Synthesis and Asymmetric Diels-Alder Reactions of Enantiopure 3-(Alkylsulfinyl)-1-methoxy-1,3-butadienes

Article abstract of DOI:10.1021/jo962286p

Simple syntheses of enantiopure (E)- and (Z)-3-(alkylsulfinyl)-1-methoxy-1,3-butadienes 2 and 3 were provided by the addition of (1S)-isoborneol-10-sulfenic and (S)-phenyl-2-hydroxyethanesulfenic acids 8 to (E)- and (Z)-1-methoxybut-1-en-3-ynes (9) and (1

Full text of DOI:10.1021/jo962286p

4376
J . Org. Chem. 1997, 62, 4376-4384
Syn th esis a n d Asym m etr ic Diels-Ald er Rea ction s of En a n tiop u r e
3-(Alk ylsu lfin yl)-1-m eth oxy-1,3-bu ta d ien es
Maria C. Aversa,* Anna Barattucci, Paola Bonaccorsi, and Placido Giannetto
Dipartimento di Chimica organica e biologica, Universita` di Messina, Salita Sperone 31 (vill. S. Agata),
98166 Messina, Italy
David Neville J ones
Department of Chemistry, University of Sheffield, Dainton Building, Brook Hill, Sheffield S3 7HF, U.K.
Received December 9, 1996X
Simple syntheses of enantiopure (E)- and (Z)-3-(alkylsulfinyl)-1-methoxy-1,3-butadienes 2 and 3
were provided by the addition of (1S)-isoborneol-10-sulfenic and (S)-phenyl-2-hydroxyethanesulfenic
acids 8 to (E)- and (Z)-1-methoxybut-1-en-3-ynes (9) and (10). These additions proceeded with
asymmetric induction, the extent of which depended upon the nature of the chiral hydroxyalkyl
group. Cycloadditions of methyl acrylate to the enantiopure dienes proceeded with complete
regioselectivity and very high stereoselectivity when catalyzed by lithium perchlorate or zinc chloride
in dichloromethane. The chirality at sulfur controlled the diastereofacial selectivity in these Diels-
Alder cycloadditions.
In tr od u ction
tiopure sulfinyl dienes have been devised,6 but informa-
tion about their participation in cycloadditions remains
scarce. Garc´ıa Ruano and co-workers have described
asymmetric DA cycloadditions of enantiopure 1-(p-tolyl-
sulfinyl)-1,3-butadienes,7 in which the reactivity of the
diene was diminished by the presence of the sulfoxide
group.1c Maignan8 reported one experiment only, which
involved reaction of (E,RS)-2-(p-tolylsulfinyl)-1,3-penta-
diene with maleimide under very mild conditions to
afford a single, enantiomerically pure adduct. Finally,
Yang and co-workers6g reported good yields and high
diastereomeric excesses in the DA reactions of N-phen-
ylmaleimide with 2-sulfinylbutadienes, which, because
of their instability, were generated in situ by thermolysis
of 4-sulfinyl-3-sulfolenes.
We now provide details of our methods for the con-
struction of enantiopure 3-(alkylsulfinyl)-1-methoxy-1,3-
dienes from enantiopure hydroxythiols and the partici-
pation of these dienes in cycloadditions with methyl
acrylate. Camphorsulfonic acid and mandelic acid, which
are readily available members of the “chiral pool”,
provided the precursors for the hydroxythiols, which were
chosen because we expected that the contiguity of the
hydroxy and sulfur functions in their derivatives would
facilitate the chromatographic separation of diastereo-
isomers and enhance diastereoface selection in pericyclic
processes. Further, we expected the augmenting direct-
ing effects of the methoxy and sulfinyl groups to maxi-
mize the regioselectivity of the cycloadditions.
The combination of Diels-Alder (DA) reaction with
asymmetric induction exerted by sulfoxides represents
a very powerful method for C-C bond formation in a
stereocontrolled manner. The notable optical activity, the
ease of convertibility into different functional groups, the
clean removal under mild conditions, and the existence
of several efficient methods of obtaining enantiopure
sulfoxides1 make them versatile auxiliaries in one of the
most effective reactions for the synthesis of six-membered
rings.
Since the first pioneering work in 1983,2 enantiopure
vinyl sulfoxides have been commonly employed as dieno-
philes in DA reactions. Their use often results in high
levels of regio- and stereoselectivity.3 Enantiopure diene
sulfoxides have received little attention, presumably
owing to difficulties in their preparation. Since our
preliminary accounts of the synthesis of enantiopure
2-sulfinyl dienes4 and their use in asymmetric DA
reactions,4b,5 other methods for the construction of enan-
* To whom correspondence should be addressed. Phone: +39-90-
6765165-6765190.
imeuniv.unime.it.
Fax:
+39-90-393895.
E-mail:
aversa@
X Abstract published in Advance ACS Abstracts, May 15, 1997.
(1) Reviews: (a) Solladie´, G. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6,
pp 148-157. (b) Walker, A. J . Tetrahedron: Asymmetry 1992, 3, 961-
998. (c) Carren˜o, M. C. Chem. Rev. 1995, 95, 1717-1760.
(2) Maignan, C.; Raphael, R. A. Tetrahedron 1983, 39, 3245-3249.
(3) (a) De Lucchi, O.; Lucchini, V.; Marchioro, C.; Valle, G.; Modena,
G. J . Org. Chem. 1986, 51, 1457-1466. (b) Arai, Y.; Matsui, M.;
Koizumi, T.; Shiro, M. J . Org. Chem. 1991, 56, 1983-1985. (c) Ronan,
B.; Kagan, H. B. Tetrahedron Asymmetry 1992, 3, 115-122. (d)
Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. J . Org. Chem. 1992,
57, 6870-6876. (e) Alonso, I.; Carretero, J . C.; Garc´ıa Ruano, J . L. J .
Org. Chem. 1993, 58, 3231-3232. (f) Fuji, K.; Tanaka, K.; Abe, H.;
Matsumoto, K.; Harayama, T.; Ikeda, A.; Taga, T.; Miwa, Y.; Node,
M. J . Org. Chem. 1994, 59, 2211-2218. (g) Yang, T.; Chen, C.; Lee,
D.; J ong, T.; J iang, Y.; Mi, A. Tetrahedron: Asymmetry 1996, 7, 57-
60.
(6) (a) Bonfand, E.; Gosselin, P.; Maignan, C. Tetrahedron Lett. 1992,
33, 2347-2348. (b) Solladie´, G.; Maugein, N.; Morreno, I.; Almario,
A.; Carren˜o, M.C.; Garc´ıa Ruano, J . L. Tetrahedron Lett. 1992, 33,
4561-4562. (c) Girodier, L.; Maignan, C.; Rouessac, F. Tetrahedron:
Asymmetry 1992, 3, 857-858. (d) Bonfand, E.; Gosselin, P.; Maignan,
C. Tetrahedron: Asymmetry 1993, 4, 1667-1676. (e) Paley, R. S.; de
Dios, A.; Ferna´ndez de la Pradilla, R. Tetrahedron Lett. 1993, 34,
2429-2432. (f) Paley, R. S.; Lafontaine, J . A.; Ventura, M. P.
Tetrahedron Lett. 1993, 34, 3663-3666. (g) Yang, T.; Chu, H.; Lee,
D.; J iang, Y.; Chou, T. Tetrahedron Lett. 1996, 37, 4537-4540.
(7) (a) Arce, E.; Carren˜o, M. C.; Cid, M. B.; Garc´ıa Ruano, J . L. J .
