α,β-Unsaturated and cyclopropyl acyl radicals, and their ketene alkyl radical equivalents. Ring synthesis and tandem cyclisation reactions

Article abstract of DOI:10.1039/b413815p

Treatment of the α,β-unsaturated selenyl esters 12 and 14 with Bu₃SnH-AIBN produces the corresponding 2-cyclohexenones 13 and 15 respectively via presumed α-ketene alkyl radical intermediates, viz. 10. By contrast, the 2,7-diene esters 34 and 39 undergo tandem radical cyclisations producing diquinanes, e.g. 38 (76%), and the corresponding allene-substituted α,β-unsaturated selenyl ester 48 gives the cyclooctadienone 56 on treatment with Bu₃SnH-AIBN in refluxing benzene. The selenyl ester 19 derived from chrysanthemic acid produces a mixture of the γ,δ- unsaturated aldehyde 22 and the corresponding dimer 25a on treatment with Bu₃SnH-AIBN. Furthermore, in the presence of methanol the only product from this reaction was the bis(methyl ester) dimer 25b, thereby lending further credence to the involvement of ketene alkyl radical intermediates in these reactions, and in the aforementioned reactions involving 2,6- and 2,7-diene selenyl esters. Treatment of the cyclopropane selenyl esters 59 and 61, containing keto- and oxy-group functionality in their side-chains, with Bu₃SnH-AIBN led to excellent syntheses of the enol lactone 66 (76%) and the trans-fused bicyclo[6.1.0]nonane 67 (80-95%) respectively.

Full text of DOI:10.1039/b413815p

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A R T I C L E
a,b-Unsaturated and cyclopropyl acyl radicals, and their ketene alkyl
radical equivalents. Ring synthesis and tandem cyclisation reactions
Christopher J. Hayes, Nicola M. A. Herbert, Nicole M. Harrington-Frost and
Gerald Pattenden*
School of Chemistry, The University of Nottingham, University Park, Nottingham, NG7 2RD,
UK
Received 7th September 2004, Accepted 27th October 2004
First published as an Advance Article on the web 16th December 2004
Treatment of the a,b-unsaturated selenyl esters 12 and 14 with Bu3SnH–AIBN produces the corresponding
2-cyclohexenones 13 and 15 respectively via presumed a-ketene alkyl radical intermediates, viz. 10. By contrast, the
2,7-diene esters 34 and 39 undergo tandem radical cyclisations producing diquinanes, e.g. 38 (76%), and the
corresponding allene-substituted a,b-unsaturated selenyl ester 48 gives the cyclooctadienone 56 on treatment with
Bu3SnH–AIBN in refluxing benzene. The selenyl ester 19 derived from chrysanthemic acid produces a mixture of the
c,d-unsaturated aldehyde 22 and the corresponding dimer 25a on treatment with Bu3SnH–AIBN. Furthermore, in the
presence of methanol the only product from this reaction was the bis(methyl ester) dimer 25b, thereby lending further
credence to the involvement of ketene alkyl radical intermediates in these reactions, and in the aforementioned
reactions involving 2,6- and 2,7-diene selenyl esters. Treatment of the cyclopropane selenyl esters 59 and 61,
containing keto- and oxy-group functionality in their side-chains, with Bu3SnH–AIBN led to excellent syntheses of
the enol lactone 66 (76%) and the trans-fused bicyclo[6.1.0]nonane 67 (80–95%) respectively.
Introduction
Acyl radicals are powerful reactive intermediates which are used
widely in the synthesis of carbon-to-carbon bonds and, particu-
larly, in the elaboration of carbo- and heterocyclic ring systems.1
Our own group, for example, has used acyl radicals generated
from polyolefinic phenyl selenyl esters to elaborate a range of
interesting polycyclic ring systems, including steroids, via con-
secutive (cascade) 6-endo-trig cyclisations.2 In contemporaneous
studies, directed towards synthesis of the natural diterpenes
lophotoxin A (1) and phomactin A (2), we evaluated the scope
for macrocyclisation reactions from the a,b-unsaturated acyl
radical precursors 3 and 5 as a route to the carbon frameworks
in these natural products. In the event, treatment of the phenyl
selenyl ester 3 with Bu3SnH–AIBN led to the macrocyclic enone
4 as a 2 : 1 mixture of E- and Z-isomers3 whereas, under
similar reaction conditions, the selenyl ester 5 gave rise to the
cyclohexenone 7 instead of the expected macrocyclic enone 6.4
We reasoned that the cyclohexenone 7 was produced from 5
as a result of a 6-exo-trig cyclisation from the Z-2-unsaturated
acyl radical intermediate 11 derived from the corresponding
E-2-unsaturated acyl radical 8 by way of the interesting a-
ketene alkyl radical species 9/10.5 In related studies the selenyl
esters 12 and 14 derived from geranoic acid and 2E,6E-
farnesoic acid, respectively, underwent similar cyclisations in
the presence of Bu3SnH–AIBN leading to ( )-piperitone 135
(86%) and bisabolone 15 (74%; 1 : 1 mixture of diastereoisomers)
respectively.6
Although a-ketene alkyl radical species have been recognised
for some time, and their structures have been the subject of
ab initio calculations,7 investigations of their scope in synthesis
have been limited. In this paper we have sought to vindicate
the intermediacy of a-ketene radical species in the conversions
of 5→7, 12→13 and 14→15, by studying the corresponding
chemistry of cyclopropylacyl radical intermediates and the
opportunity for a,b-unsaturated acyl radical species containing
additional unsaturation in their structures to participate in
tandem cyclisation processes.8 In the accompanying papers we
present our studies of the chemistry of vinylcyclopropylacyl
radicals in the synthesis of cyclohexenones, and the applications
of a-ketenyl radicals in the total synthesis of the triquinane
natural products pentalenene and modhephene.
3 1 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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Results and discussion
Although the cyclopropylmethyl radical 16 is well known to
undergo exothermic ring opening (21 kJ mol−1) and isomerisa-
tion to the corresponding but-3-enyl radical,9 the cyclopropyl
acyl radical 17 shows little propensity for similar ring opening
leading to the corresponding ketene species, viz. 18.10 We
reasoned, however, that the presence of additional unsatura-
tion on the cyclopropane ring of an cyclopropyl acyl species
would provide sufficient additional impetus for such species to
undergo ring opening and the production of b-ketene radicals.
Accordingly, we treated the selenyl ester 1911 derived from trans-
chrysanthemic acid with Bu3SnH–AIBN in hot benzene and
found that the major product was the c,d-unsaturated aldehyde
22, whose formation was accompanied by the corresponding
dimer 25a. The compounds 22 and 25a are produced from 19
via the acyl radical 20, which first undergoes ring opening to the
b- and d-ketene radicals 21 and 24, respectively. Reduction of the
ketene unit in 24, preceded, or followed by H-abstraction, leads
to the aldehyde 2212 whereas dimerisation and reduction of the
enol stannane precursor 23 produces the corresponding dimer
25a. When the same reaction between the selenyl ester 19 and
Bu3SnH–AIBN was carried out in the presence of methanol, as
a ketene trap, the sole product isolated was the corresponding
bis(ester) dimer 25b.
Intriguingly, when the vinylcyclopropyl selenyl ester 26
lacking gem-dimethyl substitution on the alkene bond was
treated with Bu3SnH–AIBN in an identical manner to 19, the
intermediate cyclopropyl acyl radical 27 underwent ring opening
to the corresponding ketene alkyl radical 28/29, which then
underwent a 6-exo-dig cyclisation leading to the cyclohexenone
30 in 52% yield. This interesting outcome was developed further
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7
3 1 7

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with other vinylcyclopropyl selenyl esters and led to a general
synthesis of cyclohexenones, details of which are described in an
accompanying paper.13
We next examined the scope for tandem radical cyclisations
from the acetylene- and allene-substituted a,b-unsaturated se-
lenyl esters 46 and 48, with a view to replicating the more
familiar Pauson–Khand method14 of preparing diquinanes, i.e.
42→43. The substituted selenyl esters 46 and 48 were both
prepared from readily available starting materials as highlighted
in Scheme 2. Disappointingly, however, when the acetylene 46
was treated with Bu3SnH–AIBN, instead of leading to 50, the
only product isolated, in 46% yield, was the aldehyde resulting
from reduction of the selenyl ester function in 46. However,
when the substituted allene selenyl ester 48 was reacted with
Bu3SnH–AIBN, the cyclooctadienone 56 was isolated in 25%
yield, together with unreacted starting material (18%) and the
corresponding aldehyde (8%). The cyclooctadienone 56 could
result from an 8-exo-dig cyclisation of the Z-a,b-unsaturated
acyl radical intermediate 52 produced from 48 or, alternatively,
via an initial 5-exo-trig cyclisation of the allene 53, leading to
54, followed by a 5-exo-dig cyclisation to the diquinane 55 and
fragmentation (Scheme 3).
The aforementioned studies with cyclopropyl acyl radical
intermediates clearly implicated b-ketene alkyl intermediates in
their conversions to acyclic and cyclohexenone products and lent
credence to the involvement of analogous a-ketene alkyl radical
intermediates in the conversions 3→4, 5→7 and 12/14→13/15,
described earlier. With a view to extending these intriguing
transformations of ketene alkyl radical intermediates to the
synthesis of diquinane products via tandem cyclisation processes
we next synthesised the 2,7-octadienyl selenyl ester 34 in six short
steps from methyl geranoate (Scheme 1). When the ester 34 was
treated with Bu3SnH–AIBN it underwent sequential 5-exo-trig
and 5-exo-dig cyclisations via the intermediate a-ketene alkyl
radical 36 and alkyl radical 37, producing the diquinane 38 in
a pleasing 76% yield.5 In a similar manner, the a,b-unsaturated
acyl radical intermediate derived from 39 underwent tandem
cyclisation to the diquinane 40 (41%), whose formation was
accompanied by that of the product of in situ reduction of the
acyl radical intermediate, viz. 41 (46%).
Scheme 2 Reagents: i, PCC, CH2Cl2, silica; ii, EtO2CCH2PO(OEt)2,
NaH, THF, 44% over two steps; iii, NaOH, EtOH–H2O, 90%; iv, NPSP,
Bu3P, CH2Cl2, 67%; v, EtO2C.CH2PO(OEt)2, NaH, HF, 87%; vi, NaOH,
EtOH–H2O, 64%; vii, NPSP, Bu3P, CH2Cl2, 82%.
Finally, and in the context of assessing the potential for
cyclopropylacyl radical intermediates in the synthesis of bi-
cyclo[4.3.0]nonanes, viz. 65, via tandem cyclisation processes,
we prepared the substituted trans-cyclopropyl selenyl esters 59
and 61, as shown in Scheme 4. Interestingly, when the keto-
substituted cyclopropyl phenyl selenyl ester 59 was treated with
Bu3SnH–AIBN, the resulting acyl radical 62 underwent ring-
opening leading to 63, which then underwent cyclisation via
the ketene enolate radical 64, leading to the enol lactone 66 as
the sole product in 76% yield; no evidence for the co-formation
of the bicyclo[4.3.0]nonandione product 65 was obtained. By
contrast, when a 1 : 1 mixture of epimeric alcohols of the
trans cyclopropyl selenyl ester 61a was treated with Bu3SnH–
AIBN, the trans-fused bicyclo [6.1.0]nonanone 67 (80–95%)
was isolated as a mixture of epimeric alcohols. The a-epimer
of 67 crystallised, and its structure and stereochemistry were
confirmed by X-ray crystal analysis.15 Likewise, the MOM ether
Scheme 1 Reagents: i, MCPBA, CH2Cl2, 90%; ii. HClO4, THF–H2O,
i
=
then KIO4, 92%; iii, CH2 CHMgCl, THF, 64%; iv, MOMCl, Pr2NEt,
CH2Cl2, 59%; v, LiOH, THF–H2O, 93%; vi, NPSP, Bu3P, CH2Cl2,
−20 ◦C, 62%; vii, Bu3SnH–AIBN, benzene, reflux, 76%.
3 1 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7

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Scheme 3
61b and the desoxy analogue 61c underwent identical 8-endo-
trig cyclisation on treatment with Bu3SnH–AIBN, leading to
the corresponding bicyclononanes 68 in excellent yields (79%).
