Stereocontrolled Synthesis and Cycloaddition of 1,4-Dialkoxy 1,3-Dienes

Article abstract of DOI:10.1021/jo980321h

An efficient and stereocontrolled access to 1(Z),3(E)-1,4-dialkoxybutadienes is described that relies on a base-induced conjugated elimination reaction on γ-alkoxy or aryloxy α,β-unsaturated acetals. The dienes have then been applied in [4 + 2] cycloaddition reactions where they demonstrate a good thermal reactivity toward activated dienophiles. Despite the 1,4-competition between oxygenated groups, both regio- and endoselectivities are total. A set of experiments has led to the conclusion that tfe (1Z,3E) pattern is responsible for these high stereocontrols. Several chiral alkoxy dienes have also been prepared following the same route. Their thermal cycloaddition with N-methylmaleimide leads to corresponding adducts in good yields and with total endoselectivities, but modest diastereoisomeric excess.

Full text of DOI:10.1021/jo980321h

5110
J . Org. Chem. 1998, 63, 5110-5122
Ster eocon tr olled Syn th esis a n d Cycloa d d ition of 1,4-Dia lk oxy
1,3-Dien es
Anne Guillam,† Lo¨ıc Toupet,‡ and J acques Maddaluno*,†
Laboratoire des Fonctions Azote´es & Oxyge´ne´es Complexes de l'IRCOF, UPRES-A 6014 CNRS, Faculte´
des Sciences, Universite´ de Rouen, 76821-Mont St Aignan Cedex, France, and Groupe de Matie`re
Condense´e et Mate´riaux, UMR 6626 CNRS, Universite´ de Rennes I, 35042-Rennes Cedex, France
Received February 20, 1998
An efficient and stereocontrolled access to 1(Z),3(E)-1,4-dialkoxybutadienes is described that relies
on a base-induced conjugated elimination reaction on γ-alkoxy or aryloxy R,â-unsaturated acetals.
The dienes have then been applied in [4 + 2] cycloaddition reactions where they demonstrate a
good thermal reactivity toward activated dienophiles. Despite the 1,4-competition between
oxygenated groups, both regio- and endoselectivities are total. A set of experiments has led to the
conclusion that the (1Z,3E) pattern is responsible for these high stereocontrols. Several chiral
alkoxy dienes have also been prepared following the same route. Their thermal cycloaddition with
N-methylmaleimide leads to corresponding adducts in good yields and with total endoselectivities,
but modest diastereoisomeric excess.
In tr od u ction
dialkoxy diene synthesis rely either on a stereospecific,
but synthetically rather unpractical, strategy11 or on a
stereouncontrolled approach.12 Several authors also
insist on the mediocre stability of these compounds due
to their sensitivity to polymerization and dioxygen.11b,13,14
The purification and separation of 1,4-dialkoxy dienes
are thus described as tedious or even “exceedingly dif-
ficult”.11b,12c Finally, the comparable reactivity of their
E,E and Z,E isomers further frustrates their applications
to cycloadditions since the adducts obtained are a mixture
of stereoisomers when the configuration of the dienic
precursors is not controlled.9a,12b,c
The conjugate elimination of an alcohol molecule from
R,â-unsaturated acetals such as ethyl acetal of crotonal-
dehyde or senecialdehyde has been known for a long
time15 but has received little attention,16 probably be-
cause of the limited functionalization of the dienes
originally prepared by this method. We have extended
these results to corresponding γ-(arylthio) R,â-unsatur-
ated acetals and obtained 1-(arylthio)-4-methoxy 1,3-
dienes with fair to good stereocontrol of the double bonds
The versatile Diels-Alder [4 + 2] cycloaddition is an
asset in the organic chemist’s toolbox because of the
simultaneous setting of ring(s), asymmetric centers, and
functional groups it triggers.1 A sustained interest for
synthetic routes to functionalized 1,3-dienes2 is observed
in the literature where a special emphasis is put on
dienes bearing heteroatom substituents. Henceforth to
be ranked among the “classic” building blocks is the most
widely used member of this class, 1-methoxy-3[(trimeth-
ylsilyl)oxy]butadiene (Danishefsky’s diene),3 which has
been given a key part in several elegant routes to natural
products4 and glycals.5 The corresponding 1,4-dialkoxy
dienes have been much less studied, despite a comparably
appealing synthetic potential. They are indeed direct [4
+ 2] precursors of the 3,6-disubstituted cyclohexenic
structure found in conduritols, a new class of glycosidase
inhibitors.6 These cyclohexenes are also powerful syn-
thons7 and key intermediates in the synthesis of various
bioactive compounds8 such as carbohydrate analogues9
and cyclitols.10 Actually, the few papers dealing with 1,4-
(10) Review: (a) Hudlicky, T. Chem. Rev. 1996, 96, 3. See also: (b)
J ung, P. M. J .; Motherwell, W. B.; Williams, A. S. Ibid. 1997, 97, 1283.
(11) (a) Meister, H. Chem. Ber. 1963, 96, 1688. (b) Scheeren, J . W.;
Marcelis, A. T. M.; Aben, R. W.; Nivard, R. J . J . R. Neth. Chem. Soc.
1975, 94, 196. (c) Keana, J . F. W.; Eckler, P. J . Org. Chem. 1976, 41,
2625. (d) Kirmse, W.; Scheidt, F.; Vater, H. J . J . Am. Chem. Soc. 1978,
100, 3045. (e) Duke, R. K.; Rickards, R. W. J . Org. Chem. 1984, 49,
1898. (f) Harvey, D. F.; Neil, D. A. Tetrahedron 1993, 49, 2145. (g)
Virgili, M.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron Lett.
1997, 38, 6921.
(12) (a) Boeckman, R. K., J r.; Dolak, T. M.; Culos, K. O. J . Am.
Chem. Soc. 1978, 100, 7098. (b) Hiranuma, H.; Miller, S. I. J . Org.
Chem. 1982, 47, 7, 5083. (c) Hiranuma, H.; Miller, S. I. J . Org. Chem.
1983, 48, 3096. (d) Vatele, J . M. Tetrahedron 1986, 42, 4443.
(13) Clennan, E. L.; L’Esperance, R. P. J . Am. Chem. Soc. 1985, 107,
5178.
† Universite´ de Rouen.
‡ Universite´ de Rennes I.
(1) Carruthers, W. Cycloaddition Reactions in Organic Synthesis;
Pergamon Press: Oxford, 1990.
(2) (a) Petrzilka, M.; Grayson, J . I. Synthesis 1981, 753. (b)
Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction; Wiley:
New York, 1990.
(3) Danishefsky, S.; Kitahara, T. J . Am. Chem. Soc. 1974, 96, 7807.
(4) See inter alia: (a) Danishefsky, S.; Kitahara, T.; Yan, C. F.;
Morris, J . J . Am. Chem. Soc. 1979, 101, 6996. (b) Danishefsky, S. Acc.
Chem. Res. 1981, 14, 400. (c) Danishefsky, S.; Barbachyn, M. J . Am.
Chem. Soc. 1985, 107, 7761. (d) Bao, J .; Dragisich, V.; Wenglowsky,
S.; Wulff, W. D. J . Am. Chem. Soc. 1991, 113, 9873.
(5) Review: Danishefsky, S. J .; Bilodeau, M. T. Angew. Chem., Int.
Ed. Engl. 1996, 35, 1380.
(6) Review: Balci, M. Pure Appl. Chem. 1997, 69, 97.
(7) (a) Ba¨ckvall, J . E.; Bystro¨m, S. E.; Nordberg, R. E. J . Org. Chem.
1984, 49, 4619. (b) Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J .
Am. Chem. Soc. 1995, 117, 9662.
(8) See inter alia: (a) Trost, B. M.; Pulley, S. R. J . Am. Chem. Soc.
1995, 117, 10143. (b) Miller, M. W.; J ohnson, C. R. J . Org. Chem. 1997,
62, 1582. (c) Acen˜a, J . L.; Arjona, O.; Plumet, J . J . Org. Chem. 1997,
62, 3360.
(14) The 1,4-dialkoxy dienic pattern has, however, been found in
fungicides of natural origin: Zapf, S.; Werle, A.; Anke, T.; Klosterm-
eyer, D.; Steffan, B.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1995,
34, 196.
(15) Mioskowski, C.; Manna, S.; Falck, J . R. Tetrahedron Lett. 1984,
25, 519.
(16) See, however: (a) Venturello, P. J . Chem. Soc., Chem. Commun.
1992, 1032. (b) Prandi, C.; Venturello, P. J . Org. Chem. 1994, 59, 3494
and 5458. (c) Prandi, C.; Venturello, P. Tetrahedron 1994, 50, 12463.
(d) Mason, P. H.; Emslie, N. D. Tetrahedron 1995, 51, 2673.
(9) (a) David, S.; Eustache, J . J . Chem. Soc., Perkin Trans. 1 1979,
2230. (b) Schmidt, R. R. Acc. Chem. Res. 1986, 19, 250.
S0022-3263(98)00321-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/08/1998

Synthesis and Cycloaddition of 1,4-Dialkoxy 1,3-Dienes
J . Org. Chem., Vol. 63, No. 15, 1998 5111
Sch em e 1
Sch em e 2
Ta ble 1. Rea ction Con d ition s for th e Syn th esis of
γ-Alk oxy Aceta ls 3-7
The γ-alkoxy acetals are prepared by condensation of
the corresponding alcoholates onto either the bromo or
chloro acetals 1 or 2. Depending on both the nature of
the alcoholate employed and that of the starting acetal,
different procedures have been developed that are sum-
marized in Table 1. The γ-alkoxy acetals are obtained
from sodium or potassium alcoholates in various solvents.
Nucleophilic substitutions on bromo acetal 1 are signifi-
cantly more rapid than on chloro acetal 2. However, this
latter remains a good substrate provided more drastic
conditions (such as addition of 20% HMPA to the THF
medium or switching from sodium to potassium alcoho-
lates in pure THF) are employed. The strong basicity of
these alcoholates has led us to add slowly the alcoholate
in solution to the halo acetal, the reverse procedure
leading to a competitive deprotonation reaction (vide
infra). Finally, γ-(aryloxy) acetals 4 are simply prepared
by vigorous stirring of a heterogeneous mixture of acetals
1 or 2 in THF and aqueous sodium phenolate. The
configuration of the double bond in all acetals 3-7 is
unaltered after substitution: while linear 3a and 4a are
obtained in their pure E form, branched 3b, 4b, 5, and 7
E/Z configurations vary between 70:30 and 80:20, de-
pending on that of chloro precursor 2.
a
b
Prepared from (-)-menthol. Prepared from (-)-8-phenylm-
enthol.
(Scheme 1).17 When opposed to various classical dieno-
philes, these sulfurized dienes exhibited a relatively
modest reactivity,17b probably because of the well-known
deactivating effect exerted by sulfur on this type of
compound.18 We thus decided to extend this methodology
to the synthesis of 1,4-dialkoxy dienes, expected to be
much more reactive compounds,1,2,19 following the same
approach.
Albeit pure enough to be used directly, these acetals
can stand a flash chromatography on silica gel. Men-
thoxy ether 6 tends to decompose slowly, even in the
freezer, leading to a mixture of dienes, as discussed
below. It still can be chromatographed in the presence
of triethylamine in 54% yield.
The encouraging preliminary results20 we have ob-
tained prompted us to extend this work to a larger family
of γ-oxygenated acetals and to the study of the reactivity
of the corresponding dienes.
Syn th esis of Dien es 8-15 a n d 17. The γ-oxygenated
acetals prepared above have then been submitted to
δ-elimination reactions following different experimental
procedures (Schemes 3 and 4). Both n-butyllithium
(method A) and potassium hexamethyldisilylamide (KH-
MDS, method B) deprotonate these compounds and
trigger the conjugated-elimination reaction. Catalytic
amounts of alkyllithium or KHMDS are uneffective since
they generate lithium or potassium methylate in the
medium and are not basic enough to deprotonate 3-7.
The same observation has already been made for the
corresponding thioethers.17 For acetals 3-5, the 1,4-
dienol diethers 8-11 are selectively recovered in high
yields and good stereocontrol, the 1Z,3E isomer being the
major one in all cases (Scheme 3 and Table 2). The
configuration of both double bonds could be established
either by direct measurement of coupling constants (for
butadienoids) or through a set of NOE and NOESY
experiments (for isoprenoids).
Resu lts a n d Discu ssion
P r ep a r a tion of Aceta ls 3-7. The required precur-
sors, viz. the R,â-unsaturated acetals 3-7, can be
prepared from γ-bromo acetal 1, obtained itself in two
steps from crotonaldehyde,17a or from industrial γ-chloro
acetal 2, a very convenient precursor21 for the isoprenoid
structures (Table 1 and Scheme 2). While 1 is obtained
under its pure E form, 2 is delivered as a ∼75:25 E/Z
mixture of isomers.
(17) (a) Gaonac’h, O.; Maddaluno, J .; Chauvin, J .; Duhamel, L. J .
Org. Chem. 1991, 56, 4045. (b) Maddaluno, J .; Gaonac’h, O.; Marcual,
A.; Toupet, L.; Giessner-Prettre, C. J . Org. Chem. 1996, 61, 5290.
(18) Branchadell, V.; Sodupe, M.; Ortuno, R. M.; Oliva, A.; Gomez-
Pardo, A.; Guingant, A.; D’Angelo, J . J . Org. Chem. 1991, 56, 4135.
(19) Kahn, S. D.; Pau, C. F.; Overman, L. E.; Herhe, W. J . J . Am.
Chem. Soc. 1986, 108, 7381.
(20) (a) Maddaluno, J .; Gaonac’h, O.; Le Gallic, Y.; Duhamel, L.
Tetrahedron Lett. 1995, 36, 8591. (b) Guillam, A.; Maddaluno, J .;
Duhamel, L. J . Chem. Soc., Chem. Commun. 1996, 1295.
(21) Industrial intermediate from Rhoˆne-Poulenc Chimie.
Let us now consider the case of menthyl derivative 6.
Its treatment by n-BuLi leads, as above, to a regioselec-
tive δ-elimination of methanol, providing chiral diene 12
(Scheme 4). Here again, 12 is obtained almost exclu-
sively under its 1Z,3E configuration. Interestingly,