Org. Chem. 1994, 59, 3421-3426. (b) Carren˜o, M. C.; Cid, M. B.;
Colobert, F.; Garc´ıa Ruano, J . L.; Solladie´, G. Tetrahedron: Asymmetry
1994, 5, 1439-1442.
(4) (a) Aversa, M. C.; Bonaccorsi, P.; Giannetto, P.; J afari, S. M. A.;
J ones, D. N. Tetrahedron: Asymmetry 1992, 3, 701-704. (b) Aversa,
M. C.; Bonaccorsi, P.; Giannetto, P.; J ones, D. N. Tetrahedron:
Asymmetry 1994, 5, 805-808.
(5) Adams, H.; J ones, D. N.; Aversa, M. C.; Bonaccorsi, P.; Giannetto,
P. Tetrahedron Lett. 1993, 34, 6481-6484.
(8) Gosselin, P.; Bonfand, E.; Hayes, P.; Retoux, R.; Maignan, C.
Tetrahedron: Asymmetry 1994, 5, 781-784.
S0022-3263(96)02286-4 CCC: $14.00 © 1997 American Chemical Society

Reactions of 3-(Alkylsulfinyl)-1-methoxy-1,3-butadienes
J . Org. Chem., Vol. 62, No. 13, 1997 4377
Sch em e 1
Sch em e 2a
a
Reagents: (i) Zn[SC(S)NMe2]2, DEAD, Ph3P; (ii) DHP, PPTS;
(iv) EtOH, PPTS.
10-Mercaptoisoborneol (1A) was chosen as a convenient
chiral auxiliary because of its availability in both enan-
tiomeric forms, its well-assessed preparation from com-
mercially available 10-camphorsulfonic acid,10 and the
expected crystallinity of 10-camphorsulfonic derivatives.
2-Hydroxy-1-phenylethanethiol (1B) and 2-hydroxy-2-
phenylethanethiol (1C) were exploited as chiral control
elements since chiral auxiliaries derived from these
vicinal hydroxy thiols potentially may be removed by
phenyloxiran formation.11 Moreover, we decided to com-
pare the behavior of the structural isomers 1B and 1C,
in order to evaluate whether the position of the asym-
metric carbon with regard to sulfur atom had any effect
on the asymmetric induction. Ethyl mandelate, com-
mercially available in both enantiomeric forms, was
employed as starting material for the preparation of
thiols 1B and 1C (Scheme 2). Hydroxy thiol 1B was
obtained from ethyl (R)-mandelate (11R) using a modi-
fication of the Mitsunobu reaction, devised by Rollin,
which occurs with complete inversion of configuration,12
followed by LiAlH4 reduction. Hydroxy thiol 1C was
obtained from ethyl (S)-mandelate (11S) in 70% overall
yield, by protection of the hydroxy group, reduction of
the ester function, followed by Mitsunobu-Rollin reaction
on the phenylethanol 13, reduction of dithiocarbamate
14, and deprotection. (S)-2-Mercapto-1-phenylethanol
(1C) was also prepared from commercially available (S)-
phenyloxirane by the shorter but less efficient Lalancette
and Freˆche procedure (30% yield overall in our hands).13
The longer procedure (Scheme 2) was also more conve-
nient because the two optically pure phenyloxiranes are
both more expensive than the optically pure ethyl man-
delates.
Resu lts a n d Discu ssion
Syn th esis of Ch ir al Dien es. The syntheses of 1-meth-
oxy-3-(alkylsulfinyl)-1,3-butadienes 2A-C and 3A-C,
based on the regioselective addition of sulfenic acids to
enynes,9 proceeded in four steps, commencing with the
base-catalyzed addition of hydroxy thiols 1A-C to acrylo-
nitrile, followed by oxidation of the adducts 6A-C with
m-CPBA to give sulfoxides 7A-C (Scheme 1). These
None of the reactions in Scheme 2 was attended by
detectable racemization despite the presence of poten-
tially sensitive benzylic centers. The optical purity of
1
hydroxy thiols 1B,C was checked by H NMR analysis
using the chiral shift reagent Eu(tfc)3 in CD3CN, which
was the solvent of choice,14 because experiments in CDCl3
failed owing to extensive broadening of signals.
Oxidation of the cyano hydroxy sulfide 6A with m-
CPBA (Scheme 1) proceeded diastereoselectively to give
a 28:1 mixture of sulfoxides 7A epimeric at sulfur. These
were easily separated by chromatography on silica gel,
but the mixture was used for the next step, since both
epimers furnish the same sulfenic acid 8A on thermolysis.
were thermolyzed in the presence of the appropriate
enynes 9 or 10 to generate transiently the corresponding
sulfenic acids 8A-C, which were trapped by the enynes
to provide the required 1-methoxy-3-(alkylsulfinyl)-1,3-
butadienes. The final cycloadditions were almost com-
pletely regioselective, but small amounts (ca. 1%) of the
dienes 4AR and 5AR were featured among the products
of reaction of 8A with the methoxyenynes 9 and 10,
respectively.
(10) Eliel, E. L.; Frazee, W. J . J . Org. Chem. 1979, 44, 3598-3599.
(11) Solladie´-Cavallo, A.; Adib, A. Tetrahedron 1992, 48, 2453-2464.
(12) Rollin, P. Tetrahedron Lett. 1986, 27, 4169-4170.
(13) Lalancette, J . M.; Freˆche, A. Can. J . Chem. 1971, 49, 4047-
4053.
(9) Bell, R.; Cottam, P. D.; Davies, J .; J ones, D. N. J . Chem. Soc.,
Perkin Trans. 1 1981, 2106-2115.
(14) Sweeting, L. M.; Crans, D. C.; Whitesides, G. M. J . Org. Chem.
1981, 52, 2273-2276.

4378 J . Org. Chem., Vol. 62, No. 13, 1997
Aversa et al.
Ta ble 1. Ch ir a l Su lfin yl d ien es 2 a n d 3 fr om Ad d ition of
Su lfen ic Acid s 8 to En yn es 9 a n d 10
sulfur, whereas for the corresponding (RS) isomers 2BR
and 3BR intramolecular hydrogen bonding requires the
adoption of relatively unfavorable conformations with
four bulky substituents gauche to each other in the
Newman projections.
entry sulfoxides enynes solventa time/min products (yield %)
1
2
3
4
5
6
7A
7A
7B
7B
7C
7C
9
10
9
10
9
xylenes
xylenes
toluene
toluene
toluene
toluene
60
30
45
45
45
45
2AR (60), 2AS (10)
3AR (63), 3AS (14)
2BR (12), 2BS (33)
3BR (10), 3BS (30)
2CR and 2CS (25b)
3CR and 3CS (25b)
10
a
b
At its bp. Combined yield.
The isomeric cyano hydroxy sulfides 6B,C behaved very
differently on oxidation with m-CPBA, 6B giving only one
cyano hydroxy sulfoxide 7B, whereas 6C gave a 1:1
mixture of epimeric sulfoxides 7C that were very difficult
to separate by chromatography.15
Sulfenic acids are generally too instable to be isolated
and consequently generated in situ by thermolysis of
suitable sulfoxides. For this purpose, we chose cyano
hydroxy sulfoxides 7 because they were stable up to 80
°C but decomposed cleanly on further warming. The
cyano hydroxy sulfoxide 7A thermolyzed at a convenient
rate in boiling xylene (140 °C), whereas 7B,C did so in
boiling toluene (110 °C). Thermolysis of 7, in the pres-
ence of enynes 9 or 10 in the appropriate boiling solvents,
provided the sulfinyl dienes 2 and 3. Reaction conditions
and results are collected in Table 1.
