Synthesis of 5-oxatrienes: Useful intermediates for the preparation of hexahydrobenzofuran structures by intramolecular Diels-Alder reaction

Article abstract of DOI:10.1055/s-1998-2134

The metalation with the Schlosser's base LICKOR (alkyl-lithium potassium alcoholate) at the γ-terminus, selectively induces 1,4-elimination reaction in cyclic α,β-unsaturated acetals, and in this way hydroxy-functionalized (E)-buta-1,3-dienes are obtained. Subsequent oxidation with TPAP gives the aldehyde group, which easily leads to trienic derivatives, suitable for intramolecular Diels-Alder cycloaddition to hexahydrobenzofuran structures.

Full text of DOI:10.1055/s-1998-2134

SYNTHESIS
August 1998
1149
Synthesis of 5-Oxatrienes: Useful Intermediates for the Preparation of
Hexahydrobenzofuran Structures by Intramolecular Diels–Alder Reaction
Annamaria Deagostino, Cristina Prandi, Paolo Venturello*
Università di Torino, Dipartimento di Chimica Generale ed Organica Applicata, Corso M. D’Azeglio 48, I-10125 Torino, Italy
E-mail: venturello@silver.ch.unito.it
Received 28 November 1997; revised 6 February 1998
Abstract: The metalation with the Schlosser's base LICKOR (alkyl-
lithium potassium alcoholate) at the γ terminus, selectively induces
1,4-elimination reaction in cyclic α,β-unsaturated acetals, and in
this way hydroxy-functionalized (E)-buta-1,3-dienes are obtained.
Subsequent oxidation with TPAP gives the aldehyde group, which
easily leads to trienic derivatives, suitable for intramolecular Diels–
Alder cycloaddition to hexahydrobenzofuran structures.
Key words: superbase, functionalized trienes, intramolecular
Diels–Alder cycloaddition, hexahydrobenzofurans
Interest in the intramolecular version of the Diels–Alder
reaction (IMDA)1 has increased considerably in the last
decades. Because of its elegant, economical, and stereo-
controlled uses in the syntheses of polycyclic skeletons of
special interest in the field of natural products,2 the IMDA
is often favored in comparison with the intermolecular
[4 + 2] counterpart. In recent years we have reported the
synthetic utility of α,β-unsaturated acetals as acyl anion
equivalents,3 and as precursors of activated trienes, suit-
able for the synthesis of medium ring lactones.4 In the
present work we wish to propose a new approach to the
Scheme 1
synthesis of the hexahydrobenzofuran nucleus by means
of an IMDA cycloaddition of functionalized trienes. The
hexahydrobenzofuran nucleus is a useful building block for
avermectin and for the α-series of milbemycin.5 These
macrolides exhibit a potent broad spectrum of antiparasitic
activity in both humans and animals6 with relatively low
toxicity,7 and have attracted considerable attention from
synthetic chemists in the last years. The synthetic strategies
followed so far have subdivided the molecule into three
segments, and the hexahydrobenzofuran moiety appears
likely to be the most difficult to be synthesized.8–10
column chromatography on silica gel (Et2O/light petro-
leum ether 10: 90). The subsequent steps were carried out
on the pure 5E,7Z major isomer.
In a previous paper we reported that an activated dieno-
phile can be introduced by esterification of the hydroxy
function with acryloyl chloride.4 In this way the IMDA
reaction yields a six–eight fused bicyclic system, accord-
ing to the tether length. On the other hand, since the ester-
ification strategy is unfeasible in the synthesis of the six–
five bicyclic arrangement present in the hexahydrobenzo-
furan system, we have considered the possibility of
achieving the required three-atoms tether through an oxi-
dation–Wittig reaction sequence.
Acetals 1a–c, that were respectively obtained from cro-
tonaldehyde, 3-methylbut-2-enal, and (E)-pent-2-enal, by
treatment with an equimolar mixture of potassium tert-
butoxide and butyllithium (Schlosser’s LICKOR11 super-
base), undergo metal–hydrogen exchange at the γ site of
the unsaturated system. The metalation reaction promotes
the 1,4-eliminative ring fission, which stereoselectively
affords (1E)-1-alkoxybuta-1,3-dienes 2a–c (Scheme 1).
