Synthesis of functionalized trienes and regioselective formation of medium-ring lactones through intramolecular Diels-Alder reaction

Full text of DOI:10.1021/jo960876h

J . Org. Chem. 1996, 61, 7597-7599
7597
Syn th esis of F u n ction a lized Tr ien es a n d
Sch em e 1
Regioselective F or m a tion of Med iu m -Rin g
La cton es th r ou gh In tr a m olecu la r
Diels-Ald er Rea ction
†
,‡
Annamaria Deagostino, J acques Maddaluno,*
†
,†
Cristina Prandi, and Paolo Venturello*
Dipartimento di Chimica Generale ed Organica Applicata,
Universit a` di Torino, C.so M. D’Azeglio,
4
8 - I 10125 Torino, Italy, and Unit e´ de Recherche Associ e´ e
au CNRS no. 464, Facult e´ des Sciences et des Techniques
and IRCOF, Universit e´ de Rouen,
7
6821 - Mont St Aignan Cedex, France
Received May 14, 1996
In tr od u ction
1
The intramolecular Diels-Alder reaction has not been
extensively applied to the synthesis of macrocyclic rings
because of problems related to regio- and exo-endo
selectivity.2 In the course of studies that explored the
reactivity of R,â-unsaturated acetals in the presence of
an equimolar mixture of butyllithium and potassium tert-
3
garded as intermediates for preparing monocyclic func-
tionalized compounds.
4
butoxide (Schlosser’s reagent LICKOR), we have devel-
oped a method to transform crotonaldehyde diethyl acetal
Resu lts a n d Discu ssion
and propylene acetal into (E)-1-ethoxybuta-1,3-diene and
Acetals 1a -c react with 1.5 equiv of LICKOR reagent
3
(E)-3-(buta-1,3-dienyloxy)-1-propanol, respectively. These
and selectively give alcohols 2a -c in their pure E form.
derivatives are promising candidates for activated dienes
for Diels-Alder cycloaddition reactions. However, we
Treatment of 2a -c with acryloyl chloride in anhydrous
ether in the presence of pyridine readily gives esters
3a -c (Scheme 1), in which the diene and dienophile
moieties are connected through a six-atom tether.
In contrast to trienes utilized by Corey and Petrzilka
(10 atoms in the bridge)2 and Thomas and co-workers
5
were particularly interested to take advantage of the
specific functionalities of the obtained conjugate alkoxy
dienes to prepare activated trienes for intramolecular
Diels-Alder cycloaddition. For instance, a strategy
a
relying on silicon6 or ether tethered trienic systems has
been developed by Craig and colleagues; it gives efficient
access to [4.4.0] bicyclic units which can later undergo
tether-cleaving. Our approach would lead to medium-
ring lactones ([4.6.0] or [3.6.1]) which have received
attention lately because of the discovery of such fused
substructures in various products of natural origin.7
Alternatively, the adducts thus obtained could be re-
a
6b
2b
(12 atoms in the bridge), that give macrocyclic lactones
either fused or bridged across the cyclohexene unit,
derivatives 3a -c show interesting features that could
promote selectively fused macrocyclic structures, because
of the activation of both diene and dienophile moieties.
Thus, according to FMO analysis,8 the selectivity for
fused cycloadducts should increase as the COOR group
increases the size of the C-1 LUMO coefficient and the
OR group increases, through conjugation, that of the
HOMO coefficient at C-12, relative to C-2 and C-9,
respectively.
