Synthesis and cycloaddition reactions of 1-(arylthio)-1,3-dienes. A combined experimental and theoretical study of bicyclic adducts structures

Article abstract of DOI:10.1021/jo9519120

A method giving simple access to various 1-(phenylthio)-4-substituted-1,3-dienes (5-10) is described. The influence of the different functionalizations introduced on the dienic systems has been tested in a set of classical [4 + 2] cycloaddition reactions. Both the endo/exo and regio selectivities have been investigated. While the endo compound is, as expected, the only or major isomer in all cases, the regio competition between sulfur and oxygen is in favor of the oxygen substituent in the case studied here, in contrast to related works. For one type of adduct, X-ray crystallographic analysis and NMR spectroscopy have been used in conjunction with ab initio and semiempirical AM1 calculations to determine the structure and conformations of products as well as the energetic pathway from the primary concave endo cycloadduct (28) to a rearranged bicyclic structure (39). The theoretical results fully support the occurrence of a photochemical [1,3] sigmatropic shift of the thiophenyl group.

Full text of DOI:10.1021/jo9519120

5290
J . Org. Chem. 1996, 61, 5290-5306
Syn th esis a n d Cycloa d d ition Rea ction s of 1-(Ar ylth io)-1,3-d ien es.
A Com bin ed Exp er im en ta l a n d Th eor etica l Stu d y of Bicyclic
Ad d u cts Str u ctu r es
J acques Maddaluno,*,† Odile Gaonac’h,† Albert Marcual,† Lo¨ıc Toupet,‡ and
Claude Giessner-Prettre§
Laboratoire de Chimie Organique, URA 464 CNRS, Faculte´ des Sciences/ IRCOF, Universite´ de Rouen,
76821 Mont St. Aignan Cedex, France, Groupe de Matie`re Condense´e et Mate´riaux, URA 804 CNRS,
Universite´ de Rennes I, 35042 Rennes Cedex, France, and Laboratoire de Chimie Organique The´orique,
URA 506 CNRS, Universite´ P. & M. Curie (Paris VI), 4 place J ussieu, 75252 Paris Cedex 05, France
Received October 26, 1995X
A method giving simple access to various 1-(phenylthio)-4-substituted-1,3-dienes (5-10) is described.
The influence of the different functionalizations introduced on the dienic systems has been tested
in a set of classical [4 + 2] cycloaddition reactions. Both the endo/exo and regio selectivities have
been investigated. While the endo compound is, as expected, the only or major isomer in all cases,
the regio competition between sulfur and oxygen is in favor of the oxygen substituent in the case
studied here, in contrast to related works. For one type of adduct, X-ray crystallographic analysis
and NMR spectroscopy have been used in conjunction with ab initio and semiempirical AM1
calculations to determine the structure and conformations of products as well as the energetic
pathway from the primary concave endo cycloadduct (28) to a rearranged bicyclic structure (39).
The theoretical results fully support the occurrence of a photochemical [1,3] sigmatropic shift of
the thiophenyl group.
In tr od u ction
cross-coupling reactions catalyzed by Ni(II) complexes.6
Among this class of compounds, and because of their
convenient substitution patterns, 1-methoxy-2-(phenylth-
io)- and 2-methoxy-3-(phenylthio)butadienes have also
been considered as key partners in applications to the
synthesis of natural products such as carvone7 or eudes-
mane sesquiterpenes precursors.8
The usefulness of the Diels-Alder reaction due to its
exceptional versatility, as well as high regio- and stereo-
selectivity, has triggered, in the last decade, a wide
interest in the synthetic routes to functionalized 1,3-
dienes;1 among these, the conspicuous success encoun-
tered by dienes bearing heteroatom substituents is
certainly worth emphasizing.2 Oxygenated dienes, for
instance, have found too many applications to be even
briefly evocked here, and the most widely used compound
of this class, 1-methoxy-3-((trimethylsilyl)oxy)butadiene
(Danishefsky diene)3 provides elegant access to several
important natural products.4 Of a more restricted dif-
fusion, sulfenylbutadienes probably did not receive the
attention they deserve albeit they appeared of special
interest in several cycloaddition reactions in inter2,5abf or
intra molecular5c-e situations. Such dienes have also
proved to behave as useful building blocks in the stereo-
selective approach of unsaturated pheromones through
However, access to 1,4-dihetero-substituted dienes is
generally known to be complicated by both the nature of
substituents and control of the stereochemistry; for
instance, the generally proposed route to these structures
based upon conrotatory opening of appropriately substi-
tuted cyclobutenes9 fails in the case of 4-methoxy-1-
(phenylthio)buta-1,3-diene, leading to a complex mixture
of isomers.10 Thus the problem of an efficient stereocon-
trolled synthesis of these potent building blocks often
constitutes the limiting step to their application.
We have previously shown11 that γ-(phenylthio)-R,â-
unsaturated acetals 4a ,b, which derive from correspond-
ing aldehydes (viz. crotonaldehyde (1a ) or senecialdehyde
(1b), respectively) through their halo acetals 2a ,b or 3,
are possible precursors for these dienes since they lead
stereoselectively to dienol ethers 5a ,b in strongly basic
medium and eventually to dienes 6-10 (Scheme 1). This
preliminary study11a has been extended, and we now
report the scope and limitations we have found for the
† Universite´ de Rouen.
‡ Universite´ de Rennes I.
§ Universite´ P. & M. Curie (Paris VI).
X Abstract published in Advance ACS Abstracts, J une 15, 1996.
(1) (a) Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction;
Wiley: New York, 1990. (b) Carruthers, W. Cycloaddition Reactions
in Organic Synthesis; Pergamon Press: Oxford, 1990.
(2) For a review, see: Petrzilka, M.; Grayson, J . I. Synthesis 1981,
753.
(3) (a) Danishefsky, S.; Kitahara, T. J . Am. Chem. Soc. 1974, 96,
7807. (b) Danishefsky, S. Acc. Chem. Res. 1981, 14, 400.
(4) See inter alia: (a) Danishefsky, S.; Kitahara, T.; Yan, C. F.;
Morris, J . J . Am. Chem. Soc. 1979, 101, 6996. (b) Danishefsky, S.;
Barbachyn, M. J . Am. Chem. Soc. 1985, 107, 7761. (c) Bao, J .;
Dragisich, V.; Wenglowsky, S.; Wulff, W. D. J . Am. Chem. Soc. 1991,
113, 9873.
(5) (a) Cohen, T.; Mura, A. J ., J r.; Shull, D. W.; Fogel, E. R.; Ruffner,
R. J .; Falck, J . R. J . Org. Chem. 1976, 41, 3218. (b) Pegram, J . J .;
Anderson, C. B. Tetrahedron Lett. 1988, 29, 6719. (c) Chou, S. S. P.;
Wey, S. J . J . Org. Chem. 1990, 55, 1270. (d) Ihara, M.; Suzuki, S.;
Taniguchi, N.; Fukumoto, K.; Kabuto, C. J . Chem. Soc., Perkin Trans.
1 1992, 2527. (e) Ihara, M.; Katsumata, A.; Egashira, M.; Suzuki, S.;
Tokunaga, Y.; Fukumoto, K. J . Org. Chem. 1995, 60, 5560. (f) Skabara,
P. J .; Bryce, M. R.; Batsanov, A. S.; Howard, J . A. K. J . Org. Chem.
1995, 60, 4644.
(6) Fiandanese, V.; Marchese, G.; Naso, F.; Ronzini, L.; Rotunno,
D. Tetrahedron Lett. 1989, 30, 243.
(7) Trost, B. M.; Vladuchick, W. C.; Bridges, A. J . J . Am. Chem. Soc.
1980, 102, 3554.
(8) Cohen, T.; Kosarych, Z. J . Org. Chem. 1982, 47, 4005.
(9) (a) J ung, M. E. Chem. Commun. 1974, 956. )b) Ingham, S.;
Turner, R. W.; Wallace, T. W. J . Chem. Soc., Chem. Commun. 1985,
1664.
(10) Trost, B. M.; Godleski, S. A.; Ippen, J . J . Org. Chem. 1978, 43,
4559.
(11) (a) Gaonac’h, O.; Maddaluno, J .; Chauvin, J .; Duhamel, L. J .
Org. Chem. 1991, 56, 4045. (b) Gaonac’h, O.; Maddaluno, J .; Ple´, G.;
Duhamel, L. Tetrahedron Lett. 1992, 33, 2473. (c) Gaonac’h, O. Ph.D.
Thesis, Rouen University, France, 1992. (d) Maddaluno, J .; Gaonac’h,
O.; Le Gallic, Y.; Duhamel, L. Tetrahedron Lett. 1995, 36, 8591.
S0022-3263(95)01912-8 CCC: $12.00 © 1996 American Chemical Society

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5291
Sch em e 1
3 and 2 and 4). While yields remain high, raising the
temperature depletes the selectivity for both 4a and 4b.
Also of prime importance is probably the original stere-
ochemistry of thioether 4 itself.13 Probing the possible
influence of the nature of the aryl group born by the
sulfur atom has led to the conclusion that this parameter
is of moderate importance, and the precise nature and
substitution pattern of the aromatic ring has very little
effect on the stereoselectivity of the reaction. For in-
stance, comparison of entries 7 and 8 indicates that the
electron-withdrawing/donating properties of substituents
on the thioaromatic ring poorly affect the configuration
of the obtained dienol ethers 5e,f. Thiophenyl itself, in
this series, gives the best selectivities obtained (entries
1 and 2) and provides the first stereoselective access to
1-(phenylthio)-4-methoxybutadiene (5a ).
Also of interest in this context is the reactivity of
thioether 4h prepared from o,o′-dimethylthiophenol and
chloro acetal 3b following method B (see above). Depro-
tonation under the usual conditions indeed led to a
mixture of expected dienol ether 5h (EE:ZE ) 73:27) with
a new “exo” diene 11 of pure E configuration (eq 1). The
overall yield was good (94%) with a 5h /11 ratio of 38:62.
Models indicate that the bulk increase due to the two
methyl groups on the aromatic ring makes access to the
R-position of the sulfur atom difficult. This is probably
at the origin of the deprotonation of the vinylic methyl
group leading, via a comparable δ-elimination, to diene
11 (kinetic acidity). Generalization of these results to
other hetero-substituted acetals is currently being pur-
sued.14
original synthetic routes and for the cycloaddition reac-
tions applied to the thus prepared dienes. We also
present extensive structural studies on several cycload-
ducts obtained, completed by theoretical calculations on
the relative energies of the different conformers of several
of them.
OMe
Syn th esis of F u n ction a lized Dien ol Eth er s
S
OMe
(5 a n d 13-18)
As mentioned above, the reaction we have described
relies on the δ-elimination of an alkoxy group upon
treatment by strong bases (such as alkyllithium com-
pounds or lithium amides) of R,â-unsaturated acetals of
type 4. It provides a gram-scale access to the corre-
sponding dienol ethers 5 (Scheme 1 and Table 1) in high
yields. Sodium methoxide is not basic enough to depro-
tonate thioethers 4a ,b; similarly, the use of catalytic
amounts of alkyllithium, which would generate lithium
methoxide in the medium, remained uneffective.
The thioether precursors 4 have themselves been
obtained through direct addition of thiophenol to bromo
acetal 2a ,b in ether in the presence of triethylamine
(method A), as described previously,11a or in a biphasic
reaction between commercial aryl thiols in aqueous soda
and chloro acetal 3b in ether (method B).12 All thioethers
4 were recovered in excellent yield by both methods, if
the reaction times were lengthened for bulky thiols. The
stereochemical outcome of the reaction is obviously
dependent on the starting acetals. Indeed, while linear
acetal 2a was prepared in its pure E form and thus gave
access to E thioether 4a , branched bromo and chloro
acetals 2b and 3b were obtained with E/Z ratios of 75:
25 and 70:30, respectively, the same ratios as for thio-
ethers 4a ,h .
4h
(1)
i. t-BuLi
ii. MeOH
ArS
ArS
+
OMe
OMe
(37:63)
5h
11
Extensions of this reaction to cyclic acetals has also
been considered, in an attempt to stabilize the corre-
sponding intermediate anions. Treatment of methyl
acetal 4b with ethyleneglycol or phenylglycol in the
presence of a trace of acid leads to the expected diox-
olanes 12a ,b11b,c (eq 2). When treated as above, these
compounds yield, through opening of the dioxolane
moieties, the corresponding dienol ethers 13. In the case
of the acetal derived from phenylglycol, this opening is
not regioselective and provides a mixture of isomeric
alcohols 13b,c (ratios undetermined). The unstability of
the dioxolane ring under these basic conditions contrasts
with related findings by our group for phosphonate
anions15 but may be considered in relation to results on
(13) A sample of pure
E 4b has once been isolated by flash
chromatography. It led to a 50:50 mixture of E,E and Z,E diene 5b
(instead of the 70:30 mixture obtained from a 70:30 E/Z ratio of 4b).
This can be accounted for if pure Z 4b leads to pure E,E 5b. The total
amount of the recovered E,E isomer would then be %E,E[5b] ) (%E[4b]
× 0.5) + (%Z[4b] × 1.0) ) 0.65 (experimentaly: 0.7).
Addition of commercial n-BuLi or t-BuLi solutions to
4 in ether or THF led to dienes 5, whose stereochemistry
appears to depend on many parameters such as the
substitution pattern in 4 (Table 1, entries 1 and 2 and 3
and 4) or the solvent/temperature effects (entries 1 and
(14) (a) Guillam, A.; Maddaluno, J .; Duhamel, L. J . Chem. Soc.,
Chem. Commun. in press. (b) Deagostino, A.; Maddaluno, J .; Prandi,
C.; Venturello, P. Submitted for publication.
(15) Duhamel, L.; Guillemont, J .; Legallic, Y; Ple´, G.; Poirier, J . M.;
Ramondenc, Y.; Chabardes, P. Tetrahedron Lett. 1990, 31, 3129.
(12) Provided by the Rhoˆne-Poulenc Chimie Co.

5292 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
Ta ble 1. Dien ol Eth er s 5 P r ep a r ed by Action of 1 Equ iva len t t-Bu Li on Aceta ls 4 in Eth er (Sch em e 1)
entry
subst
R
Ar
T, °C
solvent
product
EE/ZEa
yield, %
1
2
3
4
5
6
7
8
9
4a
4b
4a
4b
4c
4d
4e
4f
H
Me
H
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
-78
-78
+34
+34
-78
-78
-78
-78
-78
-78
THF
THF
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
5a
5b
5a
5b
5c
5d
5e
5f
>95:5
85:15
63:23b
60:40
65:35
57:43
65:35
55:45
63:37
73:27
90
90
95
96
91
97
89
98
93
36c
â-naphthyl
o-MeC6H4
p-MeOC6H4
p-ClC6H4
2-Pyr
4g
4h
5g
5h
10
o,o′-Me2C6H3
Refers to the 1E,3E/1Z,3E ratio. Small amounts of other isomers also in the medium. c Yield for 5h only, a 38:62 mixture of 5h and
a
b
11 being recovered in 95% total yield.
Sch em e 2
unsaturated dioxolanes16 or with recent papers about
opening of unsaturated dioxane derivatives.14b,17
O
OMe
OMe
ref 11b
PhS
PhS
O
12a
(E/Z = 75/25)
4b
ref 11b
O
Ph
PhS
PhS
PhS
O
O
(2)
12b
HO
13a
PhS
O
O
HO
+
HO
Ph
Ph
13c
13b
The intermediate lithium alcoholates derived from the
dioxolane ring cleavage can be directly trapped by acid
chlorides, yielding the corresponding esters 14-16
(Scheme 2). This easy access to trienic structures leads
to potential precursors for hetero-bicyclic systems through
intramolecular Diels-Alder (IMDA) reactions. A com-
parable approach has, for instance, been recently adopted
by Craig et al.18 to take advantage of an ether tethering
during ring closure. Fine tuning of the electronic proper-
ties of the dienic part is further possible through the mild
MCPBA oxidation of the sulfur atom19 into the corre-
sponding sulfoxide, thus converting the purely donor
diene part into a push-pull type.11b This has been
achieved on esters 14 and 15 (60 and 44% yields,
respectively), and the oxidation does not interfere with
the rest of these highly unsaturated molecules. Prelimi-
nary IMDA attempts on trienes 14-18 have remained,
however, unsuccessful to date, under thermal conditions
(toluene, 110 °C, 6 days: starting material) as well as in
DMSO20 at room temperature.
Chain shortening influence on methoxy elimination has
also been examined (eq 3); starting from (phenylthio)-
acetaldehyde dimethyl acetal (20), prepared from com-
mercial bromoacetaldehyde dimethyl acetal (19), we
observed a comparable â-elimination taking place at -70
°C, leading in almost quantitative yield to the corre-
sponding enol ether 21 in a 90:10 E/Z ratio.21 Dioxolane
22 similarily led to enol ether 23, with the same stere-
ochemical outcome.
(3)
(16) Mioskowski, C.; Manna, S; Falck, J . R. Tetrahedron Lett. 1984,
25, 519.
(17) (a) Venturello, P. J . Chem. Soc., Chem. Commun. 1992, 1032.
Lewis acid assistance in basic opening of dioxolane has been de-
scribed: (b) Gassman, P. G.; Burns, S. J .; Pfister, K. B. J . Org. Chem.
1993, 58, 1449. See also the related elimination taking place on
thioacetal described in ref 5a.
(18) (a) Craig, D.; Reader, J . C. Synlett 1992, 757. (b) Ainsworth, P.
J .; Craig, D.; Reader, J . C.; Slawin, A. M. Z.; White, A. J . P.; Williams,
D. J . Tetrahedron 1996, 52, 695. See also: (c) 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 ref 6 therein.
(19) Evans, D. A.; Bryan, C. A.; Sims, C. L. J . Am. Chem. Soc. 1972,
94, 2891.
(20) (a) J ung, M. E. Synlett 1990, 186. (b) J ung, M. E.; Gervay, J .
J . Am. Chem. Soc. 1991, 113, 224.
(21) For related exemples see: (a) Nagata, W.; Hayase, Y. J . Chem.
Soc. C 1969, 460. (b) Le Gallic, Y. Ph.D. Thesis, Rouen University,
France, 1992.