5112 J . Org. Chem., Vol. 63, No. 15, 1998
Guillam et al.
Ta ble 2. Ster eoch em ica l Ra tios of Va r iou s Iosm er s of Dien es 8-15 a s a F u n ction of th e Elim in a tion Con d ition s
(Meth od s A-D)
a
b
d
The configuration of the 1,2 double bond is 100% E. n-BuLi, -40 °C, THF. c KHMDS, rt, THF. DIPEA, TMSOTf, -40 °C then rt,
CH2Cl2. e Thermal cracking. f Configuration of the vinylic diene.
Sch em e 3
3). The pure 1E “allylic” diene 13 thus obtained is
relatively stable and does not need further purification.
This is worth emphasizing since 6 gives a 100% selective
access to dienes 12 or 13 by a simple base swap (Scheme
4, Table 2). Comparatively, 8-phenylmenthyl derivative
7 is not so easily deprotonated, probably because of the
steric hindrance around the allylic positions. It requires
the use of a large excess of base and warming the medium
to room temperature (BuLi) or to reflux of THF (KH-
MDS). A mixture of 1Z,3E vinylic 14 and 1E allylic 15
dienes is obtained in a 33:67 ratio with method A,
whereas pure 15 is recovered with method B. An achiral
set of comparable allylic dienes had been prepared
previously,22 but in relatively modest yields and stereo-
controls.
Sch em e 4
We then tried to put into evidence a possible role for
the metallic cation in this somewhat puzzling high 1,2-Z
selectivity. Acetal 4b was deprotonated following method
A modified by preloading the reaction medium with LiBr
or KI. No effect at all could be observed, either on the
chemical yield or on the stereoselectivity. The possible
role of THF could also be ruled out since slowly adding a
commercial solution of n-BuLi in hexanes to neat 4b
leads to the same 9b mixture. Similarly, adding 18-
crown-6 (1.7 to 5 equiv with respect to 4b) to the medium
in method B does not alter significantly the stereochem-
ical outcome. No impact of the original configuration of
the acetal 4b double bond on the stereoselectivity of this
reaction could be observed either; when treated by n-BuLi
under similar conditions, both (E)- and (Z)-4b, separated
by flash column chromatography, provide 9b in an
identical 1E,3E/1Z,3E ) 8:92 ratio by contrast with our
treatment of 6 by KHMDS (method B) triggers the
regioselective deprotonation of the methylene position,
this time in sharp contrast with acetals 3 and 4 (Scheme
(22) Mandai, T.; Osaka, K.; Kawagishi, M.; Kawada, M.; Otera, J .
J . Org. Chem. 1984, 49, 3595.

Synthesis and Cycloaddition of 1,4-Dialkoxy 1,3-Dienes
J . Org. Chem., Vol. 63, No. 15, 1998 5113
â-elimination step takes place in an anti fashion, the
antiperiplanar arrangement of one of the methoxy groups
with respect to the metal prefigures the 3,4-double bond
E configuration.
Within this mechanistic framework, the potassium
bases appeared of particular interest. A catalytic amount
of potassium tert-butylate in THF at rt is uneffective on
the usual E/Z mixture of 4b, but a stoicchiometric
amount of this same base leads to a mixture of enol ether
16, together with allylic diene 10 and a small amount
diene 9b (Scheme 6). Actually, the configuration of the
4b double bond turns out to be of prime importance this
time, for both the ratio and the stereochemistry of the
different products. Enol ether 16 is always the main
product, but the dominance of the Z isomer is dependent
on the E/Z configuration of 4b. Finally, we resorted to
nonmetallic bases. DBU (1.5 equiv, THF, Rfx, 12 h) does
not deprotonate 4b, whereas Schwesinger’s t-Bu-P4 base
(1 equiv, THF, rt, 1h), in which pKa in THF is reported
to be comparable to that of KHMDS,28 leads to a mixture
of enol ether 16 and diene 9b (Scheme 6), the Z isomer
still being the major product.
F igu r e 1. A1,2 and A1,3 allylic interactions in R,â-unsaturated
acetals.
Sch em e 5
The major (1Z) isomer of acetal 16 can be separated
by flash column chromatography. It undergoes a â-e-
limination when treated with n-BuLi in conditions simi-
lar to method A, leading in 95% yield to diene 9b in its
pure 1Z,3E configuration (Scheme 7).
own finding on corresponding thioethers17b and with
related works on unsaturated ethers by Schlosser et al.23
On a mechanistic point of view, it is worth noting that
the stereoselectivity of the deprotonation correlates to the
C-Y bond length (Scheme 5): while the sulfinyls (C-S
≈ 1.81 Å), seleninyls (C-Se ≈ 1.98 Å), and phosphonates
(C-P ≈ 1.87 Å) provide mainly the EE dienes,24 the
ethers (C-O ≈ 1.43 Å), alkyls (C-C ≈ 1.53 Å), and
amines (C-N ≈ 1.47 Å) favor the corresponding ZE
dienes.25 Such an observation could be explained within
the framework of an early transition-state hypothesis,
considering that the starting acetal conformation can
depend on the C-X bond length (Figure 1). We suppose
that long C-X bonds (X ) SR, PO(OEt)2, SeR) generate
A1,3 allylic strains in favor of the A-type conformations,
while short C-X bonds (X ) OR, NR2, alkyl) are at the
origin of A1,2 tensions avoided in B type conformations.
Coming back to the γ-oxygenated acetals 3-5, the very
first step of the conjugated elimination reaction is likely
to consist of a C1 deprotonation of the B-type conformer,
leading to a delocalized species (ion pair). The mesomeric
form placing the metal on C3 appears favored over its C1
counterpart since the chelation can involve both the
acetal function and the ether’s oxygen, thanks to the Z
double bond (Scheme 5). Such a stabilized allylic lithium
compound is supposed to favor some C-M covalency26
with a partial localization of the double bond.27 Depend-
ing on the metal, this latter chelation by the acetal has
been calculated to involve only one oxygen when M is a
lithium or both when M is a potassium.27 If the final
Efficient access to enol ethers from acetals by amine-
induced alcohol eliminations in the presence of a Lewis
acid has also been reported (method C).29 We have
applied Gassman et al.s original procedure to acetal 4b
in an attempt to get the corresponding conjugated
elimination. We observe in this case that the methylene
and methyl vinylic sites are now competing for deproto-
nation, leading to 9b in a 10:90 1E,3E/1Z,3E ratio
together with pure E allylic diene 10 (Scheme 8). At
room temperature in methylene chloride, the 9b/10 ratio
is 70:30. 10 can easily be separated by flash column
chromatography since it is relatively more stable than
its isomer 9b.
The A and B deprotonation-elimination procedures
can easily be converted to a multigram scale. On the
basis of NMR and GC data, dienes 8-15 obtained are
pure enough to be used as such. These oily compounds
are reasonably stable and keep for several days in the
freezer under argon in the absence of acidic traces.
Interestingly, the elimination reaction on acetals 3b and
4 also takes place upon heating (method D)30 or at room
temperature for 6, providing 8b, 9, and 12 as a complex
mixture of isomers (Scheme 9 and Table 2). The balanced
ratio does not seem to be due to a thermal equilibration
occurring between the species after the elimination
process, as indicated by warming an original 8:92 1E,3E/
1Z,3E mixture of diene 4b and recovering it unaltered.
Advantage has been taken of the configuration hetero-
(27) Fossey, J .; Ghigo, G.; Tonachini, G.; Venturello, P. Tetrahedron
1997, 53, 7937.
(23) Margot, C.; Matsuda, H.; Schlosser, M. Tetrahedron 1990, 46,
2430.
(24) (a) Sulfinyl: ref 17. (b) Seleninyl: Outurquin, F. Unpublished
results. (c) Phosphonyl: ref 20a.
(25) (a) Alkoxy: ref 20a, this work, and: Lanc¸ois, D.; Maddaluno,
J . Tetrahedron Lett. 1998, 39, 2335. (b) Alkyl: Deagostino, A. M.;
Maddaluno, J .; Mella, M.; Prandi, C.; Venturello, P. J . Chem. Soc.,
Perkin Trans. 1 1998, 881. (c) Amino: Martin, C.; Maddaluno, J .;
Duhamel, L. Tetrahedron Lett. 1996, 37, 8169.
(28) Schwesinger, R.; Schlemper, H. Angew. Chem., Int. Ed. Engl.
1987, 99, 1212.
(29) (a) Gassman, P. G.; Burns, S. J .; Pfister, K. B. J . Org. Chem.
1993, 58, 1449. (b) Saalfrank, R. W.; Hafner, W.; Markmann, J .; Welch,
A.; Peters, K.; von Schnering, H. G. Z. Naturforsch. B 1994, 49, 389.
(c) Dujardin, G. Rossignol, S.; Brown, E. Tetrahedron Lett. 1995, 36,
1653.
(30) (a) Duhamel, L.; Duhamel, P.; Ancel, J . P. Tetrahedron Lett.
1994, 35, 1209. (b) De Guigne´, C. Ph.D. Thesis, University of Rouen,
1997.
(26) Fraenkel, G.; Qiu, F. J . Am. Chem. Soc. 1997, 119, 3571.

5114 J . Org. Chem., Vol. 63, No. 15, 1998
Guillam et al.
Sch em e 6
Sch em e 7
Sch em e 10
Sch em e 8
8:92 1E,3E/1Z,3E ratio in 9b decreases to 25:75 in 17,
still in favor of the same isomer. Thus, it is not the
control of the 3,4 double bond, on which the alkyl
incorporation occurs, that is affected but the 1,2 bond.
When replacing tert-butyllithium by n-butyllithium, the
same regiocontrolled addition-elimination takes place
but leads, this time, to a complex mixture of at least three
stereoisomers, in agreement with our own previous
results on sulfurized dienes.17 Three main factors may
be evoked to justify this total regioselectivity viz. (i) the
configuration of the double bond (E vs Z), (ii) the nature
of the leaving group (MeO vs PhO), and (iii) the presence
of a methyl group in the 2 position (and not in the 3
position). We have not tried to determine the respective
influence of these parameters, but the partial loss in the
stereocontrol of diene 17 configuration may occur through
an addition-elimination mechanism32 leading to a lithi-
ated intermediate of poorly controlled geometry.
Cycloa d d ition s w ith N-Meth ylm a leim id e. The
papers describing cycloadditions of 1,4-dialkoxybuta-1,3-
dienes are scarce.9a,11a,e,12a-c,33 In those, stereoisomeric
mixtures of dienes have been opposed to various dieno-
philes, leading to several diastereoisomers and hamper-
ing a systematic study of the stereoselectivity of these
reactions. We decided to investigate successively the
reactivity of 8-15 with symmetrical (N-methylmaleim-
ide) and unsymmetrical (methyl acrylate) dienophiles to
probe the regioselectivity and endo/exo selectivities this
type of dienes can afford. The eventual diastereoselec-
tivity of the addition on the five different chiral dienes
11-15 onto N-methylmaleimide was then estimated.
Finally, the relative diastereoselectivities provided by the
1E,3E and 1Z,3E isomers of 12 could also be ascertained.
Let us first consider 1Z,3E dienes 9a ,b prepared
following method A (Table 2). Refluxing them in toluene
with 1.2 equiv of N-methylmaleimide (NMM) and small
amounts of hydroquinone33 yields the expected adducts
18a ,b in a few hours (Scheme 11).
Sch em e 9
geneity obtained thermally to evaluate the influence of
1E,3E and 1Z,3E stereochemistry on diastereoselectivity
and regioselectivity in cycloaddition reactions involving
these dienes (see below).
Finally, the elimination reaction may also be triggered
by catalytic amounts of acids, as reported for the corre-
sponding phenylthio acetals.31 For instance, a nonneu-
tralized CDCl3 solution of 6 is quantitatively converted
into 12 overnight at room temperature. But the 1E,3E/
1Z,3E ratio is 35:65, in fine agreement with our own
previous results in similar conditions.31 This reaction
also takes place on acetal 4b in the presence of small
amounts of an HCl/Et2O solution with a similar stereo-
selectivity. Once more, this balanced result does not
seem to be due to a postelimination equilibration phe-
nomenum, as checked by placing a 8:92 1E,3E/1Z,3E
mixture of 6 under the same conditions and recovering
it unchanged.
We have previously reported that an excess of alkyl-
lithium reagent or of lithium amide leads, in the case of
dienol thioethers, to the chemioselective substitution of
the methoxy group by the base itself.17 We have checked
the possible application of this reaction to diene 9b,
keeping in mind that the higher similarity between
methoxy and phenoxy groups was likely to jeopardize the
chemioselectivity. When 4b was treated with an excess
of tert-butyllithium at -70 °C and then room temperature
in ether, diene 17, in which the MeO group had been
substituted by a t-Bu, was recovered (Scheme 10).
Compound 17 is the only regioisomer obtained; it is
isolated in 55% yield after flash chromatography on silica
gel. From a configurational point of view, the original
(32) For the addition of alkyllithium on olefins, see inter alia: (a)
Glaze, W. H.; J ones, P. C. Chem. Commun. 1969, 1434. (b) Wei, X.;
Taylor, R. J . K. J . Chem. Soc., Chem. Commun. 1996, 187.
(33) Broekhuis, A. A.; Scheeren, J . W.; Nivard, R. J . F. Rec. J . R.
Neth. Chem. Soc. 1980, 99, 6.
(31) Gaonac’h, O.; Maddaluno, J .; Ple´, G.; Duhamel, L. Tetrahedron
Lett. 1992, 33, 2473.