The major and chromatographically more mobile sul-
foxide isomer obtained by peroxy acid oxidation of the
hydroxy sulfide 6A may be allocated the preferred
conformation a (R ) CH2CH2CN) and therefore the (SS)
configuration at sulfur by the same arguments, which is
in complete accord with the configuration assigned on the
basis of the well-established directing effect of a proximal
hydroxy group on the stereoselectivity of peroxy acid
oxidation at sulfur in the preferred conformation of the
corresponding sulfide.15 Similar considerations of hy-
droxy-directed oxidation at sulfur were employed by De
Lucchi et al. to assign configuration at sulfur in the
related (RS,Z)-1-[(1S)-isoborneol-10-sulfinyl]-2-(phenyl-
sulfonyl)ethylene, a conclusion that was anchored by
X-ray analysis of a DA adduct of the aforesaid vinyl
sulfoxide with cyclopentadiene.3a It is clear that the
major sulfoxide formed by peroxy acid oxidation of a
hydroxy sulfide should always be chromatographically
more mobile than its epimer at sulfur, since similar
hydrogen-bonding effects influence both stereoselectivity
of oxidation and chromatographic characteristics.
Analogous hydrogen-bonding effects involving hydroxy
and sulfenic acid groups may account for the predomi-
nance of one sulfoxide epimer from addition of the
sulfenic acids 8A,B to the methoxy enynes 9 and 10
(Scheme 1). These represent the first examples of
asymmetric induction in sulfenic acid-alkyne additions,
and the proposed influence of intramolecular hydroxy-
sulfenic acid hydrogen bonding on the stereochemical
consequences of this pericyclic process is supported by
observations that intramolecular hydrogen bonding in
other hydroxy sulfenic acids is strong17 and contributes
so significantly to their stability that in some cases they
may be isolated.
Each of the sulfinyl dienes 2 and 3 were formed as
mixtures epimeric at sulfur. For the sulfinyl dienes 2A,B
and 3A,B, the epimers were readily separated by chro-
matography on silica gel, the major isomers 2AR, 3AR,
2BS, and 3BS being more mobile than their respective
minor isomers 2AS, 3AS, 2BR, and 3BR. By contrast, the
epimeric sulfinyl dienes 2CR and 2CS were formed in
approximately equal amounts and were chromatographi-
cally almost identical, so separation was too difficult to
be practicable on a preparatively useful scale. The
sulfinyl dienes 3CR and 3CS shared these characteristics.
Assign m en ts of con figu r a tion . The configuration
of 2AR was assigned as (RS) on the basis of X-ray
crystallographic analysis of its cycloadduct 15AR with
methyl acrylate (see later), a result that strengthened
our confidence in assigning the configurations of hydroxy
sulfoxides 2A,B and 3A,B on the basis of their chromato-
graphic behavior. The more mobile epimers 2AR and 3AR
were initially allocated the (RS) configuration and the
more mobile epimers 2BS and 3BS the (SS) configuration.4
This followed from the recognition that sulfoxides form
strong intramolecular hydrogen bonds with suitably
oriented contiguous hydroxy groups,16 a phenomenon that
is associated with enhanced chromatographic mobility by
virtue of the consequent reduction in the effective polarity
of the sulfoxide group. Models reveal that the (RS)
isomers 2AR and 3AR can readily adopt an unhindered
conformation (a ) that involves intramolecular hydrogen
bonding, whereas for the (SS) isomers 2AS and 3AS
intramolecular hydrogen bonding requires the adoption
of a less favorable conformation (as a , but with R and
the sulfur lone electron pair interchanged). For the
hydroxysulfinyl dienes 2BS and 3BS the preferred hy-
drogen-bonded conformation was considered to be b,
which led to the assignment of the (SS) configuration to
Asym m etr ic DA Ad d ition s to Meth yl Acr yla te.
Most of our investigations involved the readily accessible
dienes 2AR, 2BS, and 2CS, but a few reactions were
performed with 2AS and 3AR. We had too little of the
other dienes for a meaningful study of their cycloaddi-
tions. Some relevant data are recorded in Table 2.
The (E)-dienes 2AR, 2AS, 2BS, and 2CS were reactive
DA participants, undergoing cycloaddition with methyl
acrylate at or below room temperature, whereas the diene
3AR reacted much more sluggishly, an expected conse-
quence of its (Z)-configuration.18 As expected,19 the
combined directing effects of the 1- and 3-substituents
(15) Glass, R. S.; Setzer, W. N., Prabhu, U. D. G.; Wilson, G. S.
Tetrahedron Lett. 1982, 23, 2335-2338.
(16) Furukawa, N.; Fujihara, H. In The Chemistry of Sulphones and
Sulphoxides; Patai, S., Rappoport, Z., Stirling, C., Eds.; J ohn Wiley &
Sons: Chichester, 1988; pp 541-581.
(17) Hogg, D. R. In The Chemistry of Sulphenic Acids and their
Derivatives; Patai, S., Ed.; J ohn Wiley & Sons: Chichester, 1990; pp
361-402.
(18) Zutterman, F.; Krief, A. J . Org. Chem. 1983, 48, 1135-1137.

Reactions of 3-(Alkylsulfinyl)-1-methoxy-1,3-butadienes
J . Org. Chem., Vol. 62, No. 13, 1997 4379
Ta ble 2. Cycloa d d ition s of Su lfin yl d ien es 2AR, 2AS, 2BS, 2CS, a n d 3AR w ith Meth yl Acr yla te
adducts
entry
diene
catalyst
solvent
T/°C
25
25
25
reflux
reflux
25
25
25
time
yield/%
endo
exo
(ratio)
1
2
3
4
5
6
7
8
9
2AR
2AR
2AS
3AR
3AR
2BS
2BS
2CS
2CS
none
none
16 h
7 h
20 h
6 d
20 h
42 h
16 h
6 d
55
70
30
68
70
20
20
25
40
15AR:16AR
15AR:16AR
15AS:16AS
17AR:18AR
17AR:18AR
15BS:16BS
15BS:16BS
15CS:16CS
15CS:16CS
:
:
:
:
:
:
:
:
:
17AR:18AR
17AR:18AR
17AS + 18AS
15AR:16AR
15AR + 16AR
17BS:18BS
17BS:18BS
17CS:18CS
17CS:18CS
(54:31:8:7)
(96:4:0:0)
(0:89:11)
(27:47:11:15)
(17:80:3)
(22:56:6:16)
(6:90:0:0)
LiClO4
ZnCl2
none
LiClO4
none
LiClO4
none
LiClO4
CH2Cl2
CH2Cl2
none
none
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
(26:44:12:19)
(2:93:0:0)
25
3 d
in the dienes ensured that cycloaddition occurred with
complete regioselectivity, but the uncatalyzed cycload-
ditions were not particularly stereoselective, giving rise
to four diastereoisomers with low endo/ exo and diaste-
reofacial selectivity.
The effect of Lewis acid catalysis was investigated in
some detail with diene 2AR. All the catalysts investi-
gated, except boron trifluoride etherate, served markedly
to increase the endo:exo ratio, and the use of zinc chloride
or lithium perchlorate in dichloromethane led also to high
diastereofacial selectivity. The best catalyst was lithium
perchlorate, the use of which as a suspension in dichlo-
romethane gave only the endo isomers 15AR and 16AR
in 70% yield in the ratio 96:4. This was the first
illustration that lithium perchlorate suspended in dichlo-
romethane-catalyzed DA reactions20 and that it did so
highly stereoselectively. Reetz and Fox21 have shown
that Mukaiyama aldol reactions and conjugate additions
were more efficiently catalyzed in this way than by 5 M
lithium perchlorate in diethyl ether, conditions that were
previously advocated for the dramatic acceleration of DA
reactions.22
F igu r e 1. Conformational preferences of cycloadducts 15AR-
18AR.
