 23.3 (C-6d1), 18.1 (C-5d2), 17.8 (C-5d1), 9.7
(CH2CH3d1), 9.6 (CH2CH3d2); nmax (CH2Cl2/cmꢁ1) 1780 (C]O
g-lac-
tone), 1738 (C]O ester), 1692 (C]C); LRMS m/z (ESIþ) 471.2
(2MþNaþ, 100%), 247.1 (MþNaþ, 82%), 225.1 (MþHþ, 56%), 279.1
(MþNaþMeOHþ, 48%); HRMS m/z (ESIþ) found [MþNa]þ 247.0944;
C12H16NaO4 requires 247.0941.
4.1.12. Dimethyl 2-(octa-4,5-dienyl)malonate 28. Synthesised from
known octa-4,5-dienyl methanesulfonate31 (1.12 g, 5.42 mmol)
according to the general procedure but using THF in place of DMF.
Purification by flash column chromatography (petroleum ether/
diethyl ether, 10:1) gave the malonate 28 as a colourless oil
(1.21 g, 5.04 mmol, 93%); Rf¼0.13 (petroleum ether/diethyl ether,
10:1); dH (500 MHz, CDCl3) 5.16 (1H, tq, J¼3.0, 6.3, H-60), 5.09 (1H,
tq, J¼3.2, 6.3, H-40), 3.74 (6H, s, 2ꢂOMe), 3.38 (1H, t, J¼7.6, H-1),
2.05–1.92 (6H, m, 2ꢂH-10, 2ꢂH-30, 2ꢂH-70), 1.44 (2H, qn, J¼7.7,
2ꢂH-20), 1.00 (3H, t, J¼7.4, CH2CH3); dC (125 MHz, CDCl3) 203.5 (C-
50), 169.9, 93.1 (C-60), 90.7 (C-40), 52.4 (OMe), 51.5 (C-1), 28.5 (C-
30), 28.2 (C-10), 26.8, (C-20), 21.9 (C-70), 13.4 (C-80); nmax (CDCl3/
cmꢁ1) 1962, 1755, 1737; LRMS m/z (ESIþ) 503.2 (2MþNaþ, 100%),
241.1 (MþHþ, 65%), 258.2 (MþNHþ4 , 60%), 263.1 (MþNaþ, 52%);
HRMS m/z (ESIþ) found [MþNa]þ 263.1257; C13H20NaO4 requires
263.1254; Found C, 64.90; H, 8.29%; C13H20O4 requires: C, 64.98;
H, 8.39%.
4.1.14. Dimethyl 2-(1-acetoxybut-1-enyl)cyclopentane-1,1-dicarboxylate
59 and dimethyl 2-(1-acetoxypropyl)cyclohex-2-ene-1,1-dicarbox-
ylate 61. Synthesised from dimethyl 2-(octa-4,5-dienyl)malonate
28 (0.116 g, 0.481 mmol) using Conditions B with copper(II) triflate.
Purified by flash column chromatography (petroleum ether/ethyl
acetate, 5:1) to give the alkenes 58 (0.0285 g, 0.119 mmol, 25%
yield, E:Z 1.7:1) and a 5.6:2:1 mixture of 59:62:61 (50 mg, ca. 43%);
the enol acetates 59 were formed as an inseparable mixture of
geometric isomers. This mixture was further purified by semi-
preparative HPLC (hexane with 1% IPA).
Enol acetate 59a; Rf¼0.18 (petroleum ether/ethyl acetate, 5:1);
dH (500 MHz, CDCl3) 5.22 (1H, t, J¼7.7, C]CH), 3.95 (1H, t, J¼8.2, H-
2), 3.73 (3H, s, OMe), 3.68 (3H, s, OMe), 2.55 (1H, ddd, J¼13.2, 9.6,
8.0, H-5), 2.29–2.20 (2H, m, CH2CH3), 2.08 (3H, s, C(O)CH3), 2.07
(1H, ddd, J¼13.2, 7.7, 3.2, H-50), 1.99 (1H, ddd, J¼12.6, 8.2, 4.5, H-3),
1.94–1.85 (1H, m, H-4), 1.75–1.65 (1H, m, H-30), 1.60–1.48 (1H, m, H-
40), 1.02 (3H, t, J¼7.5, CH2CH3); dC (125 MHz, CDCl3) 172.6, 170.9,
169.4 (C(O)CH3), 145.1 (C]CH), 123.0 (C]CH), 63.3 (C-1), 52.7
(OMe), 52.5 (OMe), 45.0 (C-2), 34.8 (C-5), 29.6 (C-3), 23.8 (C-4), 21.1
(C(O)CH3), 20.1 (CH2CH3), 14.2 (CH2CH3); nmax (CH2Cl2/cmꢁ1), 1756,
1732,1642; LRMS m/z (ESIþ) 321.1 (MþNaþ,100%); HRMS m/z (ESIþ)
found [MþNa]þ 321.1310; C15H22NaO6 requires 321.1309.