In particular, in the case of acetal 1c the 1,4-elimination
reaction provides alkoxydiene 2c as a mixture of 5E,7Z
and 5E,7E stereoisomers. The Z configuration of the
C(7)–C(8) double bond of the major isomer has been de-
duced by 1H NMR analysis: irradiation of the signal cor-
responding to the allylic (δ = 1.68) C(7)Me group gives
rises to an Overhauser enhancement of the signal assigned
to C(5)H of the conjugate double bond (δ = 6.57). Indeed,
the value of the coupling constant (J7,8 = 12.0 Hz) does not
allow an unequivocal assignment of the configuration.
The two isomers can be separated (5E,7Z/5E,7E, 9:1) by
The oxidation of the primary alcohols 2a–c was carried
out with tetrapropylammonium perruthenate (TPAP),12
and aldehydes 3a–c were obtained in good yield, free
from carboxylic acid, and without affecting the other
functionalities of these derivatives.
Activated dienophile was obtained when an ethoxycarbo-
nylvinyl substituent was produced by reaction with ethyl
diethoxyphosphorylacetate according to the Wittig–
Horner13 procedure. In this case the C(2)–C(3) double
bond in trienes 4a–c shows a Jtrans coupling constant (16.0
1
Hz) in the H NMR spectrum, and no extraneous peaks
could be attributed to the cis isomer. The stereoselective
outcome of the reaction is not surprising when phospho-
nate carbanions are involved.14

SYNTHESIS
Papers
1150
was used, and r.t. stands for 25°C. Anhyd THF was obtained by dis-
tillation over sodium wire and benzophenone, after the persistent blue
color of sodium diphenylketyl was observed.16 t-BuOK, obtained
from Merck, was sublimed in vacuo prior to the reaction. 1.6 M BuLi
in hexanes was purchased from Aldrich. All commercially available
chemicals were reagent grade and were used without further purifica-
tion. Purification of products was carried out by preparative column
chromatography on Merck silica gel 60 eluting with light petroleum
1
Scheme 2
ether (bp 30–60°C)/Et2O. H NMR spectra were recorded at 300 or
400 MHz in CDCl3, using TMS as internal standard. Coupling con-
stants (J) are given in Hz, and coupling patterns are described by the
abbreviations: s (singlet), d (doublet), q (quartet), m (multiplet), br
(broad). 13C NMR were recorded at 100.4 or 75.5 MHz as CDCl3 so-
lutions, and chemical shifts were determined relative to the residual
solvent peak (77.0 ppm). GC-MS spectra were recorded at 70 eV ion-
isation potential using a cross-linked methyl silicone capillary col-
umn (25 m × 0.2 mm × 0.33 mm film thickness).
Starting α,β-unsaturated acetals 5,5-dimethyl-2-(prop-1-enyl)-1,3-di-
oxane (1a), 5,5-dimethyl-2-(2-methylprop-1-enyl)-1,3-dioxane (1b),
and 5,5-dimethyl-2-(but-1-enyl)-1,3-dioxane (1c), obtained from cro-
tonaldehyde, 3-methylbut-2-enal, and (E)-pent-2-enal, have been
synthesized according to the standard method in a Dean–Stark appa-
ratus, using toluene as a solvent and PPTS as a catalyst, and have been
previously described, as well as alkoxydienes 2a and 2b.3
As regards the tether connecting diene and dienophile, we
take advantage of the gem-disubstitution that makes the
cycloaddition easier.15 As regards the stereochemistry of
the cycloaddition, both exo and endo orientations are
strain free and compatible with the E configuration of the
diene, and both cis and trans isomers have indeed been
obtained. The results of the cycloaddition reaction are re-
ported in the Table.
(5E,7Z)-2,2-Dimethyl-4-oxanona-5,7-dien-1-ol (2c); Typical Pro-
cedure:
A solution of 1.6 M BuLi in hexanes (12.5 mL, 20.0 mmol) was evap-
orated under reduced pressure.17 Precooled (–95°C) THF (10 mL),
acetal 1c (1.7 g, 10.0 mmol) and sublimed t-BuOK (2.24 g,
20.0 mmol) were consecutively added with stirring at –95°C. After a
few seconds the solution turned purple and was stirred at –95°C for
2 h. After this time the reaction was quenched with a THF soln of H2O
(10 mL), and the color was discharged. The two phases were separat-
ed, and the aqueous one was extracted with Et2O (3 × 20 mL). The
combined organic phases were washed with brine (2 × 15 mL), dried
(Na2SO4), and concentrated to give crude 2c as a pale orange oil
which was purified by column chromatography (light petroleum
ether/Et2O 70:30); yield: 1.63 g (96%).