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5293
Ta ble 2. 1,3-Dien es 6-10 P r ep a r ed by Action of 3 Equ iva len t of Lith ia ted Sp ecies on Aceta ls 4 in Eth er or THF
(Sch em e 1)
substituents
starting
material
isomer ratios
entry
product
R
R′
Ar
solvent
T, °C
(EE:ZEa)
yield, %
1
2
3
4
5
6
7
8
9
4a
4b
4b
4a
4b
4b
4a
4b
4c
4f
6a
6b
6b
7a
7b
7b
8a
8b
8c
8d
9
H
n-Bu
n-Bu
n-Bu
t-Bu
t-Bu
t-Bu
morpholino
morpholino
morpholino
morpholino
piperidino
NEt2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Et2O
THF
Et2O
THF
THF
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
35
-60
35
-60
-60
35
35
35
35
35
60:40
50
45
60
40
60
80
80
80
80
80
80
80
Me
Me
H
Me
Me
H
Me
Me
Me
Me
Me
61:25:10:4b
30:40:10:20b
64:36
70:30
57:43
53:47
50:50
56:44
50:50
55:45
50:50
â-naphthyl
p-ClC6H4
Ph
10
11
12
4b
4b
35
35
10
Ph
a
b
Refers to the 1E,3E/1Z,3E ratio. No attribution to the 4 possible stereoisomers.
Sch em e 3
Syn th esis of F u n ction a lized 1,3-Dien es (6-10)
As previously reported,11a the use of an excess of
lithium reagent in the above-described reactions leads
to incorporation of the base itself in the 4-position of the
diene structure (Scheme 1 and Table 2). This reaction,
to be considered in relation to results for lithio compound
addition onto butadiene,22c styrene,22d or ynol ethers,22a,b
takes place on enol ethers 5 or directly with 2-3 equiv
of base on acetals 4. It gives access to alkyl dienes (6, 7)
or dienamines (8-10) in decent yields. We wish to
underline the handy access this method provides to these
latter compounds which are very versatile tools in organic
synthesis. We have, for instance, established that di-
enamines 8b, 9, and 10 are direct precursors to the
corresponding ketene dithioacetals23 when exposed to air
at room temperature in the presence of 3 equiv of aryl
thiols in THF (eq 4).
this paper have been restricted to isoprenyl type com-
pounds (R ) Me, Scheme 1). These dienes have been
opposed to either symmetrical (maleic anhydride or
methyl/phenylmaleimides) or unsymmetrical (ethyl acry-
late) dienophiles in an attempt to evaluate the regio and
endo/exo selectivities this type of diene can afford.
We have first considered the case of 1-(phenylthio)-
2,5,5-trimethylhexa-1,3-diene (7b), taken as a represen-
tative of the 4-alkyl dienes class. The bicyclic adduct 25
was obtained after 2 days with maleic anhydride at reflux
of xylenes (Scheme 3). Only the E,E isomer of 7b is
reactive here as proved by the recovery of over 90% of
the Z,E isomer.25 After control of the crude medium, solid
adduct 25 was isolated and characterized as the pure
endo isomer, both by NMR and X-ray crystallography
analysis (Figure 1), in excellent agreement with many
related examples.26 A conformational study of 25 is
proposed below.
(4)
In regard to the control this method affords on the
configurations of the two double bonds, the situation is
quite contrasted: while the 3,4 one is in most cases
recovered in its pure E form, the 1,2 bond stereoselec-
tivity in favor of the E isomer varies between 0 (entries
8, 10, 12) and 40% (entry 5).
Similarly, the addition reaction of morpholine lithium
amide on shorter chain homologue 21 leads stereoselec-
tively and in high yields to the known24 trans-1-(phe-
nylthio)-2-morpholinoethylene (24) (eq 3).
By contrast, results obtained with ethyl acrylate have
turned out to be of little interest. A mixture of the four
possible regio/endo-exo isomers 26 and 27 (Scheme 3)
is indeed recovered in unattractive ratios,27 indicating
that the regiocontrol exerted by the tert-butyl and phe-
nylthio groups on the acrylate approach are not too
different, a surprising result in comparison to related
Cycloa d d ition Rea ction s
The 1-(arylsulfenyl)-substituted compounds prepared
above may be classified into three categories: (i) 4-alkyl-,
(ii) 4-alkoxy-, and (iii) 4-amino-1,3-dienes. We have
studied a few [4 + 2] Diels-Alder cycloaddition reactions
involving a selected item among each of these classes (5b,
7b, 8b). For the sake of simplicity, results presented in
(25) Stereochemistry of diene 7b is not thermally altered, as checked
by warming it alone.
(22) (a) Montijn, P. P.; Harryvan, E.; Brandsma, L. Recl. Trav. Chim.
Pays-Bas 1964, 83, 1211. (b) Kooyman, J . G. A.; Hendriks, H. P. G.;
Montijn, P. P.; Brandsma, L.; Arens, J . F. Ibid. 1968, 87, 69. (c) Glaze,
W. H.; J ones, P. C. Chem. Commun. 1969, 1434. (d) Wei, X.; Taylor, J .
K. J . Chem. Soc., Chem. Commun. 1996, 187.
(23) Freidanck, F.; Maddaluno, J . F.; Gaonac’h, O.; Duhamel, L.
Tetrahedron Lett. 1993, 34, 3871.
(26) See for instance: (a) Danishefsky, S.; Yan, C. F.; Mc Curry, P.
M. J . Org. Chem. 1977, 42, 1819. (b) Overman, L. E.; Petty, C. B.;
Ban, T.; Huang, G. T. J . Am. Chem. Soc. 1983, 105, 6335. (c) Blatcher,
P.; Warren, S. J . Chem. Soc., Perkin Trans. 1 1985, 1055. (d) Tripathy,
R.; Franck, R. W.; Onan, K. D. J . Am. Chem. Soc. 1988, 110, 3257. (e)
Branchadell, V.; Sodupe, M.; Ortuno, R. M.; Oliva, A.; Gomez-Pardo,
A.; Guingant, A.; D’Angelo, J . J . Org. Chem. 1991, 56, 4135.
(27) As checked by 1H NMR spectroscopy; selectivities have not been
determined.
(24) Duhamel, L.; Chauvin, J .; Messier, A. J . Chem. Res., Synop.
1982 (S), 48.

5294 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
F igu r e 1. Structures of adduct 25 from (A, top) X-ray
crystallographic analysis and (B, bottom) AM1 computations.
examples in the literature.2 As expected, 26 appears to
be the main product. The mediocre endo/exo selectivity
provided by ethyl acrylate has been well-known for many
years.28 These four isomers have not been separated.
We next studied 4-methoxy-2-methyl-1-(phenylthio)-
buta-1,3-diene (5b), which was interacted with the same
categories of dienophiles. We have retained in this case
N-phenyl- and N-methylmaleimides instead of maleic
anhydride since yields proved low with this latter com-
pound, probably because of the sensitivity of the enol
ether function in 5b to hydrolysis in the presence of acid
traces. Warming an ether solution of N-phenylmaleimide
up to reflux with the crude diene mixture 5b, in the
presence of catalytic amounts of hydroquinone, leads to
almost total consumption of the 1E,3E diene in 2 days
and progressive precipitation of a white solid (Scheme
4). At this stage the 1Z,3E isomer sits in the medium;
however, pushing the warming further leads to its slow
cycloaddition and gives access to both adducts 28 and
29. If needed, these may be readily separated by flash
chromatography. The discussion will be limited here to
the syn adducts 28. Analysis of the crude mixture led
us to the conclusion that there is also only one stereo-
isomer in this case,29 and both NMR and X-ray crystal-
lographic analysis after purification indicated this com-
pound to be the endo isomer (Figure 2). In solution, 28
undergoes a photoinduced thioallylic rearrangement
(leading to 39, vide infra).
F igu r e 2. Structure of adduct 28a from (A, top) X-ray
crystallographic analysis and (B, bottom) AM1 computations.
Sch em e 4
When refluxed in neat ethyl acrylate, 5b leads after 3
days to the expected adduct as a mixture of the isomers
30-32 (Scheme 4); these have been assayed in the crude
medium prior to being separated and fully characterized.
The main products (87%) are the endo/exo stereoisomers
30 and 31 (75:25) of the same regioisomer, as demon-
strated by 1H/1H and 1H/13C NMR correlation experi-
ments. The 13% remaining consisted of the endo/exo
mixture of the other regioisomer 32. It thus appears that
the approach of ethyl acrylate is mainly guided by the
oxygen donor effect rather than that of the sulfur.
(28) Mellor, J . M.; Webb, C. F. J . Chem. Soc., Perkin Trans. 2 1974,
17.
(29) Adduct 29 is also obtained as a single (endo) isomer.

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5295
Sch em e 5
Sch em e 6
from the single EE diene has indeed been established in
a second experiment using 0.3 equiv of TCNE. These
conditions lead to the kinetic selective addition of the EE
diene,31 confirmed by the selective disparition of the NMR
signals corresponding to the E,E isomer. The simulta-
neous apparition of the peaks of only two adducts permits
their attribution to 34a /35a and 34b/35b, respectively,
in the original experiment. While modest, these excess
values are comparable to those reported for cycloaddition
reactions involving dienes bearing comparable chiral
auxiliaries.32 The sense of the induction for the two
newly created asymmetric centers of these adducts has
not been determined.
Finally, we decided to study 2-methyl-4-morpholino-
1-(phenylthio)buta-1,3-diene (8b) in the same reactions
(Scheme 6). N-Phenylmaleimide leads, after 4 days at
reflux of ether, to the expected addition product 36 in a
low 23% yield. The major contaminant is the corre-
sponding aromatization product 37.33 36 has been de-
termined to be the endo form derived from the EE diene
8b; however, no conformational conclusion could be
drawn from a complementary NOE study.
Competition between O and S regiodirectivities has been
examined for 1,2- and 2,3-disubstituted butadienes in the
literature.5a,7,8 In both cases, it has been clearly estab-
lished that sulfur is the directing element, and Trost even
indicates that it takes the replacement of the phenyl by
a strongly π-deficient aromatic system (such as 2-pyrim-
idyl) on the sulfur atom to reverse the regioselectivity in
favor of the oxygen in 2,3-disubstituted dienes.7 The
relative R positions (1,2 or 2,3, eq 5) of S and O in these
latter examples, by contrast to the δ (1,4) pattern in our
case, is however to be kept in mind in relation to the
competition between FMO30 and dipole-dipole interac-
tions supposed to be at the origin of the regioselectivity
in such cases.7
As above, the regioselectivity provided by 8b has been
examined opposing this diene to ethyl acrylate (Scheme
6). The reaction is slow, and after 10 days at 40 °C, the
expected adduct 38 is recovered in low yield as a mixture
with the starting EE and ZE dienamines. NMR spec-
troscopy performed on both the crude and chromatogra-
phied adduct 38 indicates its structure to be the one
represented on Scheme 6. This endo adduct thus pre-
sents a regioselectivity totally controlled by the nitrogen
atom, as clearly established by a COSY experiment. This
result is in fine agreement with the only other report we
are aware of in the literature probing the competition
between regiodirectivities imposed by nitrogen and sulfur
through a 2,4-thiosubstituted dienamine34 and with
results by Overman and colleagues about carbamate-
(5)
The corresponding dienol ethers bearing a chiral
moiety are also within reach since 4b, in the presence of
secondary alcohols and a trace of acid, undergoes a
coupled trans-acetalization-conjugate elimination reac-
tion, directly giving access to dienol ethers.11b,c Those
derived from L-(-)-menthol (33a ) and (-)-8-phenylmen-
thol (33b) have been studied in this reaction (Scheme 5).
These very sensitive compounds, difficult to purify, can
efficiently add tetracyanoethylene (TCNE) at low tem-
perature in THF. After a few minutes, a mixture of
adducts 34 and 35, resulting from the rapid addition of
both 33 1E,3E and 1Z,3E isomers, is recovered. These
cycloadducts were not separated since TLC analysis
showed the four epimers of both 34 and 35 to be very
(31) Ru¨cker, C.; Lang, D.; Sauer, J .; Friege, H.; Sustmann, R. Chem.
Ber. 1980, 113, 1663.
(32) (a) Dauben, W. G.; Bunce R. A. Tetrahedron Lett. 1982, 23, 4975.
(b) Thiem, R.; Rotscheidt, K.; Breitmaier, E. Synthesis 1989, 836. (c)
Arnold, T.; Reissig, H. U. Synlett 1990, 514.
(33) The unusually large amount of aromatic material 37 recovered
could however be due to an easy double 1,2-diaxial anti elimination
made possible by a convex structure of the following type:
1
intricate. However H NMR spectra of the raw material
directly provides the diastereoselectivity figures indicated
on Scheme 5. Identity of the diastereoisomers derived
(30) Kahn, S. D.; Pau, C. F.; Overman, L. E.; Herhe, W. J . J . Am.
Chem. Soc. 1986, 108, 7381.
(34) Murase, M.; Hosaka, T.; Yoshida, N.; Tobinaga, S. Chem.
Pharm. Bull. 1992, 40, 1343.