Synthesis and Cycloaddition of 1,4-Dialkoxy 1,3-Dienes
J . Org. Chem., Vol. 63, No. 15, 1998 5115
F igu r e 2. Conformations of bicycles 18.
Sch em e 11
After flash chromatography, 18a ,b are recovered in
reasonable yields. The standard thermal conditions
applied to perform these reactions indicate the unfavor-
able 1Z,3E configuration of dienes 9 can be overcome by
their high reactivity in direct demand Diels-Alder ad-
ditions. As indicated in Scheme 11, the stereoisomers
derive from pure endo approaches, in fine agreement with
comparable situations.17b,34 NMR coupling constants as
well as a NOESY experiment further indicate these
bicyclic structures to adopt a convex boat-type folding
(Figure 2).
The trans relationship between methoxy and phenoxy
groups, imposed by the 1Z,3E configuration of the
original diene, puts the methoxy in an axial position and
the phenoxy in an equatorial one. This could be con-
firmed in the case of 18b by a single-crystal X-ray
analysis (Figure 3). The preference of such flexible
systems as 18 for convex conformations has been dis-
cussed lately.17b It is worth noticing, however, that while
the convex-boat flipping appears favorable to both 18a
and 18b (three equatorial vs one axial substituents) it
generates, for 18b, an unfavorable allylic A1,2 strain
between the vinylic methyl and equatorial allylic phenoxy
groups.
For further synthetic applications, the incorporation
of a chiral appendage onto those structures might be of
interest, albeit only a limited number of chiral dienes
have proved to act as efficient inductors in cycloaddition
reactions.35 We decided to evaluate the diastereoselec-
tivity that a Z-borne R-methylbenzyloxy, a menthyloxy,
or a phenylmenthyloxy group could induce in Diels-
Alder reactions. The availability of both 1Z,3E and
1E,3E isomers by the four methods presented above
allows the evaluation of the influence of the double bond
configuration on the relative reactivities and selectivities
F igu r e 3. ORTEP representation of adduct 18b.
of these isomers. Let us first discuss the case of 1Z,3E
isomers 11, 12, and 14. Those have been prepared from
acetals 5, 6, and 7, following method A. For consistency
with the above results, the retained dienophile is once
more NMM. The reaction takes place at reflux of THF
and the adducts 19-24, derived from dienes 11, 12, and
14, are obtained as a mixture of two isomers in each case
(Scheme 12). Strong similarities between NMR spectra
of these adducts and 18 indicate they all derive from pure
endo approaches. Therefore, the stereoheterogeneity in
19/20, 21/22, and 23/24 should stem from the control of
centers 1, 2, 3, and 6 relative to those of the chiral
moieties. The de measured directly on the crude spectra
are rather low, and the highest figure (42%) is obtained
in the case of the menthyl derivatives 21 and 22.36
Although phenylmenthyl was anticipated to behave as a
better inductor, the de for 23/24 is dramatically low. Both
diastereoisomers of R-methylbenzyloxy and menthyloxy
derivatives 19/20 and 21/22 were isolated by flash column
chromatography in respectable yields, whereas purifica-
tion of the phenylmenthoxy adducts 23/24 has not been
achieved because of a limited supply of starting material.
The absolute configuration of the major diastereoisomers
has not been determined. We thought that these modest
(34) Danishefsky, S.; Yan, C. F.; Singh, R. K.; Gammill, R. B.;
McCurry, P. M.; Fritsch, N.; Clardy, J . J . Am. Chem. Soc. 1979, 101,
7001.
(35) See, for instance: (a) Krohn, K. Organic Synhesis Highlights;
Verlag Chemie: Weinhein, 1990. (b) Winterfeld, E. Chem. Rev. 1993,
93, 827. (c) Gawley, R. E.; Aubey, J . Principles of Asymmetric Synthesis;
Pergamon Press: Oxford, 1996.
(36) Interestingly, 12 adds also to TCNE at -78 °C in CDCl3 and
exhibits a 50% de from NMR data.

5116 J . Org. Chem., Vol. 63, No. 15, 1998
Guillam et al.
Sch em e 12
Sch em e 14
Sch em e 13
results could, in part, be ascribed to the thermal activa-
tion conditions; we thus performed the reaction between
11 and NMM in methylene chloride at 20 °C under high
pressure (13 kbar). Disappointingly enough, the 21/22
ratio remained the same.
We finally decided to check the influence of the double-
bond configuration by reacting the 1E,3E isomer of
menthyl diene 12. When working with a 35:65 1E,3E/
1Z,3E mixture, the selective addition of the 1E,3E isomer
reaches completion in 1 day at room temperature in THF.
Two diastereoisomers 25 and 26 are also obtained in a
low 8% de this time, a frustrating result in regard to
those obtained with 2-methyl-1(E)-menthoxybuta-1,3-
diene,17b,37 but very related to values by Pericas and
collaborators.38 When heated to reflux for 2 days, the
cycloaddition of remaining (1Z,3E)-12 is obtained as
above with 42% de, and the four adducts are purified by
flash column chromatography. The EE isomer is, as
expected, more reactive than the ZE isomer, but the
induction exerted by the menthoxy moiety is much
weaker in the former case. Therefore, 1Z,3E dienes can
increase the efficiency of a chiral group provided this
latter is borne by the Z double bond.
At this stage, it was worth considering the reactivity
of the allylic dienes 13 and 15. We retained NMM to
evaluate the reactivity, the endo selectivity, and the
diastereoselectivity (induced by the chiral alkoxymethyl
group in the 3 position) this family of dienes could afford.
Actually, the addition takes place at rt in THF in a few
minutes to a few hours, leading in both 13 and 15 cases
to a mixture of two isomers only, 27/28 and 29/30,
respectively (Scheme 13). The flash chromatography
purification of these adducts, followed by NMR analysis,
indicates that all these additions take place through an
endo-type approach, the diastereoisomery steming from
the relative control of the newly formed asymmetric
centers with respect to those of the chiral moiety. When
the chiral moiety is a menthyl group (diene 13), the de
measured on the crude 27/28 mixture is 32%. With a
phenylmenthyl moiety (diene 15), it reaches 52% for 29/
30.
Cycloa d d ition s w ith Meth yl Acr yla te. Both endo
and regioselectivities are difficult to predict when methyl
acrylate is used as a dienophile. This latter is indeed
known for its modest endo performances,39 while the
competing influences of the oxygenated groups in its 1
and 4 positions should endorse diene 9b with a weak
electronic polarization.2b,19,40 Warming 9b with methyl
acrylate in toluene in a sealed tube (140 °C) with a trace
amount of hydroquinone leads to the cyclic adduct 31b
in 2 days (Scheme 14). It may be recovered, after
absorption of the partly polymerized reaction medium,
on silica gel followed by flash chromatography, in 71%
yield. A GC/MS and NMR study indicates a single isomer
to be obtained following a regio- and endo-controlled
approach. The same three factors evoked above, viz.
configuration of the double bond, nature of the alkoxy/
(39) Mellor, J . M.; Webb, C. F. J . Chem. Soc., Perkin Trans. 2 1974,
(37) Rotscheid, K.; Breitmaier, E. Synthesis 1989, 836.
(38) Virgili, P.; Perica`s, M. A.; Moyano, A.; Riera, A. Tetrahedron
1997, 53, 13427.
17.
(40) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: New York, 1976.

Synthesis and Cycloaddition of 1,4-Dialkoxy 1,3-Dienes
J . Org. Chem., Vol. 63, No. 15, 1998 5117
aryloxy group, and presence of a vinylic methyl substitu-
ent, can contribute to this selectivity and have been
probed separately through the set of experiments pre-
sented in Scheme 14.
We have first investigated the effect of the double-bond
configuration preparing diene 9b (1E,3E) by method D,
which provides a mixture containing 40% of this isomer.
At reflux of methyl acrylate (80 °C), it reacts almost
selectively to afford two stereoisomers corresponding to
the endo and exo adducts 32b/33b (in a 57:43 ratio) of
the same regioisomer. Therefore, and in the frame of this
regiocontrolled approach, the Z configuration of diene 9b
seems to be essential to the endo/exo selectivity. Next
were the origins of the regiodirectivity. To evaluate the
pure phenoxy vs methoxy effect, we prepared butadienic
9a (1E,3E) following method D, which provides 17% of
this isomer. Its higher reactivity leads to a reasonable
recovery of the corresponding adducts 32a /33a . Once
again, a lack of endocontrol is observed while the regio-
control remains total. This result indicates that the
methoxy group imposes its regiodirection over the phe-
noxy one, a difference that may originate from the
decreased contribution of the PhO oxygen lone pair to
the dienic system due to its involvement in the phenyl
ring conjugation. A related example of regiocompetition
has been reported recently.41 Thus, the vinylic methyl
group is not necessary to the regiocontrol. In addition,
a total endocontrol is recovered for 31a when switching
from (1E,3E)- to (1Z,3E)-9a and confirming the essential
role of the ZE configuration.
F igu r e 4. Endo and exo approaches of methyl acrylate onto
(1Z,3E) dienes 8 and 9.
Ta ble 3. AM1 Coefficien ts for th e HOMO of s-Cis (ZE)-
a n d (EE)-1,4-Dia lk oxybu ta d ien es 8 a n d 9
To supress the methoxy vs phenoxy effect, we then
prepared the 1,4-dimethoxybutadienes 8a and isoprenes
8b. Particularly, in diene 8b (1E,3E), the pure effect of
the vinylic methyl group is at work, leading to four
isomers 34, 35, 36, and 37 in a 42:34:18:6 ratio. These
compounds were purified but could not be separated by
flash column chromatography. The GC/MS and NMR
analysis on the mixture indicate that they correspond to
the combination of the regio and endo-exo approaches.
Therefore, the methyl substituent is unable to account
for the total regiocontrol observed in the case of 9b,42 and
the (1E,3E) configuration leads once more to a mixture
of endo and exo isomers. By contrast, the (1Z,3E)-8b
isomer selectively gives access to adduct 38. Finally,
1Z,3E diene 8a provides the pure Z vs E configurational
effect on the regioselectivity. Only one isomer, 39, is
detected that derives from a pure endo and regiocon-
trolled approach. Hence, the ZE configuration is suf-
ficient to steady both controls.
Two effects can be proposed to link endo selectivities
and ZE configuration. First, strong steric repulsions may
arise in the exo-type approach between the Z-borne
alkoxy group of the diene and the ester moiety of the
acrylate (Figure 4), whereas these interactions are avoided
in the endo approach. Second, the exo approach puts the
polar groups of both diene and dienophile in the same
half-space while the endo mode corresponds to a better
overall balance for the system.43
F igu r e 5. Electronic origin of (ZE) diene polarization.
observed orientations. The coefficients corresponding to
the C1 atomic orbital in the s-cis conformer’s HOMO are
indeed systematically larger than that for C4, favoring
the overlap between C1 and acrylate â-carbon (Table 3).
This trend is amplified in isoprenoid 9b, probably because
of the vinylic methyl contribution. Comparing the EE
to the ZE isomers clearly shows that the Z double bond
reinforces the 1,4-orbital disymmetry. The origin of the
decreased electronic contribution of the Z-borne alkoxy
group may be accounted for on a steric basis, considering
that the oxygen substituent is probably pushed off the
diene plane in the s-cis reactive conformer, preventing
the fine alignment of oxygen p-orbitals with those of the
sp2 carbons of the diene (Figure 5). The E-borne 4-meth-
oxy group should therefore be better conjugated than its
1-Z counterpart. Steric considerations can be added to
The orbitalar control of the Diels-Alder reaction
implies that the HOMO coefficients rule its regioselec-
tivity. We have thus undertaken a set of AM1 semiem-
pirical calculations for both EE and ZE isomers of dienes
8 and 9, and the results qualitatively account for the
(42) Isoprene itself is known for its modest regiodirectivity toward
methyl acrylate (Inukai, T.; Kojima, T. J . Org. Chem. 1971, 36, 924),
and the case of diene 8b opposed to juglone derivatives has also been
discussed in the literature (see ref 12a).
(41) Olsen, R. K.; Feng, X.; Campbell, M.; Shao, R. L.; Math, S. K.
J . Org. Chem. 1995, 60, 6025.
(43) We thank Dr. Andre´ Guingant (CNRS/Universite´ de Nantes)
for suggesting this hypothesis.