4.1.13. Dimethyl 2-(but-1-enyl)cyclopentane-1,1-dicarboxylate 58
and methyl 1-ethyl-3-oxo-1,3,3a,4,5,6-hexahydroisobenzofuran-3a-
carboxylate 62. Synthesised from dimethyl 2-(octa-4,5-dien-
yl)malonate 28 (0.102 g, 0.424 mmol) using Conditions A. Purified
by flash column chromatography (petroleum ether/ethyl acetate,
5:1) to give an inseparable mixture of alkenes 58 as a colourless oil
(57.3 mg, 0.238 mmol, 56%, E:Z 1.5:1); characterisation is on the
mixture. Further elution of the column gave
a mixture of

10890
L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
Enol acetate 59b; Rf¼0.17 (petroleum ether/ethyl acetate, 5:1);
3.9, H-2), 2.29 (1H, ddd, J¼13.0, 5.4, 2.6, H-6), 2.11 (3H, s, OAc) 1.98–
1.94 (1H, m, H-3), 1.93–1.87 (1H, m, H-60), 1.74–1.67 (2H, m), 1.52–
1.41 (3H, m); dC (125 MHz, CDCl3) 172.2, 170.5, 169.0, 156.0
(C]CH2), 104.0 (C]CH2), 57.9 (C-1), 52.6 (OMe), 52.0 (OMe), 44.7
(C-2), 32.2, 26.2, 23.9, 22.3, 21.2; nmax (film/cmꢁ1) 2949, 1733; LRMS
m/z (ESIþ) 307.1 (MþNaþ, 98%), 591.2 (2MþNaþ, 100%); HRMS m/z
(ESIþ) found [MþNa]þ 307.1153; C14H20NaO6 requires 307.1152.
dH (500 MHz, CDCl3) 5.19 (1H, t, J¼7.3, ]CH), 3.73 (3H, s, OMe), 3.68
(3H, s, OMe), 3.50 (1H, dd, J¼10.4, 7.1, H-2), 2.55 (1H, ddd, J¼13.7,
8.7, 8.6, H-5), 2.13 (3H, s, C(O)CH3), 2.05–1.94 (2H, m, H-3, H-50),
1.94–1.81 (3H, m, CH2CH3, H-4), 1.73–1.64 (1H, m, H-30), 1.62–1.52
(1H, m, H-40), 0.94 (3H, t, J¼7.5, CH2CH3); dC (125 MHz, CDCl3) 172.6,
171.2, 170.0, 145.9 (C]CH), 120.5 (C]CH), 63.3 (C-1), 52.6 (OMe),
52.2 (OMe), 49.8 (C-2), 34.8 (C-5), 29.0 (C-3), 23.1 (C-4), 20.7
(C(O)CH3), 19.0 (CH2CH3), 13.5 (CH2CH3); nmax (CH2Cl2/cmꢁ1) 1753,
1731, 1699, 1685; LRMS m/z (ESIþ) 321.1 (MþNaþ, 100%), 316.2
(MþNHþ4 , 77%), 619.2 (2MþNaþ, 70%), 299.1 (MþHþ, 64%); HRMS
m/z (ESIþ) found [MþNa]þ 321.1309; C15H22NaO6 requires 321.1309.
Allylic acetate 61; Rf¼0.13 (petroleum ether/ethyl acetate, 5:1);
dH (500 MHz, CDCl3) 6.17 (1H, t, J¼3.9, H-3), 5.41 (1H, dd, J¼8.1, 5.3,
CHOC(O)CH3), 3.75 (3H, s, OMe), 3.70 (3H, s, OMe), 2.29 (1H, ddd,
J¼13.1, 7.8, 3.1, H-6), 2.21–2.15 (3H, m, H-4, H-40, H-60), 2.02 (3H, s,
C(O)CH3), 1.82–1.64 (3H, m, CH2CH3, H-5), 1.53 (1H, dddd, J¼13.9,
13.5, 6.9, 3.1, H-50), 0.89 (3H, t, J¼7.4, CH2CH3); dC (125 MHz, CDCl3)
171.6, 171.4, 170.2, 133.2 (C-2), 131.4 (C-3), 75.0 (CHOC(O)CH3), 58.0
(C-1), 52.7 (OMe), 52.5 (OMe), 31.4 (C-6), 28.1 (CH2CH3), 24.9 (C-4),
21.3 (C(O)CH3), 18.6 (C-5), 10.4 (CH2CH3); nmax (CH2Cl2/cmꢁ1) 1732,
1659; LRMS m/z (ESIþ) 619.2 (2MþNaþ, 100%), 614.3 (2MþNH4,
86%), 316.2 (MþNHþ4 , 86%), 321.1 (MþNaþ, 66%); HRMS m/z (ESIþ)
found [MþNa]þ 321.1305; C15H22NaO6 requires 321.1309.
4.1.18. Nona-5,6-dienyl methanesulfonate. The known alcohol
nona-5,6-dien-1-ol33 (1.34 g, 9.97 mmol) in DCM (30 mL) was
added triethylamine (1.95 mL, 14.0 mmol) and the mixture
was cooled to 0 ꢀC. Methanesulfonyl chloride (0.93 mL, 12.0 mmol)
was added and the reaction allowed to warm to room temperature
and was stirred for 1.5 h. The reaction was quenched with 1.0 M
aqueous HCl (60 mL) and extracted with DCM (3ꢂ50 mL). The or-
ganic layers were combined and dried (MgSO4) and the solvent
removed in vacuo to give crude hepta-3,4-dienyl methanesulfonate
(2.08 g, 9.56 mmol, 96%) as an orange oil, which was used in the
next reaction without further purification; dH (500 MHz, CDCl3)
5.19–5.14 (1H, m, H-3 or H-5), 5.12–5.07 (1H, m, H-3 or H-5), 4.24
(2H, t, J¼6.5, H-1, H-10), 3.00 (3H, s, CH3SO2), 2.06–1.96 (4H, m, H-4,
H-40, H-8, H-80), 1.84–1.78 (2H, m, H-2, H-20), 1.53 (2H, qn, J¼7.6, H-
3, H-30),1.00 (3H, t, J¼7.6, CH2CH3); dC (125 MHz, CDCl3) 203.6 (C-6),
93.4, 90.6, 69.8 (C-1), 37.4 (CH3SO2), 28.5 (C-3), 28.2, 24.8 (C-3),
21.9, 13.4 (C-9); nmax (film)/cmꢁ1 2965, 2937, 1961; HRMS m/z (EI)
found Mþ 218.0973; C10H18O3S requires 218.0977.