5296 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
Ta ble 3. Exp er im en ta l a n d Th eor etica l Va lu es of H-H
Dih ed r a l An gles a n d Cou p lin g Con sta n ts (Hz) for 25
a
Φ (J calc
)
H-H
crystal
AM1
J exp
1-6
3-4
4-5
5-6
-43 (5.8)
-134 (6.6)
39 (6.5)
-53 (4.0)
-116 (3.2)
72 (1.4)
4.2
5.0
7.3
9.2
11 (10.2)
3 (10.5)
a
J in C6D6 and Φ calculated according to the following modified
1
F igu r e 3. Conformation and H coupling constants of adduct
38.
Karplus equation:49 J H-H ) 10.81 cos2 Φ - 0.96 cos Φ + 0.70.
3
and crystal conformations. Such a concave shape is to
be considered as the frozen picture of the endo transition
state; its good stability39 may appear surprising since,
for cyclohexene itself, the boat conformers are expected
to lie between 5.5 and 6.5 kcal/mol higher in energy than
their half-chair counterparts.40 However, the rigidity
induced by the 5-membered-ring anhydride or imide
functions renders the compounds studied here more
comparable to cyclohexadienic structures than to regular
[4.3.0] bicyclic ones. A boat conformation is therefore not
substituted dienamines.26b From a conformational point
of view, H coupling constants of 38 are clearly in favor
1
of a half-chair structure in which the morpholino group
occupies an axial position (Figure 3). This conformer
minimizes the number of axial substituents over the
other possible half-chair. The obtention of a single endo
isomer is somewhat unexpected in regard to related
results dealing with cycloaddition reactions of (1E,3E)-
1-(dimethylamino)buta-1,3-diene for which a 61:39 endo
selectivity in the reaction with methyl acrylate is re-
ported.35 There is however a significant difference of
chemical reactivity between these dienes: while the
reaction described by Sustmann and colleagues is almost
quantitative at room temperature, the one presented here
shows very little progress after the same amount of time
in refluxing ether. The deactivating effect of the sulfur
group26e is at work here again.
unlikely.40e
The AM1 computations carried out on 25 led
to conformational parameters presented together with
related experimental data in Table 3 and Figure 1B. This
theoretical study confirms the absence of any stable half-
chair conformer for this compound and leads to a boat-
shaped bicyclic structure. However, the distorsion un-
dergone by the anhydride ring is underestimated by
∼20°, a difference partly responsible for the discrepancies
between vicinal coupling constants calculated from the
torsion angles taken in the crystal and in the theoretical
structure with respect to those measured from NMR
data. Crystal packing effects could, in addition to the
possible defects of the AM1 method, contribute to dis-
agreements between some results of Table 3.
Discu ssion a n d Str u ctu r e Deter m in a tion s
Conformations of bicyclic structures such as those
obtained above represent an interesting problem which,
to our knowledge, has never been the subject of a general
study.36 The control of the overall shape of taylor-made
molecules has become lately a real challenge to organic
chemists since this parameter is the key assett in
supramolecular chemistry. It has, for instance, been
shown37 that advantage may be taken from the confor-
mational rigidity imposed by a chiral tricyclic system to
induce asymmetry through an efficient Diels-retro Diels
sequence of reactions. We have thus tried to determine
the exact conformation of these adducts from available
experimental data on the one hand and quantum me-
chanical calculations on the other.
(6)
Let us first consider adduct 25. Single-crystal X-ray
diffraction (Figure 1A) indicates this endo isomer to be,
in the solid state, in a boat-shaped concave conformation
(“folded” after Danishefsky’s naming for related bicyclic
compounds38) with both tert-butyl and phenylthio ap-
pendages in expected equatorial positions. The clear out-
of-the-plane distorsion induced on the anhydride moiety
can be attributed to the steric strain exerted by the tert-
butyl group on the five-membered ring. The conforma-
tional data deduced from the X-ray analysis give reason-
able account for both the measured proton-proton
coupling constants and a strong 1-4 NOE effect (10%
difference), indicating a close similarity between solution
When the conformation of 28a is considered, the single-
crystal X-ray analysis shows this endo adduct to still be
(35) Sustmann, R.; Rogge, M.; Nu¨chter, U.; Bandmann, H. Chem.
Ber. 1991, 125, 1647.
(36) See however the excellent conformational analysis by Bucourt,
R. in Topics in Stereochemistry, Vol. 8; J . Wiley & Sons: New York,
1974.
(37) (a) Bloch, R.; Seck, M. Tetrahedron 1989, 45, 3731. (b) Beck-
mann, M.; Hildebrandt, H.; Winterfeldt, E. Tetrahedron: Asymm. 1990,
1, 335. (c) Bloch, R.; Bortolussi, M.; Girard, C.; Seck, M. Tetrahedron
1992, 48, 453. (d) Winterfeldt, E.; Wray, V. Chem. Ber. 1992, 125, 2159.
(38) 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.
(39) Warming up 25 to reflux of xylenes only leads to a slow
degradation/aromatization of this structure.
(40) This problem is still at the heart of active debates: (a) Rivera-
Gaines, V. E.; Leibowitz, S. J .; Laane, J . J . Am. Chem. Soc. 1991, 113,
9735. (b) Anet, F. A. L.; Freedberg, D. I.; Storer, J . W.; Houk, K. N. J .
Am. Chem. Soc. 1992, 114, 10969. (c) Anet, F. A. L. In The Confor-
mational Analysis of Cyclohexenes, Cyclohexadienes, and Related
Hydroaromatic Compounds; Rabideau, P. W., Ed.; VCH: New York,
1989. (d) Laane, J .; Choo, J . J . Am. Chem. Soc. 1994, 116, 3889. (e)
Sieburth S. Mc. N. J . Chem. Soc., Chem. Commun. 1994, 1663.

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5297
(7)
shielding observed for the ortho protons born by the
thiophenyl group; they go, in C6D6, from an unusual 7.89
in 28a and 28b to 7.38 and 7.22 ppm in 39a and 39b,
respectively, probably because of the proximity of these
aromatic protons to one of the imide carbonyl groups in
the convex forms of 28.41 The rearrangement takes place
in all solvents tested (CDCl3, C6D6, CD2Cl2, CD3OD, d5-
pyridine)42 for both adducts 28a ,b at different rates with
the exception of d10-diethyl ether in which 28 is nearly
insoluble. While the migration is a little faster when the
temperature is raised, this thiophenyl migration proceeds
much faster upon strong irradiation in methylene chlo-
ride (Figure 5). It remains limited (<20%) during the
synthesis of 28 because this compound precipitates out
of the ether solution. The driving force for such an
isomerization is at least 2-fold: (i) releasing the strong
1,4-diaxial interaction in 28 by going to the flatter system
39; (ii) placing the double bond in the thermodynamically
favored R-â position (instead of â-γ) with respect to the
cis hydrindane type junction.36 This kind of thioallylic
rearrangement is well-known; its mechanism has been
the subject of many discussions44 and may even depend
on reaction conditions.45 The rearrangement takes place
here under very mild conditions, and its dramatic ac-
celeration under illumination (Figure 5) is definitely in
favor of a photoinduced radical mechanism.46 It also
nicely fits the theoretical results for the excited state of
28 which are presented below. Interesting in this regard
is the excellent stability of adduct 25 in the solid state
as well as in solution (CH2Cl2) in the dark or after a 17-
h-long intense irradiation in a quartz vessel (eq 7). This
difference of behavior shows the homolytic cleavage of
the C-S bond to be much easier when the thiophenyl
group is in an axial position (i.e., in the convex situation)
than when it occupies an equatorial position (which is
the case for the concave compounds). This hypothesis is
supported by the stability of the corresponding sulfone
(40) under the same conditions (eq 7), while the easy
F igu r e 4. Top view of a compact model of 28a .
in the boat form but of the convex type this time,
surprisingly placing both methoxy and phenylthio sub-
stituents in axial positions (Figure 2A). Such a situation,
while avoiding the allylic A1,2 strain40c between the
phenylthio and vinylic methyl groups induced by the
concave boat conformation, is at the origin of an extremly
short oxygen-sulfur distance (∼3.0 Å) in this compound,
a trend clearly showing up on the compact model
representation of Figure 4. Thus, decreasing the bulki-
ness of the substituent in the 4-position (such as when
going from t-Bu in 25 to MeO in 28) makes its passage
to an axial position spontaneous and leads to cyclohexenic
adduct 28 conformationally comparable to the one de-
scribed previously by Danishefsky’s group38 (eq 6). These
authors also proposed a rearrangement from an eventual
primary concave boat into a more stable convex con-
former. A major difference between their case and ours
is the fact that the bulky substituent sits at the vinylic
position (TMSO in Danishefsky’s example) while it oc-
cupies the allylic position in our case. Since release of
the A1,2 strain requires the relative motion of the allylic
group, a concave-convex folding is conceivable in their
case or for adducts 28 but just impossible for 25 which
is locked in its concave shape by the cumbersome tert-
butyl. An AM1-optimized structure for the corresponding
diaxial compound is 50 kcal/mol higher in energy than
that of diconvex 25.
Despite their apparent intramolecular strain, both
28a ,b are perfectly stable in the solid state and may be
kept for months in the refrigerator without any decom-
position. On the other hand their solutions undergo a
relatively slow sigmatropic 1,3-shift at room temperature,
easily followed by NMR. It leads quantitatively and
stereospecifically to the transposition products 39a ,b (eq
7), as determined through a COSY-NOESY-COLOC set
of NMR experiments.
The NMR spectra of the starting adduct and rear-
ranged material are very different, and several protons
undergo a dramatic chemical shift during this process
(see experimental data). Especially worthy of note is the
(41) See ref 37d for a comparable observation.
(42) Since the isomerization takes place in all solvents, we did not
think it essential to explicitely take into account the solvent effect in
our computations.43
(43) (a) Cramer, C. J .; Truhlar, D. G. J . Comput. Chem. 1992, 13,
1089. (b) Karelson, M.; Tamm, T.; Zerner, M. C. J . Phys. Chem. 1993,
97, 11901.
(44) (a) Brownbridge, P.; Warren, S. J . Chem. Soc., Perkin Trans. 1
1976, 2125. (b) Reference 26c and references cited therein. (c) Kwark,
H. Phosphorus Sulfur 1983, 15, 293. (d) Bernard, A. M.; Piras, P. P.
J . Chem. Soc., Chem. Commun. 1994, 257.
(45) Apparao, S.; Rahman, A.; Ila, H.; J unjappa, H. Tetrahedron Lett.
1982, 23, 971.
(46) In agreement with a personal suggestion by Dr. S. Warren but
in contradiction with Kwart, H.; J ohnson, N. J . Am. Chem. Soc. 1970,
92, 6064 and ref 44c. See also in relation recent evidences about
photochemical [1,3]-stannyl migration of 3-aryl-substituted allyltins:
Takuwa, A.; Kanaue, T.; Nishigaichi, Y.; Iwamoto, H. Tetrahedron Lett.
1995, 36, 575.

5298 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
Ta ble 4. Exp er im en ta l a n d Th eor etica l Va lu es of H-H
Dih ed r a l An gles a n d Cou p lin g Con sta n ts (Hz) for 28b
a
Φ (J calc
)
AM1
28bR (concave)
H-H
crystal
28bâ (convex)
J exp
1-6
3-4
4-5
5-6
-35 (7.2)
21 (9.2)
41 (6.1)
-36 (7.0)
25 (8.7)
32 (7.7)
2 (10.5)
58 (3.2)
106 (1.8)
-60 (5.6)
-10 (10.2)
8.1
5.6
5.2
-4 (10.5)
10.3
a
J in C6D6 and Φ calculated according to the following modified
Karplus equation:49 J H-H ) 10.81 cos2 Φ - 0.96 cos Φ + 0.70.
3
F igu r e 5. 28b f 39b rearrangement in CH2Cl2, in the dark
and under visible light irradiation.
Sch em e 7
rearrangement of allylic sulfones is well documented.47
The possible role of the tert-butyl steric hindrance in both
25 and 40 is however to be kept in mind.
A better understanding of the driving forces at the
origin of this cascade of transformations (28a [concave]
f 28a [convex] f 39a ) and of their thermodynamic
consistency required further calculations. In a first step,
complete optimizations of the concave and convex “naked”
bicyclic skeletons of 28, viz. imide 41 and its 1-methyl-
substituted equivalent 42, have been performed (Scheme
7). It indicates in the case of 41 an energetic preference
for the original concave structure of 0.2 kcal/mol at the
AM1 level. This negligible difference prompted us to
check this preference at the ab initio DFT level. The
most stable conformation of 41 is still found to be a
concave boat but by 1.2 kcal/mol this time. By contrast,
the substituted structure 42 is more stable under its
convex form â by 0.8 kcal/mol (AM1), probably because
such a conformation releases the allylic strain between
methyl groups, as mentioned above (Scheme 7). These
results thus indicate that the steric constraints induced
by the substitution patterns of the adducts studied here
(and particularly the vinylic methyl group) are at the
origin of the general preference for a convex boat, a
concave one being encountered in the single case of tert-
butyl-substituted 25.
F igu r e 6. AM1 energy and puckering angle variations
occurring during the 28a concave-convex conformational
change.
4 and Figure 2 together with the relevant experimental
data. The AM1 energies of the two optimized conformers
differ by 0.9 kcal/mol, the concave f convex flip taking
place through an “early” transition state associated with
a 4.6 kcal/mol activation energy barrier (Figure 6). The
change of sign of the torsion angles characterizing the
convex/concave switch indeed takes place after the pas-
sage through the transition state, as illustrated on Figure
6 with dihedral angle φ(3,4,5,6) as a function of the φ-
(7,1,6,5) angle (reaction coordinate). It is clear from
Figure 7 that this transition state is of the half-chair type
with the thiophenyl group in a pseudoaxial position.
These results also indicate that the theoretical convex
arrangement fits both the crystal and NMR data (Table
4). It is worth underlining that the coupling constants
measured for 28a in d10 ether are identical to those in
other deuterated solvents, indicating that the absence of
rearrangement in ether (Figure 7) is not due to a peculiar
conformation imposed by this solvent but only to the poor
solubility of 28.
The calculated characteristics for the most stable form
of the two boat conformers of 28a are reported in Table
(47) See for instance: (a) Liu, P.; Whitham, G. H. J . Chem. Soc.,
Chem. Commun. 1983, 1102. (b) Padwa, A.; Bullock, W. H.; Dyszlewski,
A. D. Tetrahedron Lett. 1987, 28, 3193; J . Org. Chem. 1990, 55, 955.
(c) J ones-Hertzog, D. K.; J orgensen, W. L. J . Am. Chem. Soc. 1995,
117, 9077.
We then considered the [1,3] shift undergone by 28 in
the next step (28 f 39). The crucial role apparently

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5299
four-electron [1,3] shift such as the one described here
to occur in a supra-supra mode48 leading to a cis
relationship between the MeO and PhS groups in 39a .
However, the likely radical mechanism we are dealing
with here precludes the application of rules restricted to
concerted mechanisms. We thus had to undertake a
complete optimization for the two possible conformers
(with the PhS group in a pseudoaxial or equatorial
position) of the two possible (cis and trans) isomers. The
following nomenclature has been adopted: the cis isomer
of 39a , corresponding to a “supra” migration of the PhS
group, is labeled 39a (s), and its conformers, in which the
thiophenyl group adopts an axial or an equatorial posi-
tion, are named 39a (s-ax) and 39a (s-eq), respectively.
Similarly, the two conformers of the trans isomer, cor-
responding to an antara migration, are called 39a -
(a-ax) and 39a (a-eq). Results of these optimization
steps are gathered in Table 5. Unfortunately, these data
do not permit an unambiguous determination of the
structure of 39a , and the complementary COSY and
NOESY experiments performed at room temperature in
this case, while confirming the presence of a single
isomer, are helpless in choosing between a dynamic
mixture of 39a (s-ax) + 39a (s-eq) and 39a (a-ax). Obvious
steric considerations (Figure 4) however support a straight-
forward supra migration of the thiophenyl group, and we
assume the rearranged product to be, in solution, under
the form of a balanced mixture of the 39a (s-ax) and
39a (s-eq) conformers shown in Figure 10. This hypoth-
esis fully accounts for the spectroscopic data presented
here.
F igu r e 7. Theoretical structure of the transition state for the
28a concave-convex conformational change.
We think the above agreements between the conforma-
tions given by the quantum mechanical calculations and
those obtained from the experimental techniques consti-
tute a fair body of evidence which improves the level of
confidence in the conformational analysis of such flexible
cis-fused bicyclic systems. The hazards of deducing
conformations of bicyclic structures on the single basis
of NMR coupling constants has been previously under-
lined by Danishefsky et al.38 This combined experimental
and theoretical approach indicates that relatively safe
milestones along nonobservable pathways are possible
as well as characterization of isolated adducts and
intermediates such as those studied here.
F igu r e 8. Theoretical structure of the bicyclic allylic radical
intermediate calculated for the 28a f 39a rearrangement.
played by the molecular excited state of 28 in this
rearrangement prompted us to undertake two other sets
of calculations. The first one concerns an optimization
of the first singlet and triplet excited states of convex 28a .
The second set deals with the separate study of the two
radicals formed after a homolytic cleavage of the C-S
bond, leading to PhS• on the one hand and the corre-
sponding allylic radical on the other. The calculated
structures for these species indicate (i) a simultaneous
shortening of the Ph-S bond from 1.70 to 1.60 Å (1.62 Å
in PhS•) and minor lengthening of the C1-S bond (from
1.80 to 1.82 Å) and (ii) a concomitant variation of the two
bonds of the ring involved in the rearrangement (1-2 and
2-3), going from 1.49 and 1.34 Å to 1.38 and 1.39 Å,
respectively, leading to an almost perfect delocalization
of the planar allylic part of the bicyclic radical (Figure
8). The energetic path corresponding to the details of
this photochemical rearrangement is illustrated in Figure
9. It clearly shows that the C-S bond breaking can
easily take place through the lowest allowed singlet
excited state and does not call for any participation of
its spin forbidden triplet equivalent. The energy barrier
to this first excited singlet is about 55 kcal/mol, a value
in reach of a 520 nm irradiation, i.e., in the visible region
as expected. Finally, the half-chair conformers of 39a
lie at least 2 kcal/mol lower than the starting material
(28a ). This energetic situation, in addition to the favor-
able topology of the convex conformer (see Figure 4),
probably explains the extreme ease and efficiency of this
reaction.
Exp er im en ta l Section
Exp er im en ta l In d ica tion s. 1H and 13C NMR spectra were
taken in perdeuteriobenzene or deuteriochloroform with Bru¨ck-
er WP-80, AM-200, 300-FT, 360-FT, or 400 FT NMR spec-
trometers. Mass spectra and high-resolution mass spectra
(HRMS) were recorded with a J EOL J MS AX-500 spectrom-
eter. The silica gel used for flash chromatography was from
the SDS Co. (230-400 mesh). All reagents were of reagent
grade and were used as such or distilled prior to use.
Analytical TLC plates for adducts were conveniently revealed
with an acidic aqueous solution of PdCl2.
X-r a y An a lysis.49,53 (a ) Ad d u ct 25. SO3C19H22
: Mr )
330.5, triclinic, P-1, a ) 6.713(7), b ) 10.177(4), and c ) 12.822-
(1) Å, R ) 85.99(6), â ) 80.00(7), and γ ) 88.23(6)°, V ) 860-
(1) Å3, Z ) 2, Dx ) 1.276 mg m-3, λ(Mo KR) ) 0.70926 Å, µ )
1.91 cm-1, F(000) ) 352, T ) 293 K, final R ) 0.092 for 1537
observations.
(48) Gilchrist, T. L.; Storr, R. C. Organic Reactions and Orbital
Symmetry; Cambridge University Press: London, 1972; p 240.
(49) (a) Fair, C. K. MolEN: an Interactive Intelligent System for
Crystal Structure Analysis; Enraf-Nonius: Delft, The Netherlands,
1990. (b) International Tables for X-Ray Crystallography, Vol. IV;
Kynoch Press: Birmingham, U.K., 1974. (c) J ohnson, C. K. ORTEP,
Report ORNL-3794, Oakridge National Laboratory, Tennessee, 1965.
The stereochemistry of 39 was however still to be
determined. The Woodward-Hoffman rules predict a