5118 J . Org. Chem., Vol. 63, No. 15, 1998
Guillam et al.
1450 cm-1; MS (EI, 0 eV), 2E isomer, m/z 128 (M•+ - 32, 30),
85 (64), 55 (100), 2Z-isomer, m/z 128 (M•+ - 32, 39), 85 (82),
55 (100); 1H NMR (200 MHz, CDCl3) δ (ppm) 2E isomer, 1.71
(3H, s), 3.30 (3H, s), 3.33 (6H, s), 3.81 (2H, s), 5.03 (1H, d, J )
6.4), 5.49 (1H, d, J ) 6.4); 2Z isomer, 1.75 (3H, s), 3.30 (3H,
s), 3.33 (6H, s), 3.95 (2H, s), 5.06 (1H, d, J ) 6.4), 5.40 (1H, d,
J ) 6.4); 13C NMR (50 MHz, CDCl3) δ (ppm) 2E isomer, 13.2,
50.7, 56.5, 76.3, 99.0, 123;2, 137.2; 2Z isomer, 20.0, 50.7, 56.5,
70.0, 96.5, 125.1, 137.7.
these electronic factors, the approach of the bulkiest
extremity of the diene, i.e., the Z 1,2-double bond, by the
less cumbersome side of the dienophile, i.e., the methyl-
ene group, making much more sense than the other way
around.
From a conformational point of view, all the above
cyclohexenic structures adopt half-chair topologies, in
which the ester function is equatorial. Therefore, the two
“para” ether moieties adopt either an axial/axial or an
axial/equatorial orientation, depending on their syn/anti
relationship. This could be established on the basis of
NMR and confirmed in a very similar case by X-ray
crystallography.44
(2E)-1,1-Dim eth oxy-4-p h en oxybu t-2-en e (4a ). A reac-
tion vessel was charged with phenol (2.72 g, 28.8 mmol, 1.2
equiv) and a solution of NaOH (40 mL, 0.75 M, 30.0 mmol,
1.25 equiv) and was stirred for 15 min. A solution of (2E)-
bromo acetal 1 (4.66 g, 24.0 mmol, 1.0 equiv) in THF (20 mL)
was added and allowed to react at 20 °C for 2 h. Ethyl acetate
(60 mL) was then added, the organic phase was separated,
and the aqueous layer was extracted twice with ethyl acetate.
The combined organic fractions were first concentrated and
then rediluted in ethyl acetate and washed with NaOH (9 M).
The organic fraction was finally dried (MgSO4) and the solvent
evaporated. The resulting yellow oil was the (2E)-acetal 4a
(3.44 g, 69% yield), which could be flash chromatographed on
silica gel using petroleum ether/ethyl acetate ) 90:10 to give
Con clu d in g Rem a r k s
The results we present indicate a fairly large set of 1,4-
dialkoxy-1,3-butadienes to be obtainable by the conjugate
elimination reactions. The dienes are obtained in good
yields and mostly in their 1Z,3E configurations. Instead
of being a drawback in terms of reactivity, the Z double
bond turns out to be at the origin of total regio- and
endoselectivities. These compounds give a simple and
convergent access to trans-1,4-disubstituted cyclohexenic
structures, which have received a great deal of attention
lately. Further extensions of this work are currently in
progress (hetero Diels-Alder, tandem additions on bis-
dienic structures, ...) and will be presented in forthcoming
papers.
a pale yellow oil: IR (neat) 1601, 1500, 1458, 1377, 1353 cm-1
;
1
MS (CI, NH3) m/z 226 (M + 18, 18), 194 (100), 177 (78); H
NMR (300 MHz, CDCl3) δ (ppm) 3.30 (6H, s), 4.55 (2H, d, J )
5.0), 4.82 (1H, d, J ) 4.5), 5.83 (1H, dd, J ) 16.4, 4.5), 6.10
(1H, dt, J ) 16.4, 5.0), 6.75-7.40 (5H, m); 13C NMR (75 MHz,
CDCl3) δ (ppm) 52.6, 67.1, 102.0, 114.6, 120.8, 129.1, 129.4,
129.7, 158.3.
(2E)- a n d (2Z)-1,1-Dim eth oxy-3-m eth yl-4-p h en oxybu t-
2-en e (4b). The same procedure as above was followed
starting from chloro acetal 2 2E/2Z ) 75:25 (10.09 g, 61.3
mmol, 1.0 equiv) in THF (50 mL), using 4.0 equiv of phenol
and 4.5 equiv of NaOH (0.75 M) and stirring at 20 °C for 2
days. The yield was 13.38 g (98%) of a 2E/2Z ) 75:25 mixture
of 4b, which can eventually be flash chromatographed on silica
gel using petroleum ether/ethyl acetate ) 80:20 as eluent to
give a pale yellow oil: IR (neat) 1682, 1601, 1499 cm-1; MS
(EI, 70 eV) m/z 222 (M•+, 9), 190 (100); HRMS analysis (EI,
Exp er im en ta l Section
Gen er a l Asp ects. 1H and 13C NMR spectra have been
taken in deuteriochloroform or deuteriobenzene on 200 and
300 MHz FT-spectrometers; coupling constants (J ) are given
in Hz. Gas chromatography analyses have been performed
on a high-resolution DB-1-type column (30 m, 0.25 mm i.d.,
0.25 µm coating). GC/MS analyses have been performed on
an instrument equipped with the same column. Transmission
IR spectra have been recorded from NaCl cells. The silica gel
used for flash chromatography was 230-400 mesh. All
reagents were of reagent grade and were used as such or
distilled prior to use.
C
13H18O3 ) 222.1256), found 222.1255; 1H NMR (200 MHz,
CDCl3) δ (ppm) 2E isomer, 1.83 (3H, s), 3.32 (6H, s), 4.43 (2H,
s), 5.12 (1H, d, J ) 5.9), 5.65 (1H, d, J ) 5.9), 6.85-7.35 (5H,
m); 2Z isomer, 1.90 (3H, s), 3.32 (6H, s), 4.57 (2H, s), 5.14 (1H,
d, J ) 5.9), 5.50 (1H, d, J ) 5.9), 6.85-7.35 (5H, m); 13C NMR
(50 MHz, CDCl3) δ (ppm) 2E isomer, 14.1, 52.0, 72.0, 99.7,
114.6, 120.7, 123.9, 129.2, 137.0, 158.4; 2Z isomer, 20.7, 52.0,
66.5, 99.3, 115.1, 119.8, 125.7, 129.2, 137.7, 158.4. Anal. Calcd
for C13H18O3: C, 70.24; H, 8.16. Found: C, 70.12; H, 8.45.
(2E)- a n d (2Z)-1,1-Dim eth oxy-3-m eth yl-4-[(r-m eth yl-
ben zyl)oxy]bu t-2-en e (5). A suspension of potassium hy-
dride (1.79 g, 44.1 mmol, 1.1 equiv) in anhydrous THF (10 mL)
was added via syringe and under argon to a solution of racemic
R-methylbenzyl alcohol (4.89 g, 40.1 mmol, 1.0 equiv) in THF
(20 mL). The reaction mixture was stirred at room temper-
ature until 977 mL of hydrogen was recovered. The resulting
alcoholate was added dropwise to a solution of chloro acetal 2
2E/2Z ) 75:25 (6.60 g, 40.1 mmol, 1.0 equiv) in THF (20 mL)
at 0 °C and the solution warmed to room temperature for 1 h.
The mixture was then quenched carefully at 0 °C with 20 mL
of water, and the organic phase was separated, washed with
saturated aqueous sodium hydrogenocarbonate solution, and
concentrated. The resulting yellow oil was poured into ethyl
acetate and dried over anhydrous magnesium sulfate and the
solvent evaporated. The crude product was purified by flash
column chromatography on silica gel using petroleum ether/
ethyl acetate ) 90:10 as eluent to give a 75:25 mixture of 2E
and 2Z acetal 5: 8.82 g (88% yield); colorless oil; IR (neat)
P r ep a r a tion of Aceta ls 3-7. (2E)-1,1,4-Tr im eth oxybu t-
2-en e (3a ). Under an atmosphere of argon, a suspension of
sodium methylate (4.38 g, 81.1 mmol, 2.5 equiv) in methanol
(30 mL) was added to a solution of (2E)-bromo acetal 1 (6.29
g, 32.4 mmol, 1.0 equiv) in methanol (20 mL), and the mixture
was refluxed for 4 h and then cooled to room temperature.
Water and ethylic ether (20 mL) were then added, the organic
phase was separated, the aqueous layer was extracted twice
with ethylic ether, and the organic fractions were dried on
anhydrous magnesium sulfate. The (2E)-acetal 3a was ob-
tained after evaporation of the solvents and flash chromatog-
raphy over silica gel using petroleum ether/ethylic ether ) 90:
10 as eluent as a pale yellow oil: 3.45 g (73% yield); IR (neat)
1731, 1457, 1380, 1263 cm-1; MS (EI, 70 eV) m/z 146 (M•+, 1),
1
114 (64), 75 (100); H NMR (200 MHz, CDCl3) δ (ppm) 3.26
(6H, s), 3.29 (3H, s), 3.80 (2H, d, J ) 5.0), 4.74 (1H, d, J )
4.5), 5.62 (1H, dd, J ) 6.4, 4.5), 5.86 (1H, dt, J ) 16.4, 5.0);
13C NMR (50 MHz, CDCl3) δ (ppm) 56.1, 60.1, 74.4, 104.9,
131.2, 133.6.
(2E)- a n d (2Z)-3-Meth yl-1,1,4-tr im eth oxybu t-2-en e (3b).
From the same procedure as above, starting from chloro acetal
2 2E/2Z ) 75:25 (5.0 g, 30.4 mmol, 1.0 equiv) and refluxing
for 20 h, 4.4 g pale yellow oil of acetal 3b 2E/2Z ) 75:25 was
obtained after evaporation of the solvents (91% yield) and could
eventually be flash chromatographed on silica gel using
petroleum ether/ethyl acetate ) 90:10 as eluent: IR (neat)
1681, 1450, 1372, 1208 cm-1; MS (EI, 20 eV) m/z 218 (M•+
-
32, 8), 105 (100); 1H NMR (200 MHz, CDCl3) δ (ppm) 2E
isomer, 1.42 (3H, d, J ) 6.5), 1.70 (3H, s), 3.29 (6H, s), 3.66,
3.80 (2H, 2dAB, J ) 12.7), 4.40 (1H, q, J ) 6.5), 5.05 (1H, d, J
) 6.4), 5.50 (1H, d, J ) 6.4), 7.29 (5H, m); 2Z isomer, 1.42
(3H, d, J ) 6.5), 1.82 (3H, s), 3.29 (6H, s), 3.81, 3.91 (2H, 2dAB
J ) 11.8), 4.38 (1H, q, J ) 6.5), 4.81 (1H, d, J ) 6.6), 5.38
,
(44) Guillam, A.; Toupet, L.; Maddaluno, J . To be published.