The latter cyclisations, leading to bicyclo[6.1.0]nonanes, further
emphasise the reluctance of cyclopropyl acyl radicals to undergo
ring cleavage to b-ketene alkyl radicals, i.e. 18, unless there is
an additional radical-stabilising group (e.g. an alkene in the
case of 20, a carbonyl group in the case of 62) attached to the
cyclopropane ring.
cyclopropane ring unsaturation, leading to alternative syntheses
13a
of a range of cyclohexenones and diquinanes, and also to new
syntheses of the naturally occurring triquinanes pentalenene and
13b
modhephene.
Experimental
For general experimental details see ref. 4.
Se-Phenyl 3,7-dimethylocta-2E,6-dienselenoate 12
N-Phenylselenophthalimide (NPSP) (100 mg, 0.33 mmol) was
added in one portion to a stirred solution of 3,7-dimethylocta-
2E-6-dienoic acid16 (40 mg, 0.24 mmol) and tributylphosphine
(120 ll, 0.48 mmol) in dichloromethane (10 ml) at −20 ◦C, and
◦
the pale yellow mixture was stirred at −20 C for 1.5 h. Water
(5 ml) was added and the mixture was then allowed to warm
to room temperature. The separated organic layer was washed
successively with water (2 × 5 ml), aqueous potassium carbonate
(2 × 5 ml, 10%) and brine (5 ml), and then dried (MgSO4). The
solvent was removed in vacuo to leave a yellow oil which was
purified by chromatography on silica using petroleum ether–
diethyl ether (9 : 1) as eluent to give the selenyl ester (60 mg, 82%)
as a pale yellow oil; mmax(soln. CHCl3)/cm−1 1695, 1614; 1H NMR
(270 MHz) d 7.62–7.54 (2H, m, Ar), 7.42–7.37 (3H, m, Ar), 6.12
Scheme 4 Reagents: i, Me2S.CHCO2Et, CH2Cl2, 77%; ii, LiOH,
THF–H2O, 93%; iii, NPSP, Bu3P, CH2Cl2, 93%; iv, NaBH4, EtOH, 98%;
i
v, LiOH, THF–H2O, 84%; vi, NPSP, Bu3P, CH2Cl2, Pr2NEt, CH2Cl2,
78%.
The studies presented in this paper demonstrate the interesting
and unusual reactivity of a,b-unsaturated and cyclopropyl acyl
radicals and their ketene alkyl equivalents, particularly in
the context of a synthesis of diquinanes, and for elaborating
cyclohexenones and bicyclo[6.1.0]nonanes. In the accompanying
papers we describe complementary studies of the chemistry
of ketene alkyl radicals which contain additional alkene and
=
=
(1H, br s, MeC CHCOSe), 5.09 (1H, m, Me2C CH), 2.19–2.15
=
(4H, m, 2 × CH2), 2.10 (3H, d, J 1 Hz, MeC CHCOSe), 1.73
(3H, s, Me), 1.64 (3H, s, Me); 13C NMR (100 MHz) d 189.5 (s),
157.8 (s), 135.8 (2 × d), 132.8 (s), 129.2 (2 × d), 128.6 (d), 127.3
(s), 124.4 (d), 122.6 (d), 40.7 (t), 25.9 (t), 25.6 (q), 20.3 (q), 17.7
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7
3 1 9

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(q); m/z (FAB) found 309.0743 (M+ + H), C16H21OSe requires
evaporated in vacuo to leave an orange residue. The residue was
purified by chromatography on silica using petroleum ether–
diethyl ether (9 : 1) as eluent to give the selenyl ester (770 mg,
83%) as a pale yellow oil; (found C, 62.4, H, 6.8. C16H21OSe
requires C, 62.5, H, 6.6%); mmax(film)/cm−1 1711, 1580; 1H
NMR (250 MHz, CDCl3) d 7.56–7.37 (5H, m, ArH), 4.91 (1H,
309.0758.
3-Methyl-6-isopropylcyclohex-2-en-1-one (piperitone) 13
AIBN (2 mg, 0.1 eq.) was added in one portion, under an
atmosphere of argon, to a stirred solution of the selenyl ester
12 (40 mg, 0.13 mmol) in dry, degassed (using argon) benzene
(44 ml), and the resulting solution was then heated to the point
of reflux. Tributyltin hydride (40 ll, 0.15 mmol) was added in
one portion and the mixture was heated under reflux for 1.5 h
and then cooled to room temperature. The solvent was removed
in vacuo and the residue was purified by chromatography on
silica using petroleum ether–diethyl ether (2 : 1) as eluent to give
the cyclohexenone (17 mg, 86%) as a colourless oil; mmax(soln.
CHCl3)/cm−1 2931, 2871, 1658, 1464, 1380, 1314, 989, 892; 1H
=
br. d, J 7.9 Hz, CHCH C), 2.34 (1H, dd, J 5.1, 7.9 Hz,
=
cyclopropyl CHCH C), 1.93 (1H, d, J 5.1 Hz, cyclopropyl
=
=
CHCHCOSePh), 1.73 (3H, s, CH3C ), 1.69 (3H, s, CH3C ),
1.26 (3H, s, CH3), 1.17 (3H, s, CH3); 13C NMR (67.8 MHz,
CDCl3) d 196.4 (s), 136.0 (s), 135.6 (2 × d), 129.1 (2 × d), 128.5
(d), 127.2 (s), 120.3 (d), 47.1 (d), 35.6 (d), 33.1 (s), 25.5 (q),
21.8 (q), 20.3 (q), 18.4 (q); m/z (FAB) found 309.0760 (M+
+
H), C16H21O80Se requires 309.0758; found 307.0749, C16H21O78Se
requires 307.0765 (M + H+).
=
NMR (250 MHz) d 5.83 (1H, q, J 1 Hz, MeC CHCO), 2.36
6,6-Bis(3,3,6-trimethylhept-4-enal) 25a
(1H, sept d, J 7, 4.8 Hz, Me2CH), 2.30 (2H, m), 2.07–1.95 (2H,
=
m), 1.93 (3H, d, J 1 Hz, MeC CHCO), 1.81 (1H, ddd, J 11.6,
Using an identical procedure to that described for the conversion
of the selenyl ester 12 into piperitone 13, the bis(aldehyde)
was prepared from the selenyl ester 19 (50 mg, 0.16 mmol),
tributyltin hydride (48 ll, 0.18 mmol), AIBN (1 mg) and
benzene (54 ml). Purification by chromatography on silica using
petroleum ether–diethyl ether (1 : 1) as eluent gave the dial
(5 mg, 55% (based on secovered selenyl ester)) as a colourless oil;
mmax(soln. CHCl3)/cm−1 2855, 1715, 1602; 1H NMR (250 MHz)
d 9.71 (2H, t, J 3.2 Hz, 2 × Me2CH2CHO), 5.51 (2H, d,
8.2, 4.1, 2.2 Hz, CH2CHHCH), 0.94 (3H, d, J 7 Hz, Me), 0.85
(3H, d, J 7 Hz, Me); 13C NMR (67.8 MHz) d 201.3 (s), 161.1 (s),
126.8 (d), 51.6 (d), 30.4 (t), 27.8 (d), 24.1 (q), 22.9 (t), 20.6 (q),
18.5 (q); m/z (EI) found 110.0730 (M+ - C3H6), C7H10O requires
110.0732.
Se-Phenyl 3,7,11-trimethyldodecatri-2E,6E,10-trienselenoate 14
The selenyl ester was prepared in an identical procedure to
that described for the synthesis of Se-phenyl 3,7-dimethylocta-
2,6-dienselenoate 12, using 2E,6E-farnesoic acid (100 mg,
0.42 mmol), NPSP (192 mg, 0.64 mmol), tributylphosphine
(211 ll, 0.84 mmol) and dichloromethane (5 ml). Purification by
chromatography on silica using petroleum ether–diethyl ether (9
: 1) as eluent gave the selenyl ester (92 mg, 58%) as a pale yellow
=
J 16.2 Hz, Me2CCH CHCMe2), 5.38 (2H, d, J 16.2 Hz,
Me2CCH CHCMe2), 2.34 (4H, d, J 3.2 Hz, 2 × Me2CH2CHO),
=
1.15 (12H, s, 4 × Me), 0.93 (12H, s, 4 × Me); 13C NMR
(67.8 MHz) d 203 (2 × d), 135.1 (2 × d), 135.0 (2 × d), 55.3
(2 × t), 40.5 (2 × s), 35.0 (2 × s), 28.2 (4 × q), 23.1 (4 × q); m/z
(EI) found 153.1258 (M+/2), C10H17O requires 153.1279.
1
oil; mmax(soln. CHCl3)/cm−1 1695, 1614; H NMR (270 MHz)
Dimethyl bis(3,3,6,6-tetramethylhex-4-en-6-yloate) 25b
d 7.57–7.54 (2H, m, Ar), 7.41–7.39 (3H, m, Ar), 6.12 (1H, s,
=
=
MeC CHCOSePh), 5.12 (2H, m, 2 × MeC CH), 2.22–2.16
A solution of tributyltin hydride (110 ll, 0.4 mmol) and AIBN
(0.15 mmol) in dry degassed benzene (2.2 ml) and methanol
(0.3 ml) was added dropwise over 2 h, via syringe pump, to a
stirred solution of the selenyl ester 19 (100 mg, 0.33 mmol) in dry
degassed benzene (120 ml) and methanol (11 ml), under reflux
in an atmosphere of argon. The mixture was stirred under reflux
overnight, then cooled to room temperature and the solvent was
evaporated in vacuo to leave a pale yellow oil. The residue was
purified by chromatography on silica gel using petroleum ether–
diethyl ether (10 : 1) as eluent to give the dimeric ester (34 mg,
78% (based on recovered starting material)) as a colourless oil;
mmax(film)/cm−1 1738; 1H NMR (400 MHz, CDCl3) d 5.45 (2H, d,
=
(4H, m, 2 × CH2), 2.11 (3H, s, MeC CHCOSePh), 2.07–2.02
(4H, m 2 × CH2), 1.71 (3H, s, Me), 1.64 (6H, s, 2 × Me); 13C
NMR (67.8 MHz) d 189.5 (s), 157.9 (s), 136.5 (s), 135.8 (2 × d),
131.4 (s), 129.2 (2 × d), 128.6 (d), 127.4 (s), 124.4 (d), 124.1 (d),
122.5 (d), 40.7 (t), 39.6 (t), 26.7 (t), 25.8 (t), 25.7 (q), 20.3 (q),
17.7 (q), 16.0 (q); m/z (CI, methane) found 377.1356 (M+ + H),
C21H29OSe requires 377.1384.
6-(1,5-Dimethylhex-4-enyl)-3-methylcyclohex-2-en-1-one
(bisabolone) 15
The cyclohexenone was prepared from Se-phenyl-3,7,11-tri-
methyldodecatri-2E,6E,10-trienselenoate 14 (58 mg, 0.15 mmol)
using an identical procedure to that described for the preparation
of piperitone 13. Purification by chromatography on silica using
petroleum ether–diethyl ether (2 : 1) as eluent gave a 1 : 1 mixture
of diastereoisomers of the cyclohexenone (24 mg, 71%) as an
=
=
J 16.1 Hz, 2 × CH CH), 5.33 (2H, d, J 16.1 Hz, 2 × CH CH),
3.62 (6H, s, 2 × CO2CH3), 2.30 (4H, s, 2 × CH2CO2Me), 1.13
(12H, s, 4 × CH3), 0.91 (12H, s, 4 × CH3); 13C NMR (67.8 MHz,
CDCl3) d 172.3 (2 × s), 135.3 (2 × d), 134.1 (2 × d), 51.1 (2 ×
q), 47.2 (2 × t), 40.2 (2 × s), 35.4 (2 × s), 27.8 (4 × q), 23.0 (4 ×
q); m/z (EI) found 335.2613 (M+ − OMe), C21H35O3 requires
335.2586).
oil; mmax(soln. CHCl3)/cm−1 1659, 1456; H NMR (250 MHz)
d 5.86/5.83 (1H, s, MeC CHCO), 5.10 (1H, m, Me2C CH),
2.30–2.28 (2H, m), 2.20–1.76 (6H, complex m), 1.93 (3H, s,
1
=
=
=
=
MeC CHCO), 1.67 (3H, s, MeMeC CH), 1.59 (3H, s,
MeMeC CH), 1.33–1.21 (2H, m), 0.93 (1.5H, d, J 6.9 Hz, Me),
Phenyl 2,2-dimethyl-3-(eth-1-enyl)cyclopropyl selenoate 26
=
Tributylphosphine (700 ll, 2.8 mmol) was added dropwise
over 10 min to a stirred solution of 2,2-dimethyl-3(eth-1-
enyl)cyclopropanecarboxylic acid18 (200 mg, 14 mmol) and
diphenyl diselenide (890 mg, 2.8 mmol) in benzene (6 ml) and
the mixture was then stirred at room temperature overnight. The
solvent was evaporated in vacuo and the residue was purified
by chromatography using petroleum ether–diethyl ether (10 :
1) as eluent to give the trans-selenyl ester (216 mg, 55%) as
a pale yellow oil; kmax(EtOH)/nm 245 (1600); mmax(film)/cm−1
0.80 (1.5H, d, J 6.8 Hz, Me); 13C NMR (100 MHz) d 201.1 (s),
161.1/160.9 (s), 131.4/131.2 (s), 127.1/127.0 (d), 124.7/124.5
(d), 51.2/49.8 (d), 34.7/33.3 (t), 30.9/30.6 (t), 30.9/30.2 (d),
26.1/26.0 (t), 25.7 (q), 24.0 (q), 23.4/22.3 (t), 17.6/17.3 (q), 15.6
(q); m/z (EI) found 220.1826 (M+), C15H24O requires 220.1827.