4.1.15. Dimethyl 2-(hepta-5,6-dienyl)malonate 29. Synthesised from
knownhepta-5,6-dienyl methanesulfonate29,30,32 (1.40 g, 7.35 mmol)
using the general procedure. Purification by flash column chroma-
tography (gradient petroleum ether/ethyl acetate, 40:1/30:1) gave
the allene 29 as a colourless oil (1.26 g, 5.04 mmol, 76%); Rf¼0.30
(petroleum ether/ethyl acetate, 9:1); dH (500 MHz, CDCl3) 5.07 (1H, tt,
J¼6.7, 6.7, H-50), 4.65 (2H, dt, J¼6.7, 3.2, 2ꢂH-70), 3.74 (6H, s, 2ꢂOMe),
3.36 (1H, t, J¼7.5, H-1), 2.00 (2H, dtt, J¼7.2, 6.7, 3.3, 2ꢂH-40),1.93–1.89
(2H, m, 2ꢂH-10),1.48–1.41 (2H, m, H-30),1.38–1.32 (2H, m, 2ꢂH-20);dC
(125 MHz, CDCl3) 208.5 (C-60),169.8 (CO), 89.6 (C-50), 74.8 (C-70), 52.4
(OMe), 51.6 (C-1), 28.6 (CH2), 28.5 (CH2), 27.8 (C-40), 26.7 (C-20); nmax
(film)/cmꢁ1 2953,1956,1753,1737; LRMS m/z (ESIþ) 475.2 (2MþNaþ,
100%), 249.1 (MþNaþ, 59%); HRMS m/z (ESIþ) found [MþNa]þ
249.1091; C12H18NaO4 requires 249.1097.
4.1.19. Dimethyl 2-(nona-5,6-dienyl)malonate 30. Synthesised from
nona-5,6-dienyl methanesulfonate (2.09 g, 9.26 mmol) according
to the general procedure. Purification by flash column chroma-
tography (gradient elution petroleum ether/ethyl acetate, 40:1/
30:1) gave the malonate 30 as a colourless oil (1.41 g, 5.54 mmol,
59%); Rf¼0.3 (petroleum ether/ethyl acetate, 9:1); dH (500 MHz,
CDCl3) 5.13 (1H, tdt, J¼6.1, 6.1, 3.0, H-50), 5.08 (1H, tdt, J¼6.4, 6.4, 3.3,
H-70), 3.74 (6H, s, 2ꢂOMe), 3.36 (1H, t, J¼7.5, H-1), 2.01–1.94 (4H, m,
2ꢂH-40 2ꢂH-80), 1.93–1.88 (2H, m, 2ꢂH-10), 1.46–1.39 (2H, m, 2ꢂH-
30), 1.38–1.31 (2H, m, 2ꢂH-20), 0.99 (3H, t, J¼7.4, CH2CH3); dC
(125 MHz, CDCl3) 203.4 (C-60), 169.9 (CO), 92.8 (C-50), 91.1 (C-70),
52.4 (OMe), 51.6 (C-1), 30.9 (CH2), 28.7 (CH2), 28.6 (CH2), 28.5 (CH2),
26.7 (C-20), 22.0, 13.4 (C-90); nmax (film)/cmꢁ1 2950, 1735; LRMS m/z
(ESIþ) 531.2 (2MþNaþ, 100%), 277.1 (MþNaþ, 87%); HRMS m/z
(ESIþ) found [MþNa]þ 277.1413; C14H22NaO4 requires 277.1410.