Synthesis and Cycloaddition of 1,4-Dialkoxy 1,3-Dienes
J . Org. Chem., Vol. 63, No. 15, 1998 5119
(1H, d, J ) 6.6), 7.29 (5H, m); 13C NMR (50 MHz, CDCl3) δ
(ppm) 2E isomer, 14.1, 23.8, 52.0, 72.5, 76.7, 99.7, 123.0, 125.9,
127.1, 128.1, 138.2, 143.5, 2Z isomer, 20.9, 23.5, 52.0, 66.5,
76.7, 99.1, 125.4, 125.9, 127.1, 128.1, 138.4, 143.5.
solution was quenched by the addition of aqueous NaOH
solution (0.25 mL, 1.0 M, 0.25 mmol, 0.11 equiv), diluted with
10 mL of petroleum ether, and refrigerated overnight to
precipitate the trialkylammonium triflate salt. The organic
phase was then separated, the aqueous layer was extracted
twice with petroleum ether, and the combined solvents were
dried (Na2CO3) and concentrated to give the crude product.
Meth od D. Neat γ-oxygenated acetal (5.0 mmol, 1.0 equiv)
was warmed to 120 °C in a round-bottom flask equipped with
a condenser under argon, until methanol reflux and a progres-
sive dark coloration of the medium were observed. The crude
product was obtained after evaporation of the methanol.
(1Z,3E)- a n d (1Z,3Z)-1,4-Dim eth oxybu ta -1,3-d ien e (8a ).
Meth od A. Starting from acetal 3a (330 mg, 2.25 mmol) and
using ethylic ether for the extractions, 243 mg (95% yield) of
crude product 8a was obtained as an oily mixture of isomers
1E,3E/1Z,3E/1Z,3Z ) 6:74:20. Meth od B. Starting from
acetal 3a (330 mg, 2.25 mmol), 251 mg (98% yield) of crude
product 8a was obtained as a 83:17 mixture of 1Z,3E/1Z,3Z
isomers: IR (neat) 1610, 1467, 1380, 1330, 1211 cm-1; MS (EI,
70 eV) 1E,3E isomer, m/z 114 (M•+, 49), 71 (100); 1Z,3E isomer,
m/z 114 (M•+, 71), 71 (100); 1Z,3Z isomer, m/z 114 (M•+, 73),
71 (100); 1H NMR (200 MHz, C6D6) δ (ppm) 1Z,3E isomer, 3.17
(6H, s), 4.96 (1H, dd, J ) 10.8, 6.1), 5.56 (1H, d, J ) 6.1), 6.06
(1H, dd, J ) 12.4, 10.8), 6.57 (1H, d, J ) 12.4); (1Z,3Z isomer,
3.15 (6H, s), 5.60 (2H, d, J ) 6.1), 5.75 (2H, m); 13C NMR (50
MHz, C6D6) δ (ppm) 1Z,3E isomer, 54.9, 58.7, 98.7, 103.1,
143.4, 148.4; 1Z,3Z isomer, 54.9, 100.1, 144.7.
(2E)- a n d (2Z)-1,1-Dim eth oxy-4-m en th oxy-3-m eth yl-
bu t-2-en e (6). A solution of L-(-)-menthol (3.32 g, 21.3 mmol,
1.0 equiv) in anhydrous THF (10 mL) was added via syringe
and under argon to a suspension of sodium hydride (614 mg,
25.6 mmol, 1.2 equiv) in THF (5 mL). The reaction mixture
was then stirred at room temperature until 512 mL of
hydrogen evolved. HMPA was added (4 mL), followed by
chloroacetal 2 2E/2Z ) 75:25 (3.30 g, 20.1 mmol, 1.0 equiv) in
THF (5 mL), and the resulting solution was warmed to reflux
for 24 h. The mixture was then quenched carefully at 0 °C
with 2 mL of water and the organic phase separated, washed
with a solution of saturated aqueous sodium hydrogenocar-
bonate, and concentrated. The resulting yellow oil was poured
into ethyl acetate and dried on anhydrous magnesium sulfate,
and the solvent was evaporated. The crude product was finally
purified by flash column chromatography on silica gel using
petroleum ether/ethyl acetate/triethylamine ) 95:4:1 as eluent
to give a 75:25 mixture of 2E and 2Z acetal 6: 3.27 g (54%
yield); colorless oil; IR (neat) 1662, 1456, 1368, 1342 cm-1; MS
(EI, 70 eV) m/z 284 (M•+, 1), 252 (17), 114 (100); 1H NMR (200
MHz, CDCl3) δ (ppm) 2E isomer, 0.70 (3H, d, J ) 6.9), 0.83
(3H, d, J ) 6.9), 0.86 (3H, d, J ) 6.9), 1.70 (3H, s), 0.65-1.05,
1.10-1.40, 1.50-1.65, 1.95-2.35 (9H, 4m), 3.05 (1H, td, J )
11.0, 4.5), 3.26 (6H, s), 3.75, 3.95 (2H, 2dAB, J ) 12.5), 5.02
(1H, d, J ) 6.7), 5.48 (1H, d, J ) 6.7); 2Z isomer, 0.70 (3H, d,
J ) 6.9), 0.83 (3H, d, J ) 6.9), 0.86 (3H, d, J ) 6.9), 1.77 (3H,
s), 0.65-1.05, 1.10-1.40, 1.50-1.65, 1.95-2.35 (9H, 4m), 3.05
(1H, td, 11.0, 4.5), 3.26 (6H, s), 3.85, 4.13 (2H, 2dAB, J ) 12.5),
5.05 (1H, d, J ) 6.7), 5.32 (1H, d, J ) 6.7); 13C NMR (50 MHz,
CDCl3) δ (ppm) 2E isomer, 14.4, 15.9, 20.7, 22.1, 23.0, 25.2,
31.3, 34.3, 40.1, 48.1, 51.9, 73.1, 78.6, 99.9, 123.0, 139.1, 2Z
isomer, 15.9, 20.7, 21.0, 22.1, 23.0, 25.2, 31.3, 34.3, 40.1, 48.1,
51.9, 66.6, 78.6, 99.4, 124.6, 139.1.
(2E)- a n d (2Z)-1,1-Dim eth oxy-3-m eth yl-4-(p h en ylm en -
th oxy)bu t-2-en e (7). See the Supporting Information.
Gen er a l P r oced u r es for th e Syn th esis of Dien es 8-15.
For the preparation of dienes 8-15, the γ-oxygenated acetals
described above were used in their 2E configuration in the case
of 3a and 4a and in their 2E/2Z ) 75:25 configuration in the
case of 3b, 4b, and 5-7. The identification as well as the
measurement of the ratio of different dienic stereoisomers
obtained were performed by 1H NMR, GC, and GC/MS
analysis. Four methods A-D have been employed for the
preparation of vinylic and allylic dienes.
Meth od A. Under an atmosphere of argon, a solution of
n-BuLi in hexane (1.35 mL, 2.0 M, 2.70 mmol, 1.2 equiv) was
added to a solution of γ-oxygenated acetal (2.25 mmol, 1.0
equiv) in anhydrous THF (3 mL) at -40 °C. After a few
seconds, the solution turned deep purple and was stirred for
15 min at this temperature. It was then quenched with 1 mL
of water, the organic phase was separated, and the aqueous
layer was extracted twice with ethyl acetate or ethylic ether.
The combined solvents were evaporated, and the resulting red-
yellow oil was rediluted in ethyl acetate or ethylic ether, dried
(MgSO4), and concentrated to give the crude product.
(1E,3E)- a n d (1Z,3E)-1,4-Dim eth oxy-2-m eth ylbu ta -1,3-
d ien e (8b). Meth od A. Starting from acetal 3b (360 mg,
2.25 mmol) and using ethylic ether for the extractions, the
crude product obtained was an oily 10:90 mixture of 1E,3E/
1Z,3E isomers 8b, 282 mg (98% yield). Meth od D. Starting
from acetal 3b (360 mg, 2.25 mmol), the crude product was
obtained as 256 mg (89% yield) of a 30:70 mixture of 1E,3E
and 1Z,3E isomers 8b: IR (neat) 1618, 1456, 1380, 1336, 1210
cm-1; MS (EI, 70 eV) 1E,3E isomer, m/z 128 (M•+, 100); 1Z,3E
isomer, m/z 128 (M•+, 100); HRMS analysis (EI, C7H12O2
)
128.0837), found 128.0833; 1H NMR (200 MHz, CDCl3) δ (ppm)
1E,3E isomer, 1.60 (3H, s), 3.50 (6H, s), 5.39 (1H, d, J ) 12.6),
5.89 (1H, s), 6.31 (1H, d, J ) 12.6); 1Z,3E isomer, 1.54 (3H, s),
3.50 (6H, s), 5.64 (1H, s), 5.87 (1H, d, J ) 13.0), 6.44 (1H, d,
J ) 13.0); 13C NMR (50 MHz, CDCl3) δ (ppm) 1E,3E isomer,
20.6, 55.7, 101.0, 143.8, 144.7; 1Z,3E isomer, 13.7, 55.4, 58.9,
100.6, 109.0, 141.4, 148.5.
(1E,3E)-, (1E,3Z)-, (1Z,3E)-, a n d (1Z,3Z)-4-Met h oxy-1-
p h en oxybu ta -1,3-d ien e (9a ). Meth od A. Starting from
acetal 4a (469 mg, 2.25 mmol) and using ethyl acetate for the
extractions, the crude product 9a (368 mg, 93% yield) was
obtained as an oily mixture of 1E,3E/1Z,3E/1Z,3Z isomers (8:
72:20). Meth od B. Starting from acetal 4a (469 mg, 2.25
mmol), the crude product was an 80:20 mixture of 1Z,3E/1Z,3Z
isomers 9a , 384 mg (97% yield). Meth od D. Starting from
acetal 4a (1.04 g, 5.0 mmol), the crude product 9a (871 mg,
99% yield) was a mixture of the 1E,3E/1E,3Z/1Z,3E/1Z,3Z
isomers (17:8:56:19): IR (neat) 1618, 1585 cm-1; MS (EI, 70
eV) 1E,3E isomer, m/z 176 (M•+, 100); 1E,3Z isomer, m/z 176
(M•+, 100); 1Z,3E isomer, m/z 176 (M•+, 100); 1Z,3Z isomer,
1
m/z 176 (M•+, 100); H NMR (200 MHz, CDCl3) attribution of
Meth od B. Under an atmosphere of argon, a solution of
potassium bis(trimethylsilyl)amide (KHMDS, 671 mg, 3.37
mmol, 1.5 equiv) in THF (5 mL) was added at 20 °C to neat
γ-oxygenated acetal (2.25 mmol, 1.0 equiv). The slowly turning
purple solution was stirred for 1 h at room temperature and
then quenched at 0 °C with 1 mL of water. The rest of the
procedure was similar to method A.
Meth od C. A reaction vessel was swept with argon and
charged with γ-oxygenated acetal (2.25 mmol, 1.0 equiv),
diisopropylethylamine (DIPEA, 873 mg, 6.75 mmol, 3.0 equiv),
and CH2Cl2 (5 mL). After the solution was cooled to -40 °C,
trimethylsilyl trifluoromethanesulfonate (TMSOTf, 1.30 mL,
1.5 g, 6.75 mmol, 3.0 equiv) was added dropwise via syringe
to the cold solution with stirring. The resulting yellow mixture
was allowed to warm to room temperature and subsequently
stirred at this same temperature for 3 h. The resulting purple
the chemical shifts to the protons of the different isomers has
been made possible by a set of homodecoupling experiments:
δ (ppm) 1E,3E isomer, 3.66 (3H, s), 5.47 (1H, t, J ) 12.4), 5.91
(1H, t, J ) 12.4), 6.53 (1H, t, J ) 12.4), 6.59 (1H, d, J ) 12.4),
7.00-7.40 (5H, m); 1Z,3E isomer, 3.63 (3H, s), 5.39 (1H, dd, J
) 12.4, 6.1), 5.92 (1H, t, J ) 12.2), 6.25 (1H, d, J ) 6.1), 6.68
(1H, d, J ) 12.4), 7.00-7.40 (5H, m); 1Z,3Z isomer, 3.60 (3H,
s), 5.51 (1H, dd, J ) 11.3, 6.1), 5.78 (1H, dd, J ) 11.3, 6.1),
5.96 (1H, d, J ) 6.1), 6.28 (1H, d, J ) 6.1), 7.00-7.40 (5H, m);
13C NMR (75 MHz, CDCl3) δ (ppm) 1Z,3E isomer, 56.0, 97.8,
108.8, 116.2, 122.4, 129.4, 137.3, 150.0, 157.4.
(1E,3E)-, (1E,3Z)-, (1Z,3E)-, a n d (1Z,3Z)-4-Met h oxy-2-
m eth yl-1-p h en oxybu ta -1,3-d ien e (9b). Meth od A. Start-
ing from acetal 4b (500 mg, 2.25 mmol), the crude product 9b
(389 mg, 91% yield) was obtained as an 8:92 mixture of the
1E,3E and 1Z,3E isomers. Starting this time from pure 1Z