Scheme 3
Table. Thermal Cycloaddition of Trienes 4a–c
Triene
Toluene
Benzonitrile
trans/cisa Yieldb Time
trans/cisc Yieldc Time
(%)
(h)
(%)
(h)
4a
4b
4c
70: 30
75:25
45
56
44
48
65:35
70:30
75:25a
47
2.5
0.5
0.5
1H NMR (300 MHz): δ = 0.95 (6H, s) 1.68 (3H, dd, J = 7.0, 1.5 Hz),
2.20 (1H, br s), 3.43 (2H, s), 3.61 (2H, s), 5.30 (1H, dq, J = 12.0,
7.0 Hz), 5.76 (1H, t, J = 12.0 Hz), 5.86 (1H, tq, J = 12.0, 1.5 Hz). 6.57
(1H, br d, J = 12.0 Hz).
60
e
–
66b
a
On the basis of the yield of the isolated isomers.
Yield of pure isolated product.
By capillary GC analysis of the crude mixture (unless stated other-
13C NMR (75.5 MHz): δ = 13.0, 21.4, 36.2, 69.4, 76.4, 77.0, 102.1,
120.8, 125.0, 150.0.
b
c
MS (EI, 70 eV): m/z (%) = 170 (M+,16), 84 (100), 55 (96), 41 (96), 39
(79).
wise).
Both isomers.
The triene was recovered unreacted after 140 h.
d
e
Oxidation of Alcohols to Aldehydes; Typical Procedure:
The configuration of fused 6 + 5 rings was not directly
deducible from the coupling constant between the protons
bonded to the junction: both cis and trans cycloadducts
show a dihedral angle compatible with the coupling con-
stant J1,6 experimentally measured. Therefore the config-
uration has been attributed on the basis of nuclear Over-
hauser experiments, that indicate that in the cis isomers
C(5)H and C(6)H occupy the pseudo-axial orientation (as
well as C(4)H, in the case of adduct exo-5). On the other
hand, trans isomers show both C(1)H and C(6)H with a
pseudo-axial orientation
To a stirred solution of alcohol (1.0 equiv), 4-methylmorpholine 4-
oxide (NMO) (1.5 equiv), and powered 4Å molecular sieves (500 mg/
mL) in CH2Cl2 (2.0 mL/mmol) at r.t. under argon, solid TPAP
(5 mol%, by weight) was added. After 1 h a TLC test (petroleum
ether/Et2O 90:10) showed the complete disappearance of the alcohol.
The mixture was then filtrated through a pad of silica gel, and eluted
with petroleum ether/Et2O 90: 10, to afford the carbonyl compound
that was used in the following step without further purification.
(5E)-2,2-Dimethyl-4-oxaocta-5,7-dienal (3a): pale orange oil (70%).
1H NMR (400 MHz): δ = 1.25 (6H, s), 3.80 (2H, s), 4.85 (1H, d, J =
11.7 Hz), 5.04 (1H, d, J = 16.4 Hz), 5.55 (1H, t, J = 11.7 Hz), 6.20
(1H, dt, J = 16.4, 11.7 Hz), 6.55 (1H, d, J = 11.7 Hz), 9.25 (1H, s).
13C NMR (100.4 MHz): δ = 18.0, 74.1, 76.5, 108.3, 112.4, 135.5,
155.2, 205.4.
Flasks and all the equipment used for the generation and reaction of
moisture-sensitive compounds were flame dried under argon. Where
a temperature of –95°C is indicated, an acetone/liquid N2 slush bath
MS (EI, 70 eV): m/z (%) = 154 (M+, 12), 85 (16), 70 (100), 55 (23),
41 (98), 39 (99).

SYNTHESIS
August 1998
1151
(5E)-2,2,7-Trimethyl-4-oxaocta-5,7-dienal (3b): pale orange oil
(68%).
MS (EI, 70 eV): m/z (%) = 238 (M+, 4), 109 (43), 83 (23), 55 (84), 41
(99).
Anal. Calc. for C14H22O3: C, 70.56; H, 9.30; found: C, 70.50; H, 9.28.
1H NMR (400 MHz): δ = 1.60 (6H, s), 1.83 (3H, br s), 3.65 (2H, s),
4.45 (1H, br s), 4.55 (1H, br s), 5.27 (1H, d, J = 12.5 Hz), 6.07 (1H,
d, J = 12.5 Hz), 9.05 (1H, s).