†
‡
Universit a` di Torino
Universit e´ de Rouen
(1) Reviews: Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1977, 16,
Intramolecular Diels-Alder reaction of trienes 3a -c
(Scheme 2) was studied in refluxing toluene, benzonitrile,
and decahydronaphthalene in order to evaluate the
influence of temperature and solvent on the regio- and
stereoselectivity of the cycloaddition. The results are
reported in Table 1. The data obtained are quite inter-
esting, in particular those obtained in toluene and decalin
compared to those determined in benzonitrile. The
chemical efficiency of this reaction is to be underlined in
relation with a very comparable case in which the dienic
1
0. Brieger, G.; Bennett, J . N. Chem. Rev. 1980, 80, 63. Taber, D. F.
Intramolecular Diels-Alder and Alder Ene Reactions; Springer: Berlin,
984. Fallis, A. G. Can. J . Chem. 1984, 62, 183. Craig, D. Chem. Soc.
1
Rev. 1987, 16, 187. Roush, W. R. Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, J ., Eds.; Pergamon Press: Oxford, 1991; Vol. 5,
p 513.
(2) (a) Corey, E. J .; Petrzilka, M. Tetrahedron Lett. 1975, 2537. (b)
Bailey, S. J .; Thomas, E. J .; Turner, W. B.; J arvis, J . J . J . Chem. Soc.,
Chem. Commun. 1978, 474.
(3) Venturello, P. J . Chem. Soc., Chem. Commun. 1992, 1032.
Prandi, C.; Venturello, P. J . Org. Chem. 1994, 59, 5458. Deagostino,
A.; Prandi, C.; Venturello, P. Tetrahedron 1996, 52, 1433, and
references therein.
(4) Schlosser, M. J . Organomet. Chem. 1967, 8, 9. For reviews see:
moiety bears a thiophenyl substituent that totally inhib-
Schlosser, M. Mod. Synth. Methods 1992, 6, 227. Mordini, A. Advances
in Carbanion Chemistry; Snieckus, V., Ed.; J AI Press Inc.: Greenwich
CT, 1992; Vol. 1, p 1. Schlosser, M.; Faigl, F.; Franzini, L.; Geneste,
H.; Katsoulos, G.; Zhong, G-f. Pure Appl. Chem. 1994, 66, 1439.
its the cycloaddition reaction.9 Comments can be made
on both the regiochemical and the stereochemical aspects.
Cycloaddition of triene 3a occurs in a regioselective
way in toluene, and only fused lactones 4a and 5a are
(
5) (E)-1-Ethoxybuta-1,3-diene and N-methylmaleimide at reflux in
toluene under argon, in the presence of hydroquinone, afforded after
h N-methyl-3-ethoxycyclohex-4-ene-1,2-dicarboxamide (50%).
6) (a) Ainsworth, P. J .; Craig, D.; Reader, J . C.; Slawin, A. M. Z.;
1
(
(8) Houk, K. N. Acc. Chem. Res. 1975, 8, 361. Eisenstein, O.; LeFour,
J . M.; Anh, N. T.; Hudson, R. F. Tetrahedron 1977, 33, 523. Fleming,
J . Orbitals and Organic Chemical Reactions; J . Wiley & Sons: London,
1976.
White, A. J . P., Williams, D. J . Tetrahedron 1995, 51, 11601. (b)
Ainsworth, P. J .; Craig, D.; Reader, J . C.; Slawin, A. M. Z.; White, A.
J . P.; Williams, D. J . Tetrahedron 1996, 52, 695.
(
7) Simonot, B.; Rousseau, G. J . Org. Chem. 1993, 58, 4, and
(9) Maddaluno, J .; Gaonac’h, O.; Marcual, A.; Toupet, L.; Giessner-
Prettre, C. J . Org. Chem., in press.
references therein.