The endo and exo pairs of adducts 15A-18A could be
separated by simple chromatography, but the composi-
tion of the mixture of four diastereoisomers was deter-
mined by proton NMR spectrometry. The endo/ exo ratio
was established from the relative intensities of the well-
separated vinyl proton signals and the ratios 15A:16A
and 17A:18A from the relative intensities of the lower
field portion of the AB spectrum associated with the
methylene group adjacent to sulfur. The relative propor-
tions of adducts 15B-18B were easily determined from
the relative intensities of the vinyl proton signals in CD3-
CN solution, while the ratio among adducts 15C-18C
was obtained by integration of the well-separated ben-
zylic signals in C6D6 (Table 2).
Crystallization (ethyl acetate-light petroleum) of the
mixture of endo-isomers (15AR + 16AR), obtained from
2AR, gave the optically pure diastereoisomer 15AR, the
absolute configuration of which was established as (3R,-
4R,RS) by X-ray crystallography.23 This result also
confirmed the configurations at sulfur in dienes 2A and
3A that were previously assigned on the basis of proper-
ties relating to intramolecular hydrogen bonding.4a Hav-
F igu r e 2. Favored approach of methyl acrylate in DA reaction
of (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-di-
ene (2AR) in the presence of LiClO4.
ing firmly established the absolute configuration of
adduct 15AR, the configurations of the exo products 17AR
1
and 18AR were assigned on the basis of H NMR data:
J
3,4 and J 4,5 of 15AR-18AR suggested the conformational
preferences depicted in Figure 1; the subsequent com-
parison of H-3 and H-4 chemical shifts in the four adducts
(see Figure 1) supported the attribution of configuration
(3R,4S) to 17AR and (3S,4R) to 18AR.
Oxidation of 15AR, derived from the (RS)-sulfinyl diene
2AR, with m-CPBA gave the sulfone 20A in good yield,
and oxidation of adduct 16AS [derived from the (SS)-
sulfinyldiene 2AS] gave the isomeric sulfone 21A (Scheme
3). This established the absolute configurations of the
adducts 15AS and 16AS. Zinc chloride-catalyzed cycload-
dition of methyl acrylate with sulfonyl diene 19A, readily
obtained by oxidation of 2AR with m-CPBA, provided a
10:1 mixture of endo (20A + 21A) and exo (22A + 23A)
adducts. The ratio 20A:21A was 1:1, which showed that
the isoborneol group did not significantly influence the
stereoselectivity of cycloaddition, and so confirmed the
fundamental role that sulfoxide chirality plays in deter-
mining diastereoselectivity of cycloadditions of 2-sulfinyl
dienes. These considerations allowed, by analogy, the
(19) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: New York, 1976.
(20) LiClO4 in Et2O-CH2Cl2 (presumably in solution) has been used
previously to catalyze cycloadditions of dienophilic sulfinyl maleates
to cyclopentadiene, with moderate diastereofacial selectivity (Alonso,
I.; Cid, M. B.; Carretero, J . C.; Garc´ıa Ruano, J . L.; Hoyos, M. A.
Tetrahedron: Asymmetry 1991, 2, 1193-1207).
(21) Reetz, M. T.; Fox, D. N. A. Tetrahedron Lett. 1993, 34, 1119-
1122.
(22) Grieco, P. A.; Nunes, J . J .; Gaul, M. D. J . Am. Chem. Soc. 1990,
112, 4595-4596.
(23) Adams, A.; Bailey, N. A.; J ones, D. N.; Aversa, M. C.; Bonac-
corsi, P.; Giannetto, P. Acta Crystallogr. 1995, C51, 1357-1359.

4380 J . Org. Chem., Vol. 62, No. 13, 1997
Aversa et al.
Sch em e 3
assignment of the absolute configurations to adducts
15BS,CS-18BS,CS.
dienes, which are not easily accessible by other synthetic
routes.6 The high degree of stereocontrol exhibited by
LiClO4-catalyzed cycloadditions of these alkylsulfinyl
dienes with methyl acrylate indicates that chiral 2-sulfi-
nyl dienes may fulfill a useful role in enantioselective
synthesis. Asymmetric induction in these DA reactions
of 2-sulfinyl dienes is overwhelmingly influenced by
sulfur configuration, while other chiral elements present
in the sulfoxide auxiliary have no significant effect. The
high degree of stereochemical control observed in the
preparation and cycloadditions of sulfinyl dienes derived
from 10-mercaptoisoborneol 1A, the good yield of cycload-
ducts, easy separation of diastereomeric mixtures, and
crystallinity of the final adducts demonstrate the utility
of camphor skeleton in the design of chiral auxiliaries
based on sulfoxides.
A tentative rationalization of stereochemical features,
observed in the cycloadditions of 3-(alkylsulfinyl)-1-
methoxy-1,3-butadienes 2 and 3 with methyl acrylate,
may take into account the relative stabilities of the
transition states originated from the endo approach of
the dienophile to different conformations of the diene
around the S--C-3 bond. The predominance of 15AR
among the products of the uncatalyzed cycloaddition of
2AR may be interpreted on the basis of Re face approach
of methyl acrylate to the diene in its c conformation; the
isolation from the same reaction mixture of a certain
percentage of the diastereomeric 16AR may be explained
by considering the Si face approach of the dienophile to
the diene in the less favored d conformation. The great
improvement of diastereoselectivity and increased reac-
tion rate observed in the LiClO4-catalyzed DA reaction
of 2AR (Table 2) suggest the approach of methyl acrylate
to the Re face of the diene in its e conformation, the
catalyst coordinating the sulfinyl oxygen of the diene and
the carbonyl oxygen of the dienophile, as depicted in
Figure 2.
Exp er im en ta l Section
Gen er a l Met h od s. Melting points were measured on a
microscopic apparatus and are uncorrected. IR spectra were
taken for neat oils, Nujol mulls, or CHCl3 solutions with an
FT spectrophotometer (see the Supporting Information). 1H
and 13C NMR spectra were recorded at 300 and 75 MHz,
respectively, in CDCl3 solutions (unless otherwise stated) with
SiMe4 as internal standard; J values are given in Hz; the
attributions are supported by attached proton test (APT),
heteronuclear shift-correlated, and decoupling experiments.
Mass spectra were measured by electron impact (EI, 70 eV)
or fast atom bombardment (FAB, glycerol or m-nitrobenzyl
alcohol). All reactions were monitored by TLC on commercially
available precoated plates (silica gel 60 F 254), and the
products were visualized with iodine. Silica gel 60 was used
for column chromatography. Petrol refers to light petroleum,
bp 60-80 °C. Elemental analyses were performed by REDOX,
Milano, Italy. Substances for which C, H, N analyses are not
reported were purified as specified and gave spectral data
consistent with being >95% of the assigned structure.
Con clu sion s
The synthetic strategy based on the regioselective
addition of sulfenic acids to enynes has been successfully
applied to the preparation of enantiopure 2-sulfinyl
(S)-(Eth oxyca r bon yl)p h en ylm eth yl N,N-Dim eth yld i-
th ioca r ba m a te (12). DEAD (9 mL, 56 mmol) was added

Reactions of 3-(Alkylsulfinyl)-1-methoxy-1,3-butadienes
J . Org. Chem., Vol. 62, No. 13, 1997 4381
dropwise at 0 °C to a stirred dry toluene (180 mL) suspension
containing ethyl (R)-mandelate (11R) (5 g, 28 mmol), Ph3P (15
g, 57 mmol), and zinc dimethyldithiocarbamate (ZIRAM, 6.4
g, 21 mmol). After the mixture was stirred 24 h at room
temperature, the workup of the reaction was effected by
concentration of the mixture under reduced pressure and direct
column chromatography: elution with petrol/EtOAc (90:10)
afforded the dimethyldithiocarbamate 12 (5.7 g, 71%) as a
crystalline compound: mp 103-105 °C; [R]25D +257 (c ) 0.012,
g (15.8 mmol) of LiAlH4 suspended in dry Et2O (80 mL) at 0
°C. Following the addition, the mixture was refluxed for 2 h.