4.1.16. Dimethyl 2-vinylcyclohexane-1,1-dicarboxylate 63. Synthesised
from allene 29 (0.114 g, 0.5 mmol) using Conditions A with 3 equiv of
manganese(III) acetate for 45 h. Purification by flash chromatography
(gradient elution petroleum ether/ethyl acetate, 40:1/20:1) gave the
known olefin 6323 as a colourless oil (0.074 g, 65%); Rf¼0.37 (petroleum
ether/ethyl acetate, 9:1); dH (500 MHz, CDCl3) 6.09 (1H, ddd, J¼17.5, 10.1,
9.3, CH]C), 5.00 (1H, ddd, J¼17.5, 2.0, 0.9, ]CHH), 4.98 (1H, ddd, J¼10.1,
2.0, 0.6, ]CHH), 3.70 (3H, s, OMe), 3.69 (3H, s, OMe), 2.76(1H, td, J¼8.4, 4.1,
H-2), 2.16 (1H, ddd, J¼13.7, 7.9, 3.3, H-6), 1.99 (1H, ddd, J¼13.7, 8.0, 4.0, H-
60), 1.82 (1H, ddt, J¼16.2, 8.0, 4.0, H-3), 1.69–1.56 (2H, m, H-30, H-4),1.47–
1.37 (3H, m, H-40, H-5, H-50); dC (125 MHz, CDCl3) 172.0, 171.0, 138.7
(CH]C),115.8 (]CH2), 59.2 (C-1), 52.2 (OMe), 52.0 (OMe), 45.9 (C-2), 30.2
(C-6), 28.4 (C-3), 22.9 (C-4), 22.4 (C-5); nmax (film/cmꢁ1) 2952,1750,1732;
LRMS m/z (ESIþ) 475.2 (2MþNaþ,100%), 249.1 (MþNaþ, 52%); HRMS m/z
(ESIþ) found [MþNa]þ 249.1093; C12H18NaO4 requires 249.1097. Data in
accord with the literature.23
4.1.20. Dimethyl 2-(but-1-enyl)cyclohexane-1,1-dicarboxylate 65. Syn-
cthesised from allene 30 (0.128 g, 0.5 mmol) using Conditions A
with 3 equiv of manganese(III) acetate for 45 h. Purification by flash
chromatography (gradient elution petroleum ether/ethyl acetate,
40:1/20:1) gave the olefins 65 as an inseparable 1.4:1 mixture of
(E):(Z) geometric isomers a colourless oil (0.077 g, 0.03 mmol, 61%);
characterisation is on the mixture; Rf¼0.42 (petroleum ether/ethyl
acetate, 9:1); dH (500 MHz, CDCl3) 5.68 (1H, ddt, J¼15.2, 9.4, 1.5,
CH]CHCH265E), 5.68 (1H, ddt, J¼12.5, 10.8, 1.6, CH]CHCH265Z),
5.45 (1H, dt, J¼15.2, 6.4, CH]CHCH265E), 5.40 (1H, dt, J¼10.8, 7.3,
CH]CHCH265Z), 3.70 (3H, s, OMeZ), 3.69 (3H, s, OMeE), 3.67 (3H, s,
OMeE), 3.66 (3H, s, OMeZ), 3.21–3.17 (1H, m, H-2Z), 2.75–2.71 (1H,
m, H-2E), 2.17–1.94 (8H, m), 1.84–1.77 (2H, m, H-3Z, H-3E), 1.66–1.30
(10H, m), 0.94 (2H, t, J¼7.5, CH2CH3Z), 0.93 (2H, t, J¼7.2, CH2CH3E);
dC (125 MHz, CDCl3) 172.1, 172.1, 171.3, 171.1, 134.0, 133.1, 128.8,
128.0, 59.4 and 58.3 (C-1E and C-1Z), 52.3, 52.1, 52.1, 51.9, 44.7 (C-
2E), 38.0 (C-2Z), 29.9, 29.3, 29.2, 25.6, 22.8, 22.5, 22.4, 20.4, 14.3,
14.0; nmax (CH2Cl2)/cmꢁ1 1735; LRMS m/z (ESIþ) 531.2 (2MþNaþ,
100%), 277.1 (MþNaþ, 40%); HRMS m/z (ESIþ) found [MþNa]þ
277.4106; C14H22NaO4 requires 277.1410.
4.1.17. Dimethyl 2-(1-acetoxyvinyl)cyclohexane-1,1-dicarboxylate
64. Synthesised from allene 29 (0.114 g, 0.5 mmol) using Condi-
tions B with copper(II) triflate. Purification by flash chromatogra-
phy (gradient elution petroleum ether/ethyl acetate, 40:1/0:1)
gave starting material 29 (13 mg, 0.057 mmol, 11%). Further elution
of the column gave the enol acetate 64 as a colourless oil (0.049 g,
35%); Rf¼0.42 (petroleum ether/ethyl acetate, 3:1); dH (500 MHz,
CDCl3) 4.96 (1H, dd, J¼2.0, 1.0, C]CHH), 4.89 (1H, d, J¼2.0,
C]CHH), 3.75 (3H, s, OMe), 3.72 (3H, s, OMe), 2.92 (1H, dd, J¼9.1,
4.1.21. (1S
*
,3aR
*
,6aS
*
)-Methyl 1-(iodomethyl)-3-oxohexahydro-1H-
,3aR ,6aS )-methyl
cyclopenta[c]furan-3a-carboxylate 67a and (1R
*
*
*

L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
10891
1-(iodomethyl)-3-oxohexahydro-1H-cyclopenta[c]furan-3a-carbox-
ylate 67b. According to the procedure of Bian5: iodine (0.144 g,
0.565 mmol) was added to a solution of alkene 24 (0.040 g,
0.189 mmol)inCH2Cl2 (2 mL) at0 ꢀC, andstirringwascontinued until
the iodine had completely dissolved. The reaction was incubated at
4 ꢀC for 15 h and was then quenched with saturated aqueous sodium
thiosulfate solution (15 mL), and further diluted with water (50 mL).
The aqueous layer was extracted with CH2Cl2 (3ꢂ30 mL). The com-
bined organic layers were washed with brine (60 mL), dried (MgSO4),
filtered and the solvent removed in vacuo. The resulting crude
compound was then absorbed onto silica and purified by flash col-
umn chromatography (petroleum ether/diethyl ether, 3:1) to give an
inseparable 7:1 mixture of lactones 67a:67b mixture of (47.9 mg,
0.148 mmol, 83%); characterisation is on the mixture.
5), 13.4 (CH2CH3); nmax (CH2Cl2/cmꢁ1) 1783, 1743; LRMS m/z (ESIþ)
370.0 (MþNHþ4 , 100%), 727.0 (2MþNaþ, 84%), 375.0 (MþNaþ, 76%),
353.0 (MþHþ, 66%); HRMS m/z (ESIþ) found [MþNa]þ 375.0056;
C12H17NaIO4 requires 375.0064; Found C, 40.93; H, 4.91%; C12H17IO4
requires: C, 40.93; H, 4.87%.