13C NMR (100.4 MHz): δ = 20.4, 37.5, 60.0, 76.3, 110.6, 112.4,
136.4, 201.0.
Intramolecular Diels–Alder Cycloaddition; Typical Procedure:
A solution of triene (2.0 mmol) in toluene (5.0 mL) or benzonitrile
(5.0 mL) was degassed with argon. The solution was refluxed in the
presence of hydroquinone under inert atmosphere, and the reaction
followed by TLC (eluent: light petroleum ether/Et2O). After the time
indicated in the Table, the mixture was washed with 10% NaOH
(5 mL). The organic phase was dried (Na2SO4) and the solvent was
removed in vacuo. Benzonitrile was stripped off by Kugelrohr distil-
lation. After column chromatography (Et2O/light petroleum ether
15:85), the cycloadducts were separated, and purified by Kugelrohr
distillation (bp 85–95°C/0.1 Torr).
MS (EI, 70 eV): m/z (%) = 168 (M+, 10), 85 (42), 84 (85), 83 (95), 41
(100), 39 (99).
(5E,7Z)-2,2-Dimethyl-4-oxanona-5,7-dienal (3c): pale orange oil
(65%).
1H NMR (400 MHz): δ = 1.30 (6H, s), 1.80 (3H, br d, J = 7.2 Hz), 3.9
(2H, s), 5.34 (1H, dq, J = 12.0, 7.2 Hz), 5.86 (1H, tq, J = 12.0, 1.5 Hz),
5.76 (1H, t, J = 12.0 Hz), 6.51 (1H, d, J = 12.0 Hz), 9.50 (1H, s).
13C NMR (100.4 MHz): δ = 18.6, 22.5, 70.4, 102.2, 122.4, 126.8,
151.6, 204.6.
MS (EI, 70 eV): m/z (%) = 168 (M+, 12), 84 (82), 83 (49), 56 (40), 41
(100).
Ethyl (1αH,6βH)-7,7-Dimethyl-9-oxabicyclo[4.3.0]non-2-en-5-
carboxylate (endo-5a):
colorless oil (light petroleum ether/Et2O 90: 10).
1H NMR (400 MHz): δ = 0.98 (3H, s), 1.19 (3H, s), 1.28 (3H, t, J =
7.0 Hz), 2.10 (2H, m), 2.30–2.35 (1H, m), 2.40–2.45 (1H, m), 3.44
(1H, d, J = 9.0 Hz), 3.55 (1H, d, J = 9.0 Hz), 4.15–4.25 (2H, m), 4.40
(1H, m), 5.92 (2H, m).
Synthesis of Trienes; Typical Procedure:
To a suspension of ethyl diethoxyphosphorylacetate (1.12 g, 5 mmol)
in THF (2 mL/mmol) at –20°C, 1.6 M BuLi in hexanes (3.12 mL,
5 mmol) was added, after 1 h the temperature was lowered to –78°C
and the carbonyl compound (5 mmol) added. The mixture was kept
for 1 h at –78°C and then for 30 min at r.t. The reaction was then
quenched with water, the two phases were separated, and the aqueous
layer was extracted with Et2O (3 × 15 mL). The combined organic
solutions were washed with brine (2 × 10 mL) and dried (Na2SO4), to
give, after evaporation of the solvent, the crude product that was pu-
rified by column chromatography and Kugelrohr distillation (bp 75–
80°C/0.1 Torr).
13C NMR (100.4 MHz): δ = 21.5, 26.6, 27.9, 28.9, 29.5, 38.0, 42.4,
47.8, 74.1, 78.8, 127.0, 127.2, 178.1.
MS (EI, 70 eV): m/z (%) = 209 (M+ – 15, 11), 151 (100), 135 (39), 77
(45), 43 (68), 41 (78).
Anal. Calc. for C13H20O3: C, 69.1; H, 8.99; found: C, 69.57; H, 8.95.
Ethyl (1βH,6βH)-7,7-Dimethyl-9-oxabicyclo[4.3.0]non-2-en-5-
carboxylate (exo-5a):
colorless oil (light petroleum ether/Et2O 90: 10).
Ethyl (2E,7E)-4,4-Dimethyl-6-oxadeca-2,7,9-trienoate (4a):
pale yellow oil (76%; light petroleum ether/Et2O 95: 5).