The reaction mixture was cooled at room temperature and
excess LiAlH4 carefully quenched by adding wet Et2O, H2O,
and finally HCl 3 N until the aqueous layer was neutral. The
water phase was extracted with Et2O (3 × 50 mL), and the
combined organic extracts were washed with saturated NaH-
CO3 solution (100 mL), dried (Na2SO4), and concentrated under
reduced pressure to afford 6.2 g of alcohol 13 as a 1:1 mixture
of diastereomers (epimeric at C-2"; clear, colorless oil, which
did not need purification; almost quantitative yield): FAB-
MS m/ z 223 (M + 1, 16), 85 (82), 75 (100). Anal. Calcd for
C13H18O3: C, 70.25; H, 8.16. Found: C, 70.29; H, 8.14. The
two epimers 13 can be separated by column chromatography
eluting with petrol/EtOAc (98:2). First eluted epimer: oil; 1H
NMR δ 7.4-7.3 (m, Ph), 4.83 (dd, J 1A,2 ) 8.1, J 1B,2 ) 3.9, H-2),
4.53 (dd, J 2",3" ) 5.3, 2.5, H-2"), 4.02 (5 lines, J 5",6"A ) 5.2, J 6"A,6"B
) 11.8, HA-6"), 3.72 (split ABd, J 1A,1B ) 11.8, HA-1), 3.67 (split
ABd, HB-1), 3.56 (5 lines, J 5",6"B ) 5.6, HB-6"), 1.9 (br s, OH),
1.9-1.4 (m, H2-3",4",5"); 13C NMR δ 138.7 (C-1′), 128.4 (C-2′,6′),
127.9 (C-4′), 126.7 (C-3′,5′), 97.9 (C-2"), 80.7 (C-2), 67.6 (C-1),
63.7 (C-6"), 31.0, 25.2, and 20.3 (C-3",4",5"). Second epimer:
oil; 1H NMR δ 7.4-7.3 (m, Ph), 4.91 (t, J 2",3" ) 3.4, H-2"), 4.74
(dd, J 1A,2 ) 6.6, J 1B,2 ) 5.2, H-2), 3.74 (split ABd, J 1A,1B ) 10.9,
HA-1), 3.72 (split ABd, HB-1), 3.59 (7 lines, J 5",6"A ) 8.2, 3.2,
J 6"A,6"B ) 11.1, HA-6"), 3.30 (5 lines, J 5",6"B ) 5.1, HB-6"), 2.0
(br s, OH), 1.9-1.5 (m, H2-3",4",5"); 13C NMR δ 139.8 (C-1′),
128.3 (C-2′,6′), 127.6 (C-4′), 126.7 (C-3′,5′), 99.1 (C-2"), 79.8 (C-
2), 66.6 (C-1), 62.6 (C-6"), 30.6, 25.2, and 19.4 (C-3",4",5").
(2S)-2-P h en yl-2-(2-tetr a h yd r op yr a n oxy)eth yl N,N-Di-
m eth yld ith ioca r ba m a te (14). The epimeric mixture 13 was
reacted as reported for the preparation of 12. After the
mixture was stirred for 12 h at room temperature, concentra-
tion under reduced pressure and direct column chromatogra-
phy [petrol/EtOAc (95:5)] afforded dimethyldithiocarbamate
14 (82%, 1:1 epimeric ratio): FAB-MS m/ z 326 (M + 1, 96),
122 (92), 121 (100). Anal. Calcd for C16H23NO2S2: C, 59.04;
H, 7.12; N, 4.30. Found: C, 59.11; H, 7.09; N, 4.30. Epimers
can be separated by further column chromatography eluting
with petrol/EtOAc (98:2). First eluted epimer: oil; 1H NMR δ
7.5-7.3 (m, Ph), 4.98 (dd, J 2",3" ) 5.6, 3.3, H-2"), 4.93 (dd, J vic
7.4, 5.1, PhCH), 3.9-3.2 (m, NMe2, CH2S, H2-6"), 1.9-1.0 (m,
H2-3",4",5"); 13C NMR δ 197.0 (CS), 141.9 (C-1′), 128.2 (C-2′,6′),
127.4 (C-4′), 126.6 (C-3′,5′), 98.8 (C-2"), 77.0 (PhCH), 62.1 (C-
6"), 45.4 and 41.4 (NMe2), 44.6 (CH2S), 30.5, 25.4, and 19.2
1
CHCl3); H NMR δ 7.5-7.3 (m, Ph), 5.74 (s, CHS), 4.29 and
4.16 (16 lines, J gem 10.7, J vic 7.1, CH2), 3.52 and 3.36 (two s,
NMe2), 1.26 (t, CH2CH3); 13C NMR δ 195.0 (CS), 170.0 (CO),
133.9 (C-1′), 128.9 and 128.8 (C-2′,3′,5′,6′), 128.5 (C-4′), 62.0
(CH2), 59.5 (CHS), 45.2 and 41.5 (NMe2), 14.0 (CH2CH3); FAB-
MS m/ z 284 (M + 1, 100), 238 (30), 163 (24). Anal. Calcd for
C13H17NO2S2: C 55.10; H, 6.05; N, 4.94. Found: C, 55.07; H,
6.13; N, 4.93.
(S)-2-Mer ca p to-2-p h en yleth a n ol (1B).24 Dimethyldithio-
carbamate 12 (5.6 g, 19.8 mmol) was slowly added to 1.5 g (40
mmol) of LiAlH4 suspended in dry Et2O (60 mL) at 0 °C.
Following the addition, the mixture was refluxed for 4 h. The
reaction mixture was cooled at room temperature and LiAlH4
carefully quenched by adding wet Et2O, H2O, finally HCl 3 N
until pH 3 was measured. The organic phase was extracted
with 10% NaOH (4 × 60 mL). HCl 12 N was added under
stirring to the alkaline water solution until pH 3 was reached
again. Then the acid water phase was extracted with Et2O (4
× 70 mL) and the ethereal solution washed with H2O (80 mL),
dried (Na2SO4), and concentrated under reduced pressure to
give the mercaptoethanol 1B, which did not need purification
(2.7 g, 86%): mp 46-48 °C; [R]25 +90 (c ) 0.022, CHCl3); 1H
D
NMR δ 7.4-7.2 (m, Ph), 4.07 (ddd, J 1A,2 ) 6.5, J 1B,2 ) 7.6, J 2,SH
) 6.7, H-2), 3.90 (split ABd, J 1A,1B ) 11.1, HA-1), 3.78 (split
ABd, HB-1), 2.23 (br s, OH), 1.97 (d, SH); 13C NMR δ 140.4
(C-1′), 128.8 (C-3′,5′), 127.8 (C-4′), 127.4 (C-2′,6′), 68.3 (C-1),
46.3 (C-2); EI-MS m/ z 154 (M+, 18), 123 (100), 91 (77). Anal.
Calcd for C8H10OS: C, 62.30; H, 6.54. Found: C, 62.29; H, 6.64.