5300 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
F igu r e 9. Calculated photochemical energetic path between 28a and 39a (values in kcal/mol).
Ta ble 5. Ma in Tor sion An gles, Vicin a l H-H Cou p lin g
Å, µ ) 2.07 cm-1, F(000) ) 672, T ) 294K, final R ) 0.025 for
1123 observations.
Con sta n ts (Hz), a n d Rela tive En er gies of th e F ou r
Differ en t Isom er s/Con for m er s of 39a
The sample (0.30 × 0.45 × 0.55 mm) was studied on a CAD4
Enraf-Nonius automatic diffractometer with graphite-mono-
chromatized Mo KR radiation. The cell parameters were
obtained by fitting a set of 25 high-θ reflections. The data
collection (2θmax ) 50°; scan ω/2θ ) 1; tmax ) 60 s; range hkl h
0.6 k 0.15 l 0.19; intensity control without appreciable decay
(0.1%) gave 1472 reflexions from which 1123 with I > 2σ(I).
After Lorenz and polarization corrections the structure was
solved with direct methods which reveal all the non-hydrogen
atoms of the molecule. After isotropic (R ) 0.076) and then
anisotropic (R ) 0.051) refinement, the hydrogen atoms are
found with a Fourier difference (between 0.3 and 0.19 e Å-3).
The whole structure was refined by the full-matrix least-
squares technique (use of F magnitude; x, y, z, âi,j for S, O, N,
and C atoms and x, y, z for H atoms; 256 variables and 1123
observations; w ) 1/σ(Fo)2 ) [σ2(I) + (0.04Fo2)2]-1/2) with the
resulting R ) 0.027, Rw ) 0.025, and Sw ) 0.72 (residual ∆F
e 0.12 e Å-3).
Com p u ta tion a l P r oced u r es a n d In p u ts. The computa-
tions have been carried out using a semiempirical quantum
mechanical method (AM1 with the Dewar original parametri-
zation51) for the two following reasons. (i) Among the very
different conformers/fragments that we had to consider, only
two compounds have been subjected to crystallographic X-ray
analysis and one of them (the tert-butyl derivative 25) is not
involved in the conformational rearrangement/isomerization
mechanism. Therefore, overall optimizations were necessary,
especially in the case of the transition state and radical
intermediates. (ii) The number of optimizations to be carried
out on systems involving 30-40 atoms prohibited a systematic
ab initio study. However, to establish the validity of our
semiempirical results, the complete geometrical optimization
of the concave and convex conformations of the smallest
compound (41) has been repeated using density functional
theory as implemented in Gaussian 92/DFT.52 For this
computation, we retained the 6-31G** basis set and the
Becke’s three parameters of the exchange functional with the
Perdew correlation functional (B3P86).
a
Φ (J calc
)
39a supra
s-ax s-eq
-44 (5.6) -78 (1.0) -68 (1.9)
61 (2.8) -66 (2.1)
-47 (5.1) 38 (6.7)
5 (10.5) -4 (10.5) -12 (10.1)
39a antara
b
H-H
1-6
3-4
4-5
5-6
a-ax
a-eq
J exp
-37 (6.8)
2.9
68 (1.9) -178 (12.5) 2.7
38 (6.7)
-44 (5.6)
4.3
-1 (10.5) 8.8
∆E (kcal/ +3.3
mol)
+2.4
0.0
+4.4
a
J
calculated according to the following modified Karplus
equation:49 J H-H ) 10.81 cos2 Φ - 0.96 cos Φ+ 0.70. In C6D6.
3
b
The sample (0.10 × 0.25 × 0.45 mm) was studied on a CAD4
Enraf-Nonius automatic diffractometer with graphite-mono-
chromatized Mo KR radiation. The cell parameters were
obtained by fitting a set of 25 high-θ reflections. The data
collection (2θmax ) 50°; scan ω/2θ ) 1; tmax ) 60 s; range hkl,
h 0.7 k -12.12 l -15.15; intensity control without appreciable
decay (0.1%) gives 3289 reflections from which 1537 were
independent (Rint ) 0.025) with I > 4σ(I).
After Lorenz and polarization corrections the structure was
solved with direct methods which reveal all the non-hydrogen
atoms of the molecule. After isotropic (R ) 0.137) and then
anisotropic (R ) 0.097) refinement, the hydrogen atoms were
found with a Fourier difference. The whole structure was
refined by the full-matrix least-squares technique (use of F
magnitude; x, y, z, âi,j for S, O, N, and C atoms and x, y, z for
H atoms; 275 variables and 1537 observations; w ) 1/σ(Fo)2 )
[σ2(I) + (0.04Fo2)2]-1/2) with the resulting R ) 0.095, Rw ) 0.092,
and Sw ) 1.37 (residual ∆F e 0.22 e Å-3). All X-ray data
calculations have been performed on a Digital Micro Vax 3100
computer.
(b) Ad d u ct 28a . SO3NC17H19: Mr ) 317.41, orthorombic,
Pna21, a ) 16.085(3), b ) 13.100(4), and c ) 7.489(3) Å, V )
1578.0 (8) Å3, Z ) 4, Dx ) 1.336 mg m-3, λ(Mo KR) ) 0.70926
Gen er a l Meth od s for P r ep a r a tion of Th ioeth er s 4.
Meth od A. To a solution of 3 in triethylamine (1.8 M) was
(50) Obtained by averaging eqs 5 and 8 in Haasnoot, C. A. G.; De
Leeuw, F. A. A. M.; Altona, C. Tetrahedron 1980, 36, 2783. The
electronegativities of substituents have been neglected for eq 8 since
the strain induced by bicyclic structures could not be taken into account
while probably of prime importance in this system. The equation
retained here gives fair account for threshold values.
(51) (a) Dewar, M. J . S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J . P.
J . J . Am. Chem. Soc. 1985, 107, 3902. (b) Dewar, M. J . S.; Yuan, Y. C.
Inorg. Chem. 1990, 29, 3881.

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5301
3
4
5.52 (1H, dq, J ) 5.8 Hz, J ) 1.2 Hz), 7.15-7.95 (7H, m); Z
isomer, 1.78 (3H, m), 3.07 (6H, s), 3.61 (2H, s), 4.91 (1H, d, J
) 6.0 Hz), 5.52 (1H, m), 7.15-7.95 (7H, m).
1,1-Dim eth oxy-3-m eth yl-4-((2-m eth ylp h en yl)th io)bu t-
2-en es (4d ). Using method B with 3 (3.2 g, 19 mmol) and
2-methylthiophenol (2.5 g, 20 mmol), 4d was recovered (4.4 g,
89%) after 5 days: IR (neat) 1672 cm-1; mass spectrum (EI)
m/ z 252 (M+•, 25), 220 (M+ - CH3OH, 18), 189 (9), 163 (45),
128 (85), 75 (100); 1H NMR 200 MHz (C6D6) δ (ppm) E isomer,
1.73 (3H, m), 2.30 (3H, s), 3.04 (6H, s), 3.17 (2H, s), 4.96 (1H,
d, J ) 5.8 Hz), 5.46 (1H, m), 6.85-7.83 (4H, m); Z isomer, 1.73
(3H, m), 2.35 (3H, s), 3.09 (6H, s), 3.44 (2H, s), 4.85 (1H, d, J
) 5.9 Hz), 5.46 (1H, m), 6.85-7.83 (4H, m).
1,1-Dim et h oxy-3-m et h yl-4-((4-m et h oxyp h en yl)t h io)-
bu t-2-en e (4e). Using method B with 3 (2.0 g, 12 mmol) and
4-methoxythiophenol (1.5 g, 12 mmol), 4e was recovered (2.8
g, 89%) after 4 days: IR (neat) 1670 cm-1; mass spectrum (EI)
1
m/ z 268 (M+•, 23), 237 (60), 205 (7), 179 (43), 139 (100); H
NMR 200 MHz (C6D6) δ (ppm) E isomer, 1.75 (3H, m), 3.03
(6H, s), 3.16 (2H, s), 3.20 (2H, s), 4.94 (1H, d, J ) 5.8 Hz), 5.31
3
4
(1H, dq, J ) 5.8 Hz, J ) 1.0 Hz), 6.60 (1H, d, J ) 8.8 Hz),
7.26 (2H, d, J ) 8.8 Hz); Z isomer, 1.75 (3H, m), 3.05 (6H, s),
3.21 (3H, s), 3.42 (2H, s), 4.63 (1H, d, J ) 6.0 Hz), 5.42 (1H, d,
3J ) 6.0 Hz,), 6.55 (1H, d, J ) 8.8 Hz), 7.40 (2H, d, J ) 8.8
Hz); 13C NMR 50 MHz (C6D6) δ (ppm) E isomer, 15.8, 45.4,
51.5, 54.7, 100.1, 114.7, 126.4, 134.4 (2C), 126.4, 137.0, 159.6;
Z isomer, 22.4, 38.8, 51.7, 54.7, 99.8, 114.9 126.8, 133.1, 126.4,
137.2, 159.6.
1,1-Dim eth oxy-3-m eth yl-4-((4-ch lor op h en yl)th io)bu t-
2-en e (4f). Using method B with 3 (2.8 g, 17 mmol) and
4-chlorothiophenol (2.6 g, 18 mmol), 4f was recovered (4.1 g,
85%) after 8 h: IR (neat) 1672 cm-1; mass spectrum (EI) m/ z
272-274 (M+•, 17-6), 240-242 (M+• - CH3OH, 42-20), 226-
1
228 (27-10), 128 (67), 75 (100); H NMR 200 MHz (C6D6) δ
4
(ppm) E isomer, 1.65 (3H, d, J ) 1.2 Hz), 3.01 (6H, s), 3.07
3
4
(2H, s), 4.89 (1H, d, J ) 5.8 Hz), 5.33 (1H, dq, J ) 5.8 Hz, J
4
) 1.2 Hz), 6.93 (4H, m); Z isomer, 1.66 (3H, d, J ) 1.3 Hz),
3.05 (6H, s), 3.34 (2H, s), 4.73 (1H, d, J ) 5.9 Hz), 5.40 (1H,
3
4
dq, J ) 5.9 Hz, J ) 1.3 Hz), 6.93 (4H, m).
1,1-Dim et h oxy-3-m et h yl-4-(2-p yr id in et h io)b u t -2-en e
(4g). Using method A with 3 (2.8 g, 17 mmol) and 2-pyridi-
nethiol (2.0 g, 18 mmol), 4g was recovered (3.9 g, 96%) after
15 days: IR (neat) 1670 cm-1; mass spectrum (EI) m/ z 239
(M+•, 6), 208 (100), 164 (41), 111 (21); 1H NMR 200 MHz (C6D6)
F igu r e 10. Theoretical structures of 39a (s-ax) (top) and 39a (s-
eq) (bottom).
4
δ (ppm) E isomer, 1.77 (3H, d, J ) 1.2 Hz), 3.10 (6H, s), 3.89
3
4
(2H, s), 5.01 (1H, d, J ) 5.8 Hz), 5.80 (1H, dq, J ) 5.8 Hz, J
) 1.2 Hz), 6.34-6.38 (1H, m), 6.70-6.87 (2H, m), 8.14-8.25
added dropwise, at 20 °C, a solution of aryl thiol in ether (9.5
M). The mixture was stirred until disappearance of 3 (GC);
the precipitate was then filtered out and washed with ether.
After evaporation of the solvent, the crude thioether 4 was
recovered in 67-97% yield as a 7:3 mixture of E and Z isomers.
Meth od B. To a mixture of aryl thiol in concentrated
aqueous soda (1.8 M) was added a solution of 3 in ether (1.0
M). The mixture was stirred until disappearance of 3 (GC);
then the aqueous phase was extracted two times by ether then
dried. After evaporation, the crude product was recovered in
78-91% yield as a 7:3 mixture of E and Z isomers.
4
(1H, m); Z isomer, 1.75 (3H, d, J ) 1.2 Hz), 3.20 (6H, s), 4.17
4
3
(2H, d, J ) 0.5 Hz), 5.35 (1H, d, J ) 6.0 Hz), 5.53 (1H, dq, J
) 6.0 Hz, 4J ) 1.2 Hz), 6.34-6.38 (1H, m), 6.70-6.87 (2H, m),
8.14-8.25 (1H, m); 13C NMR 50 MHz (C6D6) δ (ppm) E isomer,
16.2, 38.1, 51.5, 100.2, 119.4, 122.4, 126.2, 135.7, 137.4, 149.6,
158.9; Z isomer, 22.5, 31.4, 51.9, 101.4,120.8, 122.2, 127.1,
137.0, 137.4, 149.4, 159.2.
1,1-Dim eth oxy-3-m eth yl-4-((2,6-d im eth ylp h en yl)th io)-
bu t-2-en es (4h ). Using method B with 3 (1.4 g, 8.5 mmol)
and 2,6-dimethylthiophenol (1.2 g, 8.9 mmol), 4h was recov-
ered (1.9 g, 84%) after 8 days: IR (neat) 1672 cm-1; mass
spectrum (EI) m/ z 266 (M+•, 25), 234 (M+• - CH3OH, 39), 128
1,1-D im e t h o x y -3-m e t h y l-4-(2-n a p h t h y lt h io )b u t -2-
en es (4c). Using method A with 3 (2.8 g, 17 mmol) and
naphthane-2-thiol (2.9 g, 18 mmol), 4c was recovered (4.1 g,
84%) after 6 days: pale yellow solid, mp 133-135 °C (Et2O);
IR (neat) 1671 cm-1; mass spectrum (EI) m/ z 288 (M+•, 31),
256 (M+• - CH3OH, 14), 225 (10), 199 (38), 128 (100), 115 (52);
1
(100); H NMR 200 MHz (C6D6) δ (ppm) E isomer, 1.75 (3H,
d, 4J ) 1.2 Hz), 2.45 (6H, s), 2.99 (2H, s), 3.02 (6H, s), 4.91
3
4
(1H, d, J ) 5.9 Hz), 5.16 (1H, dq, J ) 5.9 Hz, J ) 1.2 Hz),
4
6.90 (3H, m); Z isomer, 1.73 (3H, d, J ) 1.4 Hz), 2.52 (6H, s),
3.03 (6H, s), 3.23 (2H, s), 4.50 (1H, d, J ) 5.5 Hz), 5.33 (1H,
4
1H NMR 200 MHz (C6D6) δ (ppm) E isomer, 1.78 (3H, d, J )
dq, J ) 5.5 Hz, J ) 1.4 Hz), 6.90 (3H, m); 13C NMR 50 MHz
(C6D6) δ (ppm) E isomer, 16.2, 22.1, 44.3, 51.4, 100.0, 125.9,
128.4, 133.6, 137.2, 143.4; Z isomer, 22.1, 22.7, 37.0, 51.6, 99.9,
126.6, 128.5, 134.1, 137.7, 143.8.
3
4
1.2 Hz), 3.00 (6H, s), 3.32 (2H, s), 4.96 (1H, d, J ) 5.8 Hz),
(52) GAUSSIAN 92, Revision B: Frisch, M. B.; Trucks, G. W.; Head-
Gordon, M.; Gill, P. M. W.; Wong, M. W.; Foresman, J . B.; J ohnson, B.
G.; Schlegel, H. B.; Robb, M.A.; Replogle, E. S.; Gonperts, R.; Andres,
J . L.; Raghavachari, K.; Binkley, J . S.; Gonzalez, C.; Martin, R. L.;
Fox, D. J .; Defrees, D. J .; Baker, J .; Stewart, J .J . P.; Pople, J . A.,
Gaussian, Inc., Pittsburgh, PA, 1992.
(53) The authors have deposited atomic coordinates for structures
25 and 28 the Cambridge Crystallographic Data Centre. The coordi-
nates can be obtained, on request, from the Director, Cambridge Crys-
tallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
1,1-Dim eth oxy-2-(ph en ylth io)eth an e (20). Using method
A with 1,1-dimethoxy-2-chloroethane (2.5 g, 20 mmol) and
thiophenol (6.1 mL, 60 mmol), 20 was recovered (1.6 g, 40%
1
conversion) after 5 days: IR (neat) 1578 cm-1; H NMR 200
MHz (C6D6) δ (ppm) 3.01 (2H, d, J ) 5.7 Hz), 3.05 (6H, s),
4.46 (1H, t, J ) 5.7 Hz), 6.85-7.40 (5H, m); 13C NMR 50 MHz
(C6D6) δ (ppm) 36.5, 53.0, 103.4, 126.1, 129.1, 129.3, 137.3.