1H NMR (400 MHz): δ = 1.15 (6H, s), 1.25 (3H, t, J = 7.3 Hz), 3.50
(2H, s), 4.20 (2H, q, J = 7.3 Hz), 4.80 (1H, dd, J = 10.8, 1.5 Hz), 4.95
(1H, dd, J = 15.5, 1.5 Hz), 5.55 (1H, t, J = 13.0 Hz), 5.80 (1H, d, J =
15.5 Hz), 6.25 (1H, ddd, J = 15.5, 13.0, 10.8 Hz), 6.50 (1H, d, J =
13.0 Hz), 6.90 (1H, d, J = 15.5 Hz).
1H NMR (400 MHz): δ = 1.04 (3H, s), 1.06 (3H, s), 1.30 (3H, t, J =
6.5 Hz), 1.83 (1H, dd, J = 12.0, 10.0 Hz), 2.44 (2H, m), 2.71 (1H, dt,
J = 12.0, 9.0 Hz), 3.72 (1H, d, J = 9.0 Hz), 3.82 (1H, d, J = 9.0 Hz),
4.15–4.25 (2H, m), 4.20 (1H, m), 5.60 (1H, ddt, J = 10.0, 3.0, 2.0 Hz),
6.03 (1H, ddt, J = 10.0, 2.0, 1.5 Hz).
13C NMR (100.4 MHz): δ = 14.0, 21.9, 26.6, 30.7, 36.6, 39.7, 53.2,
60.3, 78.3, 83.1, 125.7, 126.7, 174.3.
13C NMR (100 MHz): δ = 10.4, 20.3, 60.5, 75.4, 76.5, 102.3, 107.6,
120.5, 134.5, 150.4, 154.6, 168.7.
MS (EI, 70 eV): m/z (%) = 209 (M+ – 15, 11), 151 (100), 135 (44), 77
(41), 43 (78), 41 (100).
MS (EI, 70 eV): m/z (%) = 224 (M+, 5), 127 (32), 109 (65), 69 (48),
55 (100), 41 (99).
Anal. Calc. for C13H20O3: C, 69.61; H, 8.99; found: C, 69.64; H, 9.03.
Anal. Calc. for C13H20O3: C, 69.61; H, 8.99; found: C, 69.65, H, 9.01.
Ethyl (1αH,6βH)-3,7,7-Trimethyl-9-oxabicyclo[4.3.0]non-2-en-5-
carboxylate (endo-5b):
Ethyl (2E,7E)-4,4,9-Trimethyl-6-oxadeca-2,7,9-trienoate (4b):
pale yellow oil (87%; light petroleum ether/Et2O 95: 5).
1H NMR (400 MHz): δ = 1.15 (6H, s), 1.30 (3H, t, J = 6.5 Hz), 1.82
(3H, s), 3.55 (2H, s), 4.25 (2H, q, J = 6.5 Hz), 4.70 (1H, s), 4.80 (1H,
s), 5.65 (1H, d, J = 13.0 Hz), 5.85 (1H, d, J = 16.0 Hz) 6.55 (1H, d, J
= 13.0 Hz), 6.95 (1H, d, J = 16.0 Hz).
pale yellow oil (light petroleum ether/Et2O 90: 10).
1H NMR (400 MHz): δ = 0.95 (3H, s), 1.20 (3H, s), 1.25 (3H, t, J =
6.5 Hz), 1.75 (3H, d, J = 1.5 Hz), 2.20 (2H, m), 2.30–2.40 (1H, m),
2.4 (1H, m), 3.45 (1 H, d, J = 9.0 Hz), 3.55 (1H, d, J = 9.0 Hz), 4.1
(1H, m), 4.15–4.25 (2H, m), 5.6 (1H, br s).
13C NMR (100.4 MHz): δ = 13.7, 21.6, 22.4, 29.6, 34.1, 39.6, 53.7,
65.5, 75.2, 79.0, 92.5, 121.0, 136.0, 167.6.
13C NMR (100.4 MHz): δ = 14.2, 24.6, 38.4, 60.1, 74.5, 77.0 108.1,
112.4, 119.8, 138.8, 148.5, 155.4, 168.8.
MS (EI, 70 eV): m/z (%) = 223 (M+ – 15, 23), 165 (100), 149 (45), 91
(42), 43 (51), 41 (62).