S0022-3263(96)00876-6 CCC: $12.00 © 1996 American Chemical Society

7
598 J . Org. Chem., Vol. 61, No. 21, 1996
Notes
Ta ble 1. Th er m a l Cycliza tion of Tr ien es
benzonitrile
toluene
decalin
b
b
c
yield (%)
yield (%)
yield (%)
triene
trans/cisa
(react. time)
trans/cisa
(react. time)
trans/cisc
(react. time)
3
3
3
a
b
c
70/30
73/27
70/30
53 (60 h)
70 (20 h)
60 (74 h)
73/27
75/25e
>99/<1
55d (1 h)
68 (0.5 h)
60 (0.5 h)
67/33
65/35f
68/32g
55 (1 h)
65 (0.5 h)
55 (0.5 h)
a
On the basis of the yield of the isolated isomers. b Yield of products isolated by column chromatography. c By capillary GC analysis
d
e
of the crude reaction mixture. The bridged lactone 6a (6%) was also obtained. After 50 h the mixture of trans- and cis-isomers is
converted to 100% trans-isomer. f After 60 h the mixture of trans- and cis-isomers is converted to 100% trans-isomer. g After 20 h the
mixture of trans- and cis-isomers is converted in 100% trans-isomer.
Sch em e 2
F igu r e 1. Different macrolactonic structures that account for
1
stereochemical assignments on the basis of H NMR spectra.
From a stereochemical point of view, data in Table 1
indicate that a thermal equilibration is more readily
attained at the same temperature in a polar solvent such
as benzonitrile than in an apolar one (decalin). Thus,
while the pure trans isomer is obtained in 30 min in
benzonitrile, it takes 20 h for the 70:30 mixture obtained
from decalin to reach complete isomerization.1 Such an
isomerization can take place through C-8H epimerization
4
(
R to the carbonyl group), which would be easier in more
15
polar solvents.
Anyway, the trans compound is as-
sumed to be the thermodynamically favored isomer, a
reasonable assumption considering that it corresponds
to the all equatorial situation.16
The stereochemistry of the cycloadducts 4a -c and
1
5
a -c was assigned on the basis of their H NMR spectra,
produced. In the lower boiling solvent (bp 111 °C) the
reaction remains under kinetic control, determined by
the interactions between HOMO and LUMO coefficients
that prevent the formation of the bridged lactone. On
the other hand, unexpected regioisomer 6a was obtained
in benzonitrile (bp 191 °C). This product probably stems
from some mechanistic leakage in the concerted pathway.
Polarization of both diene and dienophile are indeed
matched and opposed to this regiodirection. A side
diradical mechanism is therefore possible which would
compete, in the less favorable situations, with the main
concerted route.1 On the contrary, trienes 3b and 3c
undergo regioselective cycloaddition and afford, in all
three solvents, the corresponding fused macrocycles. In
these cases, the regioselective outcome can be ascribed
to the effect of buttressing11 of the methyl substituents
on the bridge which tends to hold the diene and the
dienophile closer to each other, enhancing both regiose-
lectivity and rate (compare reaction time for 3b with that
for 3a ).12 When diene and dienophile are forced closer
by the gem-dimethyl groups, the tether “acts” shorter and
the cyclization mode which would give the bridged
considering the patterns of the bridgehead protons, C-1H
and C-8H (Figure 1). Albeit conformational analysis of
floppy bicycles, based on single NMR coupling constant
is risky,17 we have been able to consider three different
1
cases in these systems (Figure 1A-C). The H NMR
coupling constants have been measured precisely after
complete attribution of the signals, thanks to COSY and
eventually NOESY experiments. In the case of trans
ring-junctions (Figure 1A, compounds 5a -c), both con-
necting atoms of the lactonic ring can adopt a (pseudo)
equatorial orientation. Therefore both C-1H and C-8H
are axial and the C-8H coupling pattern displays a large
triplet (J g 9.5 Hz) in all cases (C-8H (5a ) ) 2.53 ppm;
C-8H (5b) ) 2.81 ppm; C-8H (5c) ) 2.75 ppm). In the
cis ring-junction situation, two conformations are to be
considered whether it is the carbonyl or the oxygen that
is in an axial orientation. In the first case (Figure 1B),
C-8H is equatorial, no large coupling constant is mea-
0
(13) The physicochemistry underlying the gem-dialkyl effect in
intramolecular Diels-Alder reaction has been studied: (a) J ung, M.