5302 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
2-((P h en ylth io)m eth yl)-1,3-dioxolan e (22). Using method
A with 2-(chloromethyl)-1,3-dioxolane (3.8 g, 31 mmol) and
thiophenol (6.1 mL, 60 mmol), 22 was recovered (2.6 g, 43%
conversion) after 7 days: IR (neat) 1582 cm-1; mass spectrum
(ppm) 1E,3E isomer, 20.3 (2C), 56.0, 108.9, 117.4, 125.9, 126.8,
128.1, 130.4, 128.0, 136.9, 137.8, 151.3; 1Z,3E isomer, 14.5,
20.3, 55.6, 103.6, 114.9, 126.1, 126.8, 128.3, 130.4, 128.0, 136.8,
137.7, 148.8.
1
(EI) m/ z 196 (M+•, 32), 135 (21), 123 (11), 73 (100); H NMR
(1E, 3E)- a n d (1Z, 3E)-4-Meth oxy-2-m eth yl-1-((4-m eth -
oxyp h en yl)th io)bu ta -1,3-d ien e (5e). Following the above
procedure, this compound was obtained as a 65:35 mixture of
E,E and Z,E isomers (89%): IR (neat) 1630 cm-1; mass
spectrum (IE) m/ z 236 (M+•, 57), 205 (29), 139 (100), 113 (28),
84 (62); 1H NMR 200 MHz (C6D6) δ (ppm) 1E,3E isomer, 1.87
(3H, s), 3.17 (3H, s), 3.25 (3H, s), 5.58 (1H, d, 12.8 Hz), 6.00
(1H, s), 6.48 (1H, d, J ) 12.8 Hz), 6.65 (2H, d, J ) 8.8 Hz),
7.29 (2H, d, J ) 8.8 Hz); 1Z,3E isomer, 1.67 (3H, s), 3.12 (3H,
s), 3.25 (3H, s), 5.80 (1H, s), 6.40 (1H, d, 12.9 Hz), 6.58 (1H, d,
J ) 12.9 Hz), 6.63 (2H, d, J ) 8.8 Hz), 7.33 (2H, d, J ) 8.8
Hz).
200 MHz (C6D6) δ (ppm) 3.01 (2H, d, J ) 4.1 Hz), 3.25-3.55
(4H, m), 5.01 (1H, t, J ) 4.1 Hz), 6.85-7.40 (5H, m); 13C NMR
50 MHz (C6D6) δ (ppm) 38.0, 65.2, 103.3, 126.0, 129.1, 129.3,
137.5.
2-(2′-Me t h yl-3′-(p h e n ylt h io)p r op -2′-e n yl)-1,3-d iox-
ola n e (12a ). To a solution of 4b (0.3 g, 1.3 mmol) and glycol
(0.1 mL, 1.8 mmol) in ether (4 mL) were added a little p-TSA
and methyl orthoformate (0.04 mL, 0.4 mmol). After 4 h at
room temperature, saturated NaHCO3 (10 mL) was added. The
organic layer was separated, dried (MgSO4), and evaporated.
The crude product was purified by chromatography on silica
gel using 3/7 ether/petroleum ether as eluent to give 12a (200
mg, 68%) as a 75:25 mixture of E and Z isomers, respectively:
IR (neat) 1675 cm-1; mass spectrum (EI) m/ z 236 (M+•, 6),
175 (23), 126 (29), 73 (100); exact mass calcd for C13H16O2S
m/ z 236.0871, found 236.0858; 1H NMR 200 MHz (C6D6) δ
(ppm) E isomer, 1.71 (3H, s), 3.17 (2H, s), 3.28-3.35 (2H, m),
3.46-3.53 (2H, m), 5.38 (1H, d, J ) 6.6 Hz), 5.51 (1H, d, J )
6.6 Hz), 6.86-7.34 (5H, m); Z isomer, 1.68 (3H, s), 3.47 (2H,
s), 3.28-3.35 (2H, m), 3.46-3.53 (2H, m), 5.30 (1H, d, J ) 6.7
Hz), 5.51 (1H, d, J ) 6.6 Hz), 6.86-7.34 (5H, m); 13C NMR 50
MHz (C6D6) δ (ppm) E isomer, 15.8, 43.3, 64.7, 100.3, 126.4,
129.0, 130.5, 136.7, 138.5; Z isomer, 22.7, 36.3, 64.7, 100.0,
126.4, 129.0, 130.5, 136.7, 138.5.
(1E, 3E)- a n d (1Z, 3E)-4-Meth oxy-2-m eth yl-1-((4-ch lo-
r op h en yl)th io)bu ta -1,3-d ien e (5f). Following the above
procedure, this compound was obtained as a 55:45 mixture of
E,E and Z,E isomers (98%): IR (neat) 1692 cm-1; mass
spectrum (EI) 242-240 (M+•, 13-31), 209 (24), 144 (26), 113
1
(100); H NMR 200 MHz (C6D6) δ (ppm) 1E,3E isomer, 1.79
4
(3H, d, J ) 0.8 Hz), 3.12 (3H, s), 5.55 (1H, d, J ) 12.7 Hz),
5.81 (1H, s), 6.47 (1H, d, J ) 12.7 Hz), 6.90-7.00 (4H, m);
1Z,3E isomer, 1.64 (3H, d, 4J ) 1.2 Hz), 3.12 (3H, s), 5.61 (1H,
s), 6.31 (1H, d, J ) 12.9 Hz), 6.65 (1H, d, J ) 12.9 Hz), 6.90-
7.00 (4H, m); 13C NMR 50 MHz (C6D6) δ (ppm) 1E,3E isomer,
20.2, 56.1, 100.0, 114.0, 129.2, 129.3, 131.6, 136.3, 138.5, 151.7;
1Z,3E isomer, 14.5, 55.7, 103.4, 116.5, 129.2, 129.3, 131.6,
136.3, 138.5, 149.3.
2-(2′-Meth yl-3′-(p h en ylth io)p r op -2′-en yl)-4-p h en yl-1,3-
d ioxola n e (12b). To a solution of 4b (0.5 g, 2.1 mmol) and
phenylglycol (0.29 g, 2.1 mmol) in ether (5 mL) were added a
little TsOH and methyl orthobenzoate (0.02 mL, 0.1 mmol).
After 4 h at room temperature, saturated NaHCO3 (10 mL)
was added. The organic layer was separated, dried (MgSO4),
and evaporated. The crude product was purified by chroma-
tography on silica gel using 15/84/1 ether/petroleum ether/
triethylamine as eluent to give 12b (430mg, 66%) as a complex
mixture of isomers: IR (neat) 1680 cm-1; mass spectrum (EI)
m/ z 312 (M+•, 12), 202 (55), 55 (100); exact mass calcd for
(1E, 3E)- a n d (1Z, 3E)-4-Meth oxy-2-m eth yl-1-(2-p yr id i-
n ylth io)bu ta -1,3-d ien e (5g). Following the above procedure,
this compound was obtained as a 63:37 mixture of E,E and
Z,E isomers (93%): IR (neat) 1628 cm-1; mass spectrum (EI)
m/ z 207 (M+•, 100), 192 (93), 174 (41), 111 (60); 1H NMR 200
4
MHz (C6D6) δ (ppm) 1E,3E isomer, 1.72 (3H, d, J ) 1.7 Hz),
3.12 (3H, s), 6.25 (1H, d, J ) 12.7 Hz), 6.41 (1H, m), 6.59 (1H,
s), 6.67 (1H, d, J ) 12.7 Hz), 6.80-6.90 (2H, m), 8.27 (1H, m);
1Z,3E isomer, 1.81 (3H, d, 4J ) 0.8 Hz), 3.10 (3H, s), 5.69 (1H,
d, J ) 12.8 Hz), 6.41 (1H, m), 6.49 (1H, d, J ) 12.8 Hz), 6.80-
6.90 (2H, m), 6.96 (1H, s), 8.27 (1H, m); 13C NMR 50 MHz
(C6D6) δ (ppm) 1E,3E isomer, 20.4, 55.7, 104.0, 112.5, 119.5,
121.5, 134.9, 135.3, 136.0, 151.0; 1Z,3E isomer, 15.1, 55.8,
109.0, 114.7, 119.6, 121.8, 134.9, 135.3, 136.0, 149.8.
(1E, 3E)- a n d (1Z, 3E)-4-Meth oxy-2-m eth yl-1-((2,6-d im -
et h ylp h en yl)t h io)bu t a -1,3-d ien e (5h ) a n d (E)-3-[((2,6-
Dim e t h ylp h e n yl)t h io)m e t h yl]-1-m e t h oxyb u t a -1,3-d i-
en e (11). Following the above procedure, this compound was
obtained as a 28:10:62 mixture of 1E,3E, 1Z,3E (5h ), and exo
isomers (11) in an overall 95% yield: IR (neat) 1668, 1640
cm-1; mass spectrum (EI) m/ z 234 (M+•, 100), 219 (13), 203
(25), 187 (46); 1H NMR 200 MHz (C6D6) δ (ppm) 5h 1E,3E
isomer, 1.85 (3H, d, 4J ) 1.0 Hz), 2.45 (6H, s), 3.11 (3H, s),
5.40 (1H, d, J ) 12.6 Hz), 5.45 (1H, s), 6.42 (1H, d, J ) 12.6
Hz), 6.90-7.00 (3H, m); 1Z,3E isomer, 1.56 (3H, d, 4J ) 1.1
Hz), 2.45 (6H, s), 3.11 (3H, s), 5.30 (1H, s), 6.36 (1H, d, J )
12.9 Hz), 6.63 (1H, d, J ) 12.6 Hz), 6.90-7.00 (3H, m); an
NOE experiment showed that irradiation at δ 1.56 resulted
in enhancements at δ 5.30 and 6.63; 11, 2.49 (6H, s), 3.11 (3H,
s), 3.20 (2H, s), 4.47 (1H, d, J ) 1.0 Hz), 4.66 (1H, d, J ) 1.0
Hz), 5.45 (1H, d, J ) 12.7 Hz), 6.77 (1H, d, J ) 12.7 Hz), 6.90-
7.00 (3H, m).
1
C19H20O2S m/ z 312.1184, found 312.1207; H NMR 200 MHz
(C6D6) δ (ppm) 1.70-1.80 (3H, m), 3.03-3.22 (2H, m), 3.33-
4.07 (2H, m), 4.60-4.96 (1H, m), 5.40-5.85 (2H, m), 6.85-
7.35 (10H, m).
Gen er a l En ol (21, 23) a n d Dien ol (5, 13) Eth er s P r ep a -
r a tion . To a solution of the corresponding thioether (4, 20,
22) in ether (0.1 M) was added dropwise, at -70 °C, exactly 1
equiv of t-BuLi in pentane. The mixture was stirred for 5 min
at -70 °C and then warmed up to 20 °C for 30 min. The
reaction was then quenched by addition of absolute methanol
(1 mL) followed by concentrated NaHCO3 (10 mL). The
medium is extracted two times with 10 mL of ether and then
dried (K2CO3) and evaporated to yield the enol (21, 23) or
dienol (5, 13) ethers in 89-98% yield. Data for compounds
5a ,b have already been reported.11a,c
(1E, 3E)- a n d (1Z, 3E)-4-Meth oxy-2-m eth yl-1-(2-n a p h -
th ylth io)bu ta -1,3-d ien e (5c). Following the above proce-
dure, this compound was obtained as a 65:35 mixture of E,E
and Z,E isomers (91%): mass spectrum (CI, CH4) m/ z 257 (M
+ H+, 100), 285 (M + C2H5+, 6); H NMR 200 MHz (C6D6) δ
1
(ppm) 1E,3E isomer, 1.90 (3H, d, 4J ) 0.9 Hz), 3.14 (3H, s),
5.62 (1H, d, J ) 13.2 Hz), 6.10 (1H, s), 6.50 (1H, d, J ) 13.2
Hz), 7.10-7.80 (7H, m); 1Z,3E isomer, 1.69 (3H, d, 4J ) 1.1
Hz), 3.15 (3H, s), 5.80 (1H, s), 6.48 (1H, d, J ) 13.6 Hz), 6.71
(1H, d, J ) 13.6 Hz), 7.10-7.80 (7H, m).
2-Meth oxy-1-(p h en ylth io)eth ylen e (21). Following the
above procedure, this compound was obtained as a 90:10
mixture of E and Z isomers (90%): 1H NMR 400 MHz (C6D6)
δ (ppm) E isomer, 2.98 (3H, s), 5.21 (1H, d, J ) 12.3 Hz), 6.77
(1H, d, J ) 12.3 Hz), 6.90-7.40 (5H, m); Z isomer, 3.03 (3H,
s), 5.04 (1H, d, J ) 5.1 Hz), 5.81 (1H, d, J ) 5.1 Hz), 6.90-
7.40 (5H, m).
(1E,3E)- a n d (1Z,3E)-4-(2-Hyd r oxyeth oxy)-2-m eth yl-1-
(p h en ylth io)bu ta -1,3-d ien e (13a ). Following the above
procedure, this compound was obtained as a 60:40 mixture of
E,E and Z,E isomers (95%): IR (neat) 3430, 1635 cm-1; mass
spectrum (EI) m/ z 236 (M+•, 31), 143 (45), 110 (62), 73 (100);
exact mass calcd for C13H16O2S m/ z 236.0871, found 236.0876;
1H NMR 400 MHz (C6D6) δ (ppm) 1E,3E isomer, 1.30 (1H, m),
(1E, 3E)- a n d (1Z, 3E)-4-Meth oxy-2-m eth yl-1-((2-m eth -
ylp h en yl)th io)bu ta -1,3-d ien e (5d ). Following the above
procedure, this compound was obtained as a 57:43 mixture of
E,E and Z,E isomers (97%): IR (neat) 1630 cm-1; mass
spectrum (EI) m/ z 220 (M+•, 100), 205 (8), 189 (42), 161 (9);
1H NMR 200 MHz (C6D6) δ (ppm) 1E,3E isomer, 1.86 (3H, d,
4J ) 1.0 Hz), 2.32 (3H, s), 3.12 (3H, s), 5.57 (1H, d, J ) 12.7
Hz), 5.91 (1H, s), 6.48 (1H, d, J ) 12.7 Hz), 6.90-7.40 (4H,
4
m); 1Z,3E isomer, 1.67 (3H, d, J ) 1.2 Hz), 2.33 (3H, s), 3.13
(3H, s), 5.71 (1H, s), 6.42 (1H, d, J ) 12.9 Hz), 6.68 (1H, d, J
) 12.9 Hz), 6.90-7.40 (4H, m); 13C NMR 50 MHz (C6D6) δ