Lactone 68b; Rf¼0.19 (petroleum ether/ethyl acetate, 3:1); dH
(500 MHz, CDCl3) 4.22 (1H, dd, J¼10.0, 3.4, H-1), 4.11 (1H, ddd,
J¼10.0, 9.0, 3.1, CHI), 3.79 (3H, s, OMe), 3.12 (1H, ddd, J¼8.2, 3.4, 3.1,
H-6a), 2.37 (1H, ddd, J¼13.4, 10.9, 6.4, H-4), 2.29 (1H, dddd, J¼13.4,
6.5, 3.4, 0.9, H-40), 2.13–2.00 (2H, m, H-6, CHHCH3), 1.90–1.76 (3H,
m, H-5, H-60, CHHCH3), 1.62–1.52 (1H, m, H-50), 1.08 (3H, t, J¼7.2,
CH2CH3); dC (125 MHz, CDCl3) 175.3, 170.5, 87.4 (C-1), 62.2 (C-3a),
53.3 (OMe), 51.9 (C-6a), 41.4 (CHI), 35.8 (C-4), 35.1 (C-6), 28.9
(CH2CH3), 25.7 (C-5), 13.4 (CH2CH3); nmax (CH2Cl2/cmꢁ1) 1779,1743;
LRMS m/z (ESIþ) 726.9 (2MþNaþ, 100%), 370.0 (MþNHþ4 , 96%),
353.0 (MþHþ, 79%), 385.0 (MþHþMeOHþ, 71%); HRMS m/z (ESIþ)
found [MþNa]þ 375.0063; C12H17NaIO4 requires 375.0064; Found
C, 41.06; H, 4.83%; C12H17IO4 requires: C, 40.93; H, 4.87%.
Lactone 68c; Rf¼0.09 (petroleum ether/ethyl acetate, 3:1); mp
80.0–82.6 ꢀC; dH (500 MHz, CDCl3) 4.15–4.09 (2H, m, CHI, H-1), 3.79
(3H, s, OMe), 3.15 (1H, ddd, J¼6.8, 4.5,1.6, H-6a), 2.40–2.31 (2H, m, H-
4, H-40), 2.04 (1H, dddd, J¼13.1, 11.8, 7.8, 6.8, H-6), 1.97–1.90 (1H, m,
H-5), 1.89–1.74 (3H, m, H-60, CH2CH3), 1.65–1.54 (1H, m, H-50), 1.09
(3H, t, J¼7.2, CH2CH3); dC (125 MHz, CDCl3) 174.9, 170.6, 87.2 (C-1),
62.4 (C-3a), 53.1 (M), 49.1 (C-6a), 38.9 (CHI), 36.8 (C-4), 35.0 (C-6),
27.4 (CH2CH3), 25.8 (C-5), 14.4 (CH2CH3); nmax (CH2Cl2/cmꢁ1) 1774,
1737; LRMS m/z (ESIþ) 726.9 (2MþNaþ,100%), 370.0 (MþNHþ4 , 94%),
722.0 (2MþNH4, 78%), 353.0 (MþHþ, 76%), 385.0 (MþHþMeOHþ,
53%); HRMS m/z (ESIþ) found [MþNa]þ 375.0061; C12H17NaIO4 re-
quires 375.0064; Found C, 40.95; H, 4.85%; C12H17IO4 requires: C,
40.93; H, 4.87%.
Lactone 67a; Rf¼0.14 (petroleum ether/diethyl ether, 3:1); dH
(500 MHz, CDCl3) 4.31 (1H, ddd, J¼9.1, 4.9, 3.2, H-1), 3.80 (3H, s,
OMe), 3.45 (1H, dd, J¼10.0, 4.9, CHHI), 3.30 (1H, dd, J¼10.0, 9.1,
CHHI), 3.01 (1H, ddd, J¼8.4, 3.2, 3.0, H-6a), 2.37 (1H, ddd, J¼13.5,
10.9, 6.5, H-4), 2.30 (1H, ddd, J¼13.5, 6.6, 3.6, H-40), 2.08 (1H, dddd,
J¼13.2,10.5, 8.4, 6.3, H-6), 1.88 (1H, dddd, J¼12.9,10.5, 6.5, 3.6, H-5),
1.84–1.77 (1H, m, H-60), 1.63–1.53 (1H, m, H-50); dC (125 MHz,
CDCl3) 175.1, 170.4, 84.7 (C-1), 62.6 (C-3a), 53.4 (OMe), 50.7 (C-6a),
35.6 (C-4), 34.8 (C-6), 25.7 (C-5), 6.2 (CH2I); nmax (CH2Cl2/cmꢁ1
)
1778, 1742; LRMS m/z (ESIþ) 342.0 (MþNH4þ, 84%), 357.0
(MþHþMeOHþ, 79%), 325.0 (MþHþ, 73%), 379.0 (MþNaþMeOHþ,
67%); HRMS m/z (ESIþ) found [MþNa]þ 346.9747; C10H13INaO4 re-
quires 346.9751. Found C, 37.13; H, 3.98%; C10H13IO4 requires: C,
37.06; H, 4.04%.