Eth yl (2S)-2-P h en yl-2-(2-tetr a h yd r op yr a n oxy)eth a n o-
a te. A solution of ethyl (S)-mandelate (11S) (5 g, 28 mmol)
and 3,4-dihydro-2H-pyran (DHP, 3.5 g, 42 mmol) in dry CH2-
Cl2 (200 mL) containing PPTS25 (0.7 g, 28 mmol) was stirred
for 12 h at room temperature. The solution was then diluted
with Et2O and washed once with half-saturated brine to
remove the catalyst. After evaporation of the solvent, ethyl
(2S)-2-phenyl-2-(2-tetrahydropyranoxy)ethanoate was obtained
in an essentially quantitative yield (7.4 g): the colorless oil,
which did not need purification, was a mixture of diastereo-
mers (epimeric at C-2" of the THP moiety) in a 1:1 ratio as
determined by integration of the signals in the 1H NMR
spectrum: FAB-MS m/ z 265 (M + 1, 14), 163 (23), 85 (100).
Anal. Calcd for C15H20O4: C, 68.16; H, 7.63. Found: C, 68.10;
H, 7.60. The two epimers can be separated by column
chromatography eluting with petrol mixed with increasing
amounts of EtOAc up to 5%. First eluted epimer: oil; 1H NMR
δ 7.5-7.3 (m, Ph), 5.31 (s, H-2), 4.89 (t, J 2",3" ) 2.7, H-2"), 4.19
and 4.15 (12 lines, J gem ) 10.9, J vic ) 7.2, CH2CH3), 3.7 and
3.5 (two m, H2-6"), 1.9-1.5 (m, H2-3",4",5"), 1.21 (t, Me); 13C
NMR δ 171.3 (C-1), 136.8 (C-1′), 128.4 (C-2′,6′), 128.2 (C-4′),
127.1 (C-3′,5′), 97.0 (C-2"), 75.6 (C-2), 61.8 (C-6"), 61.1 (CH2-
CH3), 30.1, 25.3, and 18.6 (C-3",4",5"), 14.1 (Me). Second
epimer: oil; 1H NMR δ 7.5-7.3 (m, Ph), 5.21 (s, H-2), 4.59 (t,
1
(C-3",4",5"). Second epimer: oil; H NMR δ 7.5-7.3 (m, Ph),
4.48 (t, J 2",3" ) 2.5, H-2"), 4.07 (m, PhCH), 3.9-3.2 (m, NMe2,
CH2S, H2-6"), 1.9-1.0 (m, H2-3",4",5"); 13C NMR δ 197.2 (CS),
140.6 (C-1′), 128.4 (C-2′,6′), 127.9 (C-4′), 127.0 (C-3′,5′), 94.8
(C-2"), 75.5 (PhCH), 61.7 (C-6"), 45.4 and 41.4 (NMe2), 45.0
(CH2S), 30.5, 25.5, and 18.9 (C-3",4",5").
(2S)-2-P h en yl-2-(2-tetr a h yd r op yr a n oxy)eth yl Mer ca p -
ta n . The epimeric mixture 14 was reacted as reported for the
preparation of 13: reflux time was 6 h. (2S)-2-Phenyl-2-(2-
tetrahydropyranoxy)ethyl mercaptan was obtained as a 1:1
ratio of diastereomers (epimers at C-2"; clear, colorless oil,
which did not need purification; almost quantitative yield): 1H
NMR δ 7.4-7.3 (m, Ph), 4.96 (t, J 2",3" ) 2.9, H-2" of one epimer),
4.78 (dd, J 1,2 ) 8.0, 5.1, H-2 of one epimer), 4.69 (dd, J 1,2
)
7.0, 5.6, H-2 of the other epimer), 4.47 (t, J 2",3" ) 3.3, H-2" of
the other epimer), 4.1-3.3 (m, H2-6"), 3.0-2.7 (m, H2-1), 1.9-
1.4 (m, H2-3",4",5", SH); 13C NMR δ 141.4 and 140.2 (C-1’),
128.5 and 128.2 (C-2’,6’), 128.1 and 127.6 (C-4’), 127.1 and
126.6 (C-3’,5’), 98.7 and 95.1 (C-2”), 80.1 and 78.2 (C-2), 62.3
and 61.9 (C-6”), 31.9 and 31.2 (C-1), 30.5, 30.4, 25.4, 25.3, 19.3,
and 19.0 (C-3”,4”,5”). Anal. Calcd for C13H18O2S: C, 65.51; H,
7.61. Found: C, 65.47; H, 7.60.
J 2",3" ) 3.3, H-2"), 4.20 and 4.13 (14 lines, J gem ) 10.8, J vic
)
7.0, CH2CH3), 4.0 and 3.5 (two m, H2-6"), 2.0-1.5 (m, H2-
3",4",5"), 1.21 (t, Me); 13C NMR δ 170.6 (C-1), 136.4 (C-1′), 128.4
(C-2′,4′,6′), 127.4 (C-3′,5′), 96.5 (C-2"), 76.8 (C-2), 62.2 (C-6"),
61.0 (CH2CH3), 30.2, 25.3, and 19.0 (C-3",4",5"), 14.0 (Me).
(2S)-2-P h en yl-2-(2-t et r a h yd r op yr a n oxy)et h a n ol (13).
The epimeric mixture of ethyl (2S)-2-phenyl-2-(2-tetrahydro-
pyranoxy)ethanoates (7.4 g, 28 mmol) was slowly added to 0.6
(S)-2-Mer ca p to-1-p h en yleth a n ol (1C).13,24a A solution of
(2S)-2-phenyl-2-(2-tetrahydropyranoxy)ethyl mercaptan (1:1
epimeric ratio) (2 g, 8.4 mmol) and PPTS (0.21 g, 0.84 mmol)
in EtOH (70 mL) was stirred at 55 °C (bath temperature) for
24 h. The solvent was evaporated in vacuo, and Et2O (100
mL) was added. The organic phase was extracted with 10%
NaOH (4 × 60 mL). HCl 12 N was added under stirring to
the alkaline water solution until pH 3 was reached again. Then
the acid water phase was extracted with Et2O (4 × 70 mL)
(24) (a) Djerassi, C.; Gorman, M.; Markley, F. X.; Oldenburg, E. B.
J . Am. Chem. Soc. 1955, 77, 568-571. (b) Alcudia, F.; Brunet, E.;
Garc´ıa Ruano, J . L.; Rodriguez, J . H.; Sanchez, F. J . Chem. Res., Synop.
1982, 284-285; J . Chem. Res., Miniprint 1982, 2826-2850.
(25) Miyashita, N.; Yoshikoshi, A.; Grieco, P. A. J . Org. Chem. 1977,
42, 3772-3774.