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5303
4
1.86 (3H, d, J ) 1.0 Hz), 3.31 (4H, m), 5.65 (1H, d, J ) 12.6
NOS m/ z 221.0875, found 221.0860; 1H NMR 200 MHz
(CDCl3) δ (ppm) 3.05 (4H, m), 3.72 (4H, m), 4.90 (1H, d, J )
13.0Hz), 6.51 (1H, d, J ) 13.0 Hz), 7.25 (5H, s); 13C NMR 50
MHz (CDCl3) δ (ppm) 48.1, 65.8, 83.8, 124.3, 125.1, 128.3,
140.6, 150.3.
Hz), 6.01 (1H, s), 6.38 (1H, d, J ) 12.6 Hz), 6.85-7.35 (5H,
m); 1Z,3E isomer, 1.30 (1H, m), 1.67 (3H, d, 4J ) 1.1 Hz), 3.31
(4H, m), 5.80 (1H, s), 6.46 (1H, d, J ) 12.8 Hz), 6.57 (1H, d, J
) 12.8 Hz), 6.85-7.35 (5H, m).
(1E, 3E)- a n d (1Z, 3E)-4-(2-H yd r oxy-1-(or 2-)p h en yl-
et h oxy)-2-m et h yl-1-(p h en ylt h io)bu t a -1,3-d ien e (13b ,c).
Following the above procedure, this compound was obtained
as a complex mixture of isomers (89%): IR (neat) 3416, 1630
cm-1; mass spectrum (EI) m/ z 312 (M+•, 20), 281 (5), 250 (11),
206 (45), 193 (41), 175 (40), 107 (100); 1H NMR 200 MHz (C6D6)
δ (ppm) 1.76 and 1.88 (3H, 2s), 3.50-3.85 (2H, m), 4.60-4.85
(1H, m), 5.55-6.80 (3H, m), 6.90-7.60 (10H, m).
(3-Met h yl-4-(p h en ylsu lfin yl)b u t a -1,3-d ien yl)-2-oxoet -
h yl Acr yla te (17). The experimental procedure is identical
to that described above for 13a except that the reaction was
quenched with neat acryloyl chloride (1 equiv) for 15 min at
-60 °C; the medium was then warmed up to room tempera-
ture. Usual workup yields crude 14 [(1E,3E)/(1Z,3E) ) 60:
40] which was not purified at this stage but used as such or
directly oxidized into the more stable corresponding sulfoxide
17, according to the following procedure.
To a CH2Cl2 solution of 14 (0.2 M) was added at 0 °C under
argon neat MCPBA (1.05 equiv). After 5 min the reaction was
quenched with sodium thiosulfate (3 equiv) and NaHCO3 (4
equiv). The solution was filtered and then evaporated, and
the crude oil obtained was directly chromatographed on silica
gel using ether/petroleum ether/triethylamine (15/84/1) as
eluent to yield 17 (60% overall): mass spectrum (CI, iBuH)
m/ z 307 (M + H+, 80), 363 (M + C4H9+, 7); 1H NMR 360 MHz
(C6D6) δ (ppm) 1E,3E isomer, 1.40 (3H, s), 3.42 (2H, m), 4.05
(2H, m), 5.25 (2H, m), 5.60-6.60 (4H, m), 7.05 (3H, m), 7.65
(2H, m); 1Z,3E isomer, 1.82 (3H, s), 3.42 (2H, m), 4.05 (2H,
m), 5.25 (2H, m), 5.60-6.60 (4H, m), 7.05 (3H, m), 7.65 (2H,
m).
1-(2-Na p h th ylth io)-2-m eth yl-4-m or p h olin obu ta -1,3-d i-
en e (8c). Following the procedure reported previously for
compounds 6, 7, and 8a ,11a,c 8c was obtained as a 56:44 mixture
of E,E and Z,E isomers (80%): IR (neat) 2852, 1620, 1500, 1446
cm-1; mass spectrum (EI) m/ z 311 (M+•, 46), 282 (84), 225 (84),
160 (100), 115 (47), 107 (67); exact mass calcd for C19H21NOS
1
m/ z 311.1344, found 311.1345; H NMR 200 MHz (CDCl3) δ
(ppm) 1E,3E isomer, 2.05 (3H, s), 3.02 (4H, m), 3.73 (4H, m),
5.77 (1H, s), 5.90 (1H, d, J ) 13.6 Hz), 6.35 (1H, d, J ) 13.7
Hz), 7.15-7.85 (7H, m); 1Z,3E isomer, δ (ppm) 2.05 (3H, s),
3.02 (4H, m), 3.73 (4H, m), 5.48 (1H, d, J ) 13.6 Hz), 6.01
(1H, s), 6.28 (1H, d, J ) 13.6 Hz), 7.15-7.85 (7H, m); 13C NMR
50 MHz (C6D6) δ (ppm) 1E,3E isomer, 20.3, 48.2, 65.7, 99.1,
109.2, 124.6, 125.0, 125.9, 126.3, 126.8, 127.6, 128.3, 131.6,
134.1, 137.0, 141.3, 141.5; 1Z,3E isomer, 20.3, 48.4, 65.7, 104.4,
111.8, 124.6, 125.0, 125.4, 126.3, 126.6, 127.3, 128.3, 131.6,
134.1, 137.0, 139.6, 141.3.
2-((3-Met h yl-4-(p h en ylsu lfin yl)b u t a -1,3-d ien yl)oxy)-
eth yl Cr oton a te (18). A similar procedure using crotonoyl
chloride led to 15 [(1E,3E)/(1Z,3E) ) 60:40]. As above, this
compound may be used as such or directly oxidized into its
more stable sulfoxide 18 (44% overall): IR (neat) 1716, 1632,
1626 cm-1; mass spectrum (CI, NH3) m/ z 321 (M + H+, 100),
338 (M + NH4+, 26); 1H NMR 360 MHz (C6D6) δ (ppm) 1E,3E
isomer, 1.33 (3H, m), 1.84 (3H, s), 3.34 (2H, t, J ) 5.3 Hz),
4.10 (2H, t, J ) 5.3 Hz), 5.17 (1H, d, J ) 13.3 Hz), 5.80 (1H,
m), 6.00 (1H, s), 6.39 (1H, d, J ) 13.3 Hz), 7.00 (1H, m), 7.12
(3H, m), 7.73 (2H, m); 1Z,3E isomer, 1.32 (3H, m), 1.39 (3H,
s), 3.34 (2H, t, J ) 5.3 Hz), 4.10 (2H, t, J ) 5.3 Hz), 5.80 (1H,
m), 5.82 (1H, s), 6.48 (1H, d, J ) 13.3 Hz), 6.59 (1H, d, J )
13.3 Hz), 7.00 (1H, m), 7.12 (3H, m), 7.73 (2H, m); 13C NMR
50 MHz (C6D6) δ (ppm) 1E,3E isomer, 14.2, 17.5, 62.1, 68.0,
108.4, 122.4, 124.3, 129.1, 129.9, 133.0, 143.6, 145.3, 147.4,
152.0, 165.7; 1Z,3E isomer, 17.5, 19.8, 62.1, 68.0, 103.3, 122.4,
124.3, 129.1, 129.9, 131.7, 142.9, 145.3, 147.4, 152.7, 165.7.
Eth yl 2-((3-Meth yl-4-(p h en ylth io)bu ta -1,3-d ien yl)oxy)-
eth yl F u m a r a te (16). A similar procedure using crotonoyl
chloride leads to 16 [(1E,3E)/(1Z,3E) ) 60:40] in 70% yield.
This compound has been used as such without any further
purification: mass spectrum (CI, iBuH) m/ z 363 (M + H+,
100), 380 (M + NH4+, 15), 419 (M + C4H9+, 35); 1H NMR 200
MHz (C6D6) δ (ppm) 1E,3E isomer, 0.87 (3H, t, J ) 7.1 Hz),
1-((4-Ch lor op h en yl)th io)-2-m eth yl-4-m or p h olin obu ta -
1,3-d ien e (8d ). Following the above procedure, this compound
was obtained as a 50:50 mixture of E,E and Z,E isomers
(80%): IR (neat) 2852, 1622, 812 cm-1; mass spectrum (EI)
m/ z 297 (M+•, 45), 295 (M+•, 46), 211 (24), 209 (59), 152 (27),
75 (100); exact mass calcd for C15H18ClNOS m/ z 297.0786 and
295.0792, found 297.0768 and 295.0797; 1H NMR 200 MHz
(CDCl3) δ (ppm) 1E,3E isomer, 1.95 (3H, s), 2.95 (4H, m), 3.70
(4H, m), 5.55 (1H, s), 5.75 (1H, d, J ) 14.0 Hz), 6.80 (1H, d, J
) 14.0 Hz), 7.10-7.35 (4H, m); (1Z,3E) isomer, δ (ppm) 1.92
(3H, s), 2.95 (4H, m), 3.70 (4H, m), 5.30 (1H, d, J ) 14.0 Hz),
5.77 (1H, s), 6.20 (1H, d, J ) 14.0 Hz), 7.10-7.35 (4H, m).
(1E,3E)- a n d (1Z,3E)-2-Meth yl-1-(p h en ylth io)-4-p ip er i-
d in obu ta -1,3-d ien e (9). The experimental procedure was
similar to that previously described for 8b (ref 11a) but
starting this time from 4b; it yielded crude 9 in 82% [(1E,3E)/
(1Z,3E) ) 55:45]: IR (neat) 1615 cm-1; mass spectrum (CI,
CH4) m/ z 260 (M + H+, 100); 1H NMR 400 MHz (CDCl3) δ
(ppm) 1E,3E isomer, 1.57 (6H, m), 1.99 (3H, s), 3.00 (4H, m),
5.55 (1H, s), 5.76 (1H, d, J ) 13.9 Hz), 6.37 (1H, d, J ) 13.9
Hz), 7.1-7.3 (5H, m); 1Z,3E isomer, 1.57 (6H, m), 1.99 (3H,
s), 3.00 (4H, m), 5.36 (1H, d, J ) 13.9 Hz), 5.81 (1H, s), 6.29
(1H, d, J ) 13.9 Hz), 7.1-7.3 (5H, m); 13C NMR 50 MHz
(CDCl3) δ (ppm) 1E,3E isomer, 20.6, 25.3, 49.5, 97.2, 107.3,
124.9, 127.0, 128.6, 138.6, 141.8, 142.1; 1Z,3E isomer, 14.5,
24.2, 49.5, 102.6, 109.8, 126.9, 127.0, 128.5, 138.1, 140.4, 143.1.
(1E,3E)- a n d (1Z,3E)-4-(Dieth yla m in o)-2-m eth yl-1-(p h e-
n ylth io)bu ta -1,3-d ien e (10). Following the above procedure,
this compound was obtained in 78% [(1E,3E)/(1Z,3E) ) 50:
50] yield: IR (neat) 1620 cm-1; mass spectrum (CI, CH4) m/ z
248 (M + H+, 100); 1H NMR 400 MHz (CDCl3) δ (ppm) 1E,3E
isomer, 1.12 (6H, m), 2.01 (3H, s), 3.12 (4H, q, J ) 7.2 Hz),
5.47 (1H, s), 5.61 (1H, d, J ) 13.8 Hz), 6.46 (1H, d, J ) 13.8
Hz), 7.1-7.3 (5H, m); 1Z,3E isomer, 1.12 (6H, m), 2.01 (3H,
s), 3.12 (4H, q, J ) 7.2 Hz), 5.23 (1H, d, J ) 13.9 Hz), 5.73
(1H, s), 6.40 (1H, d, J ) 13.9 Hz), 7.1-7.3 (5H, m); 13C NMR
50 MHz (CDCl3) δ (ppm) 1E,3E isomer, 13.0, 20.5, 45.2, 94.9,
104.5, 124.5, 126.7, 128.5, 138.9, 139.8, 142.7; 1Z,3E isomer,
13.0, 14.4, 45.2, 99.6, 106.6, 124.5, 126.4, 128.9, 138.1, 139.4,
144.7. Anal Calcd for C15H21NS: C, 72.82; H, 8.55; N, 5.66.
Found: C, 72.59; H, 8.58; N, 5.45.
4
1.83 (3H, d, J ) 0.8 Hz), 3.39 (2H, t, J ) 4.8 Hz), 3.93 (4H,
m), 5.62 (1H, d, J ) 12.7 Hz), 6.00 (1H, s), 6.35 (1H, d, J )
12.7 Hz), 6.85-7.07 (4H, m), 7.28 (2H, m); 1Z,3E isomer, 0.87
4
(3H, t, J ) 7.1 Hz), 1.67 (3H, d, J ) 1.1 Hz), 3.39 (2H, t, J )
4.8 Hz), 3.93 (4H, m), 5.79 (1H, s), 6.37 (1H, d, J ) 12.9 Hz),
6.56 (1H, d, J ) 12.9 Hz), 6.85-7.07 (4H, m), 7.28 (2H, m);
13C NMR 50 MHz (C6D6) δ (ppm) 1E,3E isomer, 13.9, 20.2,
61.0, 63.4, 67.5, 105.0, 115.8, 125.9, 128.2, 129.2, 132.9, 133.7,
137.2, 147.4, 164.4; 1Z,3E isomer, 13.9, 14.5, 61.0, 63.2, 66.9,
110.5, 118.5, 125.9, 128.2, 129.2, 132.9, 133.7, 137.2, 149.9,
164.4.
6-(1,1-Dim eth yleth yl)-4-m eth yl-3-(ph en ylth io)cycloh ex-
4-en e-1,2-d ica r boxylic An h yd r id e (25). To a solution of 7b
(0.9 g, 3.9 mmol) in mixed xylenes (15 mL) were added maleic
anhydride (0.7 g, 7.6 mmol) and a little hydroquinone. The
mixture was stirred for 2 days at 140 °C. The solvent was
then evaporated and the crude material crystallized from ethyl
acetate/petroleum ether to yield 25 (680 mg, 62%). The 1Z,3E
unreacted isomer of 7b was recovered (180 mg) by flash
chromatography using ethyl acetate/petroleum ether (15/85)
as eluent: mp 156-158 °C; IR (neat) 1774 cm-1; mass
spectrum (EI) m/ z 330 (M+•, 15), 279 (3), 241 (8), 110 (67), 57
(100); exact mass calcd for C19H22O3S m/ z 330.1290, found
330.1297; 1H NMR 200 MHz (CDCl3) δ (ppm) 0.96 (9H, s), 1.48
2-Mor p h olin o-1-(p h en ylth io)eth ylen e (24). Following
the above procedure, this compound was obtained in 82% in
its pure E form: yellow solid, mp ) 67-68 °C; IR (neat) 2852,
1950, 1598 cm-1; mass spectrum (EI) m/ z 221 (M+•, 100), 188
(29), 162 (29), 130 (76), 86 (27); exact mass calcd for C12H15
-