Phenyl trans-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane
selenoate 19
1
Tributylphosphine (1.5 ml, 6.0 mmol) was added dropwise over
10 min to a stirred solution of ( )-trans-chrysanthemic acid17
(0.5 g, 3.0 mmol) and diphenyl diselenide (1.9 g, 6.0 mmol) in
benzene (12 ml) at room temperature. The resulting mixture was
stirred at room temperature for 24 h and then the solvent was
1709, 1636; H NMR (270 MHz, CDCl3) d 7.60–7.38 (5H, m,
=
=
ArH), 5.56 (1H, m, CH CH2), 5.17 (2H, m, CH CH2), 2.32
(1H, dd, J 5.1, 8.6 Hz, cyclopropyl CH), 2.14 (1H, d, J 5.1 Hz,
cyclopropyl CH), 1.27 (3H, s, CH3), 1.20 (3H, s, CH3); 13C NMR
(67.8 MHz, CDCl3) d 196.4 (s), 135.7 (2 × d), 134.4 (d), 129.3
3 2 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7

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(2 × d), 128.8 (d), 127.1 (s), 117.1 (t), 45.9 (d), 39.5 (d), 33.1 (s),
21.6 (q), 20.3 (q); m/z (EI) found 280.0365 (M++), C14H16O80Se
requires 280.0366; found 123.0821 (M–SePh+, 100%), C8H11O
requires 123.0810.
13C NMR (100 MHz) d 167.0 (s), 159.5 (s), 137.8 (d), 117.5
(t), 115.2 (d), 93.7 (t), 76.6 (d), 55.4 (q), 50.6 (q), 36.4 (t), 33.0
(t), 18.7 (q); m/z (EI) found 197.1180 (M+ − OMe), C11H17O3
requires 197.1178.
5,5,-Dimethylcyclohex-3-en-1-one 30
( )-Se-Phenyl 3-methyl-6-methoxymethyloxyocta-2E,7-
dienselenoate 34
A solution of tributyltin hydride (100 ll, 0.3 mmol) and AIBN
(2 mg) in dry degassed benzene (2 ml) was added over 4 h
via syringe pump to a stirred solution of the selenyl ester 26
(50 mg, 0.18 mmol) and AIBN (2 mg) in benzene (60 ml)
under reflux in an atmosphere of argon. The mixture was stirred
under reflux for 12 h then cooled to room temperature and the
solvent was evaporated in vacuo. The residue was purified by
chromatography using petroleum ether–diethyl ether (9 : 1 to 5 :
1) as eluent to give the cyclohexenone (12 mg, 52%) as a colourless
oil; mmax(film)/cm−1 1699; 1H NMR (400 MHz, CDCl3) d 5.74–
Lithium hydroxide monohydrate (35 mg, 0.83 mmol) was added
in one portion to a stirred solution of the ester 33b (80 mg,
0.35 mmol) in THF (2.5 ml) and water (2.5 ml), and the mixture
was stirred at room temperature for 36 h. The mixture was
acidified to pH ∼2 with hydrochloric acid (ca. 2 ml, 2 M) and
then diluted with water (2 ml) and ether (10 ml). The separated
aqueous phase was extracted with ether (3 × 10 ml), and the
combined organic layers were washed with brine (10 ml) and
then dried (MgSO4). The solvent was removed in vacuo to
leave a colourless oil which was purified by chromatography
on silica using petroleum ether–diethyl ether (1 : 1) as eluent
to give the corresponding carboxylic acid (70 mg, 93%) as a
colourless oil; mmax(soln. CHCl3)/cm−1 3200 (br), 1693, 1644;
1H NMR (270 MHz) d 5.71 (1H, ddd, J 17.5, 9.9, 7.6 Hz,
=
=
5.62 (2H, m, CH CH), 2.83 (2H, m, C(O)CH2CH ), 2.39
(2H, s, CH2C(O)), 1.04 (3H, s, CH3), 0.98 (3H, s, CH3); 13C
NMR (67.8 MHz, CDCl3) d 209.1 (s), 141.7 (d), 121.4 (d), 48.1
(t), 27.9 (t), 29.8 (s), 18.0 (2 × q).
( )-Methyl 6-hydroxy-3-methylocta-2E,7-dienoate 33a
=
=
CH2 CHCH(O)), 5.72 (1H, br s, MeC CHCO2), 5.23 (1H,
=
br. d, J 17.5 Hz, CHH CHCH(O)), 5.22 (1H, br. d, J 9.9 Hz,
Vinylmagnesium chloride (900 ll, 15 wt.% in THF) was added
dropwise over 10 min to a stirred solution of the aldehyde
3219 (200 mg, 1.28 mmol) in THF (10 ml) at 0 ◦C, and the
resulting brown solution was then stirred at this temperature
for 1 h. Aqueous saturated ammonium chloride (1 ml) was
added carefully and the mixture was then allowed to warm
to room temperature. Ether (20 ml) and water (10 ml) were
added and the separated aqueous layer was extracted with
ether (3 × 20 ml). The combined organic extracts were washed
with brine (10 ml) and then dried (MgSO4). The solvent was
removed in vacuo to leave a brown oil which was purified
by chromatography on silica using petroleum ether–diethyl
ether (1 : 1) as eluent to give the alcohol (150 mg, 64%)
as a colourless oil; mmax(soln. CHCl3)/cm−1 3380, 1713, 1650;
1H NMR (250 MHz) d 5.84 (1H, ddd, J 17.3, 10.4, 6.3 Hz,
=
CHH CHCH(O)), 4.71 (1H, d, J 6.8 Hz, MeOCHHO), 4.54
=
(1H, d, J 6.8, MeOCHHO), 3.99 (1H, m, CH2 CHCH(O)), 3.38
=
(3H, s, MeO), 2.37–2.21 (2H, m, CH2MeC CH), 2.18 (3H, d, J
1.3 Hz, MeC CHCO2), 1.86–1.62 (2H, m, CH2CH(OH)); 13C
=
NMR (67.8 MHz) d 172.0 (s), 162.5 (s), 137.7 (d), 117.8 (t), 115.3
(d), 93.7 (t), 76.7 (d), 55.5 (q), 36.8 (t), 33.0 (t), 19.1 (q); m/z (EI)
found 169.0866 (M+ − CH2OMe), C9H13O3 requires 169.0865.
The selenyl ester was prepared from the carboxylic acid
(70 mg, 0.33 mmol) in an identical procedure to that de-
scribed for the preparation of Se-phenyl 3,7-dimethylocta-2,6-
dienselenoate 12, using NPSP (148 mg, 0.49 mmol), trib-
utylphosphine (163 ll, 0.65 mmol) and dichloromethane (5 ml).
Purification by chromatography on silica using petroleum ether–
diethyl ether (3 : 1) as eluent gave the selenyl ester (72 mg,
62%) as a 2 : 1 mixture of 2E and 2Z geometric isomers.
Data for 2E isomer only: mmax(soln. CHCl3)/cm−1 1696, 1615;
1H NMR (270 MHz) d 7.67–7.52 (2H, m, Ar), 7.42–7.33 (3H,
=
=
CH2 CHCH(O)), 5.67 (1H, q, J 1.2 Hz, MeC CHCO2), 5.21
=
(1H, br. d, J 17.3 Hz, CHH CHCH(O)), 5.11 (1H, br. d, J
=
=
10.4 Hz, CHH CHCH(O)), 4.07 (1H, m, CH2 CHCH(O)),
3.66 (3H, s, MeO), 2.22 (2H, m, CH2MeC CH), 2.14 (3H,
=
m, Ar), 6.14 (1H, q, J 1.3 Hz, MeC CHCOSe), 5.69 (1H,
ddd, J 17.5, 9.9, 7.6 Hz, CH2 CHCH(O)), 5.23 (1H, br. d,
=
=
=
d, J 1.2 Hz, MeC CHCO2), 2.04 (1H, br s, OH), 1.67 (2H,
m, CH2CH(OH)); 13C NMR (67.8 MHz) d 167.1 (s), 159.8 (s),
140.6 (d), 115.1 (d), 114.7 (t), 72.0 (d), 50.6 (q), 36.4 (t), 34.3 (t),
18.6 (q); m/z (EI) found 169.0864 (M+ − Me), C9H13O3 requires
169.0865.
=
J 17.5 Hz, CHH CHCH(O)), 5.22 (1H, br. d, J 9.9 Hz,
=
CHH CHCH(O)), 4.72 (1H, d, J 6.8 Hz, MeOCHHO), 4.56
=
(1H, d J 6.8 Hz, MeOCHHO), 4.01 (1H, m, CH2 CHCH(O)),
=
3.41 (3H, s, MeO), 2.31–2.17 (2H, m, CH2MeC CH), 2.10 (3H,
=
d, J 1.3 Hz, MeC CHCOSe), 1.85–1.62 (2H, m, CH2CH(OH));
( )-Methyl 3-methyl-6-methoxymethyloxyocta-2E,7-dienoate
33b
13C NMR (67.8 MHz) d 189.5 (s), 157.5 (s), 137.7 (d), 135.8 (2 ×
d), 129.2 (2 × d), 128.7 (d), 127.1 (s), 124.5 (d), 117.9 (t), 93.8
(t), 76.5 (d), 55.6 (q), 36.4 (t), 32.9 (t), 20.3 (q); m/z (EI) found
197.1170 (M+ − SePh), C11H17O3 requires 197.1178.
Chloromethyl methyl ether (70 ll, 0.92 mmol) was added in
one portion to a stirred solution of the alcohol 33a (150 mg,
0.82 mmol) and diisopropylethylamine (150 ll, 0.86 mmol) in
dichloromethane (5 ml), and the resulting solution was stirred
at room temperature for 18 h. Water (2 ml) was added and the
mixture was stirred vigorously for 30 min. Dichloromethane
(10 ml) and water (5 ml) were added and the separated
aqueous layer was extracted with dichloromethane (3 × 10 ml).