E.; Gervay, J . J . Am. Chem. Soc. 1991, 113, 224. (b) Giessner-Pretter,
C.; Huckel, S.; Maddaluno, J .; J ung, M. E. In preparation.
(14) We have checked that the primary 67:33 mixture obtained from
decalin isomerizes quickly when placed into refluxing benzonitrile.
1
3
adducts is prohibitively strained.
(
15) We thank one of the referees for this suggestion. A retro-Diels-
(
(
10) Wilker, S.; Erker, G. J . Am. Chem. Soc. 1995, 117, 10922.
11) Wilson, S. R.; Mao, D. T. J . Am. Chem. Soc. 1978, 100, 6289.
Alder sequence can also be evoked. See in relation: Zylber, J .; Tubul,
A.; Brun, P. Tetrahedron Asymm. 1995, 6, 377.
Taber, D. F.; Saleh, S. A. J . Am. Chem. Soc. 1980, 102, 5085.
Boeckman, R. K., J r.; Ko, S. S. J . Am. Chem. Soc. 1982, 104, 1033.
(16) Posner, G. H.; Cho, C.-G.; Anjeh, T. E. N.; J ohnson, N.; Horst,
R. L.; Kobayashi, T.; Okano, T.; Tsugawa, N. J . Org. Chem. 1995, 60,
4617, and references therein.
(12) The gem-dialkyl effect in seven to eleven-membered ring
clousure by iodolactonization has also been observed: Simonot, B.;
Rousseau, G. Tetrahedron Lett. 1993, 34, 4527.
(17) Danishefsky, S.; Yan, C. F.; Singh, R. K.; Gammill, R. B.; Mc
Curry, P. M.; Fritsch, M.; Clardy, J . J . Am. Chem. Soc. 1979, 101, 7001.

Notes
J . Org. Chem., Vol. 61, No. 21, 1996 7599
sured, and its signal appears as a multiplet, even at 500
MHz. This is the case for 4b (C-8H ) 2.73 ppm). In the
second case (Figure1C), C-8H is axial and thus presents
a relatively large axial-axial coupling constant of 12.8
Hz for 4a (C-8H ) 2.71 ppm) and of 7.9 Hz for 4c (C-8H
H, m), 2.53 (1 H, dt 3.7, 14.2 Hz), 3.40-3.75 (2 H, m), 4.00-
4
.15 (1 H, m), 4.10-4.35 (2 H, m), 5.85 (1 H, m), 5.95 (1 H, m);
trans-ring junction relationship, corresponding to the exo-
approach; 13C NMR (50 MHz, CDCl
) δ 16.3, 25.1, 25.1, 44.6,
0.3, 64.1, 71.1, 124.5, 132.7, 172.7. Anal. Calcd for C10
C, 65.92; H, 7.74. Found: C, 65.85, H, 7.70.
,4-Dim eth yl-2,6-d ioxa bicyclo[6.4.0]-1rH,8rH-d od ec-11-
en -7-on e (4b): white needles (light petroleum ether/Et O), mp
3
6
14 3
H O :
)
2.63 ppm). The preference for B or C type conforma-
4
tion in such cis-fused systems, probably depends on small
steric and/or stereoelectronic factors of which clarification
lies beyond the scope of this study.
The suggested cis-bridged structure of macrolactone 6a
was deduced from the large coupling constant value of
C-1H (4.21 ppm; J ) 15.7 Hz), and of C-8H (2.52 ppm; J
2
•+
114-116 °C; MS (EI, 70 eV): m/z (relative intensity): 210 (M
,
)
1
8
), 80 (87), 79 (76), 69 (33), 55 (100); H NMR (500 MHz, CDCl
3
δ 0.73 (3 H, s), 1.13 (3 H, s), 1.82 (1 H, m), 1.95 (2 H, m), 2.32 (1
H, m), 2.73 (1 H, m), 3.34 (1 H, d, 11.8 Hz), 3.59 (1 H, d, 11.8
Hz), 4.04 (1 H, d, 12.7 Hz), 4.20 (1 H, m), 4.26 (1 H, d, 12.7 Hz),
5
.72 (1 H, dm, 8.9 Hz), 5.92 (1 H, dm, 8.9 Hz); cis-ring junction
1
3
)
10.2 Hz), measured at 500 MHz in C
the two protons both occupy axial positions.