5304 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
(1H, m), 1.88 (3H, m), 2.62 (1H, dd, J ) 9.2 Hz, J ) 7.3 Hz),
2.90 (1H, dd, J ) 9.2 Hz, J ) 4.2 Hz), 3.34 (1H, m), 5.54 (1H,
m), 6.45-7.00 (3H, m), 7.20-7.23 (2H, m); NOE experiments
showed that irradiation at δ 3.34 ppm resulted in enhance-
ments at 1.48, 2.62, and 2.90 ppm; 13C NMR 50 MHz (CDCl3)
δ (ppm) 21.5, 28.2, 31.9, 43.5, 47.2, 47.3, 49.6, 124.6, 126.6,
129.4, 138.0, 140.4, 170.7, 171.7. Anal Calcd for C19H22O3S:
C, 69.09; H, 6.67. Found: C, 69.19; H, 6.83.
E t h yl 5-(1,1-Dim et h ylet h yl)-3-m et h yl-2-(p h en ylt h io)-
cycloh ex-3-en oa te (26) a n d Eth yl 6-(1,1-Dim eth yleth yl)-
4-m eth yl-3-(p h en ylth io)cycloh ex-4-en oa te (27). A solu-
tion of 7b (0.9 g, 3.9 mmol) in neat ethyl acrylate (10 mL) with
a little hydroquinone was stirred for 8 days at 100 °C. After
evaporation of the dienophile, the crude material was purified
by flash chromatography using ethyl acetate/petroleum ether
(2.5/97.5) as eluent to give unreacted 7b (300 mg, (1E,3E)/
(1Z,3E) ) 30/70) and a mixture of 26 and 27 (520 mg, 60%):
IR (neat mixture) 1732, 1582 cm-1; mass spectrum (EI) m/ z
332 (M+•, 32), 223 (59), 57 (100). NMR data follows.
Major isomer of 26: 1H NMR 360 MHz (CDCl3) δ (ppm) 0.86
(9H, s), 1.23 (3H, t, J ) 7.2 Hz), 2.24 (1H, ddd, J ) 14.4 Hz,
J ) 5.8 Hz, J ) 3.6 Hz), 2.33 (1H, m), 2.35 (1H, m), 2.72 (1H,
m), 3.59 (1H, t, J ) 5.8 Hz), 4.07 (2H, m), 5.68 (1H, m), 7.18-
7.41 (5H, m); 13C NMR 50 MHz (CDCl3) δ (ppm) 13.6, 22.5,
28.9, 31.7, 34.3, 41.1, 46.9, 49.0, 60.1, 126.5, 126.6, 129.0, 130.1,
135.6, 174.5.
4.36 ppm, that irradiation at δ 4.36 ppm resulted in enhance-
ments at 3.14 ppm, that irradiation at δ 2.96 ppm resulted in
enhancements at 4.48 ppm, and that irradiation at δ 4.48 ppm
resulted in enhancements at 2.96 ppm.
Spectral data for 28a : colorless solid, mp ) 151-152 °C;
IR (neat) 1776, 1698 cm-1; mass spectrum (EI) m/ z 317 (M+•
,
1
30), 123 (100); H NMR 200 MHz (C6D6) δ (ppm) 1.60 (3H, d,
4J ) 1.5Hz), 2.36 (1H, dd, J ) 10.4 Hz, J ) 5.5 Hz), 2.70 (1H,
dd, J ) 10.4 Hz, J ) 8.0 Hz), 2.76 (3H, s), 3.02 (3H, s), 3.58
(1H, d, J ) 8.0 Hz), 3.97 (1H, dd, J ) 5.5 Hz, J ) 5.0 Hz), 5.28
(1H, d, J ) 5.0 Hz), 6.92-7.15 (3H, m), 7.89 (2H, d, J ) 7.0
Hz); a NOE experiment showed that irradiation at δ 3.97 ppm
resulted in enhancements at 2.36, 3.03, and 5.28 ppm; 1H NMR
200 MHz (Pyr-d5) δ (ppm) 2.03 (3H, s), 3.12 (3H, s), 3.35 (3H,
s), 3.49 (1H, dd, J ) 5.0 Hz, J ) 9.7 Hz), 3.97 (1H, dd, J ) 8.3
Hz, J ) 10.2 Hz), 4.28 (1H, d, J ) 8.1 Hz), 4.56 (1H, dd, J )
5.2 Hz, J ) 5.6 Hz), 5.98 (1H, d, J ) 5.7 Hz), 7.45 (3H, m),
8.10 (2H, d, J ) 7.1 Hz); a set of NOE experiments showed
that irradiation at δ 4.56 ppm resulted in enhancements at δ
3.49 and 5.98 ppm and that irradiation at δ 4.28 ppm resulted
in enhancements at δ 3.97 ppm; 13C NMR 50 MHz (C6D6) δ
(ppm) 21.7, 24.6, 43.5, 45.7, 49.8, 55.3, 69.5, 122.6, 127.3, 129.1,
132.4, 140.4, 144.3, 175.2, 176.1. Anal Calcd for C17H19NO3S:
C, 64.33; H, 6.03; N, 4.41. Found: C, 64.14; H, 6.17; N, 4.33.
E t h yl 6-Met h oxy-4-m et h yl-3-(p h en ylt h io)cycloh ex-4-
en oa tes (30, 31) a n d Eth yl 5-Meth oxy-3-m eth yl-2-(p h e-
n ylth io)cycloh ex-3-en oa tes (32). To a solution of diene 5b
(0.4 g, 2.0 mmol) in neat ethyl acrylate (10 mL) was added a
little hydroquinone. The mixture was stirred for 3 days at
100 °C; then the dienophile was evaporated and the crude
material purified by flash chromatography using ethyl acetate/
petroleum ether (5/95) as eluent to give a mixture of 30, 31,
and 32a ,b (300 mg total, 72%): IR (neat mixture): 1732, 1582
cm-1; mass spectrum (EI) m/ z 306 (M+•, 16), 274 (22), 197 (51),
123 (100), 109 (25). Anal. Calcd for C17H22O3S: C, 66.67; H,
7.19. Found: C, 66.54; H, 7.07.
Minor isomer of 26: 1H NMR 360 MHz (CDCl3) δ (ppm) 0.86
(9H, s), 1.23 (3H, t, J ) 7.2 Hz), 2.00 (2H, m), 2.50 (1H, d, J
) 10.8 Hz), 2.98 (1H, dt, J ) 10.8 Hz, J ) 2.9 Hz), 3.54 (1H,
s), 4.07 (2H, m), 5.55 (1H, s), 7.18-7.41 (5H, m); 13C NMR 50
MHz (CDCl3) δ (ppm) 13.8, 22.1, 27.3, 32.5, 33.2, 36.8, 46.3,
48.3, 60.1, 126.5, 127.2, 129.0, 130.1, 136.0, 177.2.
Major isomer of 27: 1H NMR 360 MHz (CDCl3) δ (ppm) 0.86
(9H, s), 0.89 (3H, m), 1.90 (6H, m), 2.83 (1H, ddd, J ) 10.8
Hz, J ) 6.7 Hz, J ) 2.7 Hz), 3.42 (1H, dq, J ) 14.4 Hz, J )
10.8 Hz) 3.88 (1H, s),3.90 (1H, m), 5.52 (1H, s), 7.18-7.41 (5H,
m); 13C NMR 50 MHz (CDCl3) δ (ppm) 13.4, 20.7, 21.8, 26.9,
32.5, 45.2, 45.7, 52.3, 59.7, 126.5, 126.8, 129.0, 130.1, 133.5,
136.6, 172.3.
Spectral data for 30 (64%): 1H NMR 360 MHz (CDCl3) δ
(ppm) 0.95 (3H, t, J ) 7.1 Hz), 1.86 (3H, s), 2.22 (1H, ddd, J
) 13.5 Hz, J ) 3.2 Hz, J ) 3.2 Hz), 2.39 (1H, dddd, J ) 13.5
4
Minor isomer of 27: 1H NMR 360 MHz (CDCl3) δ (ppm) 0.87
(9H, s), 1.20 (3H, t, J ) 7.1 Hz), 1.91 (3H, s), 1.95 (1H, m),
1.98 (2H, m), 2.91 (1H, s), 4.02 (1H, s), 4.10 (2H, dq, J ) 7.1
Hz, J app ) 3.0 Hz), 5.55 (1H, s), 7.18-7.41 (5H, m); 13C NMR
50 MHz (CDCl3) δ (ppm) 14.1, 20.8, 22.9, 27.1, 32.6, 42.5, 44.2,
48.6, 60.4, 126.4, 127.6, 129.0, 130.1, 131.8, 136.5, 173.4.
N-Meth yl- a n d N-P h en yl-6-m eth oxy-4-m eth yl-3-(p h e-
n ylth io)cycloh ex-4-en e-1,2-d ica r boxa m id es (28, 29). To
a solution of 5b (0.4 g, 2.0 mmol) in ether (10 mL) were added
N-phenylmaleimide (1.0 g, 6.0 mmol) and a little hydro-
quinone. The mixture was stirred for 3 days at 40 °C. The
solvent was then evaporated, and the crude material was
purified by flash column chromatography on silica gel using
ethyl acetate/petroleum ether (80:20) as eluent to give 28b (315
mg, 70%) and a mixture of 39b and 29b.
Hz, J ) 6.3 Hz, J ) 3.2 Hz, J ) 1.0 Hz), 2.64 (1H, ddd, J )
13.5 Hz, J ) 13.5 Hz, J ) 11.2 Hz), 3.07 (3H, s), 3.20 (1H, m),
3.98 (3H, m), 5.59 (1H, m), 6.95 (3H, m), 7.34 (2H, m); 13C NMR
50 MHz (CDCl3) δ (ppm) 14.3, 22.5, 27.9, 45.5, 43.3, 56.2, 60.1,
72.7, 124.3, 127.0, 129.0, 132.2, 135.1, 140.6, 171.5.
Spectral data for 31 (23%): 1H NMR 360 MHz (CDCl3) δ
(ppm) 0.89 (3H, t, J ) 7.0 Hz), 1.78 (3H, t, J ) 1.4 Hz), 1.95
(1H, m), 2.12 (1H, m), 3.24 (3H, s), 3.20 (1H, m), 3.41 (1H, m),
3.98 (2H, m), 4.33 (1H, d, J ) 9.4 Hz), 5.54 (1H, s), 6.95 (3H,
m), 7.34 (2H, m); 13C NMR 50 MHz (CDCl3) δ (ppm) 14.1, 22.0,
32.0, 41.6, 49.3, 55.7, 60.4, 77.3, 126.3, 127.2, 129.2, 131.1,
135.4, 140.6, 174.6.
Spectral data for 32a (7%): 1H NMR 360 MHz (CDCl3) δ
(ppm) 0.76 (3H, t, J ) 7.1 Hz), 1.75 (3H, t, J ) 1.6 Hz), 2.16
(1H, ddd, J ) 13.1 Hz, J ) 13.1 Hz, J ) 10.2 Hz), 2.10 (1H,
m), 2.57 (1H, ddd, J ) 13.1 Hz, J ) 4.1 Hz, J ) 2.5 Hz), 3.09
(3H, s), 3.45 (1H, dq, J ) 11.6 Hz, J ) 7.1 Hz), 3.58 (1H, m),
3.83 (1H, m), 3.90 (1H, dq, J ) 11.6 Hz, J ) 7.1 Hz), 5.50 (1H,
s), 6.93 (3H, m), 7.45 (2H, m); 13C NMR 50 MHz (CDCl3) δ
(ppm) 13.9, 21.5, 26.0, 44.5, 52.8, 54.9, 60.2, 75.6, 127.0, 128.9,
129.2, 132.2, 136.0, 137.2, 171.1.
The same procedure using N-methylmaleimide leads to 28a
(37%) and to a mixture of 29a and 39a .
Spectral data for 28b: colorless solid, mp ) 169-170 °C;
IR (neat) 1778, 1708, 1656 cm-1; mass spectrum (EI) m/ z 379
1
(M+•, 56), 269 (23), 173 (64), 144 (48), 123 (99), 108 (100); H
NMR 200 MHz (C6D6) δ (ppm) 1.63 (3H, s), 2.56 (1H, dd, J )
10.4 Hz, J ) 5.0 Hz), 2.88 (1H, dd, J ) 10.4 Hz, J ) 8.0 Hz),
3.04 (3H, s), 3.65 (1H, d, J ) 8.0 Hz), 4.02 (1H, dd, J ) 5.0
Hz, J ) 4.7 Hz), 5.33 (1H, d, J ) 4.7 Hz), 6.94-7.15 (6H, m),
7.61 (2H, d, J ) 7.7 Hz), 7.85 (2H, d, J ) 7.2 Hz); a NOE
experiment showed that irradiation at δ 4.02 ppm resulted in
enhancements at 2.56 and 3.04 ppm and that irradiation at δ
Spectral data for 32b (6%): 13C NMR 50 MHz (CDCl3) δ
(ppm) 14.3, 22.3, 26.2, 40.9, 49.8, 56.8, 60.2, 72.9 124.1, 127.2,
129.3, 131.5, 132.4, 137.0, 172.4.
(1E,3E)- a n d (1Z,3E)-4-[L-(-)-Men th yloxy]-2-m eth yl-1-
(p h en ylth io)bu ta -1,3-d ien es (33a ). To a solution of 4b (0.1
g, 0.4 mmol) and L-(-)-menthol (0.2 g, 1.3 mmol) in ether (5
mL) were added 2,2-dimethoxypropane (0.1 mmol) and a little
p-TSA. The mixture was stirred for 2 h at 40°C. After the
solution was cooled to room temperature, anhydrous K2CO3
(1.0 g) was added and the medium was washed with saturated
NaHCO3 (10 mL), dried (MgSO4), filtered, and concentrated
to give the crude product 33a . The compound was obtained
as a 50:50 mixture of the E,E and Z,E isomers. Chromatog-
raphy on silica gel using ether/petroleum ether/triethylamine
(10/89/1) as eluent may be performed yielding 33a (26 mg,
20%): mass spectrum (CI, NH3) m/ z 331 (M + H+, 100); exact
2.88 ppm resulted in enhancements at 3.65 and 2.56 ppm; 13
C
NMR 50 MHz (C6D6) δ (ppm) 21.7, 43.4, 45.7, 50.1, 55.6, 69.7,
122.7, 127.1, 127.4, 128.1, 129.0, 129.1, 132.5, 133.2, 140.2,
144.5, 174.3, 175.4. Anal Calcd for C22H21NO3S: C, 69.63; H,
5.58; N, 3.69. Found: C, 69.64; H, 5.87; N, 3.61.
Spectral data for 29b: 1H NMR 200 MHz (C6D6) δ (ppm)
1.64 (3H, m), 2.96 (1H, dd, J ) 8.5 Hz, J ) 2.1 Hz), 3.14 (1H,
dd, J ) 8.5 Hz, J ) 8.5 Hz), 4.36 (1H, m), 4.48 (1H, d, J ) 2.1
Hz), 5.66 (1H, m), 6.88-7.45 (10H); a NOE experiment showed
that irradiation at δ 3.14 ppm resulted in enhancements at