The combined organic extracts were washed with brine, dried
(MgSO4) and then concentrated in vacuo to leave a pale yellow
oil. Purification by chromatography on silica using petroleum
ether–diethyl ether (3 : 1) as eluent gave the ether (110 mg, 59%)
as a colourless oil; mmax(soln. CHCl3)/cm−1 1711, 1649; 1H NMR
6ab-Methyl-4b-methoxymethyloxy-1,2,3,3ab,4a,5,6,6a-
hexahydropentalen-2-one and 6ab-methyl-4a-
methoxymethyloxy-1,2,3,3ab,4b,5,6,6a-hexahydropentalen-
2-one 38
A solution of tributyltin hydride (60 ll, 0.22 mmol) in dry,
degassed (using argon) benzene (5 ml) was added via syringe
pump, over 2 h, to a refluxing solution of the selenyl ester
34 (70 mg, 0.20 mmol) and AIBN (3 mg) in dry, degasssed
(using argon) benzene (60 ml). The solution was heasted under
reflux for 1 h and then cooled to room temperature. The solvent
was removed in vacuo to leave a residue which was purified by
chromatography on silica using petroleum ether–diethyl ether (3
: 1) as eluent to give a 2 : 1 mixture of diastereoisomers of the
diquinane (26 mg, 76%) as an oil; mmax(soln. CHCl3)/cm−1 1732,
1668; 1H NMR (400 MHz) data for major isomer: d 4.65 (1H, d, J
6.8 Hz, MeOCHHO), 4.62 (1H, d, J 6.8 Hz, MeOCHHO), 3.85
(1H, m, CH2CH(O)), 3.36 (3H, s, MeO), 2.60 (1H, dd, J 18.8,
=
(400 MHz) d 5.63 (1H, ddd, J 17, 10, 7 Hz, CH2 CHCH(O)),
=
5.65 (1H, br s, MeC CHCO2), 5.18 (1H, br. d, J 17 Hz,
=
=
CHH CHCH(O)), 5.17 (1H, br. d, J 10 Hz, CHH CHCH(O)),
4.65 (1H, d, J 6.8 Hz, MeOCHHO), 4.48 (1H, d, J 6.8 Hz,
=
MeOCHHO), 3.94 (1H, m, CH2 CHCH(O)), 3.63 (3H, s,
MeO), 3.33 (3H, s, MeO), 2.24–2.17 (2H, m, CH2MeC CH),
2.13 (3H, s, MeC CHCO2), 1.75–1.60 (2H, m, CH2CH(OH));
=
=
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7
3 2 1

View Article Online
9.8 Hz, COCHHCH), 2.50 (1H, d, J 14.5 Hz, CHHCOCH2CH),
2.34–1.61 (7H, complex m), 1.27 (3H, s, Me); data for minor
isomer (where not obscured by major isomer): d 4.63 (1H, d, J
6.7 Hz, MeOCHHO), 4.54 (1H, d, J 6.7 Hz, MeOCHHO), 4.18
(1H, m, CH2CH(O)), 3.35 (3H, s, MeO), 1.19 (3H, s, Me); 13C
NMR (67.8 MHz) data for major isomer: d 219.0 (s), 95.4 (t),
85.0 (d), 55.3 (q), 53.0 (d), 52.5 (t), 45.3 (s), 42.7 (t), 37.8 (t),
31.4 (t), 28.6 (q); data for minor isomer (where not obscured by
major isomer) 219.9 (s), 80.0 (d), 55.5 (q), 53.3 (t), 51.0 (d), 45.5
(s), 38.3 (t), 37.7 (t), 28.9 (q); m/z (EI) found 198.1263 (M+),
C11H18O3 requires 198.1256.
atmosphere of argon, and the mixture was then heated under
reflux for 1 h. The mixture was cooled to room temperature
and the benzene was then evaporated in vacuo. The residue was
purified by chromatography on silica using petroleum ether–
diethyl ether as eluent to give: (i), the aldehyde 41 (8 mg, 46%)
(eluted first) as a colourless oil; mmax(soln. CHCl3)/cm−1 1731,
1666; 13C NMR (100.6 MHz, CDCl3) d 191.0 (d), 171.2 (s),
138.7 (d), 137.8 (d), 127.4 (t), 39.9 (t), 33.1 (t), 26.3 (q), 23.0 (t);
m/z (EI) (found 109.1018. C8H13 requires 109.1017 (M+ − CHO,
4%), and (ii), the diquinane 40 (7 mg, 41%) (eluted second) as an
oil; mmax(soln. CHCl3)/cm−1 2850, 1731 (lit.22 (soln. CHCl3)/cm−1
2861, 1737); 1H NMR (400 MHz, CDCl3) d 2.54 (2H, dd, J 9.1,
18.6 Hz, CHCH2C(O)), 2.25 (1H, d, J 18.6 Hz, CHHC(O)),
2.15 (1H, d, J 18.6 Hz, CHHC(O)), 2.11–1.98 (3H, m, CH +
CH2), 1.75 (2H, app. qn, J 7.6 Hz, CH2CH2CH2), 1.66–1.58 (2H,
m, CH2), 1.18 (3H, s, CH3); 13C NMR (100.6 MHz, CDCl3) d
217.0 (s), 51.7 (t), 46.9 (s), 46.8 (d), 5.0 (t), 39.9 (t), 32.9 (t), 27.8
(s), 27.5 (q), 24.3 (t); m/z (EI) found 138.1056 (M+), C9H14O
requires 138.1045.
S-[2-(2-Iodophenyl)ethyl] thio-3-methylocta-2,7-dienoate 39
Following the general procedures described in the accompanying
paper, a solution of hept-6-en-2-one20 (200 mg, 1.8 mol) in
13a
THF (1 ml) was treated with sodium hydride (60% dispersion,
170 mg, 4.3 mmol) and triethylphosphonoacetate (0.9 ml,
4.5 mmol) in THF (3 ml). Sodium hydroxide (200 mg) was added
in one portion to a solution of the crude a,b-unsaturated ester in
refluxing ethanol (3.0 ml) and water (0.3 ml). The mixture was
stirred under reflux for 1 h, then cooled to room temperature
and evaporated in vacuo. The residue was washed with diethyl
ether (20 ml), and the separated aqueous layer was acidified
with HCl (2 mol dm−3) and extracted with diethyl ether (3 ×
20 ml). The combined organic extracts were dried (MgSO4) and
concentrated in vacuo to leave a 1 : 4 mixture of the Z- and
E-isomers of 3-methylocta-2,7-dienoic acid (219 mg, 94%), as
a clear colourless viscous oil; mmax(film)/cm−1 2936 (br), 1690,
1639; 1H NMR (250 MHz, CDCl3) d 5.79 (1H, ddt, J 6.7,
Ethyl 3-methyloct-2-en-7-yn-1-oate 45
Dichloromethane (30 ml) was added in one portion to a
vigorously stirred mixture of pyridinium chlorochromate (4.9 g,
22.5 mmol) and silica (4.9 g) at room temperature, and the
mixture was stirred for 5 min. A solution of hept-6-yn-2-ol 44
(1.7 g, 15 mmol) in dichloromethane (1 ml) was added in one
portion and the mixture was stirred at room temperature for
2 h and then filtered through a short column of silica using
dichloromethane as eluent. The filtrate was evaporated to leave
a solution of 6-heptyn-2-one23 in CH2Cl2 which was used directly
in the next stage.
A solution of triethylphosphonoacetate (9.3 ml, 47 mmol)
in THF (16 ml) was added dropwise over 15 min to a stirred
suspension of sodium hydride (1.1 g, 45 mmol) in THF (8 ml) at
room temperature. The mixture was stirred at room temperature
for 30 min and then the solution of the 6-heptyn-2-one23 in
dichloromethane (5 ml) and THF (8 ml) was added dropwise
via cannula, over 5 min. The mixture was stirred for 2 h, then
saturated NH4Cl solution (10 ml) was added dropwise over
10 min, and the mixture was evaporated in vacuo. The residue was
partitioned between water (50 ml) and diethyl ether (50 ml) and
the separated aqueous layer was then extracted with diethyl ether
(3 × 30 ml). The combined organic extracts were washed with
water (30 ml) and brine (30 ml), dried (MgSO4) and concentrated
under reduced pressure to leave a yellow oil. The residue was
purified by chromatography on silica using petroleum ether–
diethyl ether as eluent to give a 1 : 4 mixture of Z- and E-
isomers of the a,b-unsaturated ester (1.2 g, 44%) as a colourless
oil; mmax(film)/cm−1 1716, 1650; 1H NMR (250 MHz, CDCl3) d
=
=
10.3, 17.0 Hz, CH CH2), 5.71 (1H, br s, CH C(CH3)), 5.08–
4.95 (2H, m, CH CH2), 2.17 (3H, s, CH C(CH3)), 2.16 (2H,
=
=
=
t, J 7.5 Hz, CH2CH2C(CH3) ), 2.06 (2H, app. q, J 7.5 Hz,
CH2CH2CH ), 1.60 (2H, app. qn, J 7.5 Hz, CH2CH2CH2); 13C
=
NMR (67.8 MHz, CDCl3) major (E) isomer: d 172.5 (s), 163.2
(s), 137.9 (d), 115.3 (d), 115.1 (t), 40.5 (t), 33.2 (t), 26.5 (t), 19.0
(q); minor (Z) isomer: d 172.0 (s), 163.7 (s), 138.3 (d), 115.8
(d), 114.2 (t), 41.8 (t), 33.7 (t), 27.4 (t), 25.5 (q); m/z (EI) found
154.099 (M+), C9H14O2 requires 154.0994.
DCC (63 mg, 0.3 mmol) and DMAP (63 mg, 0.5 mmol) were
added in one portion to a stirred solution of the carboxylic
acid (40 mg, 0.26 mmol) in dichloromethane (4 ml) at room
temperature. The mixture was stirred at room temperature for
5 min, and then a solution of 2-(2-iodophenyl)ethanethiol21
(82 mg, 0.3 mmol) in dichloromethane (0.5 ml) was added in one
portion. The mixture was stirred at room temperature for 3 h,
and the solvent was then evaporated in vacuo to leave a residue.
Purification by chromatography on silica using petroleum ether–
diethyl ether (10 : 1) as eluent gave a 1 : 4 mixture of Z- and
E-isomers of the thiol ester (93 mg, 89%) as a colourless oil;
mmax(film)/cm−1 1673, 1622; 1H NMR (400 MHz, CDCl3) d 7.82
(1H, d, J 8.1 Hz, ArH), 7.32–7.27 (2H, m, ArH), 6.91 (1H, m,
=
5.70 (1H, s, CH C), 4.18–4.11 (2H, m, OCH2CH3), 2.29–2.24
=
(2H, m, CH2C ), 2.21 (2H, dt, J 2.6, 7.0 Hz, CH2C≡), 2.17
=
=
ArH), 5.99 (1H, br s, CH C(CH3)), 5.80 (1H, ddt, J 6.7, 10.4,
17.1 Hz, CH CH2), 5.06–4.97 (2H, m, CH CH2), 3.15 (2H,
t, J 8.4 Hz, CH2CH2S), 3.02 (2H, t, J 8.4 Hz, CH2CH2S), 2.17
(3H, s, CH C(CH3)), 1.99 (1H, t, J 2.6 Hz, CH≡C), 1.72 (2H,
m, CH2CH2CH2), 1.30–1.22 (3H, m, OCH2CH3); 13C NMR
(100.6 MHz, CDCl3) major (E) isomer: d 201.2 (s), 158.6 (s),
116.2 (d), 83.6 (s), 68.9 (d), 59.5 (t), 29.7 (t), 26.2 (t), 18.7 (q),
17.9 (t), 14.3 (q); minor (Z) isomer: d 201.2 (s), 157.6 (s), 116.9
(d), 84.5 (s), 68.5 (d), 59.5 (t), 32.6 (t), 27.1 (t), 18.5 (q), 17.9 (t),
14.1 (q); m/z (EI) found 135.0824 (M+ − OEt), C9H11O requires
135.0810.
=
=
=
(3H, s, CH3), 2.12 (2H, t, J 7.5 Hz, CH2CH2C(CH3) ), 2.07 (2H,
app. q, J 7.5 Hz, CH2CH2CH ), 1.55 (2H, app qn, J 7.5 Hz,
=
CH2CH2CH2); 13C NMR (100.6 MHz, CDCl3) major isomer: d
188.9 (s), 157.0 (s), 142.8 (s), 139.5 (d), 137.9 (d), 130.0 (d), 128.3
(d), 128.2 (d), 100.4 (s), 40.7 (t), 40.0 (t), 33.1 (t), 28.7 (t), 26.5
(t), 19.7 (q); minor isomer: d 188.3 (s), 156.4 (s), 142.8 (s), 139.5
(d), 138.4 (d), 130.0 (d), 128.3 (d), 128.2 (d), 123.4 (d), 114.7 (t),
100.4 (s), 40.7 (t), 40.6 (t), 33.8 (t), 28.7 (t), 27.4 (t), 24.9 (q); m/z
(CI) found 401.0436 (M+ + H), C17H21IOS requires 401.0436.