6
D
6
, that indicate
relationship, corresponding to the endo-approach; C NMR (50
MHz, CDCl ) δ 19.5, 22.7, 23.6, 23.7, 38.9, 38.9, 75.5, 75.5, 78.3,
25.8, 131.3, 177.2. Anal. Calcd for C12 : C, 68.55; H, 8.63.
Found: C, 68.40; H, 8.70.
,4-Dim eth yl-2,6-d ioxa bicyclo[6.4.0]-1âH,8rH-d od ec-11-
en -7-on e (5b): pale orange oil; MS (EI, 70 eV): m/z (relative
3
1
18 3
H O
Exp er im en ta l Section
4
All compounds of commercial origin were ACS grade reagents.
•+
1
2
-(Prop-2-enyl)-1,3-dioxane (1a ), 2-(5,5-dimethylprop-2-enyl)-1,3-
intensity) 210 (M , 18), 141 (39), 79 (39), 55 (100); H NMR (500
MHz, CDCl ) δ 0.89 (3 H, s), 0.91 (3 H, s), 1.85 (2 H, m), 2.05 (2
dioxane (1b), and 5,5-dimethyl-2-(2-methylprop-1-enyl)-1,3-di-
oxane (1c) were prepared in anhydrous toluene according to
standard procedure using a Dean-Stark trap in the presence
of PPTS. Starting reagents were crotonaldehyde and propane-
3
H, m), 2.81 (1 H, dt, 5.2, 9.5 Hz), 3.04 (1 H, d, 12.7 Hz), 3.53 (1
H, d, 12.7), 3.66 (1 H, d, 11.9), 3.97 (1 H, m), 4.45 (1 H, d, 11.9
Hz), 5.58 (1 H, ddd, 10.1, 4.1, 1.8 Hz), 5.78 (1 H, dm, 10.1 Hz);
trans-ring junction relationship, corresponding to the exo-
1
,3-diol for acetal 1a (or 2,2-dimethylpropane-1,3-diol, case 1b),
approach; 13C NMR (50 MHz, CDCl
) δ 20.8, 21.8, 24.0, 24.3,
38.9, 42.5, 72.7, 75.9, 80.9, 126.6, 129.2, 176.6. Anal. Calcd for
: C, 68.55; H, 8.63. Found: C, 68.45; H, 8.73.
4,4,11-Tr im eth yl-2,6-d ioxa bicyclo[6.4.0]-1rH,8rH-d od ec-
11-en -7-on e (4c): white needles (light petroleum ether / Et O),
mp 99-102 °C; MS (EI, 70 eV): m/z (relative intensity) 224 (M
and 3-methylbut-2-enal and 2,2-dimethylpropane-1,3-diol for
acetal 1c. Preparative column chromatography was carried out
on Merck silica gel 60 with diethyl ether-light petroleum ether
3
12 18 3
C H O
(
bp 30-60 °C) as an eluant. Melting points are uncorrected
Rep r esen ta tive P r oced u r e for th e Syn th esis of 4a -6a .
2
•
+
Sublimed t-BuOK (1.68 g, 15.0 mmol), 1a (1.28 g, 10.0 mmol),
and n-BuLi (9.4 mL, 1.6 M, 15.0 mmol) were consecutively added
with stirring to anhydrous THF (10 mL) at -95 °C, under argon.