4382 J . Org. Chem., Vol. 62, No. 13, 1997
Aversa et al.
and the ethereal solution washed with H2O (80 mL), dried
(Na2SO4), and concentrated under reduced pressure to give the
4.1, H-2), 3.15 (ABd, J 10A,10B ) 13.0, HA-10), 3.1-2.9 (m, H2-
1′,2′), 2.60 (ABd, HB-10), 2.8 (br s, OH), 1.9-1.1 (m, H2-3,5,6,
H-4), 1.10 (s, H3-8), 0.90 (s, H3-9).
mercaptoethanol 1C, which did not need purification (1.11 g,
1
86%): oil; [R]25 +50 (c ) 0.009, CHCl3); H NMR δ 7.4-7.2
(S,RS)-2-[(2-Cyan oeth yl)su lfin yl]-2-ph en yleth an ol (7BR):
D
(m, Ph), 4.71 (dd, J 1,2A ) 4.1, J 1,2B ) 8.2, H-1), 2.86 (8 lines,
J 2A,2B ) 13.8, J 2A,SH ) 9.0, HA-2), 2.79 (8 lines, J 2B,SH ) 8.2,
HB-2), 1.44 (t, SH); 13C NMR δ 142.0 (C-1′), 128.4 (C-2′,6′),
127.9 (C-4′), 125.8 (C-3′,5′), 74.6 (C-1), 33.5 (C-2); EI-MS m/ z
154 (M+, 2), 107 (100), 85 (94). Anal. Calcd for C8H10OS: C,
62.30; H, 6.54. Found: C, 63.36; H, 6.52.
yield 89%; white crystals mp 137-138 °C; [R]25 +220 (c )
D
0.005, CHCl3); 1H NMR δ 7.4-7.3 (m, Ph), 4.53 (split ABd,
J 1A,2 ) 7.4, J 1A,1B, 12.3, HA-1), 4.21 (split ABd, J 1B,2 ) 3.8, HB-
1), 4.08 (dd, H-2), 2.9-2.7 (m, CH2CH2CN), 2.5 (br s, OH); 13
C
NMR δ 131.4 (C-1′), 129.7 (C-2′,6′), 129.4 (C-4′), 128.6 (C-3′,5′),
117.2 (CN), 69.0 (C-2), 64.0 (C-1), 44.6 (SCH2), 10.6 (CH2CN);
FAB-MS m/z 224 (M + 1, 35), 121 (100), 45 (27). Anal. Calcd
for C11H13NO2S: C, 59.17; H, 5.87; N, 6.27. Found: C, 59.25;
H, 5.79; N, 6.20. The formation of (S,SS)-2-[(2-cyanoethyl)-
sulfinyl]-2-phenylethanol (minor diastereomer) was not ob-
served in a notable amount.
2-Cyan oeth yl Su lfides 6A-C. Gen er al P r ocedu r e. Acry-
lonitrile (0.81 mL, 12.5 mmol) was added slowly to a solution
(THF, 45 mL) of an equimolar amount of mercaptoalkanols
1A,10 1B, or 1C and benzyltrimethylammonium hydroxide
(Triton B, 0.4 mL, 40 wt % solution in MeOH) at -78 °C. The
reaction mixture was slowly brought to room temperature, and
water (80 mL) was added. The crude product was extracted
with Et2O (4 × 80 mL). The combined organic layers were
washed with saturated NaHCO3 solution (3 × 50 mL) and
dried (Na2SO4). Evaporation of the solvent gave an oily
residue that was purified by column chromatography eluting
with petrol/Et2O (85:15) to give [(cyanoethyl)thio]alkanols
6A-C as pale yellow oils.
(S)-2-[(2-Cya n oeth yl)su lfin yl]-1-p h en yleth a n ol (7C): al-
most quantitative yield of 1:1 oil mixture of sulfur epimers,
hard to separate by column chromatography; 1H NMR (epimer-
ic mixture) δ 7.4-7.3 (m, Ph), 5.37 (dd, J 1,2 ) 8.7, 3.5) and
5.27 (dd, J 1,2 ) 10.2, 2.3) (H-1), 3.3-2.7 (m, 3 × CH2, OH); 13
C
NMR (epimeric mixture) δ 141.9 and 141.8 (C-1′), 128.8 (C-
2′,6′), 128.3 (C-4′), 125.7 and 125.5 (C-3′,5′), 117.4 (CN), 68.6
and 67.6 (C-1), 60.8 and 58.3 (C-2), 46.7 and 46.5 (CH2CH2-
CN), 11.1 (CH2CN); FAB-MS m/ z 224 (M + 1, 61), 206 (M -
H2O + 1, 100), 154 (89), 137 (62), 104 (81). Anal. Calcd for
C11H13NO2S: C, 59.17; H, 5.87; N, 6.27. Found: C, 59.37; H,
5.89; N, 6.30.
(1S)-10-[(2-Cya n oeth yl)th io]isobor n eol (6A): yield 91%;
1H NMR δ 3.87 (dd, J 2,3 ) 7.7, 3.9, H-2), 2.88 (ABd, J 10A,10B
)
10.9, HA-10), 2.61 (ABd, HB-10), 2.8-2.6 (m, H2-1′,2′), 2.17 (br
s, OH), 1.8-1.0 (m, H2-3,5,6, H-4), 1.06 (s, H3-8), 0.85 (s, H3-
9); 13C NMR δ 118.4 (C-3′), 76.5 (C-2), 52.1 (C-1), 47.7 (C-7),
45.1 (C-4), 39.5 (C-3), 32.1 (C-10), 30.9 and 27.0 (C-5,6), 28.8
(C-1′), 20.6 and 19.9 (C-8,9), 18.8 (C-2′); EI-MS m/ z 239 (M+,
2), 221 (M+ - H2O, 16), 109 (79), 108 (100). Anal. Calcd for
C13H21NOS: C, 65.23; H, 8.84; N, 5.85. Found: C, 65.20; H,
8.65; N, 5.90.
1-Meth oxy-3-su lfin ylbu ta -1,3-d ien es 2 a n d 3. Gen er a l
P r oced u r e. The sulfoxides 7 (1 g, 4.5 mmol) in toluene or
mixed xylenes (12 mL) (see Table 1) containing (E)- or (Z)-1-
methoxy-1-buten-3-yne (1.1 mL, 13.5 mmol) were maintained
at reflux temperature [(E)-enyne 9 was prepared following the
Brandsma procedure;26 (Z)-isomer 10, commercially available
in MeOH/H2O (4:1), was extracted with Et2O and distilled
under reduced pressure just before use]. When the reaction
appeared complete by TLC, the solvent was removed under
reduced pressure and the reaction mixture was separated by
column chromatography.
(S)-2-[2-Cya n oeth yl)th io]-2-p h en yleth a n ol (6B): yield
1
84%; [R]25 +275 (c ) 0.005, CHCl3); H NMR δ 7.4-7.3 (m,
D
Ph), 4.08 (dd, J 1,2 ) 7.6, 6.2, H-2), 3.9 (m, H2-1), 2.7 and 2.5
(two m, CH2CH2CN), 1.8 (br s, OH); 13C NMR δ 139.7 (C-1′),
130.1 (C-3′,5′), 129.3 (C-4′), 129.1 (C-2′,6′), 119.1 (CN), 66.9
(C-1), 54.3 (C-2), 27.7 (SCH2), 19.9 (CH2CN); FAB-MS m/ z 208
(M + 1, 14), 137 (100), 89 (71). Anal. Calcd for C11H13NOS:
C, 63.74; H, 6.32; N, 6.76. Found: C, 63.75; H, 6.42; N, 6.66.
(S)-2-[(2-Cya n oeth yl)th io]-1-p h en yleth a n ol (6C): yield
Reaction of (1S)-10-[(2-Cyan oeth yl)su lfin yl]isobor n eols
7A w ith (E)-En yn e 9. The following products were obtained
by elution with petrol containing increasing amounts of Et2
O
up to 30% and are reported in order of raising retention times.
80%; [R]25 +58 (c ) 0.050, CHCl3); 1H NMR δ 7.4-7.3 (m,
(RS,E)-3-[(1S)-Isobor n eol-10-su lfin yl]-1-m eth oxybu ta -
D
1
1,3-d ien e (2AR): oil; [R]25 +39 (c ) 0.002, CHCl3); H NMR
Ph), 4.84 (dd, J 1,2A ) 4.0, J 1,2B ) 8.4, H-1), 2.97 (split ABd,
J 2A,2B ) 14.0, HA-2), 2.88 (split ABd, HB-2), 2.80 and 2.64 (two
t, J vic ) 7.0, CH2CH2CN), 1.6 (br s, OH); 13C NMR δ 142.3 (C-
1′), 128.7 (C-2′,6′), 128.2 (C-4′), 125.7 (C-3′,5′), 118.0 (CN), 73.2
(C-1), 41.6 (C-2), 28.2 (SCH2CH2), 19.0 (CH2CN); EI-MS m/ z
207 (M+, 2), 107 (100), 43 (83). Anal. Calcd. for C11H13NOS:
C, 63.74; H, 6.32; N, 6.76. Found: C, 63.70; H, 6.31; N, 6.68.