Lactone 67b; Rf¼0.14 (petroleum ether/diethyl ether, 3:1); dH
(500 MHz, CDCl3) 4.93 (1H, ddd, J¼9.9, 5.8, 5.8, H-1), 3.80 (3H, s,
OMe), 3.48 (1H, dd, J¼10.0, 5.8, CHHI), 3.16 (1H, ddd, J¼8.2, 8.2, 5.8,
H-6a), 3.13 (1H, dd, J¼10.0, 9.9, CHHI), 2.46 (1H, dddd, J¼14.0, 7.9,
6.1, H-4), 2.32–2.23 (1H, m, H-40), 2.00 (1H, ddt, J¼12.3, 8.2, 5.8,, H-
6), 1.92–1.84 (1H, m, H-5), 1.79–1.69 (1H, m, H-60), 1.67–1.60 (1H, m,
H-50); dC (125 MHz, CDCl3) 175.2, 170.0, 79.8 (C-1), 64.0 (C-3a), 53.3
(OMe), 49.8 (C-6a), 34.2 (C-4), 26.24 (C-6), 26.17 (C-5), 0.2 (CH2I).
4.1.23. (1S
penta[c]furan-3a-carboxylate 69. To a stirring solution of lactone
68b (32 mg, 91.7 mol) and AIBN (0.2 mg, 1.38 mol) was added
tributyltin hydride (34 L, 128 mol) followed quickly by degassed
*
,3aS
*
,6aR
*
)-Methyl
3-oxo-1-propylhexahydro-1H-cyclo-
m
m
m
m
acetonitrile (1.5 mL). The reaction mixture was heated under reflux
for 1 h, then allowed to cool. The resulting solution was diluted
with water (30 mL) and extracted with ethyl acetate (3ꢂ30 mL).
The combined organic layers were washed with brine (3ꢂ30 mL),
dried (MgSO4), filtered and the solvent removed in vacuo. The
resulting crude compound was purified by flash column chroma-
tography with KF silica34 (petroleum ether/ethyl acetate, 5:1) to
4.1.22. (1S
cyclopenta[c]furan-3a-carboxylate 68a, (1R
((S )-1-iodopropyl)-3-oxohexahydro-1H-cyclopenta[c]furan-3a-carb-
oxylate 68b and (1R ,3aS ,6aR )-methyl 1-((R )-1-iodopropyl)-3-oxo-
*
,3aS
*
,6aR
*
)-Methyl 1-(1-iodopropyl-3-oxohexahydro)-1H-
*
,3aS ,6aR )-methyl 1-
*
*
*
*
*
*
*
hexahydro-1H-cyclopenta[c]furan-3a-carboxylate 68c. According to
the procedure of Bian5: iodine (0.29 g, 1.14 mmol) was added to
a solution dimethyl 2-(but-1-enyl)cyclopentane-1,1-dicarboxylate
(91.5 mg, 0.381 mmol, approximate ratio E:Z, 1.6:1) in CH2Cl2
(4.6 mL) at 0 ꢀC. The resulting mixture was stirred at 0 ꢀC until the
iodine had completely dissolved. The reaction was incubated at 4 ꢀC
for 15 h was then quenched with saturated aqueous sodium thio-
sulfate solution (15 mL), and diluted with water (30 mL). The aque-
ous layer was extracted with CH2Cl2 (3ꢂ30 mL), the combined
organic layers were washed with brine (50 mL), dried (MgSO4), fil-
tered and the solvent removed in vacuo. The resulting crude com-
pound was purified by flash column chromatography to give lactone
give lactone 69 as a colourless oil (20.1 mg, 88.8
a stirring solution of lactone 68c (30 mg, 85.2
(0.2 mg, 1.38 mol) was added tributyltin hydride (34
m
mol, 97%); To
mol) and AIBN
L, 128 mol)
m
m
m
m
followed quickly by degassed acetonitrile (1.5 mL). The reaction
mixture was heated under reflux for 2 h, then allowed to cool. The
resulting solution was diluted with water (30 mL) and extracted
with ethyl acetate (3ꢂ30 mL). The combined organic layers were
washed with brine (3ꢂ30 mL), dried (MgSO4), filtered and the
solvent removed in vacuo. The resulting crude compound was
purified by flash column chromatography with KF silica34 (petro-
leum ether/ethyl acetate, 5:1) to give lactone 60 as a colourless oil
68a as a colourless oil (9.5 mg, 27.0 mmol, 7%), lactone 68b as a col-
ourless oil (72.4 mg, 0.206 mol, 54%) and lactone 68c as a white
crystalline solid(51.3 mg, 0.146 mmol, 38%), which was recrystallised
using diethyl ether.