Phenyl 3-methyloct-2-en-7-ynyl selenoate 46
Following the general procedures described in the accompanying
13a
paper, a solution of the ester 45 (400 mg, 2.2 mmol) in
ethanol (5 ml) and water (0.5 ml) was treated with sodium
hydroxide (400 mg) to give a 1 : 4 mixture of Z- and E-
isomers of 3-methyloct-2-en-7-yn-1-oic acid (300 mg, 90%), as
cis-Hexahydro-3a-methylpentalen-2(1H)-one 40 and
3-methylocta-2,7-dien-1-al 41
Tributyltin hydride (60 ll, 0.16 mmol) was added in one portion
to a stirred solution of the thiol ester 39 (50 mg, 0.13 mmol)
and AIBN (2 mg) in dry degassed benzene (42 ml), under an
a yellow oil; mmax(film)/cm−1 3302 (br), 2963 (br), 1693, 1643;
1
=
H NMR (400 MHz, CDCl3) d 5.69 (1H, br s, CH C(CH3)),
2.25 (2H, app. q, J 7.1 Hz, CH2C(CH3)), 2.18 (2H, dt, J 7.1,
3 2 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7

View Article Online
=
=
2.9 Hz, CH2C≡CH), 2.14 (3H, s, CH3), 1.93 (1H, t, J 2.9 Hz,
CH2C≡CH), 1.69 (2H, app. qn, J 7.1 Hz, CH2CH2CH2); 13C
NMR (67.8 MHz, CDCl3) major (E) isomer: d 172.1 (s), 162.6
(s), 115.6 (d), 83.7 (s), 69.1 (d), 39.8 (t), 26.0 (t), 19.0 (q), 17.9 (t);
minor (Z) isomer: d 171.5 (s), 163.2 (s), 115.9 (d), 84.2 (s), 68.7
(d), 42.3 (t), 28.7 (t), 24.6 (q), 18.6 (t); m/z (EI) found 152.0837
(M+), C9H12O2 requires 152.0837.
6.7 Hz, CHCH2), 5.65–5.67 (1H, m, CHCO2Et); 2Z isomer:
(360 MHz, CDCl3) d 1.27 (3H, t, J 7.1 Hz, CO2CH2CH3), 1.55–
=
=
1.64 (2H, m, CHCH2CH2), 1.89 (3H, d, J 1.4 Hz, CCH3),
2.02–2.10 (2H, m, CHCH2), 2.64–2.68 (2H, m, C(CH3)CH2),
4.14 (2H, q, J 7.1 Hz, CO2CH2CH3), 4.66 (2H, dt, J 6.7, 3.3 Hz,
=
=
=
=
CH2), 5.13 (1H, app. qn, J 6.7 Hz, CHCH2), 5.65–5.68 (1H,
m, CHCO2Et); 13C NMR (125 MHz) 2E isomer: d 14.3 (q),
18.7 (q), 26.6 (t), 27.5 (t), 40.2 (t), 59.4 (t), 75.0 (t), 89.3 (d), 115.8
(d), 159.6 (s), 166.8 (s), 208.6 (s); 2Z isomer: d 14.3 (q), 25.1 (q),
27.6 (t), 28.2 (t), 32.8 (t), 59.4 (t), 74.8 (t), 89.7 (d), 116.3 (d),
160.1 (s), 166.3 (s), 208.6 (s); m/z (EI) found 194.1298 (M+),
C12H18O2 requires 194.1307.
=
A solution of the carboxylic acid (200 mg, 1.3 mmol) in
dichloromethane (18 ml) was then treated with tributylphos-
phine (500 ll, 2.0 mmol) and N-phenylselenophthalimide
(600 mg, 2.0 mmol). The crude product was purified by
chromatography on silica using petroleum ether–diethyl ether
(10 : 1) as eluent to give a 1 : 4 mixture of Z- and E -
isomers of the selenyl ester (250 mg, 67%) as a pale yellow
oil; mmax(film)/cm−1 1951, 1875, 1698, 1614; major (E) isomer:
1H NMR (400 MHz, CDCl3) d 7.55–7.38 (5H, m, ArH), 6.14
A solution of the mixture of isomers of ethyl 3-methyl-
2,7,8-nonatrienoate (315 mg, 1.62 mmol) in methanol (7.5 ml)
and water (6 ml) was heated with sodium hydroxide (128 mg,
3.20 mmol) at 70 ◦C for 2 h. The methanol was removed under
reduced pressure and the residue was then extracted into ether.
Saturated aqueous NH4Cl was added to the aqueous phase,
and the product was extracted twice into ether. The combined
ether extracts were dried and the solvents were evaporated to
leave a 7 : 2 mixture of E- and Z-isomers of the corresponding
carboxylic acid (170 mg, 64%) as a colourless oil. No satisfactory
microanalytical data could be obtained; mmax(film)/cm−1 3500–
2500 (br), 1956, 1692, 1639; H NMR 2E isomer: (360 MHz,
CDCl3) d 1.59–1.67 (2H, m, CHCH2CH2), 1.98–2.06 (2H, m,
CHCH2), 2.18 (3H, d, J 1.2 Hz, CH3), 2.20–2.24 (2H, m,
C(CH3)CH2), 4.69 (2H, dt, J 6.7, 3.3 Hz, CH2), 5.10 (1H,
app. qn, J 6.7 Hz, CHCH2), 5.69–5.72 (1H, m, CHCO2H);
2Z isomer: 1.57–1.67 (2H, m, CHCH2CH2), 1.94 (3H, d, J
1.3 Hz, CH3), 2.02–2.09 (2H, m, CHCH2), 2.67–2.70 (2H, m,
=
(1H, s, CH C(CH3)), 2.60 (2H, t, J 7.2 Hz, CH2C(CH3)), 2.20
(2H, dt, J 2.5, 7.2 Hz, CH2C≡CH), 1.95 (1H, t, J 2.5 Hz,
CH2C≡CH), 1.89 (3H, s, CH3), 1.69 (2H, m, CH2CH2CH2);
13C NMR (67.8 MHz, CDCl3) d 189.8 (s), 157.3 (s), 135.8 (2 ×
d), 129.3 (2 × d), 128.9 (s), 128.8 (d), 125.5 (d), 83.4 (s), 68.7
(d), 34.0 (t), 26.9 (t), 24.2 (q), 18.5 (t); minor (Z) isomer (where
observed): 1H NMR (400 MHz, CDCl3) d 1.99 (1H, t, J 2.5 Hz,
CH2C≡CH), 1.86 (3H, s, CH3); 13C NMR (67.8 MHz, CDCl3)
d 126.4 (d), 22.3 (q); m/z (FAB) found 293.0439 (M+ + H),
C15H17O80Se requires 293.0445; found 291.0500, C15H17O78Se
requires 291.0452.
1
=
=
=
=
=
=
=
3-Methyloct-2-en-7-yn-1-al
=
=
=
C(CH3)CH2), 4.68 (2H, dt, J 6.6, 3.3 Hz, CH2), 5.10–5.16
A solution of tributyltin hydride (110 ll, 0.3 mmol) and AIBN
(2 mg) in dry degassed benzene (2 ml) was added dropwise
over 5 h, via syringe pump, to a stirred solution of the selenyl
ester 46 (80 mg, 0.27 mmol) and AIBN (3 mg), in benzene
(90 ml) under reflux in an atmosphere of argon. The mixture
was stirred under reflux for 6 h, then cooled to room temperature
and the benzene was evaporated in vacuo to leave a colourless
oil. The oil was purified by chromatography on silica using
petroleum ether–diethyl ether (5 : 1) as eluent to give the aldehyde
(1H, m, CHCH2), 5.71 (1H, br. s, CHCO2H); 13C NMR
(125 MHz) 2E isomer: 19.0 (q), 26.6 (t), 27.5 (t), 40.4 (t), 75.1
(t), 89.3 (d), 115.3 (d), 163.0 (s), 172.3 (s), 208.6 (s); 2Z isomer:
d 25.5 (q), 27.5 (t), 28.1 (t), 32.9 (t), 74.9 (t), 89.6 (d), 115.6 (d),
163.5 (s), 170.7 (s), 208.6 (s); m/z (EI) found 166.0985 (M+),
C10H14O2 requires 166.0994, 148.0888 (M+ − H2O), C10H14O2
requires 148.0888.
=
=
Tri-n-butylphosphine (0.40 ml, 1.61 mmol) was added to a
solution of the above carboxylic acid (180 mg, 1.08 mmol) in
dry CH2Cl2 (5 ml) at −35 ◦C under a nitrogen atmosphere, and
1
(17 mg, 46%) as a colourless oil; H NMR (400 MHz, CDCl3)
d 10.00 (1H, d, J 8.0 Hz, CHO), 5.91 (1H, br. d, J 8.0 Hz,
◦
the mixture was stirred at −30 C for 20 min. NPSP (492 mg,
=
=
C CHCHO), 2.35 (2H, t, J 6.9 Hz, CH2CH2C(CH3) ), 2.23
(2H, dt, J 2.5, 6.9 Hz, CH2C≡CH), 2.18 (3H, s, CH3), 2.00 (1H,
t, J 2.5 Hz, CH2C≡CH), 1.8–1.68 (2H, m, CH2CH2CH2); 13C
NMR (67.8 MHz, CDCl3) d 191.2 (d), 162.2 (s), 127.6 (d), 83.4
(s), 69.2 (d), 39.3 (t), 25.8 (t), 23.4 (t), 17.9 (q); m/z (EI) found
121.0651(M+ − CH3), C8H9O requires 121.0653.
1.63 mmol) was added in one portion, and the resulting yellow
mixture was stirred at −30 ◦C for 15 min. The cooling bath was
removed, and the mixture was diluted with ether (40 ml). The
solution was washed with water (2 × 20 ml), then brine, and
dried. The solvents were removed under reduced pressure to
leave a residue which was purified by chromatography on silica
using 0–1% diethyl ether–petroleum ether as eluent to give an
8 : 3 mixture of E- and Z-isomers of the selenyl ester (270 mg,
82%) as a pale yellow oil. No satisfactory microanalytical data
could be obtained; kmax(EtOH)/nm 2Z isomer: 299 (5400);
Se-Phenyl (E,Z)-3-methyl-2,7,8-nonatrieneselenoate 48
Triethyl phosphonoacetate (1.10 ml, 5.54 mmol) was added to a
stirred suspension of sodium hydride (60% dispersion in mineral
oil; 210 mg, 5.25 mmol), previously washed with dry THF, in dry
THF (6 ml) at 0 ◦C under a nitrogen atmosphere. The resulting
colourless solution was stirred at room temperature for 30 min,
then a solution of octa-6,7-dien-2-one (451 mg, 3.63 mmol)24
in THF (1 ml) was added, and the mixture was stirred at room
temperature for 4 h. Saturated aqueous NH4Cl was added, then
water, and the mixture was extracted with ether. The combined
organic extracts were washed with brine, dried and evaporated
in vacuo. The residue was purified by chromatography on silica
using petroleum ether as eluent to give a 7 : 2 mixture of E-
and Z-isomers of ethyl 3-methyl-2,7,8-nonatrienoate (610 mg,
87%) as a colourless liquid (found, C, 74.4%; H, 9.3%. C12H18O2
requires C, 74.2%; H, 9.3%); mmax(film)/cm−1 1956, 1715, 1648;
1H NMR 2E isomer: (360 MHz, CDCl3) d 1.27 (3H, t, J 7.1 Hz,
mmax(film)/cm−1 1954, 1700, 1615, 1578; H NMR 2E isomer:
(360 MHz, CDCl3) d 1.62–1.68 (2H, m, CHCH2CH2), 2.01–
1
=
=
2.06 (2H, m, CHCH2), 2.10 (3H, d, J 1.2 Hz, CH3), 2.15–2.19
=
=
(2H, m, C(CH3)CH2), 4.73 (2H, dt, J 6.7, 3.3 Hz, CH2),
=
5.11 (1H, app. qn, J 6.7 Hz, CHCH2), 6.11–6.14 (1H, m,
=
CHCOSePh), 7.36–7.42 (3H, m, 3 × ArH), 7.52–7.57 (2H,
=
m, 2 × ArH); 2Z isomer: d 1.53–1.62 (2H, m, CHCH2CH2),
=
1.88 (3H, d, J 1.3 Hz, CH3), 1.99–2.07 (2H, m, CHCH2),
=
2.54–2.58 (2H, m, C(CH3)CH2), 4.66 (2H, dt, J 6.7, 3.3 Hz,
CH2), 5.09 (1H, app. qn, J 6.7 Hz, CHCH2), 6.10–6.12 (1H,
=
=
=
m, CHCOSePh), 7.38–7.43 (3H, m, 3 × ArH), 7.50–7.58 (2H,
m, 2 × ArH); 13C NMR 2E isomer: d 20.2 (q), 26.5 (t), 27.5 (t),
40.0 (t), 75.2 (t), 89.2 (d), 124.6 (d), 127.2 (s), 128.7 (d), 129.2
(2 × d), 135.8 (2 × d), 157.9 (q), 189.5 (s), 208.6 (s); 2Z isomer:
d 24.5 (q), 27.4 (t), 28.1 (t), 34.3 (t), 74.9 (t), 89.5 (d), 125.1 (d),
127.2 (s), 128.7 (d), 129.2 (2 × d), 135.7 (2 × d), 158.4 (s), 188.9
(s), 208.5 (s); m/z (ES) found 307.0612 (M+ + H), C16H18OSe
requires 307.0601.