After a few seconds the solution turned purple and was stirred
at -95 °C for 2 h. After this time the reaction was quenched
,
1
16), 94 (80), 79 (87), 69 (73) 55 (100); H NMR (500 MHz, CDCl
3
)
δ 0.70 (3 H, s), 1.12 (3 H, s), 1.68 (3 H, s), 1.75-2.00 (3 H, m),
2.15 (1 H, br d, 14.7 Hz), 2.63 (1 H, dm, 7.9 Hz), 3.31 (1 H, d,
12.5 Hz), 3.57 (1 H, d, 12.5 Hz), 4.01 (1 H, d, 10.9 Hz), 4.16 (1
H, m), 4.25 (1 H, d, 11.3 Hz), 5.46 (1 H, br s); cis-ring junction
relationship, corresponding to the endo-approach; 1 C NMR (50
with a THF solution of H
2
O (5 mL), and the color was discharged.
3
The mixture was poured into water, the organic phase was
separated, and the aqueous phase was extracted twice with
diethyl ether (50 mL). The combined organic phases were
3
MHz, CDCl ) δ 19.8, 22.9, 23.5, 23.8, 28.8, 39.1, 44.0, 75.6, 75.6,
79.4, 120.9, 139.8, 177.8. Anal. Calcd for C13
H, 8.99. Found: C, 69.40; H, 8.90.
20 3
H O : C, 69.61;
2 4
washed with brine, dried (Na SO ), and concentrated to give
1
crude 2a (1.0 g, 80%). H NMR and GC analyses of the reaction
mixture indicate that the dienes 2a , 2b, and 2c are obtained
nearly pure and can be used without any further purification.
4
,4,11-Tr im eth yl-2,6-d ioxa bicyclo[6.4.0]-1âH,8rH-d od ec-
1
1-en -7-on e (5c): pale orange oil; MS (EI, 70 eV): m/z (relative
•+
1
intensity) 224 (M , 14), 141 (40), 79 (25), 69 (45), 55 (100); H
NMR (500 MHz, CDCl ) δ 0.89 (3 H, s), 0.91 (3 H, s), 1.67 (3 H,
s), 1.80-2.05 (4 H, m), 2.75 (1 H, dt, 4.4, 9.5 Hz), 3.03 (1 H, d,
2.8 Hz), 3.52 (1 H, d, 12.8 Hz), 3.65 (1 H, d, 11.9 Hz), 3.94 (1
H, bd, 9.5 Hz), 4.45 (1 H, d, 11.9 Hz), 5.30 (1 H, br s); trans-ring
2
a (0.64 g, 5.0 mmol) was dissolved in Et
with H CdCHCOCl (0.90 g, 10.0 mmol), in the presence of
pyridine (0.87 g, 11.0 mmol) at 25 °C. After 10 min, the reaction
mixture was treated with 5% aqueous NaHCO (15 mL). The
2
O (50 mL) and treated
3
2
1
3
two phases were separated, and the aqueous phase extracted
with diethyl ether (50 mL). The combined organic phases were
13
junction relationship, corresponding to the exo-approach;
NMR (50 MHz, CDCl ) δ 20.9, 21.9, 22.8, 24.7, 29.0, 39.0, 42.7,
2.7, 75.9, 81.6, 123.1, 137.5, 178.9. Anal. Calcd for C13
C, 69.61; H, 8.99. Found: C, 69.70; H, 9.05.