(12.2 mg, 53.9
m
mol, 63%); Rf¼0.14 (petroleum ether/ethyl acetate,
5:1); dH (500 MHz, CDCl3) 4.07 (1H, ddd, J¼8.1, 5.4, 3.8, H-1), 3.78
(3H, s, OMe), 2.81 (1H, ddd, J¼7.9, 3.8, 2.8, H-6a), 2.34 (1H, ddd,
J¼13.4, 11.0, 6.4, H-4), 2.26 (1H, ddd, J¼13.4, 6.8, 3.1, H-40), 1.95 (1H,
dddd, J¼12.9, 11.0, 7.9, 6.6, H-6), 1.85 (1H, ddddd, J¼12.6, 6.6, 6.4,
3.2, 3.1, H-5), 1.78 (1H, dddd, J¼13.7, 10.0, 8.1, 5.1, CHHCH2CH3),
1.72–1.66 (1H, m, H-60), 1.65–1.53 (2H, m, H-50, CHHCH2CH3), 1.53–
1.36 (2H, m, CH2CH3), 1.25 (3H, t, J¼7.2, CH2CH3); dC (125 MHz,
CDCl3) 175.9, 171.1, 85.9 (C-1), 62.3 (C-3a), 53.1 (OMe), 50.8 (C-6a),
38.3 (CH2CH2CH3), 35.5 (C-4), 34.0 (C-6), 25.7 (C-5), 18.6 (CH2CH3),
13.7 (CH2CH3); nmax (CH2Cl2/cmꢁ1) 1772, 1742; LRMS m/z (ESIþ)
475.2 (2MþNaþ, 100%), 227.1 (MþHþ, 67%), 244.1 (MþNHþ4 , 63%),
Lactone 68a; Rf¼0.24 (petroleum ether/ethyl acetate, 3:1); dH
(500 MHz, CDCl3) 4.84 (1H, dd, J¼11.6, 5.4, H-1), 3.92 (1H, ddd,
J¼11.6, 9.1, 2.9, CHI), 3.82 (3H, s, OMe), 3.22 (1H, ddd, J¼8.6, 8.4, 5.4,
H-6a), 2.48 (1H, dddd, J¼13.7, 7.8, 5.9, 0.8, H-4), 2.28 (1H, ddd,
J¼13.7, 7.5, 7.4, H-40), 2.18–2.08 (2H, m, H-6, CHHCH3), 1.85 (1H,
ddq, J¼14.4, 9.1, 7.2, CHHCH3),1.81–1.69 (2H, m, H-5, H-50), 1.60 (1H,
dddd, J¼12.9, 8.9, 8.6, 7.1, H-6), 1.10 (3H, t, J¼7.2, CH2CH3); dC
(125 MHz, CDCl3) 175.6, 170.1, 82.5 (C-1), 63.8 (C-3a), 53.3 (OMe),
51.6 (C-6a), 34.8 (CHI), 34.1 (C-4), 30.1 (CH2CH3), 26.6 (C-6), 25.9 (C-

10892
L. Curry et al. / Tetrahedron 65 (2009) 10882–10892
470.3 (2MþNHþ4 , 48%); HRMS m/z (ESIþ) found [MþNa]þ 249.1098;
C12H18NaO4 requires 249.1097; Found C, 63.60; H, 7.97%; C12H18O4
requires: C, 63.70; H, 8.02%.
15. Apparu, M.; Crandall, J. K. J. Org. Chem. 1984, 49, 2125–2130.
16. Shi, J.; Zhang, M.; Fu, Y.; Liu, L.; Guo, Q. X. Tetrahedron 2007, 63, 12681–
12688.
17. The connectivity was confirmed by COSY and HSQC experiments.
18. Treatment of the allene 25 with manganese(III) acetate in acetonitrile with no
copper(II) salt, gave a whole myriad of products including the dimers 37, the
acetates 39 and 41, and the diols 40 and 42.
Acknowledgements
19. Kharasch, M. S.; Sosnovsky, G. J. Am. Chem. Soc. 1958, 80, 756.
20. Beckwith, A. L. J.; Zavitsas, A. A. J. Am. Chem. Soc. 1986, 108, 8230–8234.
We thank the EPSRC for funding part of this work and the Oxford
Chemical Crystallography Service for the use of the instruments.
21. Infrared analysis clearly showed the presence of a
g-lactone and an ester (nmax
1780, 1738 cmꢁ1) and the connectivity was confirmed by COSY and HSQC
experiments.
22. Bentrude, W. G. Annu. Rev. Phys. Chem. 1967, 18, 283.
23. Streiff, S.; Welter, C.; Schelwies, M.; Lipowsky, G.; Miller, N.; Helmchen, G.
Chem. Commun. 2005, 2957–2959.
24. The structure was determined from single crystal X-ray diffraction data
collected at low temperature with an Oxford Cryosystems Cryostream N2
open-flow cooling device [Ref: Cosier, J.; Glazer, A. M. J. Appl. Crystallogr.
1986, 19, 105–107] Data were collected using an Enraf-Nonius KappaCCD
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.09.112.
References and notes
diffractometer (Mo
K
a
radiation
(l¼0.71073 Å) and processed using the
DENZO-SMN package [Ref: Otwinowski, Z.; Minor, W. Processing of X-ray
Diffraction Data Collected in Oscillation Mode In Methods in Enzymology;
Carter, C. W., Sweet, R. M., Eds.; Academic: 1997; p 276;], including inter-
frame scaling (which was carried out using Scalepack within DENZO-SMN)
The structure was solved using SIR92 [Ref: Altomare, A.; Cascarano, G.;
Giacovazzo, G.; Guagliardi, A.; Burla, M. C.; Polidori, G.; Camalli, M. J. Appl.
Crystallogr. 1994, 27, 435] Refinement was carried out using full-matrix least-
squares within the CRYSTALS suite [Ref: Betteridge, P. W.; Carruthers, J. R.;
Cooper, G. I.; Prout, C. K.; Watkin, D. J. J. Appl. Crystallogr. 2003, 36, 1487], on
either F2. In general, all non-hydrogen atoms were refined with anisotropic
displacement parameters however, in both molecules, the atomic displace-
ment ellipsoids for the methyl ester groups were prolate and the larger of
these was modelled as disordered over two positions with isotropic dis-
placement parameters. Hydrogen atoms were generally located in the dif-
ference map and the positions and isotropic displacement parameters were
refined using restraints prior to inclusion into the model with riding con-
straints. For further details see the Supplementary information (CIF). Full
crystallographic data have also been deposited with the Cambridge Crystal-
lographic Data Centre, CCDC 746459. Copies of these data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
1. Powell, L. H.; Docherty, P. H.; Hulcoop, D. G.; Kemmitt, P. D.; Burton, J. W. Chem.
Commun. 2008, 2559–2561.