=
CO2CH2CH3), 1.56–1.64 (2H, m, CHCH2CH2), 1.96–2.03
(2H, m, CHCH2), 2.15 (3H, d, J 1.3 Hz, CCH3), 2.15–2.21
=
=
=
(2H, m, C(CH3)CH2), 4.13 (2H, q, J 7.1 Hz, CO2CH2CH3),
4.67 (2H, dt, J 6.7, 3.3 Hz, CH2), 5.08 (1H, app. qn, J
=
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7
3 2 3

View Article Online
2,7-Dimethylcycloocta-2,7-dienone 56
kmax(EtOH)/nm 260 (5570); mmax(film)/cm−1 1694, 1641, 1579; 1H
NMR (400 MHz, CDCl3) d 7.53–7.37 (5H, m, ArH), 5.81 (1H,
ddt, J 6.5, 10.2, 17.1 Hz, CH2CH CH2), 5.07 (1H, dd, J 2.0,
A solution of tributyltin hydride (0.28 ml, 1.04 mmol) and AIBN
(22 mg, 0.13 mmol) in dry, degassed benzene (5 ml) was added
dropwise (via syringe pump) over 6.5 h to a stirred, refluxing
solution of a 2 : 1 mixture of E- and Z-isomers of the selenyl
ester 48 (245 mg, 0.80 mmol) and AIBN (17 mg, 0.10 mmol)
in dry, degassed benzene (285 ml), under an argon atmosphere.
The mixture was heated under reflux for a further 8.5 h, then
allowed to cool to room temperature and evaporated under
reduced pressure. The residue was purified by chromatography
on silica using 0.3% diethyl ether–petroleum ether as eluent
to give: (i), the cyclooctadienone (30 mg, 25%), as a colourless
oil; kmax(EtOH)/nm 254 (7100); mmax(film)/cm−1 1673; 1H NMR
=
=
=
17.1 Hz, CH CHH), 5.02 (1H, dd, J 2.0, 10.2 Hz, CH CHH),
2.74–2.62 (4H, m, CH2C(O) and 2 × cyclopropyl CH), 2.36
=
(2H, app. q, J 6.5 Hz, CH2CH2CH ), 1.57 (2H, m, cyclopropyl
CH2); 13C NMR (67.8 MHz, CDCl3) d 205.9 (s), 197.7 (s), 136.5
(2 × d), 135.6 (d), 129.3 (2 × d), 129.0 (d), 115.5 (t), 43.8 (t), 35.1
(d), 30.9 (d), 27.5 (t), 18.6 (t); m/z (CI) found 309.04079 (M+ +
H), C15H16O280Se requires 309.0394.
6-(3-Butenyl)-3,4-dihydro-2-pyrone 66
A solution of tributyltin hydride (150 lg, 0.42 mmol) and AIBN
(4 mg) in dry degassed benzene (2 ml) was added dropwise over
2 h via syringe pump, to a stirred solution of the selenyl ester 59
(100 mg, 0.33 mmol) and AIBN (4 mg) in dry degassed benzene
(106 ml) under reflux in an atmosphere of argon. The mixture
was stirred under reflux for a further 2 h and then cooled to
room temperature. The solvent was removed in vacuo to leave
a residue which was purified by chromatography on silica using
petroleum ether–diethyl ether (5 : 1) as eluent to give the enol
lactone (37 mg, 76%) as a colourless oil; mmax(film)/cm−1 3076,
=
(360 MHz, CDCl3) d 1.67–1.76 (2H, m, CCH2CH2), 1.94–1.95
=
(6H, m, 2 × CH3), 2.23–2.32 (2H, m, CHCH2), 2.36–2.39 (2H,
=
=
m, C(CH3)CH2), 6.16 (1H, tq, J 9.0, 1.4 Hz, CHCH2), 6.24
(1H, q, J 1.3 Hz, CHCO); 13C NMR 20.4 (q), 25.0 (t), 26.3
(q), 27.0 (t), 30.4 (t), 132.2 (d), 135.6 (d), 140.9 (s), 152.5 (s),
194.6 (s); m/z (EI) 150.1047 (M+), C10H14O requires 150.1045,
and (ii), unreacted starting material (44 mg, 18%).
=
Ethyl trans-2-(1-oxo-4-pentenyl)cyclopropanoate 58
1
1764, 1641; H NMR (400 MHz, CDCl3) d 5.79 (1H, ddt, J
Ethyl(sulfuranylidene) acetate25 (4.7 g, 32 mmol) was added
dropwise over 5 min to a stirred solution of hepta-1,6-dien-
3-one 57 (3.3 g, 30 mmol) in dichloromethane (60 ml) at
room temperature, and the mixture was then stirred at room
temperature for 24 h. The mixture was evaporated under reduced
pressure to leave a pale yellow oil which was purified by
chromatography on silica using petroleum ether–diethyl ether
(5 : 1) as eluent to give the cyclopropyl ester (4.5 g, 77%) as a
colourless, sweet smelling oil; (found C, 67.0; H, 8.4. C11H16O3
requires C, 67.3; H, 8.2%); mmax(film)/cm−1 1734, 1704, 1642; 1H
NMR (400 MHz, CDCl3) d 5.80 (1H, ddt, J 6.5, 10.6, 17.5 Hz,
=
=
6.5, 10.2, 16.9 Hz, CH2CH CH2), 5.08–4.98 (3H, m, CH +
=
CH CH2), 2.57 (2H, t, J 7.6 Hz, C(O)CH2), 2.30–2.20 (6H, m,
3 × CH2); 13C NMR (67.8 MHz, CDCl3) d 169.3 (s), 152.8 (s),
137.0 (d), 115.4 (t), 99.9 (d), 32.3 (t), 30.4 (t), 28.7 (t), 18.6 (t);
m/z (EI) found 152.08343 (M+), C9H12O2 requires 152.08372.
Ethyl trans-2-(1-hydroxy-4-pentenyl)cyclopropanoate 60
A solution of the cyclopropyl ester 58 (500 mg, 2.5 mmol) in
ethanol (5 ml) was added dropwise over 10 min to a stirred
solution of sodium borohydride (120 mg, 3 mmol) in ethanol
(50 ml) at 0 ◦C. The mixture was allowed to warm to room
temperature over 1 h, and was then diluted with water (20 ml)
and reduced in vacuo. The residue was partitioned between water
(10 ml) and diethyl ether (40 ml) and the separated aqueous layer
was extracted with diethyl ether (3 × 50 ml). The combined
organic extracts were washed with water (20 ml) and brine
(20 ml), dried (MgSO4) and evaporated in vacuo to leave a
colourless oil. Chromatography on silica gel using petroleum
ether–diethyl ether (5 : 3) as eluent gave a 1 : 1 mixture of
diastereoisomers of the alcohol (495 mg, 98%), as a colourless
oil; (found C, 66.5; H, 9.6. C11H18O3 requires C 66.6; H 9.2%.);
=
=
CH2CH CH2), 5.04 (1H, dd, J 1.5, 17.5 Hz, CH CHH), 4.98
(1H, dd, J 1.5, 10.6 Hz, CH CHH), 4.14 (2H, q, J 7.1 Hz,
=
OCH2CH3) d 2.71 (2H, t, J 7.2 Hz, C(O)CH2CH2), 2.45 (1H, m,
=
C(O)CH), 2.35 (2H, app.q, J 7.2 Hz, CH2CH2CH ), 2.15 (1H,
m, CHCO2Et), 1.42 (2H, app. t, J 7.2 Hz, cyclopropyl CH2),
1.26 (3H, t, J 7 Hz, OCH2CH3); 13C NMR (100.6 MHz, CDCl3)
d 206.6 (s), 171.9 (s), 136.7 (d), 115.3 (t), 60.9 (t), 42.9 (t), 28.9
(d), 27.6 (t), 23.9 (d), 16.9 (t), 14.1 (q); m/z (EI) found 196.1093
(M+), C11H16O3 requires 196.1099.
Phenyl trans-2-(1-oxo-4-pentenyl)cyclopropylselenoate 59
1
mmax(film)/cm−1 3434, 3076, 1726, 1641; H NMR (400 MHz,
Following the general procedures described in the accompanying
=
CDCl3) d 5.82 (1H, ddt, J 6.7, 10.3, 17.1 Hz, CH CH2),
13a
paper, a solution of the cyclopropyl ester 58 (1.0 g, 5.0 mmol)
=
5.06 (1H, d, J 17.1 Hz, CH CHH), 4.99 (1H, d, J 10.2 Hz,
in THF (25 ml) and water (25 ml) was treated with lithium
hydroxide (350 mg, 15 mmol) to give the corresponding acid
as an oil which solidified on standing. Recrystallisation from
petroleum ether–diethyl ether gave the cyclopropyl acid (0.8 g,
93%) as needles, m.p. 39–42 ◦C; (found C, 64.2; H, 7.3. C9H12O3
requires C, 64.3; H, 7.2%); mmax(film)/cm−1 2922, 1697, 1642; 1H
NMR (270 MHz, CDCl3) d 8.99 (1H, s, CO2H), 5.72 (1H, ddt, J
=
CH CHH), 4.16–4.10 (2H, m, OCH2CH3), 3.26 (0.5 H, br
m, CHOH), 3.14 (0.5 H, br m, CHOH), 2.25–2.19 (2H, m,
=
CH2CH CH2), 1.73–1.54 (4H, m, CH2 + 2 × cyclopropyl CH),
1.27 (3H, s, OCH2CH3), 1.23–1.15 (1H, m, cyclopropyl CHH),
0.97–0.84 (1H, m, cyclopropyl CHH); 13C NMR (67.8 MHz,
CDCl3) d 174.3 (s), 138.2 (d), 114.9 (t), 73.0 (d), 72.1 (d), 67.8
(t), 36.2 (t), 29.8 (t), 28.6 (d), 27.9 (d), 17.8 (d), 14.1 (q), 12.5
(t), 11.9 (t); m/z (EI) found 198.1252 (M+), C11H18O3 requires
198.1256.
=
6.5, 10.2, 17.2 Hz, CH2CH CH2), 4.97 (1H, dd, J 2.0, 17.2 Hz,
CH CHH), 4.93 (1H, dd, J 2.0, 10.2 Hz, CH CHH), 2.65 (2H,
t, J 6.5 Hz, C(O)CH2CH2), 2.44 (1H, m, cyclopropyl C(O)CH),
=
=
=
2.27 (2H, app. q, J 6.5 Hz, CH2CH2CH CH2), 2.07 (1H, m,
Phenyl trans-2-(1-hydroxy-4-pentenyl)cyclopropyl selenoate 61a
cyclopropyl CHCO2H), 1.38 (2H, t, J 7.3 Hz, cyclopropyl CH2);
13C NMR (67.8 MHz, CDCl3) d 206.8 (s), 176.7 (s), 136.4 (d),
115.2 (t), 42.9 (t), 29.9 (d), 27.6 (t), 23.5 (d), 17.1 (t); m/z (EI)
found 168.0788 (M+), C9H12O3 requires 168.0786.