5120 J . Org. Chem., Vol. 63, No. 15, 1998
Guillam et al.
acetal 16 (see below, 500 mg, 2.25 mmol) and working at -10
°C in THF for the deprotonation, diene 9b (406 mg, 95% yield)
was obtained under its pure 1Z,3E configuration. Meth od
B. Starting from acetal 4b (500 mg, 2.25 mmol), the crude
product was obtained as a 15:85 mixture of 1E,3E and 1Z,3E
isomers 9b, 423 mg (99% yield). Meth od D. Starting from
acetal 4b (1.11 g, 5.0 mmol), 893 mg (94% yield) of crude
product 9b was obtained as a 40:10:40:10 mixture of 1E,3E,
1E,3Z, 1Z,3E, and 1Z,3Z isomers: IR (neat) 1618, 1590, 1488,
1384, 136, 1230 cm-1; MS (EI, 70 eV) m/z 190 (M•+, 100);
HRMS analysis (EI, C12H14O2 ) 190.0994), found 190.0995;
1H NMR (200 MHz, C6D6) δ (ppm) 1E,3E isomer, 1.78 (3H, s),
3.14 (3H, s), 5.55 (1H, d, J ) 12.9), 6.32 (1H, s), 6.50 (1H, d,
J ) 12.9), 6.80-7.25 (5H, m); 1Z,3E isomer, 1.54 (3H, s), 3.14
(3H, s), 6.01 (1H, s), 6.32 (1H, d, J ) 13.1), 6.62 (1H, d, J )
13.1), 6.80-7.25 (5H, m); NOE experiments showed that
irradiation at δ 6.01 resulted in enhancement at δ 1.54, and
irradiation at δ 1.54 resulted in enhancements at both δ 6.01
and 6.62; 13C NMR (50 MHz, C6D6) δ (ppm) 1E,3E isomer, 14.1,
55.7, 104.6, 111.8, 115.2, 119.9, 129.4, 137.5, 146.8, 156.5;
1Z,3E isomer, 14.1, 55.1, 100.3, 115.8, 116.0, 122.1, 129.4,
135.2, 148.3, 157.8. Anal. Calcd for C12H14O2: C, 75.76; H,
7.42. Found: C, 75.41; H, 7.83.
(1E)-1-Met h oxy-3-(m en t h oxym et h ylen e)b u t a -1,3-d i-
en e (13). Meth od B. Starting from acetal 6 (640 mg, 2.25
mmol), 561 mg of a yellow oil, which was the pure allylic
isomer 13 (99% yield) in its 1E configuration, was obtained;
IR (neat) 1642, 1456, 1360, 1211 cm-1; MS (EI, 70 eV) m/z
252 (M•+, 100); HRMS analysis (EI, C16H28O2 ) 252.2089),
found 252.2088; 1H NMR (200 MHz, CDCl3) δ (ppm) 0.69 (3H,
d, J ) 6.9), 0.84 (3H, J ) 6.9), 0.88 (3H, d, J ) 6.9), 0.65-
1.05, 1.10-1.40, 1.50-1.65, 2.00-2.32 (9H, 4m), 3.05 (1H, td,
J ) 10.5, 4.0), 3.52 (3H, s), 3.90, 4.16 (2H, 2dAB, J ) 11.6),
4.87 (2H, s), 5.45 (1H, d, J ) 13.0), 6.74 (1H, d, J ) 13.0); 13
C
NMR (50 MHz, CDCl3) δ (ppm) 15.7, 20.8, 22.1, 22.9, 25.0, 31.3,
34.4, 39.8, 48.1, 55.9, 67.0, 77.8, 104.9, 112.1, 140.7, 149.2.
(1Z,3E)-4-Meth oxy-2-m eth yl-1-(p h en ylm en th oxy)bu ta -
1,3-d ien e (14) a n d (1E)-1-Meth oxy-3-[(p h en ylm en th oxy)-
m eth yl]bu ta -1,3-d ien e (15). Meth od A. Starting from
acetal 7 (500 mg, 1.39 mmol), the deprotonation was done this
time in ethylic ether and required 5.0 equiv of n-BuLi and
warming to room temperature for 1 h. The yield was 420 mg
of the crude product (92%), which was an oily 33:67 mixture
of vinylic 1Z,3E isomer 14 and allylic 1E isomer 15. Meth od
B. Starting from acetal 7 (150 mg, 0.42 mmol), the deproto-
nation required 5.0 equiv of KHMDS and warming to reflux
of THF followed by stirring at 20 °C for 12 h. The yield was
127 mg in pure 1E allylic diene 15 (95%). Vinylic diene 14:
1H NMR (200 MHz, CDCl3) δ (ppm) 0.84 (3H, d, J ) 6.4), 1.33
(3H, s), 1.41 (3H, s), 1.58 (3H, s), 0.60-1.00, 1.10-1.50, 1.60-
1.85 (8H, 4m), 3.10 (1H, m), 3.55 (3H, s), 5.63 (1H, s), 5.82
(1H, d, J ) 12.8), 6.40 (1H, d, J ) 12.8), 7.00-7.40 (5H, m).
(1E)-1-Meth oxy-3-(p h en oxym eth ylen e)bu ta -1,3-d ien e
(10). Meth od C. Starting from acetal 4b (500 mg, 2.25
mmol), 350 mg (82% yield) of crude product was obtained as a
70:30 mixture of vinylic 9b and allylic 10 dienes. While 9b
was a 1E,3E/1Z,3E ) 10:90 mixture, 10 was pure E. 10 was
separated by flash column chromatography on silica gel using
petroleum ether/ethyl acetate ) 95:5 as eluent to give a
colorless oil: IR (neat) 1618, 1590 cm-1; MS (EI, 70 eV) m/z
190 (M•+, 100); HRMS analysis (EI, C12H14O2 ) 190.0994),
found 190.0992; 1H NMR (200 MHz, CDCl3) δ (ppm) 3.61 (3H,
s), 4.62 (2H, s), 5.06 (2H, s), 5.59 (1H, d, J ) 13.1), 6.80 (1H,
d, J ) 13.1), 6.90-7.40 (5H, m); 13C NMR (50 MHz, CDCl3) δ
(ppm) 56.0, 68.8, 104.5, 112.8, 114.7, 120.8, 129.3, 139.0, 149.2,
158.4.
Allylic diene 15: IR (neat) 1644, 1601, 1456, 1368, 1210 cm-1
;
MS (EI, 70 eV) m/z 328 (M•+, 57), 214 (73), 131 (85), 99 (100);
1H NMR (200 MHz, CDCl3) δ (ppm) 0.84 (3H, d, J ) 6.4), 1.33
(3H, s), 1.41 (3H, s), 0.60-1.00, 1.10-1.50, 1.60-1.85, 1.95-
2.15 (8H, 4m), 3.10 (1H, m), 3.57 (3H, s), 3.76, 4.11 (2H, 2dAB
,
J ) 12.5), 4.87 (2H, s), 5.47 (1H, d, J ) 12.8), 6.66 (1H, d, J )
12.8), 7.00-7.40 (5H, m); 13C NMR (50 MHz, C6D6) δ (ppm)
21.8, 24.7, 27.3, 30.3, 31.2, 34.7, 40.3, 46.4, 53.2, 55.0, 68.4,
80.8, 105.1, 110.6, 124.5, 125.9, 127.5, 141.3, 148.7, 150.4.
(1E)- a n d (1Z)-4,4-Dim eth oxy-2-m eth yl-1-p h en oxybu t-
1-en e (16). Usin g t-Bu OK. A solution of potassium tert-
butylate (740 mg, 6.6 mmol, 1.1 equiv) in THF (10 mL) was
added under argon to a solution of acetal 4b (1.33 g, 6.0 mmol,
1.0 equiv) in THF (10 mL). This slowly turning purple mixture
was stirred at room temperature for 20 h and then quenched
carefully with 20 mL of water. Ethyl acetate was added, and
the organic fraction was separated and concentrated. The
resulting yellow oil was then rediluted in ethyl acetate and
dried (MgSO4). After elimination of the solvent, a mixture of
several compounds was obtained. Its ratio (as determined by
1H NMR analysis) depended on the conformation of the
starting acetal 4b. While pure 2E isomer 4b led to a 19:40:
38:3 mixture of 1E acetal 16, 1Z acetal 16, 1Z,3E vinylic diene
9b, and 1E allylic diene 10, pure 2Z isomer 4b gave a 0:77:
13:10 ratio of the same products. In this latter case, acetal
16 of the 1Z configuration was isolated after flash column
chromatography as 812 mg of a colorless oil (61% yield).
Usin g t-Bu P 4. A solution of t-BuP4 in hexane (0.45 mL, 1.0
M, 1.0 equiv) was added, under argon and at 20 °C, to 100 mg
of acetal 4b 1E/1Z ) 75:25 in 1 mL of THF. After being stirred
at 20 °C for 1 h, 3 mL of ethyl ether was added to the resulting
purple solution, and the organic solution was separated from
an oily residue. After evaporation, 67 mg (70% yield) of a
yellow oil containing acetal 16 (1E,1Z) and diene 9b (1Z,3E)
as a 26:44:30 mixture was obtained. Acetal 16: IR (neat)
1Z,3E isomer, 1680, 1593, 1491, 1375, 1288 cm-1; MS (EI, 70
eV) m/z 222 (M•+, 5), 190 (8), 75 (100); 1H NMR (200 MHz,
CDCl3) δ (ppm) 1E isomer, 1.74 (3H, s), 2.28 (2H, d, J ) 5.9),
3.35 (6H, s), 4.49 (1H, t, J ) 5.9), 6.30 (1H, s), 6.95-7.35 (5H,
m); 1Z isomer, 1.74 (3H, s), 2.53 (2H, d, J ) 5.9), 3.32 (3H, s),
4.57 (1H, t, J ) 5.9), 6.28 (1H, s), 6.95-7.32 (5H, m); a NOESY
experiment showed a cross-peak between the ethylenic proton
at δ 6.28 and the vinylic methyl at δ 1.74; 13C NMR (50 MHz,
CDCl3) δ (ppm) 1Z isomer, 17.8, 32.4, 52.5, 102.9, 115.8, 116.2,
122.0, 129.3, 137.0, 157.4.
(1E,3E)- a n d (1Z,3E)-4-Meth oxy-2-m eth yl-1-[(r-m eth -
ylben zyl)oxy]bu ta -1,3-d ien e (11). Meth od A. Starting
from acetal 5 (563 mg, 2.25 mmol), the yield was 480 mg of
the crude product 11 (98%), which was an oily mixture of the
1E,3E and 1Z,3E isomers (7:93): IR (neat) 1611, 1456, 1375,
1338, 1210 cm-1; MS (CI, CH4) m/z 219 (M + 1, 94), 218 (100);
1H NMR (200 MHz, CDCl3) δ (ppm) 1E,3E isomer, 1.52 (3H,
d, J ) 6.5), 1.76 (3H, s), 3.48 (3H, s), 4.43 (1H, q, J ) 6.5),
5.51 (1H, d, J ) 12.8), 5.97 (1H, s), 6.35 (1H, d, J ) 12.8),
7.15-7.45 (5H, m); 1Z,3E isomer, 1.52 (3H, d, J ) 6.5), 1.58
(3H, s), 3.60 (3H, s), 4.74 (1H, q, J ) 6.5), 5.74 (1H, s), 6.13
(1H, d, J ) 12.8), 6.49 (1H, d, J ) 12.8), 7.15-7.45 (5H, m);
13C NMR (50 MHz, CDCl3) δ (ppm) 1Z,3E isomer, 14.6, 23.7,
56.1, 79.3, 101.6, 109.8, 125.8, 127.4, 128.4, 139.3, 143.4, 146.9.
(1E,3E)- a n d (1Z,3E)-1-Men th oxy-4-m eth oxy-2-m eth -
ylbu ta -1,3-d ien e (12). Meth od A. Starting from acetal 6
(640 mg, 2.25 mmol), 414 mg of the pure vinylic compound 12
(73%) was obtained as an oily 8:92 mixture of 1E,3E and 1Z,3E
isomers. Meth od D. Starting from neat acetal 6, the dark
coloration appeared at room temperature in 6 days, leading
to a 35:65 mixture of 1E,3E/1Z,3E dienes 12: IR (neat) 1618,
1458, 1371, 1334, 1210 cm-1; MS (EI, 70 eV) m/z 252 (M•+
,
14), 114 (100); HRMS analysis (EI, C16H28O2 ) 252.2089),
found 252.2077; 1H NMR (200 MHz, CDCl3) δ (ppm) 1E,3E
isomer, 0.75 (3H, d, J ) 6.9), 0.87 (6H, 2d, J ) 6.9), 1.66 (3H,
s), 0.70-1.12, 1.25-1.50, 1.52-1.85, 1.90-2.30 (9H, 4m), 3.32
(1H, td, J ) 11.0, 4.5), 3.57 (3H, s), 5.44 (1H, d, J ) 12.9),
6.06 (1H, s), 6.32 (1H, d, J ) 12.9); 1Z,3E isomer, 0.75 (3H, d,
J ) 6.9), 0.87 (6H, 2d, J ) 6.9), 1.58 (3H, s), 0.70-1.12, 1.25-
1.50, 1.52-1.85, 1.90-2.30 (9H, 4m), 3.32 (1H, td, J ) 11.0,
4.5), 3.57 (3H, s), 5.77 (1H, s), 5.97 (1H, d, J ) 12.9), 6.43 (1H,
d, J ) 12.9); 13C NMR (50 MHz, CDCl3) δ (ppm) 1Z,3E isomer,
14.5, 16.2, 20.5, 21.9, 23.4, 25.7, 31.4, 34.2, 41.4, 47.6, 56.0,
81.2, 101.7, 108.6, 139.7, 146.2.