2. For the synthesis of g-lactones using: (a) manganese(III) acetate and copper(II)
acetate see: Snider, B. B.; McCarthy, B. A. J. Org. Chem. 1993, 58, 6217–6223; (b)
cerium(IV) ammonium nitrate see: Baciocchi, E.; Paolobelli, A. B.; Ruzziconi, R.
Tetrahedron 1992, 48, 4617–4622.
3. For reviews of the use of manganese(III) acetate in organic synthesis see: (a)
Snider, B. B. Chem. Rev. 1996, 96, 339–363; (b) Melikyan, G. G. Org. React. 1997,
49, 427–675; (c) Melikyan, G. G. Aldrichimica Acta 1998, 31, 50–64; (d) Demir,
A. S.; Emrullahoglu, M. Curr. Org. Synth. 2007, 4, 323–351.
4. The stereochemical outcome of this reaction is in accord with the Beckwith–
Houk model for the 5-exo-trig cyclisation of 5-hexenyl radicals see: Beckwith,
A. L. J. Tetrahedron 1981, 37, 3073–3100; Beckwith, A. L. J.; Schiesser, C. H. Tet-
rahedron Lett. 1985, 26, 373–376; Rudolf, K.; Spellmeyer, D. C.; Houk, K. N. J. Org.
Chem. 1987, 52, 3708–3710.
5. For precedent for the formation of [3.3.0]-bicyclic g-lactones by iodocyclisation
of a cyclopentylmalonate onto a terminal alkene see: Bian, J. W.; Van Wing-
erden, M.; Ready, J. M. J. Am. Chem. Soc. 2006, 128, 7428–7429.
6. Kates, S. A.; Dombroski, M. A.; Snider, B. B. J. Org. Chem. 1990, 55, 2427–2436.
7. Hulcoop, D. G.; Sheldrake, H. M.; Burton, J. W. Org. Biomol. Chem. 2004, 2, 965–967.
25. For other examples and discussion see: Jacques, J.; Collet, A.; Wilen, S. H. En-
antiomers, Racemates and Resolutions; Krieger Publishing Company: Malabar,
1981.
26. Landor, S. R.; Miller, B. J.; Regan, J. P.; Tatchell, A. R. J. Chem. Soc., Chem. Commun.
1966, 585–586.
8. It has previously been reported that exposure of b-dicarbonyl and related com-
pounds to allylsilanes and manganese(III) acetates provides products inwhich the
silyl group is retained, see: Warsinsky, R.; Steckhan, E. J. Chem. Soc., Perkin Trans. 1
1994, 2027–2037; Hwu, J. R.; Chen, C. N.; Shiao, S. S. J. Org. Chem.1995, 60, 856–862.
9. For the reduction of vinyl radicals with ethanol in the presence of man-
ganese(III) acetate see: Ref 2a and Snider, B. B.; Merritt, J. E.; Dombroski, M. A.;
Buckman, B. O. J. Org. Chem. 1991, 56, 5544–5553.
27. Landor, S. R.; Miller, B. J.; Regan, J. P.; Tatchell, A. R. J. Chem. Soc., Perkin Trans. 1
1974, 557–561.
28. Jacobs, T. L.; Macomber, R. S. J. Am. Chem. Soc. 1969, 91, 4824–4837.
29. Bates, R. W.; Ramadevi, T.; Ko, H. H. Tetrahedron 1995, 51, 12939–12954.
30. Bates, R. W.; Devi, T. R. Tetrahedron Lett. 1995, 36, 509–512.
31. Delair, T.; Doutheau, A.; Gore, J. Bull. Soc. Chim. Fr. 1988, 125–131.
32. Gallagher, T.; Davies, I. W.; Jones, S. W.; Lathbury, D.; Mahon, M. F.; Molloy,
K. C.; Shaw, R. W.; Vernon, P. J. Chem. Soc., Perkin Trans. 1 1992, 433–440.
33. Doutheau, A.; Gore, J. Bull. Soc. Chim. Fr. 1984, 297–306.
10. Gill, G. B.; Pattenden, G.; Roan, G. A. Tetrahedron Lett. 1996, 37, 9369–9372.
11. Hiemstra, H.; Sno, M.; Vijn, R. J.; Speckamp, W. N. J. Org. Chem.1985, 50, 4014–4020.
12. Kitagawa, O.; Fujiwara, H.; Suzuki, T.; Taguchi, T.; Shiro, M. J. Org. Chem. 2000,
65, 6819–6825.
13. For the use of copper(II) triflate in conjunction with manganese(III) acetate see:
Toyao, A.; Chikaoka, S.; Takeda, Y.; Tamura, O.; Muraoka, O.; Tanabe, G.; Ishi-
bashi, H. Tetrahedron Lett. 2001, 42, 1729–1732, Refs 1, 7 and 14.
34. Harrowven, D. C.; Guy, I. L. Chem. Commun. 2004, 1968–1969.
14. Hulcoop, D. G.; Burton, J. W. Chem. Commun. 2005, 4687–4689.