A solution of the cyclopropyl carboxylic acid (200 mg,
1.2 mmol) in CH2Cl2 (27 ml) was treated with tributylphosphine
(360 mg, 1.8 mmol) and N-phenylselenophthalimide (540 mg,
1.8 mmol). The crude product was purified by chromatography
on silica using petroleum ether–diethyl ether (10 : 1) as eluent
to give the selenyl ester (340 mg, 93%) as a pale yellow oil;
(found C, 58.3; H, 6.0. C15H16O2Se requires C, 58.3; H, 5.9%);
Following the general procedures described in the accompanying
13a
paper,
a solution of the cyclopropyl ester 60 (500 mg,
2.5 mmol) in THF (10 ml) and water (10 ml) was treated with
lithium hydroxide (10 mg, 3.8 mmol) to give a 1 : 1 mixture of
diastereoisomers of trans-2-(1-hydroxy-4-pentenyl)cyclopropyl
carboxylic acid (370 mg, 2.1 mmol, 84%), as a pale yellow
oil; mmax(film)/cm−1 3461, 2923, 1713, 1643, 1442; 1H NMR
(270 MHz, CDCl3) d 6.11 (1H, ddt, J 6.6, 10.2, 17.1 Hz,
=
=
CH2CH CH2), 5.1 (1H, dd, J 2.0, 10.2 Hz, CH CHH), 5.05
(1H, d, J 10.2 Hz, CH CHH), 3.35 (0.5H, br. app. q, J 6.6 Hz,
=
3 2 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7

View Article Online
CH2CH(OH)CH), 3.15 (0.5 H, br. app. q,
J
6.6 Hz,
and the mixture was stirred vigorously for 0.5 h and then
diluted with CH2Cl2 (10 ml) and water (10 ml). The separated
aqueous layer was extracted with CH2Cl2 (3 × 10 ml) and the
combined organic extracts were washed with brine (10 ml),
dried (MgSO4) and concentrated in vacuo to leave a colourless
oil. Column chromatography on silica, using petroleum ether–
diethyl ether (5 : 1) as eluent gave an inseparable 1 : 1 mixture
of diastereoisomers of the corresponding MOM ether (95 mg,
78%) as a colourless oil; (found C, 64.5; H, 9.4, C13H22O4 requires
CH2CH(OH)CH), 2.26 (2H, m, CH2CH2CH(OH)) 1.80–1.59
(4H, m, 2 × CH2) 1.35–1.25 (2H, m, cyclopropyl CH2) 1.11–0.93
(2H, m, 2 × cyclopropyl CH); 13C NMR (67.8 MHz, CDCl3) d
178.9 (s), 178.8 (s), 138.0 (d), 115.0 (t), 73.5 (d), 72.0 (d), 35.9
(t), 29.6 (t), 29.2 (d), 28.4 (d), 18.1 (d), 17.6 (d), 13.3 (t), 12.6
(t); m/z (EI) found 152.08367 (M+ − H2O), C9H12O2 requires
152.08372.
The trans-2-(1-hydroxy-4-pentenyl)cyclopropyl carboxylic
acid (100 mg, 0.6 mmol) then gave the selenyl ester (107 mg,
59%), as a 1 : 1 mixture of diastereoisomers which could be
separated by chromatography on silica using petroleum ether–
diethyl ether (3 : 1) as eluent. First eluted isomer: (found C, 58.3;
H, 6.0. C15H19O2Se requires C, 58.3; H, 5.9%); mmax(film)/cm−1
3408, 1704, 1640; 1H NMR (400 MHz, CDCl3) d 7.55–7.36 (5H,
1
C, 64.4; H, 9.2%); mmax(film)/cm−1 1727; H NMR (400 MHz,
=
CDCl3) d 5.82 (1H, ddt, J 6.6, 10.2, 16.9 Hz, CH CH2),
=
5.04 (1H, d, J 16.9 Hz, CH CHH), 5.00 (1H, d, J 10.2 Hz,
=
CH CHH), 4.78 (0.5H, d, J 6.9 Hz, d, CH3OCHHO), 4.73
(0.5H, d, J 6.9 Hz, CH3OCHHO), 4.61 (0.5H, d, J 6.9 Hz,
CH3OCHHO), 4.59 (0.5H, d, J 6.9 Hz, CH3OCHHO), 4.13
(2H, q, J 7.1 Hz, OCH2CH3), 3.37 (3H, s, CH3OCH2O), 3.12
(1H, br. app. q, J 5.1 Hz, CHOMOM), 3.04 (0.5H, br. app.
=
m, ArH), 5.83 (1H, ddt, J 6.7, 10.3, 16.9 Hz, CH CH2), 5.07
=
(1H, dd, J 1.6, 16.9 Hz, CH CHH), 5.01 (1H, dd, J 1.6, 10.3 Hz,
CH CHH), 3.29 (1H, br. app. q, J 6.4 Hz, CHOH), 2.28–2.17
=
=
q, J 5.1 Hz, CHOMOM), 2.20 (2H, m, CH2CH ), 1.76–1.67
(3H, m, CH2 + cyclopropyl CH), 1.81–1.75 (1H, m, cyclopropyl
CH), 1.69 (2H, app. q, J 7.5 Hz, CH(OH)CH2CH2), 1.48–1.43
(1H, m, cyclopropyl CHH) 1.10–1.06 (1H, cyclopropyl CHH);
13C NMR (67.8 MHz, CDCl3) d 198.9 (s), 138.0 (d), 135.8 (2 ×
d), 129.3 (2 × d), 126.4 (s), 115.2 (t), 72.1 (d), 36.1 (t), 31.6 (d),
29.8 (d), 29.7 (t), 15.3 (t). Second eluted isomer: mmax(film)/cm−1
3411, 3074, 2923, 1704, 1640, 1580; 1H NMR (400 MHz, CDCl3)
d 7.6–7.5 (2H, m, ArH), 7.4–7.3 (3H, m, ArH), 5.8 (1H, ddt, J
(2H, m, CH2CH2CHOH), 1.52–1.4 (2H, m, 2 × cyclopropyl
CH), 1.29–0.74 (5H, m, CH3 + cyclopropyl CH2); 13C NMR
(100.6 MHz, CDCl3) d 173.8 (s), 138.2 (d), 114.8 (t), 94.9 (t),
95.1 (t), 78.2 (d), 77.4 (d), 60.5 (t), 55.3 (d), 34.5 (t), 29.4 (t), 26.1
(d), 25.6 (d), 19.3 (d), 17.2 (d), 14.2 (q), 13.6 (t), 11.9 (t); m/z
(FAB) found 243.1594 (M+), C13H22O4 requires 243.1596.
The ethyl ester (90 mg, 0.4 mmol), from the above procedure,
was treated with lithium hydroxide (20 mg, 0.7 mmol) in THF
(1 ml) and water (1 ml) using the general procedure15 to give
the corresponding carboxylic acid (60 mg, 78%) as an oil;
mmax(film)/cm−1 3190 (br), 1697, 1640; 1H NMR (400 MHz,
=
6.8, 10.2, 17.0 Hz, CH2CH CH2), 5.1 (1H, dd, J 1.6, 17.0 Hz,
=
=
CH CHH), 5.0 (1H, d, J 10.2 Hz, CH CHH), 3.4 (1H, dt, J
6.5 Hz, CH2CH(OH)CH), 2.3–2.2 (3H, m, CH2 + cyclopropyl
CH), 1.8–1.62 (3H, m, CH2 + cyclopropyl CH), 1.4–1.1 (2H,
m, cyclopropyl CH2); 13C NMR (67.8 MHz, CDCl3) d 199.3
(s), 138.3 (d), 136.1 (2 × d) 129.6 (2 × d), 129.2 (d), 126.7 (s),
115.6 (t), 71.9 (d), 36.5 (t), 31.1 (d), 30.4 (d), 30.1 (t), 15.1 (t);
m/z (FAB) found 311.0537 (M+ + H), C15H19O280Se requires
311.0550.
=
CDCl3) d 5.81 (1H, ddt, J 6.5, 10.2, 17.1 Hz, CH CH2) 5.04 (1H,
=
=
d, J 17.1 Hz, CH CHH), 4.98 (1H, d, J 10.2 Hz, CH CHH),
4.77 (0.5H, d, J 6.9 Hz, CH3OCHHO), 4.73 (0.5H, d, J 6.9 Hz,
CH3OCHHO), 4.61 (0.5H, d, J 6.9 Hz, CH3OCHHO), 4.60
(0.5H, d, J 6.9 Hz, CH3OCHHO), 3.38 (1.5H, s, CH3OCH2O),
3.37 (1.5H, s, CH3OCH2O), 3.15 (0.5H, br. app. q, J 7.4 Hz,
CHOMOM), 3.05 (0.5H, br. app. q, J 7.4 Hz, CHOMOM), 2.19
=
trans-7-Hydroxybicyclo[6.1.0]nona-2-one 67
(2H, m, CH2CH2CH ), 1.78–0.82 (6H, m, CH2 + cyclopropyl
CH2 and 2 × CH); 13C NMR (100 MHz, CDCl3) d 180.0 (s),
138.1 (d), 114.9 (t), 95.4 (t), 95.1 (t), 78.2 (d), 77.5 (d), 55.5
(q), 34.6 (t), 32.7 (t), 27.2 (d), 26.8 (d), 19.2 (d), 17.2 (d), 14.6
(t), 12.9 (t); m/z (EI) found 159.0640 (M+), C7H11O4 requires
A solution of tributyltin hydride (84 ll, 0.24 mmol) and AIBN
(2 mg) in dry degassed benzene (2 ml) was added dropwise over
2 h, via syringe pump, to a stirred solution of the selenyl ester 61a
(50 mg, 0.16 mmol) and AIBN (2 mg) in dry degassed benzene
(60 ml) under reflux in an atmosphere of argon. The mixture was
stirred under reflux for a further 2 h and then cooled to room
temperature. The solvent was removed in vacuo to leave a yellow
residue which was purified by chromatography on silica using
petroleum ether–diethyl ether (1 : 1) then diethyl ether as eluents
to give: (i), the bicyclic nonanone (10 mg, 38%) (eluted first)
159.0657.
Following the general procedure,
13a
the trans-cyclopropyl
carboxylic acid (50 mg, 0.2 mmol) was treated with N-
phenylselenophthalimide (110 mg, 0.35 mmol) and tributylphos-
phine (70 mg, 0.35 mmol) in CH2Cl2 (5 ml). The crude product
was purified by chromatography on silica using petroleum
ether–diethyl ether (3 : 1) as eluent to give a 1 : 1 mixture
of diastereoisomers of the selenyl ester (74 mg, 89%) as a
as a colourless oil; mmax(film)/cm−1 3408, 2930, 1682; H NMR
1
(400 MHz, CDCl3) d 4.3 (1H, m, CH2CH(OH)CH), 2.6 (1H, dt,
J 3, 13.1 Hz, cyclopropyl CH), 2.5 (1H, q, J 6.5 Hz, CH2CHCH),
2.38–0.83 (11H, m); 13C NMR (67.8 MHz, CDCl3) d 212.9 (s),
65.1 (d), 46.5 (t), 40.4 (t), 31.1 (t), 30.2 (d), 21.4 (d), 21.42 (t), 6.1
(t); m/z (EI) found 154.09963, C9H14O2 requires 154.09938 (M+
13%); and (ii), the diastereoisomeric bicyclic compound (10 mg,
38%) (eluted second) as a colourless oil; mmax(film)/cm−1 3409,
1
pale yellow viscous oil; mmax(film)/cm−1 1707, 1640; H NMR
(400 MHz, CDCl3) d 7.53 (2H, m, ArH), 7.38 (3H, m, ArH),
=
=
5.82 (1H, m, CH CH2) 5.05 (1H, m, CH CH2), 4.77 (0.5H, d,
J 6.9 Hz, CH3OCHHO), 4.73 (0.5H, d, J 6.9 Hz, CH3OCHHO),
4.62 (0.5H, d, J 6.9 Hz, CH3OCHHO), 4.58 (0.5H, d, J
6.9 Hz, CH3OCHHO), 3.42 (3H, s, CH3OCH2O), 3.37 (3H, s,
CH3OCH2O), 3.20 (0.5H, br. app. q, J 7.1 Hz, CHOMOM),
3.15 (0.5H, br. app. q, J 7.1 Hz, CHOMOM), 2.34–2.05 (3H, m,
CH2 + cyclopropyl CH), 1.79 (3H, m, CH2 + cyclopropyl CH),
1.51–0.97 (2H, m, cyclopropyl CH2); 13C NMR (100.6 MHz,
CDCl3) d 198.9 (s), 138.1 (d), 135.8 (d), 134.4 (d), 129.3 (d),
126.4 (s), 115.0 (t), 95.2 (t), 95.0 (t), 77.4 (d), 77.3 (d), 55.7 (q),
55.5 (q), 34.4 (t), 31.4 (d), 29.6 (t), 29.5 (d), 29.2 (d), 28.9 (d),
16.5 (t), 14.9 (t); m/z (FAB) found 355.0826 (M+ + H), C17H22O3
requires 355.0824.