Synthesis and Cycloaddition of 1,4-Dialkoxy 1,3-Dienes
J . Org. Chem., Vol. 63, No. 15, 1998 5121
(1E,3E)- a n d (1Z,3E)-1-P h en oxy-2,5,5-tr im eth ylh exa -
1,3-d ien e (17). 4.5 mL of t-BuLi in pentane (2.5 M, 11.25
mmol, 5.0 equiv) were added under argon to a solution of acetal
4b (500 mg, 2.25 mmol, 1.0 equiv) in anhydrous ethyl ether
(5 mL) at -70 °C. After 15 min at this temperature, the purple
solution was warmed to room temperature for 24 h and then
quenched at 0 °C with 3 mL of water. The organic phase was
separated and the aqueous layer extracted twice with ethyl
ether. The combined organic fractions were dried (MgSO4) and
the solvents evaporated. The resulting reddish oil was a 25:
75 mixture of 1E,3E and 1Z,3E isomers of diene 17 (from NMR
data). The 1Z,3E isomer was isolated after flash column
chromatography on silica gel using petroleum ether/ethyl
acetate ) 95:5 as eluent to give 267 mg of a colorless oil (55%
yield): IR (neat) 1Z,3E isomer 1609, 1494, 1241 cm-1; MS (EI,
70 eV) m/z 216 (M•+, 68), 201 (17), 123 (97), 107 (100); HRMS
N-Meth yl-7,9-d ioxo-2-m en th oxy-5-m eth oxy-3-m eth yl-
8-a za bicyclo[4.3.0]n on -3-en es (21) a n d (22). See the Sup-
porting Information.
N-Met h yl-7,9-d ioxo-5-m et h oxy-3-m et h yl-2-(p h en yl-
m en th oxy)-8-a za bicyclo[4.3.0]n on -3-en es (23) a n d (24).
See the Supporting Information.
N-Meth yl-7,9-d ioxo-2-m en th oxy-5-m eth oxy-3-m eth yl-
8-a za bicyclo[4.3.0]n on -3-en es (25) a n d (26). A 35:65 mix-
ture of 1E,3E and 1Z,3E dienes 12, prepared following method
D (437 mg, 2.0 mmol), in THF was first stirred at 20 °C for 1
day. The selective cycloaddition of the 1E,3E isomer was
observed leading to a mixture of two stereoisomers 25, 26 in
35% NMR yield and with 8% diastereoisomeric excess. This
solution was then warmed to reflux for 4 days, putting the
1Z,3E isomer into reaction. After flash chromatography, the
expected adducts 21 and 22 (described above) were isolated
(de ) 42%) as well as the two new adducts 25 and 26 derived
from diene 1E,3E. This yielded 545 mg of a colorless oil (77%
yield): IR (neat) 1704, 1434, 1382, 1284 cm-1; MS (CI, CH4)
m/z 392 (M + 29, 81), 364 (M + 1, 65), 332 (49), 294 (38), 266
(100); HRMS analysis (EI, C21H33NO4 ) 363.2410), found
1
analysis (EI, C15H20O ) 216.1514), found 216.1504; H NMR
(200 MHz, CDCl3) δ (ppm) 1E,3E isomer, 1.08 (9H, s), 1.77
(3H, s), 5.75 (1H, d, J ) 12.9), 6.20 (1H, s), 6.60 (1H, d, J )
15.5), 6.80-7.10 (5H, m); 1Z,3E isomer, 1.08 (9H, s), 1.77 (3H,
s), 5.72 (1H, d, J ) 15.5), 6.28 (1H, s), 6.65 (1H, d, J ) 15.5),
6.80-7.10 (5H, m); NOE experiments on the 1Z,3E isomer
showed that irradiation at δ 6.28 resulted in enhancement at
δ 1.77, irradiation at δ 5.72 resulted in enhancement at δ 1.77,
and irradiation at δ 1.77 resulted in enhancements at both δ
5.72 and 6.28; 13C NMR (50 MHz, CDCl3) δ (ppm) 1Z,3E
isomer, 14.6, 30.1, 33.3, 116.3, 117.8, 119.0, 122.3, 129.4, 137.3,
141.3, 157.5.
1
363.2412; H NMR (200 MHz, CDCl3) δ (ppm), 25, 0.74 (3H,
d, J ) 6.9), 0.93 (6H, d, J ) 6.9), 1.80 (3H, s), 0.65-1.45, 1.50-
1.75, 1.90-2.70 (9H, 3m), 2.90 (3H, s), 3.00-3.33 (3H, m), 3.44
(3H, s), 4.05 (2H, m), 5.57 (1H, m); 26, 0.68 (3H, d, J ) 6.9),
0.83 (3H, d, J ) 6.9), 0.91 (3H, d, J ) 6.9), 1.83 (3H, s), 0.65-
1.45, 1.50-1.75, 1.90-2.70 (9H, 3m), 2.92 (3H, s), 3.00-3.33
(3H, m), 3.44 (3H, s), 4.01 (1H, m), 4.13 (1H, t, J ) 5.5), 5.66
(1H, m); 13C NMR (50 MHz, CDCl3) δ (ppm) 25, 15.8, 21.3,
21.6, 22.3, 22.8, 24.2, 24.5, 30.6, 34.4, 40.9, 42.3, 43.4, 48.4,
56.7, 72.0, 73.3, 79.2, 122.6, 141.1, 175.3, 176.3; 26, 15.8, 21.1,
22.2, 22.6, 22.8, 24.2, 24.7, 31.5, 34.4, 40.9, 42.3, 43.9, 48.4,
57.2, 72.0, 72.7, 77.4, 123.3, 141.1, 176.3, 177.9.
Gen er a l P r oced u r e for th e Cycloa d d ition Rea ction s
of Vin ylic a n d Allylic Dien es w ith N-Meth ylm a leim id e.
The solvents (anhydrous THF or toluene), the temperature,
and the length of the reaction were dependent on the starting
diene. Under an atmosphere of argon, neat N-methylmale-
imide (2.4 mmol, 1.2 equiv) and 100 mg of hydroquinone was
added to a solution of diene (2.0 mmol, 1.0 equiv) in the solvent
(20 mL). This resulting mixture was stirred at a selected
temperature until the starting reactive dienes completely
disappeared. The solvent was then evaporated and the crude
product purified by flash column chromatography on silica gel
using a 80:20 petroleum ether/ethyl acetate mixture as eluent
for adducts derived from vinylic dienes. A 60:40 ratio was
retained for those derived from allylic dienes.
N-Meth yl-7,9-dioxo-5-m eth oxy-2-ph en oxy-8-azabicyclo-
[4.3.0]n on -3-en e (18a ). Starting from 1E,3E/1Z,3E/1Z,3Z )
8:72:20 diene 9a prepared following method A (352 mg, 2.0
mmol) and refluxing for 6 h in toluene, 339 mg of adduct 18a
was isolated as a colorless oil. This adduct was derived from
the 1Z,3E diene (59% yield, 82% conversion of this isomer):
IR (neat) 1706, 1599, 1496, 1230 cm-1; MS (CI, t-BuH) m/z
288 (M + 1, 100); HRMS analysis (EI, C16H17NO4 ) 287.1158),
found 287.1170; 1H NMR (200 MHz, CDCl3) δ (ppm) 2.97 (3H,
s), 3.13 (1H, dd, J ) 9.6, 4.6), 3.25 (3H, s), 3.33 (1H, dd, J )
9.6, 3.5), 4.30 (1H, m), 5.21 (1H, d, J ) 4.9), 6.20 (2s, 2H),
6.75-7.40 (5H, m); 13C NMR (75 MHz, CDCl3) δ (ppm) 24.6,
43.0, 44.3, 56.6, 69.6, 70.7, 116.2, 121.6, 129.5, 133.4, 134.0,
156.9, 176.0, 177.7.
N-Meth yl-7,9-d ioxo-4-(m en th oxym eth yl)-2-m eth oxy-8-
a za bicyclo[4.3.0]n on -3-en es (27) a n d (28). Stirring (1E)
allylic diene 13, prepared following method B (437 mg, 2.0
mmol), for 10 min in THF, a mixture of diastereoisomers 27
and 28 was obtained with a 32% de (measured by quantitative
13C NMR and HPLC on the crude product), leading to 530 mg
of a colorless oil after purification (73% yield): IR (neat) 1704,
1438, 1387, 1285 cm-1; MS (EI, 70 eV) m/z 363 (M•+, 9), 225
(92), 92 (100); HRMS analysis (EI, C21H33NO4 ) 363.2410),
found 363.2412; 1H NMR (200 MHz, CDCl3) δ (ppm) 27, 0.65-
1.06, 1.10-1.45, 1.50-1.80, 1.95-2.30, 2.40-2.60 (20H, 5m),
2.92 (3H, s), 2.90-3.15 (3H, m), 3.17 (3H, s), 3.75, 4.06 (2H,
2dAB, J ) 14.0), 4.20 (1H, t, J ) 3.9), 5.98 (1H, d, J ) 4.1); 28,
0.65-1.06, 1.10-1.45, 1.50-1.80, 1.95-2.30, 2.40-2.60 (20H,
5m), 2.92 (3H, s), 2.90-3.15 (3H, m), 3.17 (3H, s), 3.81, 4.02
(2H, 2dAB, J ) 14.0), 4.20 (1H, t, J ) 3.9), 5.98 (1H, d, J )
4.1); 13C NMR (50 MHz, CDCl3) δ (ppm) 27, 16.1, 20.8, 22.2,
23.2, 23.6, 24.5, 25.5, 31.4, 34.3, 37.2, 40.2, 42.4, 48.1, 56.5,
71.0, 72.0, 79.5, 122.8, 141.7, 176.7, 179.8; 28, 16.1, 20.8, 22.2,
23.2, 23.6, 24.5, 25.5, 31.4, 34.3, 37.2, 40.2, 42.4, 48.1, 56.5,
70.7, 72.0, 79.1, 122.4, 141.7, 176.7, 179.8.
N-Met h yl-7,9-d ioxo-2-m et h oxy-4-[(p h en ylm en t h oxy)-
m eth yl]-8-a za bicyclo[4.3.0]n on -3-en es (29) a n d (30). See
the Supporting Information.
N-Meth yl-7,9-d ioxo-5-m eth oxy-3-m eth yl-2-p h en oxy-8-
a za bicyclo[4.3.0]n on -3-en e (18b). Starting from 1E,3E/
1Z,3E ) 8:92 diene 9b prepared following method A (380 mg,
2.0 mmol) and refluxing for 12 h in toluene, 385 mg of white
solid 18b was isolated (64% yield), which was derived from
the 1Z,3E isomer of 9b (70% conversion of this diene). After
recrystallization in Et2O: mp 108-110 °C; IR (neat) 1706,
Gen er a l P r oced u r e for th e Cycloa d d ition Rea ction s
of 1E,3E or 1Z,3E Dien es w ith Meth yl Acr yla te. Under
an atmosphere of argon, 100 mg of hydroquinone was added
to a solution of diene (2.0 or 4.0 mmol, 1.0 equiv) in a mixture
of toluene (5 mL) and methyl acrylate (15 mL). The reaction
conditions were dependent on the configuration of the starting
diene: 1E,3E isomers were reacted at reflux of methyl acrylate
(80 °C) in a round-bottom flask equipped with a condenser,
whereas 1Z,3E were put in sealed tubes and warmed to 140
°C for several days. After NMR and GC control of the mixture,
the polymers of methyl acrylate were adsorbed on silica gel,
the solvents were removed, and the crude product was purified
by flash column chromatography on silica gel using petroleum
ether/ethyl acetate ) 80:20 or 90:10 as eluent.
1600, 1490, 1431, 1266 cm-1; MS (EI, 70 eV) m/z 301 (M•+
,
17), 208 (79), 176 (41), 123 (100); HRMS analysis (EI, C17H19
-
NO4 ) 301.1314), found 301.1313; 1H NMR (200 MHz, CDCl3)
δ (ppm) 1.85 (3H, s), 2.94 (3H, s), 3.22 (1H, dd, J ) 9.1, 5.5),
3.32 (3H, s), 3.35 (1H, dd, J ) 9.1, 4.0), 4.31 (1H, t, J ) 5.5),
5.18 (1H, d, J ) 4.0), 5.85 (1H, d, J ) 5.5), 6.90-7.35 (5H, m);
13C NMR (50 MHz, CDCl3) δ (ppm) 20.3, 24.5, 42.3, 44.4, 56.8,
71.8, 72.5, 116.1, 121.6, 125.2, 129.5, 139.9, 157.6, 175.6, 177.2.
Anal. Calcd for C17H19NO4: C, 67.77; H, 6.31; N, 4.65.
Found: C, 67.92; H, 6.73; N, 4.73.
3-Meth oxy-4-(m eth oxyca r bon yl)-1-m eth yl-6-p h en oxy-
cycloh ex-1-en e (31b). Cycloa d d ition of 1Z,3E Isom er .
Warming 380 mg (2.0 mmol) of 1E,3E/1Z,3E ) 8:92 diene 9b,
prepared following method A, at 140 °C for 2 days, 465 mg of
a single stereoisomer 31b, derived from the 1Z,3E isomer, was
N-Met h yl-7,9-d ioxo-5-m et h oxy-3-m et h yl-2-(r-m et h yl-
ben zyloxy)-8-a za bicyclo[4.3.0]n on -3-en es (19) a n d (20).
See the Supporting Information.