MS (EI, 70 eV): m/z (%) = 238 (M+, 2), 155 (25), 109 (40), 81 (44),
41 (100), 39 (49).
Anal. Calc. for C14H22O3: C, 70.56; H, 9.30; found: C, 70.65; H, 9.38.
Anal. Calc. for C14H22O3: C, 70.56; H, 9.30; found: C, 70.58, H, 9.34.
Ethyl (1βH,6βH)-3,7,7-Trimethyl-9-oxabicyclo[4.3.0]non-2-en-5-
carboxylate (exo-5b):
pale yellow oil (light petroleum ether/Et2O 90: 10).
Ethyl (2E,7E,9Z)-4,4-Dimethyl-6-oxaundeca-2,7,9-trienoate (4c):
pale yellow oil (97%; light petroleum ether/Et2O 95: 5).
1H NMR (400 MHz): δ = 1.12 (6H, s), 1.30 (3H, t, J = 6.5 Hz), 1.70
(3H, dd, J = 6.5, 1.5 Hz), 3.55 (2H, s), 4.20 (2H, q, J = 6.5 Hz), 5.30
(1H, dq, J = 12.0, 6.5 Hz), 5.73 (1H, t, J = 12.0 Hz), 5.83 (1H, d, J =
16.0 Hz), 5.88 (1H, br t, J = 12.0 Hz), 6.55 (1H, d, J = 12.0 Hz), 6.95
(1H, d, J = 16.0 Hz).
1H NMR (400 MHz): δ = 1.05 (3H, s), 1.07 (3H, s), 1.30 (3H, t, J =
6.5 Hz), 1.7 (3H, br s), 1.77 (1H, dd, J = 12.0, 10.0 Hz), 2.25–2.4 (2H,
m), 2.68 (1H, ddd, J = 12.0, 10.0, 7.0 Hz), 3.65 (1H, d, J = 9.0 Hz),
3.75 (1H, d, J = 9.0 Hz), 4.10–4.25 (3H, m), 5.71 (1H, br s).
13C NMR (100.4 MHz): δ = 14.1, 22.1, 22.3, 28.8, 35.6, 38.7, 39.6,
53.7, 60.5, 79.1, 83.3, 123.2, 134.0, 174.4.
13C NMR (100.4 MHz): δ = 14.5, 24.3, 38.6, 60.4, 75.0, 76.5, 102.2,
120.2, 122.4, 126.8, 150.7, 155.4, 169.8.

SYNTHESIS
(3) Venturello, P. J. Chem. Soc., Chem. Commun. 1992, 1032.
Papers
1152
MS (EI, 70 eV): m/z (%) = 223 (M+ – 15, 23), 165 (100), 149 (52), 91
(46), 43 (77), 41 (93).
Anal. Calc. for C14H22O3: C, 70.56; H, 9.30; found: C, 70.56; H, 9.35.
Prandi, C.; Venturello, P. J. Org. Chem. 1994, 59, 5458.
Deagostino, A.; Prandi, C.; Venturello, P. Tetrahedron 1996,
52, 1433, and references therein.
Ethyl (1αH,6βH)-4,7,7-Trimethyl-9-oxabicyclo[4.3.0]non-2-en-5-
carboxylate (endo-5c):
(4) Deagostino, A.; Maddaluno, J.; Prandi, C.; Venturello, P.
J. Org. Chem. 1996, 61, 7597.
yellow oil (light petroleum ether/Et2O 95: 5).
(5) Kupchan, S. M; Baxter, R. L.; Chiang, C. K.; Gilmore, C. J.;
Bryan, R. F. J. Chem. Soc., Chem. Commun. 1973, 842.
(6) Grieco, P. A.; Oguri, T.; Gilman, S.; DeTitta, G. T. J. Am.
Chem. Soc. 1978, 100, 1616.
Grieco, P. A.; Oguri, T. and Gilman, S. J. Am. Chem. Soc. 1980,
102, 5886.
(7) Fisher, M. H. In Recent Advances in the Chemistry of Insect
Control; Janes, N. F., Ed.; The Royal Society of Chemistry:
London, 1985; p 53.