Synthesis and Cycloadditions of 1-(Arylthio)-1,3-dienes
J . Org. Chem., Vol. 61, No. 16, 1996 5305
mass calcd for C21H30OS m/ z 330.2017, found 330.2019; 1H
NMR 200 MHz (C6D6) δ (ppm) 1E,3E isomer, 0.60-2.40 (18H,
m), 1.96 (3H, s), 2.90-3.50 (1H, m), 5.98 (1H, d, J ) 12.0 Hz),
6.00 (1H, s), 6.43 (1H, d, J ) 12.0 Hz), 6.88-7.35 (5H, m);
1Z,3E isomer, 0.60-2.40 (18H, m), 1.76 (3H, s), 2.90-3.50 (1H,
m), 5.82 (1H, s), 6.60 (1H, d, J ) 12.8 Hz), 6.81 (1H, d, J )
12.8 Hz).
132.5, 133.2. 34a minor: 1H NMR 200 MHz (CDCl3) δ (ppm)
0.75 (3H, d, J ) 6.0 Hz), 0.80-1.20 (5H, m), 1.05 (1H, m), 1.32
(3H, s), 1.40 (3H, s), 1.50 (3H, s), 1.58 (1H, m), 1.95 (1H, m),
3.09 (1H, dt, J ) 10.0 Hz, J ) 4.0 Hz), 4.17 (1H, m), 4.88 (1H,
m), 5.18 (1H, m), 6.90 (3H, m), 7.20 (5H, m), 7.40 (2H, m).
35a major: 1H NMR 200 MHz (CDCl3) δ (ppm) 0.76 (3H, d, J
) 6.0 Hz), 0.90-1.20 (5H, m), 1.10 (1H, m), 1.37 (3H, s), 1.42
(3H, s), 1.58 (3H, s), 1.60 (1H, m) 1.95 (1H, m), 3.10 (1H, dt, J
) 10.5 Hz, J ) 4.9 Hz), 3.73 (1H, m), 4.95 (1H, m), 4.76 (1H,
m), 6.90 (3H, m), 7.20 (5H, m) 7.40 (2H, m); 13C NMR 50 MHz
(C6D6) δ (ppm) 21.9, 22.0, 27.9, 30.9-31.1 (3C), 34.4, 39.8, 40.5,
40.8, 41.2, 51.8, 56.5, 71.3, 80.0, 109.1, 110.3, 111.4, 112.2,
122.1, 125.7, 126.5, 128.4, 129.7, 130.0, 132.5, 133.8, 133.9.
35a minor: 1H NMR 200 MHz (CDCl3) δ (ppm) 0.76 (3H, d, J
) 6.0 Hz), 0.90-1.20 (5H, m), 1.10 (1H, m), 1.37 (3H, s), 1.42
(3H, s), 1.53 (3H, s), 1.60 (1H, m), 1.95 (1H, m), 3.10 (1H, dt,
J ) 10.5 Hz, J ) 4.9 Hz), 3.73 (1H, m), 4.72 (1H, m), 5.12 (1H,
m), 6.90 (3H, m), 7.20 (5H, m), 7.40 (2H, m).
(1E,3E)- a n d (1Z,3E)-4-[((-)-8-P h en ylm en th yl)oxy]-2-
m eth yl-1-(p h en ylth io)bu ta -1,3-d ien es (33b). The same
procedure as above was applied to a solution of 4b (0.1 g, 0.4
mmol) and (-)-8-phenylmenthol (0.29 g, 1.2 mmol) to yield
crude 33b. This compound was obtained as a 50:50 mixture
of E,E and Z,E isomers: mass spectrum (CI, CH4) m/ z 407
(M + H+, 7), 215 (100); exact mass calcd for C27H34OS m/ z
1
406.2330, found 406.2337; H NMR 200 MHz (C6D6) δ (ppm)
1E,3E isomer, 0.45-1.90 (15H, m), 1.94 (3H, s), 3.20-3.50 (1H,
m), 5.86 (1H, d, J ) 12.0 Hz), 6.01 (1H, s), 6.23 (1H, d, J )
12.0 Hz), 6.85-7.35 (10H, m); 1Z,3E isomer, 0.45-1.90 (15H,
m), 1.77 (3H, s), 3.20-3.50 (1H, m), 5.82 (1H, s), 6.38 (1H, d,
J ) 12.5 Hz), 6.67 (1H, d, J ) 12.5 Hz), 6.85-7.35 (10H, m).
4-(Men th yloxy)-2-m eth yl-1-(p h en ylth io)-5,5,6,6-tetr a -
cya n ocycloh ex-2-en e (34a , 35a ). A crude 33a ether solution
was cooled to -78 °C. Tetracyanoethylene was then added
slowly (3 equiv, 0.25 M in THF); after 5 min at -78 °C, the
mixture was warmed up to 20 °C and concentrated, and the
crude material was purified by flash column chromatography
using methylene chloride/petroleum ether (35/65) as eluent to
give 34a and 35a (65%): IR (neat) 2280, 1662 cm-1; mass
spectrum (EI) m/ z 458 (M+, 20), 330 (21), 192 (100); exact mass
calcd for C27H30N4OS m/ z 458.2140, found 458.2176. 34a
major: 1H NMR 200 MHz (CDCl3) δ (ppm) 0.75 (1H, m), 0.75-
0.92 (8H, m), 0.98 (3H, d, J ) 6.6 Hz), 1.20 (1H, m), 1.30-
1.45 (3H, m), 1.53 (3H, s), 1.70 (1H, m), 2.73 (1H, hd, J ) 6.0
Hz, J ) 2.6 Hz), 3.40 (1H, td, J ) 10.2 Hz, J ) 4.3 Hz), 3.81
(1H, s), 4.45 (1H, m), 5.19 (1H, m), 6.92 (3H, m), 7.23 (2H, m);
13C NMR 50 MHz (C6D6) δ (ppm) 16.0, 20.2-22.3 (3C), 22.7,
25.1, 31.1, 34.1, 41.2, 42.8, 45.0, 48.7, 56.3, 73.2, 82.8, 109.1,
110.1, 111.7, 111.8, 124.0, 129.8, 130.0, 133.5, 133.8. 34a
minor: 1H NMR 200 MHz (CDCl3) δ (ppm) 0.75-0.92 (9H, m),
0.66 (3H, d, J ) 6.9 Hz), 1.00 (1H, m), 1.05 (1H, m), 1.30-
1.45 (2H, m), 1.60 (3H, s), 1.70 (1H, m), 2.73 (1H, hd, J ) 6.0
Hz, J ) 2.6 Hz), 3.40 (1H, td, J ) 10.3 Hz, J ) 4.3 Hz), 3.81
(1H, s), 4.45 (1H, m), 5.22 (1H, m), 6.92 (3H, m), 7.23 (2H, m);
13C NMR 50 MHz (C6D6) δ (ppm) 15.5, 20.2-22.3 (3C), 23.0,
25.2, 31.6, 34.0, 39.6, 42.8, 45.0, 47.8, 56.5, 71.7, 79.8, 109.1,
110.1, 111.7, 111.8, 121.7, 129.8, 130.0, 133.5, 133.8. 35a
major: 1H NMR 200 MHz (CDCl3) δ (ppm) 0.75-0.92 (9H, m),
0.68 (3H, d, J ) 7.0 Hz), 1.00 (1H, m), 1.15 (1H, m), 1.30-
1.45 (2H, m), 1.57 (3H, d, 4J ) 1.1 Hz), 2.00 (1H, m), 2.16 (1H,
hd, J ) 7.0 Hz, J ) 2.3 Hz), 2.96 (1H, td, J ) 10.2 Hz, J ) 4.3
Hz), 4.18 (1H, s), 4.65 (1H, m), 5.22 (1H, m), 6.92 (3H, m),
7.23 (2H, m); 13C NMR 50 MHz (C6D6) δ (ppm) 16.2, 21.0-
22.2 (3C), 23.2, 25.4, 31.5, 33.4 39.6, 46.9, 47.9, 48.1, 56.2, 72.1,
79.4, 109.2, 110.1, 111.1, 111.6, 123.7, 130.1, 130.2, 131.5,
133.7, 134.0. 35a minor: 1H NMR 200 MHz (CDCl3) δ (ppm)
0.75 (1H, m), 0.75-0.92 (8H, m), 0.95 (3H, d, J ) 7.0 Hz), 1.20
(1H, m), 1.30-1.45 (3H, m), 1.50 (3H, d, 4J ) 1.0 Hz), 1.70
(1H, m), 2.53 (1H, hd, J ) 7.0 Hz, J ) 2.0 Hz), 3.42 (1H, td, J
) 10.2 Hz, J ) 4.3 Hz), 4.18 (1H, s), 4.74 (1H, m), 5.22 (1H,
m), 6.92 (3H, m), 7.23 (2H, m); 13C NMR 50 MHz (C6D6) δ
(ppm) 16.3, 21.0-22.2 (3C), 22.8, 25.3, 31.0, 34.1 41.2, 46.9,
48.1 48.7, 56.0, 73.9, 83.0, 109.2, 110.1, 111.1, 111.6, 126.0
130.1, 130.2, 131.5, 133.7, 134.0.
N-P h en yl-4-m eth yl-6-m or p h olin o-3-(p h en ylth io)cyclo-
h ex-4-en e-1,2-d ica r boxa m id e (36). To a solution of diene
8b (0.4 g, 1.5 mmol) in ether (10 mL) were added N-
phenylmaleimide (0.5 g, 2.9 mmol) and a little hydroquinone.
The mixture was stirred for 4 days at 40 °C. The solvent was
then evaporated, and the crude material was purified by flash
column chromatography using ethyl acetate/petroleum ether
(3/7) as eluent to give 36 (155 mg, 23%): IR (neat) 1776, 1702
cm-1; mass spectrum (CI, CH4) m/ z 435 (M + H+, 60), 324
(100); 1H NMR 200 MHz (CDCl3) δ (ppm) 1.79 (3H, t, J ) 1.5
Hz), 2.68 (4H, m), 3.39 (1H, dd, J ) 8.3 Hz, J ) 1.5 Hz), 3.58
(1H, dd, J ) 8.3 Hz, J ) 8.3 Hz), 3.65 (1H, m), 3.72 (4H, t, J
) 4.6 Hz), 4.30 (1H, d, J ) 1.5 Hz), 5.82 (1H, s), 7.06-7.50
(10H, m); a NOE experiment showed that irradiation at δ 4.30
ppm resulted in enhancements at δ 3.39; 13C NMR 50 MHz
(CDCl3) δ (ppm) 22.4, 41.1, 45.1, 47.1, 52.2, 60.2, 66.7, 126.1,
126.2, 127.6, 128.4, 128.8, 129.2, 131.5, 133.6, 135.7, 174.4,
176.2. Anal. Calcd for C25H26N2O3S: C, 68.97; H, 5.99; N,
6.45. Found: C, 68.94; H, 5.77; N, 6.61.
Eth yl 4-Meth yl-6-m or p h olin o-3-(p h en ylth io)cycloh ex-
4-en oa te (38). To a solution of diene 8b (0.4 g, 1.5 mmol) in
Et2O (10 mL) were added ethyl acrylate (1 mL) and a little
hydroquinone. The mixture was stirred for 10 days at 40 °C.
The solvent was then evaporated and the crude material
purified by flash column chromatography using ethyl acetate/
petroleum ether (15/85) as eluent to give 38 (120 mg, 21%):
IR (neat) 1732, 1672 cm-1; mass spectrum (EI) m/ z 361 (M+,
13), 261 (100), 251 (32), 225 (33), 175 (59); exact mass calcd
1
for C20H27NO3S m/ z 361.1712, found 361.1705; H NMR 360
MHz (CDCl3) δ (ppm) 1.21 (3H, t, J ) 7.23 Hz), 2.02 (3H, s),
2.06 (1H, m), 2.20 (1H, ddd, J ) 9.3 Hz, J ) 3.7 Hz, J ) 3.7
Hz), 2.35 (2H, m), 2.61 (1H, ddd, J ) 13.8 Hz, J ) 5.8 Hz, J )
3.7 Hz), 3.31 (1H, m), 3.44 (3H, m), 4.10 (2H, m), 5.67 (1H,
m), 7.24 (5H, m), 7.43 (2H, m); 13C NMR 50 MHz (CDCl3) δ
(ppm) 14.5, 22.8, 29.6, 52.7, 59.7, 59.9, 67.7, 123.7, 127.8, 129.0,
133.8, 134.3, 138.9, 172.3.
N-Meth yl- a n d N-P h en yl-3-m eth oxy-5-m eth yl-4-(p h e-
n ylth io)cycloh ex-5-en e-1,2-d ica r boxa m id es (39). These
compounds were obtained directly, keeping a solution (see
solvents in text) of 28 at room temperature and daylight in
an NMR tube for 15-60 days. A quicker procedure is as
follows: 28a (10 mg, 0.03 mmol) was disolved in methylene
chloride (1.6 mL) and irradiated for 48 h under a 500 W
halogen lamp in an air-cooled quartz (UV type) cuvette. After
evaporation of the solvent, 39a (10 mg, 0.03 mmol) was
recovered.
4-((8-P h e n ylm e n t h yl)oxy)-2-m e t h yl-1-(p h e n ylt h io)-
5,5,6,6-tetr a cya n ocycloh ex-2-en e (34b, 35b). The same
procedure as above was applied to a solution of crude diene
33b, leading to a mixture of 34b and 35b (65%): IR (neat)
2280, 1662 cm-1; mass spectrum (EI) m/ z 534 (M+•, 1), 406
(4), 119 (100). 34a major: 1H NMR 200 MHz (CDCl3) δ (ppm)
0.75 (3H, d, J ) 6.0 Hz), 0.80-1.20 (5H, m), 1.05 (1H, m), 1.32
(3H, s), 1.40 (3H, s), 1.55 (3H, s), 1.58 (1H, m) 1.95 (1H, m),
3.09 (1H, dt, J ) 10.0 Hz, J ) 4.0 Hz), 4.17 (1H, m), 4.66 (1H,
Spectral data for 39a : 1H NMR 300 MHz (C6D6) δ (ppm)
1.82 (3H, dd, J ) 1.6 Hz, J ) 3.2 Hz), 2.77 (3H, s), 2.80 (3H,
s), 3.39 (1H, dd, J ) 5.2 Hz, J ) 7.8 Hz), 3.53 (1H, d, J ) 3.2
Hz), 4.08 (1H, t, J ) 3.2 Hz), 6.01 (1H, m), 7.04 (3H, m), 7.35
1
(2H, m); H NMR 300 MHz (Pyr-d5) δ (ppm) 1.93 (3H, d, J )
1.8 Hz), 2.95 (3H, s), 3.11 (3H, s), 3.54 (1H, m), 3.83 (1H, dd,
J ) 4.3 Hz, J ) 9.0 Hz), 4.00 (1H, d, J ) 2.7 Hz), 4.19 (1H, dd,
J ) 2.8 Hz, J ) 4.3 Hz), 6.10 (1H, m), 7.29 (3H, m), 7.61 (2H,
d, J ) 8.9 Hz); 13C NMR 75 MHz (Pyr-d5) δ (ppm) 22.1, 24.5,
39.8, 40.8, 47.9, 57.8, 77.7, 119.5, 128.0, 129.7, 132.1, 134.8,
177.0, 177.4. The COSY, NOESY, and COLOC sets of experi-
m), 4.82 (1H, m), 6.90 (3H, m), 7.20 (5H, m), 7.40 (2H, m); 13
C
NMR 50 MHz (C6D6) δ (ppm) 21.4, 21.5, 27.5, 31.1-31.3 (3C),
34.1, 39.3, 40.6, 46.5, 48.0, 51.5, 56.0, 77.7, 79.3, 109.2, 109.7,
110.8, 111.2, 123.3, 125.4, 126.0, 128.0, 129.7, 129.9, 133.6,

5306 J . Org. Chem., Vol. 61, No. 16, 1996
Maddaluno et al.
ments performed on that compound show the expected cor-
relations between nuclei.
m); 13C NMR 50 MHz (C6D6) δ (ppm) 20.4, 28.0, 32.0, 43.5,
45.6, 47.9, 63.5, 127.5, 128.6, 129.4, 134.2, 139.0, 170.4, 178.6.
Spectral data for 39b: mass spectrum (EI) m/ z 379 (M+•
,
64), 347 (5), 269 (50), 186 (8), 123 (100), 91 (44); IR: 2932,
Ack n ow led gm en t. We express our deep gratitude
to Dr. Lucette Duhamel and Prof. Pierre Duhamel for
their constant support as well as critical reading of the
manuscript. Special thanks to Mr. Didier Gaonac’h
(Interor Cy) for his great help and to Dr. Stuart Warren
(University of Cambridge), Prof. John Mellor (Southamp-
ton University), and Prof. Michael E. J ung (University
of California, Los Angeles) for their wise comments and
discussions. A generous gift of chloro acetal 3b samples
by the Rhoˆne-Poulenc-Chimie Co. is appreciated. The
AM1 computations were carried out on a Cray YMP-
EL at the Centre de Calculs pour la Recherche (CCR,
Universite´ P. & M. Curie).
1
1708, 1080 cm-1; H NMR 200 MHz (C6D6) δ (ppm) 1.76 (3H,
m), 2.70 (1H, m), 2.76 (3H, s), 3.45 (1H, dd, J ) 9.0 Hz, J )
4.4 Hz), 3.50 (1H, d, J ) 2.8 Hz), 4.06 (1H, dd, J ) 4.4 Hz, J
) 2.8 Hz), 5.96 (1H, m), 6.92-7.47 (10H); a set of NOE
experiments showed that irradiation at δ 4.06 ppm resulted
in enhancements at 3.45 and 3.50 ppm; 13C NMR 50 MHz
(C6D6) δ (ppm) 22.2, 39.5, 40.6, 49.0, 57.7, 78.2, 119.4, 126.9,
128.2, 128.3, 129.0, 129.5, 131.8, 132.6, 133.3, 135.1, 175.0,
175.7.
6-(1,1-Dim et h ylet h yl)-4-m et h yl-3-(p h en ylsu lfon yl)cy-
cloh ex-4-en e-1,2-d ica r boxylic An h yd r id e (40). To a solu-
tion of adduct 25 (85 mg, 0.26 mmol) in CH2Cl2 (2 mL) at 0 °C
was added a solution of 65% MCPBA (140 mg, 1.25 mmol) in
the same solvent (3 mL). After 1 h, the medium was allowed
to warm up to room temperature overnight and washed with
sodium thiosulfate and NaHCO3 saturated solutions (2 × 2
mL). The organic phase was then dried (MgSO4) and evapo-
rated, yielding sulfone 40 (72 mg, 76%): yellow solid, mp 158-
Su p p or tin g In for m a tion Ava ila ble: NMR spectra (72
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.
1
160 °C; IR (neat) 2966, 1784, 1149 cm-1; H NMR 200 MHz
(CDCl3) δ (ppm) 1.05 (9H, s), 1.60 (1H, m), 2.18 (3H, s), 3.52
(1H, dd, J ) 8.0 Hz, J ) 8.0 Hz), 3.73 (1H, m), 3.85 (1H, dd,
J ) 4.0 Hz, J ) 8.0 Hz), 5.80 (1H, m), 7.65 (3H, m), 8.05 (2H,
J O9519120