1
2926, 1694; H NMR (500 MHz, CDCl3) d 3.1 (1H, dt, J 4.8,
7.2 Hz, CH2CH(OH)CH), 2.61–2.17 (5H, m), 1.91 (1H, app. q,
J 7.2 Hz), 1.63–1.45 (4H, m), 0.88 (2H, m, cyclopropyl CH2);
13C NMR (125 MHz, CDCl3) d 210.0 (s), 77.4 (d), 46.5 (t), 40.8
(t), 30.4 (d), 29.3 (t), 26.0 (d), 25.1 (t), 8.8 (t); m/z (EI) found
136.0893 (M+ − H2O), C9H12O requires 136.0888.
Phenyl trans-2-(1-methoxymethyloxy-
4-pentenyl)cyclopropylselenoate 61b
trans-7-(Methoxymethyloxy)bicyclo[6.1.0]nona-2-one 68a
Methoxymethyl chloride (80 mg, 1.0 mmol) was added in one
portion to a stirred solution of the cyclopropyl ester 60 (100 mg,
0.5 mmol) and diisopropylethylamine (260 ll, 1.5 mmol) in
CH2Cl2 (3 ml) at room temperature and the mixture was then
stirred at this temperature for 24 h. Water (1 ml) was added
A solution of tributyltin hydride (66 ll, 0.18 mmol) and AIBN
(2 mg) in dry degassed benzene (2 ml) was added dropwise over
2 h, via syringe pump, to a stirred solution of a 1 : 1 mixture of
diastereoisomers of the selenyl ester 61b (50 mg, 0.14 mmol) and
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7
3 2 5

View Article Online
AIBN (2 mg) in dry degassed benzene (47 ml) under reflux in an
atmosphere of argon. The mixture was stirred under reflux for a
further 2 h and then cooled to room temperature. The benzene
was removed in vacuo to leave a residue which was purified by
chromatography on silica using petroleum ether–diethyl ether (5
: 3) as eluent to give a 2 : 3 mixture of diastereoisomers of the
bicyclic ketone (26 mg, 0.13 mmol, 93%) as an oil. Minor isomer:
mmax(film)/cm−1 1692; 1H NMR (400 MHz, CDCl3) d 4.61 (1H,
d, J 7.0 Hz, OCHHOCH3), 4.52 (1H, J 7.0 Hz, OCHHOCH3),
3.31 (3H, s, CH3), 2.61 (1H, dt, J 3.1, 13.1 Hz, CHOMOM),
2.43–2.15 (4H, m), 1.94 (2H, m), 1.58–1.34 (2H, m), 0.93–0.82
(2H, m); 13C NMR (67.8 MHz, CDCl3) d 212.4 (s), 95.1 (t),
70.9 (d), 55.4 (q), 46.6 (t), 37.5 (t), 31.2 (t), 29.1 (d), 22.2 (d),
21.9 (t), 6.2 (t); m/z (EI) found 198.1257 (M+, 0.5%), C11H18O3
requires 198.1256; found 153.0909, C9H13O2 requires 153.0916
(M+). Major isomer: mmax(film)/cm−1 1704; 1H NMR (400 MHz,
CDCl3) d 4.83 (1H, d, J 7.0 Hz, OCHHOCH3), 4.57 (1H, d, J
7.0 Hz, OCHHOCH3), 3.35 (3H, s, OCH2OCH3), 3.09 (1H, m,
CHOCH2OCH3), 2.65–2.20 (5H, m), 1.88 (1H, app. q, J 7 Hz),
1.67–1.49 (4H, m), 0.89 (2H, m, cyclopropyl CH2); 13C NMR
(67.8 MHz, CDCl3) d 210.1 (s), 93.9 (t), 80.4 (d), 55.1 (q), 46.6
(t), 38.8 (t), 29.3 (t), 28.1 (d), 25.3 (d), 25.2 (t), 9.7 (t); m/z (EI)
found 198.1265 (M+), C11H18O3 requires 198.1256.
mixture of cis- and trans-isomers of the corresponding aldehyde
(16 mg, 33%) (eluted first); 1H NMR (400 MHz, CDCl3) (major
=
isomer) d 9.02 (1H, d, J 6 Hz, CHO), 5.78 (1H, m, CH CH2),
4.99 (2H, m, CH CH2), 2.65 (1H, m, cyclopropyl CHCHO),
=
2.24–0.61 (9H, m); 13C NMR (100.6 MHz, CDCl3) d 202.1 (s),
138.7 (d), 115.3 (t), 33.7 (t), 32.5 (t), 31.3 (d), 27.5 (d), 16.0 (t); 1H
NMR (400 MHz, CDCl3) (minor isomer) d 9.38 (1H, d, J 7.3 Hz,
CHCHO); 13C NMR (100.6 MHz, CDCl3) d 201.4 (s), 139.2 (d),
114.8 (t), 33.3 (t), 31.9 (t), 30.9 (d), 27.0 (d), 18.1 (t), and (ii),
the bicyclo[6.1.0]nonanone (10 mg, 41%)27 eluted second; as an
oil mmax(film)/cm−1 1698, 1455; H NMR (400 MHz, CDCl3) d
1
2.66 (1H, dt, J 2.2, 13.1 Hz, C(O)CH(CH2)CH), 2.39 (13H, m);
13C NMR (67.8 MHz, CDCl3) d 211.6 (s), 46.9 (t), 34.3 (t), 32.2
(t), 31.2 (t), 29.8 (d), 28.0 (t), 27.5 (d), 10.1 (t); m/z (EI) found
138.1047 (M+), C9H14O requires 138.1045.
References
1 For a recent review on acyl radical chemistry, see: C. Chatgilialoglu,
D. Crich, M. Komatsu and I. Ryu, Chem. Rev., 1999, 99, 1991–2070.
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(g) S. Handa, P. S. Nair and G. Pattenden, Helv. Chim. Acta, 2000,
83, 2629–2643, and references cited therein..
3 (a) M. P. Astley and G. Pattenden, Synthesis, 1992, 101–106; (b) M.
Cases, G. Pattenden and F. G.-L. de Turiso, Synlett, 2001, 1869–1872.
4 K. M. Foote, C. J. Hayes, M. P. John and G. Pattenden, Org. Biomol.
Chem., 2003, 1, 3917–3948.
5 (a) Preliminary communication: C. J. Hayes and G. Pattenden,
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bibliography of the generation of a-ketenyl radicals under a variety
of circumstances see: T. T. Tidwell, Ketenes, Wiley, New York, 1995.
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butylperoxide, see: J.-P. Montheard, C.R. Acad. Sci., Se. Paris, 1965,
260, 577.
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9271; (c) cf.C. E. Brown, A. G. Neville, D. M. Rayner, K. U. Ingold
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8 Preliminary communications; see: (a) ref. 5; (b) N. M. A. Herbert
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Phenyl 2-(4-pentenyl)cyclopropyl selenoate 61c
Following the general procedures described in the accompanying
13a
paper, a solution of a 1 : 1 mixture of cis- and trans-isomers
of ethyl 2-(4-pentenyl)cyclopropanoate26 (100 mg, 0.6 mmol)
in ethanol (1.5 ml) and water (two drops) was treated with
sodium hydroxide (100 mg) to give a 1 : 1 mixture of cis-
and trans-isomers of the corresponding carboxylic acid (93 mg,
1
∼100%) as an oil; mmax(film)/cm−1 2926 (br), 1694, 1642; H
NMR (270 MHz, CDCl3) d 11.20 (1H, br. s, CO2H), 5.87–6.73
=
=
(1H, m, CH CH2), 5.03–4.92 (2H, m, CH CH2), 2.07 (2H, q,
J 6.9 Hz, CH2CH CH2), 1.70–0.74 (8H, complex m); 13C NMR
=
(67.8 MHz, CDCl3) d 181.2 (s), 180.0 (s), 138.7 (d), 138.5 (d),
114.6 (t), 114.4 (t), 33.3 (t), 33.2 (t), 32.3 (t), 28.7 (t), 28.2 (t),
26.3 (t), 23.9 (d), 22.9 (d), 20.1 (d), 18.0 (d), 16.3 (t), 14.4 (t);
m/z (EI) found 154.0988 (M+), C9H14O2 requires 154.0994.
A solution of the carboxylic acid (50 mg, 0.3 mmol) in dichlo-
romethane (7 ml) was treated with N-phenylselenophthalimide
(147 mg, 0.5 mmol) and tributylphosphine (123 ll, 0.5 mmol).
The crude product was purified by chromatography on silica
using petroleum ether then petroleum ether–diethyl ether (10 :
1) as eluent, to give a 1 : 1 mixure of cis- and trans-isomers of the
selenyl ester (61 mg, 88%) as a pale yellow oil; (found C, 61.7; H,
6.4. C15H18OSe requires C, 61.4; H, 6.2%); kmax (EtOH)/nm 220.7
1
(124400), 260 (34500); mmax(film)/cm−1 1710, 1640; H NMR
9 (a) D. Griller and K. U. Ingold, Acc. Chem. Res., 1980, 13, 317–323;
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1990, 2729–2734; (f) G. B. Gill, G. Pattenden and S. J. Reynolds,
Tetrahedron Lett., 1989, 30, 3229–3232; (g) V. F. Patel and G.
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and A. Papadatos, J. Am. Chem. Soc., 1992, 114, 8313–8314; (l) S. Z.
(270 MHz, CDCl3) d 7.48–7.27 (5H, m, ArH), 5.81–5.64 (1H,
m, CH CH2) 4.98–4.84 (2H, m, CH CH2), 2.24–1.84 (3H, m,
=
=
=
CH2CH + cyclopropyl CH), 1.58–1.05 (6H, m, 2 × CH2 +
2 × cyclopropyl CH), 0.87–0.77 (1H, m, cyclopropyl CH); 13
C
NMR (67.8 MHz, CDCl3) d 198.6 (s), 197.3 (s), 138.7 (d), 138.4
(d), 135.8 (4 × d), 129.2 (4 × d), 128.7 (2 × d), 126.7 (s), 126.0
(s), 114.7 (t), 114.4 (t), 33.3 (t), 33.2 (t), 32.9 (d), 32.8 (t), 30.7
(d), 28.9 (t), 28.1 (t), 26.5 (t), 26.4 (d), 26.2 (d), 18.8 (t), 16.3
(t); m/z (FAB) found 295.0600 (M+ + H), C15H19O80Se requires
295.0601.
trans-Bicyclo[6.1.0]nona-2-one 68b
A solution of tributyltin hydride (92 ll, 0.26 mmol) and AIBN
(2 mg) in dry degassed benzene (2 ml) was added dropwise over
2 h, via syringe pump, to a stirred solution of the selenyl ester 58c
(50 mg, 0.17 mmol) and AIBN (3 mg) in dry degassed benzene
(57 ml) under reflux in an atmosphere of argon. The mixture
was stirred under reflux for a further 3 h and then cooled to
room temperature. The solvent was removed in vacuo to leave
a residue which was purified by chromatography on silica using
petroleum ether–diethyl ether (5 : 3) as eluent to give: (i), a 3 : 1
3 2 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7

View Article Online
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See http://www.rsc.org/suppdata/ob/b4/b413815p/ for crystallo-
graphic data in .cif format..
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 1 6 – 3 2 7
3 2 7