1H NMR (400 MHz): δ = 0.99 (3H, s), 1.04 (3H, d, J = 7.0 Hz), 1.14
(3H, s), 1.29 (3H, t, J = 7.0 Hz), 1.95 (1H, dd, J = 12.0, 10.0 Hz), 2.18
(1H, m), 2.31 (1H, dd, J = 12.0, 6.0 Hz), 3.44 (1H, d, J = 9.0 Hz), 3.57
(1H, d, J = 9.0 Hz), 4.18 (2H, m), 4.41 (1H, m), 5.64 (1H, dt, J = 10.0,
1.5 Hz), 5.88 (1H, dt, J = 10.0, 3.0 Hz).
13C NMR (100.4 MHz): δ = 9.6, 18.8, 22.6, 28.8, 34.6, 42.4, 48.7,
49.95, 62.4, 74.6, 78.7, 126.2, 135.4, 176.8.
MS (EI, 70 eV): m/z (%) = 223 (M+ – 15, 12), 165 (100), 149 (24),
109 (51), 43 (50), 41 (76).
(8) White, J. D; Bolton, G. L.;. Dantanarayana, A. P.; Fox, C. M. J.;
Hiner, R. N.; Jackson, R. W.; Sakuma, K.; Warrier, U. S. J. Am.
Chem. Soc. 1995, 117, 1908.
Anal. Calc. for C14H22O3: C, 70.56; H, 9.30; found: C, 70.58; H, 9.32.
Ethyl (1βH,6βH)-4,7,7-Trimethyl-9-oxabicyclo[4.3.0]non-2-en-5-
carboxylate (exo-5c):
(9) White, J. D.; Dantanarayana, A. P. Tetrahedron Lett. 1987, 28,
6417.
yellow oil (light petroleum ether/Et2O 95: 5).
(10) Fujiwara, S.; Smith,.A. B. Tetrahedron Lett. 1992, 33, 1185.
(11) Schlosser, M. J. Organomet. Chem. 1967, 8, 9.
For reviews see: Schlosser, M. Mod. Synth. Met. 1992, 6, 227.
A. Mordini, Advances in Carbanion Chemistry; Snieckus, V.,
Ed.; JAI Press Inc.: Greenwich CT, 1992; Vol. 1, pp 1–45.
Schlosser, M.; Faigl, F.; Franzini, L.; Geneste, H.; Katsoulos,
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(12) Griffith, W. P.; Ley, S. V.; Whitcombe, G. P.; White, A. D.
J. Chem. Soc., Chem. Commun. 1987, 1625.
1H NMR (400 MHz): δ = 0.94 (3H, s), 0.96 (3H, d, J = 7.0 Hz), 1.23
(3H, s), 1.27 (3H, t, J = 7.0 Hz), 1.79 (1H, dd, J = 10.5, 12.0 Hz), 2.75
(1H, m), 2.80 (1H, dd, J = 12.0, 6.5 Hz), 3.61 (1H, d, J = 9.0 Hz), 3.80
(1H, d, J = 9.0 Hz), 4.01 (ddd, J = 10.0, 3.0, 1.5 Hz), 4.16 (2H, m),
5.48 (1H, dt, J = 10.0, 3.0 Hz), 5.96 (1H, dt, J = 10.0, 1.5 Hz).
13C NMR (100.4 MHz): δ = 10.0, 17.2, 22.6, 28.8, 34.6, 38.15, 44.8,
49.0, 60.0, 80.2, 84.6, 128.4, 134.3, 174.2.
MS (EI, 70 eV): m/z (%) = 223 (M+ – 15, 18), 165 (100), 149 (45),
109 (45), 43 (55), 41 (84).
Anal. Calc. for C14H22O3: C, 70.56; H, 9.30; found: C, 70.60; H, 9.35.
Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis
1994, 639.
(13) Horner, L.; Hoffmann, H.; Wippel, H. G.; Klahre Chem. Ber.
1959, 92, 2499.
This work was supported by grants from Italian CNR and MURST.
We wish to thank Dr Mariella Mella (Università di Pavia) for NOE
experiments.
Wadsworth, W. S.; Emmons, W. D. J. Am. Chem. Soc. 1961, 83,
1733.
Unactivated dienophiles have also been obtained in good yields,
by reaction with alkyltriphenylphosphonium salts, according to
the Wittig reaction. The reaction yields were lower in the fol-
lowing cyclization step.
(1) Reviews: Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1977, 16,
10.
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(17) It is advantageous to strip off the hexanes from BuLi, and to use
an excess of LICKOR in order to increase the strength of the re-
agent, as the metalation takes place at an allylic methylene
group. For analogous elimination promoted by metalation at a
methylene group see for example: Mordini, A.; Ben Rayana, E.;
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