,6-Dioxa bicyclo[6.3.1]-1âH,8âH-d od ec-10-en -7-on e (6a ):
C
3
then washed with brine (15 mL), dried (K
concentrated to give crude 3a . The reaction mixture was
purified by column chromatography (Et O:light petroleum ether,
0:70) affording pure triene 3a (0.64 g, 70%). A solution of 3a
0.36 g, 1.98 mmol) in benzonitrile (5.0 mL) was refluxed under
argon, in the presence of hydroquinone. After 1 h the solvent
was removed in vacuo and, after column chromatography (Et O:
2 3
CO ), filtered, and
7
20 3
H O :
2
2
3
(
•+
pale orange oil; MS (EI, 70 eV): m/z (relative intensity) 182 (M
,
4), 113 (100), 80 (24), 79 (42), 77 (20); 1H NMR (200 MHz,
1
CDCl ) δ 1.88 (2 H, pent, 6.0 Hz), 2.20-2.50 (1 H, m), 2.25 (1 H,
m), 2.45 (1 H, m), 3.68 (2 H, t, 6.0 Hz), 4.31 (2 H, t, 6.0 Hz), 6.05
1 H, dd, 8.0, 5.0 Hz), 6.14 (1 H, dt, 8.0, 3.5 Hz), 6.98 (1 H, dd,
3
2
light petroleum ether, 5:95), 4a (0.05 g, 14%), 5a (0.14 g, 39%),
and 6a (0.02 g, 6%) were isolated.
(
5
1
1
.0, 1.5 Hz); H NMR (500 MHz, C
6 6
D ) δ 1.65-1.80 (4 H, m),
2
,6-Dioxa bicyclo[6.4.0]-1rH,8rH-d od ec-11-en -7-on e (4a ):
.70 (2 H, pent, 6.18 Hz), 2.00 (1 H, dtm, 2.8, 10.2 Hz), 2.52 (1
•+
pale orange oil; MS (EI, 70 eV): m/z (relative intensity) 182 (M
), 113 (93), 80 (23), 79 (31), 55 (100); H NMR (200 MHz, CDCl
,
H, dt, 10.2, 1.3 Hz), 3.51 (2 H, t, 6.03 Hz), 4.21 (1 H, dt, 15.7,
.3 Hz), 4.29 (2 H, t, 6.23 Hz), 5.87 (2 H, m); cis-bridged
1
1
3
)
6
δ 1.59 (1 H, m), 1.55-1.85 (2 H, m), 2.05-2.25 (2 H, m), 2.18 (1
H, m), 2.71 (1 H, ddd, 3.4, 4.9, 12.8 Hz), 3.53 (1 H, dd, 6.9, 10.9),
13
structure; C NMR (125 MHz, CDCl
9.9, 61.9, 66.5, 124.6, 134.5, 168.6. Anal. Calcd for C10
C, 65.92; H, 7.74. Found: C, 65.98, H, 7.77.
3
) δ 15.9, 21.4, 23.5, 32.6,
5
14 3
H O :
3
(
.87 (1 H, ddd, 5.5, 10.6, 12.1), 4.13 (1 H, m), 4.21 (1 H, m), 4.74
1 H, dd, 6.9, 10.9 Hz), 5.72 (1 H, dm, 8.9 Hz), 5.92 (1 H, dm, 8.9
Hz); cis-ring junction relationship, corresponding to the endo-
1
3
Ack n ow led gm en t. This work was supported by
grants from Italian CNR, MURST, and “Progetto Stra-
tegico Tecnologie Chimiche”. We wish to warmly thank
Miss Isabelle Salliot (Universit e´ de Rouen) for excellent
expertise with 500 MHz NMR.
approach; C NMR (50 MHz, CDCl
4.1, 72.2, 79.3, 126.3, 131.3, 176.2. Anal. Calcd for C10
C, 65.92; H, 7.74. Found C, 65.98, H, 7.80.
,6-Dioxa bicyclo[6.4.0]-1âH,8rH-d od ec-11-en -7-on e (5a ):
pale orange oil; MS (EI, 70 eV): m/z (relative intensity): 182
3
) δ 16.7, 24.0, 30.2, 45.2,
6
14 3
H O :
2
•
+
1
(M
, 2) 113 (100), 80 (18), 79 (28), 55 (64); H NMR (200 MHz,
CDCl ) δ 1.80-1.95 (2 H, m), 1.90-2.05 (2 H, m), 2.05-2.30 (2
3
J O960876H