5122 J . Org. Chem., Vol. 63, No. 15, 1998
Guillam et al.
isolated as a white solid (64% yield, 70% with respect to the
1Z,3E diene). A recristallization was done in petroleum ether/
ethyl acetate ) 70:30. The same reaction was also performed
in anhydrous methanol under high pressure (13 kbar), using
4 equiv of methyl acrylate and leading in 4 days to the same
adduct 31b with a comparable yield: mp 77-78 °C; IR (neat)
1739, 1596, 1491, 1221 cm-1; MS (EI, 70 eV) m/z 276 (M•+, 4),
245 (8), 183 (100), 123 (81); 1H NMR (200 MHz, CDCl3) δ (ppm)
1.85 (3H, s), 2.10 (1H, td, J ) 13.8, 4.8), 2.28 (1H, ddd, J )
13.8, 4.0, 2.2), 2.96 (1H, dt, J ) 13.6, 4.8), 3.36 (3H, s), 3.70
(3H, s), 4.04 (1H, t, J ) 4.7), 4.61 (1H, m), 5.97 (1H, d, J )
5.5), 6.80-7.35 (5H, m); 13C NMR (50 MHz, C6D6) δ (ppm) 21.1,
24.7, 40.6, 51.2, 56.7, 73.0 116.0, 121.2, 124.2, 129.9, 137.6,
158.7, 172.6. Anal. Calcd for C16H20O4: C, 69.55; H, 7.29.
Found: C, 69.24; H, 7.20.
3-Meth oxy-4-(m eth oxyca r bon yl)-1-m eth yl-6-p h en oxy-
cycloh ex-1-en es (32b) a n d (33b). Cycloa d d ition of 1E,3E
Isom er . Warming 760 mg (4.0 mmol) of a 40:10:40:10 mixture
of 1E,3E/1E,3Z/1Z,3E/1Z,3Z 9b isomers, prepared following
method D, at 80 °C for 2 days, led to an almost quantitative
consumption of the 1E,3E diene, while other isomers remained
nearly unreactive in these conditions. Two adducts were thus
obtained as a 57:43 mixture of endo-32b and exo-33b diaste-
reoisomers, corresponding to a regiocontrolled cycloaddition
of 1E,3E diene and leading to 353 mg of colorless oil after
purification (32% yield, 81% corresponding to 1E,3E diene):
IR (neat) 1740, 1597, 1494, 1234 cm-1; MS (EI, 70 eV) m/z
276 (M•+, 1), 183 (47), 123 (100); HRMS analysis (EI, C16H20O4
) 276.1362), found 276.1365; 1H NMR (200 MHz, CDCl3) δ
(ppm) 32b, 1.82 (3H, s), 2.08 (1H, q, J ) 13.5), 2.40 (1H, ddd,
J ) 12.4, 5.4, 2.6), 2.66 (1H dt, J ) 13.1, 2.9), 3.35 (3H, s),
3.69 (3H, s), 3.99 (1H, m), 4.64 (1H, dd, J ) 10.9, 5.5), 5.87
(1H, dm, J ) 5.1), 6.75-7.20 (5H, m); 33b, 1.82 (3H, s), 2.03
(1H, td, J ) 13.9, 3.3), 2.22 (1H, dt, J ) 13.9, 3.3), 2.87 (1H,
ddd, J ) 12.4, 9.1, 3.3), 3.39 (3H, s), 3.67 (3H, s), 4.01 (1H, d,
J ) 7.3), 4.53 (1H, m), 5.76 (1H, m), 6.75-7.20 (5H, m); 13C
NMR (50 MHz, CDCl3) δ (ppm) 32b, 19.4, 24.0, 43.7, 51.8, 57.0,
72.6, 75.8, 115.9, 121.1, 122.6, 129.6, 141.2, 158.2, 172.3; 33b,
20.4, 29.0, 41.1, 51.7, 55.9, 72.1, 76.7, 115.8, 121.0, 125.8, 129.4,
134.9, 158.1, 174.8. Anal. Calcd for C16H20O4: C, 69.55; H,
7.29. Found: C, 69.34; H, 7.43.
4.4), 2.24 (1H, dm, J ) 10.9), 3.06 (1H, dt, J ) 11.3, 4.5), 3.37
(3H, s), 3.70 (3H, s), 4.07 (1H, t, J ) 4.4), 4.85 (1H, dd, J )
4.5, 2.3), 6.11 (1H, dd, J ) 10.0, 5.1), 6.24 (1H, dd, J ) 10.0,
4.6), 6.75-7.40 (5H, m); 13C NMR (50 MHz, CDCl3) δ (ppm)
24.3, 40.3, 51.5, 57.3, 66.3, 72.1, 115.5, 120.9, 128.8, 129.1,
129.4, 157.2, 172.9.
3,6-Dim eth oxy-4-(m eth oxycar bon yl)-1-m eth ylcycloh ex-
1-en es (34), (35), (36), a n d (37). Cycloa d d ition of 1E,3E
Isom er . Warming 512 mg (4.0 mmol) of a 30:70 mixture of
1E,3E/1Z,3E diene 8b, prepared following method D, at 80 °C
for 4 days, led to complete cycloaddition of both 1E,3E and
1Z,3E dienes, providing a mixture of five cycloadducts, as
determined from NMR and GC/MS analysis on the crude
product. Four of them, 34/35/36/37 ) 42:34:18:6, were derived
from 1E,3E diene, the last one, 38, being derived from the
1Z,3E diene 8b (as clearly identified by cycloaddition of this
nearly pure isomer in the same conditions, see below). These
compounds were purified but not separated by flash column
chromatography, leading to 436 mg of colorless oil (51%
yield): IR (neat) 1740, 1433 cm-1; MS (EI, 70 eV), isomer 34,
m/z 182 (M•+ - 32, 10), 123 (100); isomer 35, m/z 214 (M•+
,
100), 182 (8), 123 (45), 91 (100); isomer 36, m/z 182 (4), 123
(320), 91 (100); isomer 37, m/z 182 (15), 123 (17), 91 (100).
3,6-Dim eth oxy-4-(m eth oxycar bon yl)-1-m eth ylcycloh ex-
1-en e (38). Cycloa d d ition of 1Z,3E Isom er . Same condi-
tions as above, starting from a 10:90 mixture of 1E,3E and
1Z,3E isomers of 8b (256 mg, 2.0 mmol), prepared following
method A, led to a single adduct 38, corresponding to the 1Z,3E
isomer of 8b. It has been isolated by flash column chroma-
tography as 270 mg (63% yield, 70% with respect to the 1Z,3E
diene) of a colorless oil: IR (neat) 1740, 1433, 1288, 1197 cm-1
;
MS (EI, 70 eV) m/z 182 (M•+ - 32, 45), 123 (100); 1H NMR
(200 MHz, CDCl3) δ (ppm) 1.76 (3H, s), 1.85 (1H, td, J ) 13.2,
4.0), 2.15 (1H, dm, J ) 13.2), 2.78 (1H, dt, J ) 13.2, 3.2), 3.29
(3H, s), 3.33 (3H, s), 3.46 (1H, m), 3.67 (3H, s), 3.90 (1H, t, J
) 4.4), 5.77 (1H, d, J ) 4.4); 13C NMR (50 MHz, CDCl3) δ (ppm)
21.0, 22.6, 39.6, 51.3, 57.0, 57.3, 72.7, 77.5, 122.4, 138.4, 173.4.
Anal. Calcd for C11H18O4: C, 61.66; H, 8.47. Found: C, 61.37;
H, 8.74.
3,6-Dim eth oxy-4-(m eth oxycar bon yl)cycloh ex-1-en e (39).
Cycloa d d ition of 1Z,3E Isom er . Warming 228 mg (2.0
mmol) of a 83:17 mixture of 1Z,3E and 1Z,3Z isomers of 8a ,
prepared following method A, at 140 °C for 2 days, led to the
selective consumption of the 1Z,3E isomer, providing a single
cycloadduct 39, whereas the 1Z,3Z isomer remained unreactive
in these conditions. 39 was isolated after flash column
chromatography as a colorless oil: 226 mg (52% yield, 68%
corresponding to 1Z,3E diene); IR (neat) 1738, 1435, 1289, 1194
3-Meth oxy-4-(m eth oxyca r bon yl)-6-p h en oxycycloh ex-
1-en es (32a ) a n d (33a ). Cycloa d d ition of 1E,3E Isom er .
Warming 740 mg (4.0 mmol) of a 17:8:56:19 mixture of 1E,3E/
1E,3Z/1Z,3E/1Z,3Z 9a isomers, prepared following method D,
at 80 °C for 5 days, led to an almost quantitative consumption
of the 1E,3E diene, while 1Z,3E and 1E,3Z isomers remained
nearly unreactive under these conditions. Two adducts where
thus obtained as a 51:49 mixture of endo-32a and exo-33a
diastereoisomers, corresponding to a regiocontrolled cycload-
dition of 1E,3E diene and leading to 126 mg of colorless oil
after purification (12% yield, 69% corresponding to 1E,3E
diene): IR (neat) 1734, 1595, 1497, 1292 cm-1; MS (EI, 70 eV)
m/z 262 (M•+, 7), 231 (6), 169 (100); HRMS analysis (EI,
1
cm-1; MS (EI, 70 eV) m/z 200 (M•+, 100); H NMR (200 MHz,
CDCl3) δ (ppm) 1.93 (1H, td, J ) 12.4, 4.1), 2.03 (1H, td J )
12.4; 2.6), 2.88 (1H, dt, J ) 12.4, 3.8), 3.30 (6H, s), 3.66 (3H,
s), 3.73 (1H, td, J ) 4.1, 2.4), 3.95 (1H, t, J ) 4.2), 6.02 (1H,
dd, J ) 10.1, 4.4), 6.10 (1H, dd, J ) 10.1, 4.3); 13C NMR (50
MHz, CDCl3) δ (ppm) 23.6, 40.2, 51.6, 56.5, 57;3, 71.8, 72.3,
128.1, 129.9, 173.6. Anal. Calcd for C10H16O4: C, 59.99; H,
8.05. Found: C, 58.14; H, 7.82.
C
15H18O4 ) 262.1205), found 262.1197; 1H NMR (200 MHz,
CDCl3) δ (ppm) 32a , 1.96 (1H, dt, J ) 13.6, 12.9), 2.37 (1H,
ddd, J ) 12.8, 6.0, 2.7), 2.70 (1H, ddd, J ) 13.6, 4.0, 2.8), 3.39
(3H, s), 3.72 (3H, s), 4.03 (1H, t, J ) 4.5), 4.80 (1H, m), 6.08
(2H, m), 6.75-7.40 (5H, m); 33a , 1.98 (1H, td, J ) 11.2, 4.3),
2.22 (1H, dt, J ) 13.0, 3.4), 2.97 (1H, ddd, J ) 12.0, 8.9, 3.4),
3.32 (3H, s), 3.74 (3H, s), 4.13 (1H, d, J ) 8.9), 4.76 (1H, m),
6.00 (2H, m), 6.75-7.40 (5H, m); 13C NMR (50 MHz, CDCl3) δ
(ppm) 32a , 25.1, 43.3, 51.8, 57.3, 67.7, 72.5, 115.8, 121.2, 126.8,
129.0, 131.1, 157.3, 172.1; 33a , 29.2, 41.2, 51.8, 56.1, 72.0, 77.5,
115.8, 121.2, 126.8, 129.0, 134.1, 157.3, 174.6.
Ack n ow led gm en t. We thank Dr. Lucette Duhamel
(Universite´ de Rouen) and Prof. Patrick Chaquin (Uni-
versite´ Paris VI) for discussions, Mr. Albert Marcual
(Universite´ de Rouen) for mass spectra, and Rhoˆne-
Poulenc-Chimie for chloroacetal 2. The workstation used
for computations and the high-pressure device were
purchased within the frame of a FIACIR grant to J .M.
3-Meth oxy-4-(m eth oxyca r bon yl)-6-p h en oxycycloh ex-
1-en e (31a ). Cycloa d d it ion of 1Z,3E Isom er . Warming
352 mg (2.0 mmol) of a 1Z,3E/1Z,3Z ) 80:20 mixture of diene
9a , prepared following method B, at 140 °C for 5 days, led to
267 mg of a single diastereoisomer 31a isolated as a colorless
oil and derived from the 1Z,3E diene (51% yield, 64% with
respect to the 1Z,3E diene): IR (neat) 1743, 1599, 1496,1234
cm-1; MS (EI, 70 eV) m/z 262 (M•+, 19), 231 (17), 169 (100);
HRMS analysis (EI, C15H18O4 ) 262.1205), found 262.1205;
1H NMR (200 MHz, CDCl3) δ (ppm) 2.17 (1H, td, J ) 10.9,
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails and spectral descriptions for compounds 7, 19-24, 29,
and 30, main crystallographical parameters for adduct 18b,
and NMR spectra of various compounds (36 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O980321H