2-Cya n oeth yl Su lfoxid es 7A-C. Gen er a l P r oced u r e.
m-CPBA carefully dried over P2O5 (2.2 g 80%, 10.2 mmol) was
dissolved in CH2Cl2 (70 mL) and slowly added to a solution of
an equimolar amount of 2-cyanoethyl sulfides 6 in CH2Cl2 (70
mL) at -15 °C. The reaction mixture was allowed to reach
room temperature and stirred for 2 h. Anhydrous KF (2.5 g)
was added and the mixture stirred overnight. After filtration,
the evaporation of the solvent under reduced pressure gave
2-cyanoethyl sulfoxides 7, usable for synthesizing sulfinyl
dienes 2 and 3 without purification.
D
δ 6.86 (d, J 1,2 ) 12.8, H-1), 5.71 and 5.59 (two s, H2-4), 5.53 (d,
H-2), 4.13 (dd, J 2′,3′ ) 8.1, 4.2, H-2′), 3.67 (s, OMe), 3.5 (br s,
OH), 3.13 (ABd, J 10′A,10′B ) 13.5, HA-10′), 2.60 (ABd, HB-10′),
1.9-1.1 (m, H2-3′,5′,6′, H-4′), 1.08 (s, H3-8′), 0.82 (s, H3-9′); 13
C
NMR δ 150.9 (C-1), 148.2 (C-3), 112.3 (C-4), 98.1 (C-2), 76.9
(C-2′), 56.7 (OMe), 56.0 (C-10′), 51.6 (C-1′), 48.2 (C-7′), 45.1
(C-4′), 38.4 (C-3′), 30.9 and 27.1 (C-5′,6′), 20.5 and 19.8 (C-
8′,9′); FAB-MS m/ z 285 (M + 1, 66), 135 (100), 83 (45).
(SS,E)-3-[(1S)-Isobor n eol-10-su lfin yl]-1-m et h oxyb u t a -
1,3-d ien e (2AS): oil; 1H NMR δ 6.92 (d, J 1,2 ) 13.0, H-1), 5.76
and 5.61 (two s, H2-4), 5.53 (d, H-2), 4.15 (dd, J 2′,3′ ) 7.6, 4.0,
H-2′), 3.65 (s, OMe), 2.7 (br s, OH), 3.38 (ABd, J 10′A,10′B ) 14.0,
HA-10′), 2.56 (ABd, HB-10′), 1.9-1.1 (m, H2-3′,5′,6′, H-4′), 1.12
(s, H3-8′), 0.83 (s, H3-9′); 13C NMR δ 151.2 (C-1), 148.2 (C-3),
112.4 (C-4), 98.6 (C-2), 76.4 (C-2′), 56.8 (OMe), 54.0 (C-10′),
52.2 (C-1′), 48.9 (C-7′), 44.7 (C-4′), 40.5 (C-3′), 31.2 and 27.4
(C-5′,6′), 20.5 and 20.3 (C-8′,9′); FAB-MS m/ z 285 (M + 1, 9),
135 (100), 55 (62).
(1S)-10-[(2-Cya n oeth yl)su lfin yl]isobor n eol (7A): yield
92% of 28:1 mixture of sulfur epimers, which can be separated
by column chromatography, eluting with petrol/EtOAc (80:
20): FAB-MS m/ z 256 (M + 1, 78), 238 (22), 135 (100). Anal.
Calcd for C13H21NO2S: C, 61.14; H, 8.29; N, 5.48. Found: C,
61.20; H, 8.32; N, 5.50.
Rea ction of (1S)-10-[(2-Cya n oeth yl)su lfin yl]isobor n eol
(7A) w ith (Z)-En yn e 10. The following products were
obtained by elution with petrol containing increasing amounts
of Et2O up to 30% and are reported in sequence of raising
retention times.
(RS,Z)-3-[(1S)-Isobor n eol-10-su lfin yl]-1-m eth oxybu ta -
1,3-d ien e (3AR): mp 95-97 °C; [R]25D +78 (c ) 0.070, CHCl3);
1H NMR δ 6.17 (d, J 1,2 6.9, H-1), 5.92 and 5.89 (two s, H2-4),
5.07 (d, H-2), 4.14 (dd, J 2′,3′ ) 8.0, 4.2, H-2′), 3.75 (s, OMe), 3.4
(br s, OH), 2.99 (ABd, J 10′A,10′B ) 13.2, HA-10′), 2.66 (ABd, HB-
10′), 1.9-1.1 (m, H2-3′,5′,6′, H-4′), 1.07 (s, H3-8′), 0.81 (s, H3-
(1S,SS)-10-[(2-Cyan oeth yl)su lfin yl]isobor n eol (7AS): first
1
eluted oil; [R]25 -46 (c ) 0.012, CHCl3); H NMR δ 4.05 (dd,
D
J 2,3 ) 8.2, 4.1, H-2), 3.37 (ABd, J 10A,10B ) 12.9, HA-10), 3.1-
2.9 (m, H2-1′,2′), 2.42 (ABd, HB-10), 2.8 (br s, OH), 1.9-1.1
(m, H2-3,5,6, H-4), 1.11 (s, H3-8), 0.85 (s, H3-9); 13C NMR δ
117.2 (C-3′), 76.8 (C-2), 53.2 (C-10), 51.3 (C-1), 48.2 (C-7), 47.7
(C-1′), 44.9 (C-4), 38.5 (C-3), 30.8 and 27.1 (C-5,6), 20.4 and
19.8 (C-8,9), 11.1 (C-2′).
(1S,RS)-10-[(2-Cyan oeth yl)su lfin yl]isobor n eol (7AR): oil;
D
(26) Brandsma, L. Preparative Acetylenic Chemistry; Elsevier: New
York, 1971.
1
[R]25 -53 (c ) 0.012, CHCl3); H NMR δ 4.03 (dd, J 2,3 ) 8.2,

Reactions of 3-(Alkylsulfinyl)-1-methoxy-1,3-butadienes
J . Org. Chem., Vol. 62, No. 13, 1997 4383
9′); 13C NMR δ 149.6 (C-1), 147.8 (C-3), 115.2 (C-4), 98.0 (C-
2), 76.9 (C-2′), 60.7 (OMe), 56.1 (C-10′), 51.6 (C-1′), 48.1 (C-
7′), 45.1 (C-4′), 38.4 (C-3′), 30.7 and 27.1 (C-5′,6′), 20.4 and
19.8 (C-8′,9′); FAB-MS m/ z 285 (M + 1, 75), 135 (100), 83 (40).
128.3 (C-4′), 125.8 (C-3′,5′), 112.6 (C-4), 96.9 (C-2), 71.3
(CHOH), 60.0 (CHCH2), 56.7 (OMe).
Rea ction of (S)-2-[(2-Cya n oeth yl)su lfin yl]-1-p h en yl-
eth a n ol (7C) w ith (Z)-En yn e 10. The mixture of dienes 3C
was obtained by eluting first with toluene to remove the excess
enyne and then with petrol containing increasing amounts of
EtOAc. Further column chromatography [benzene/2-propanol
(98:2) as eluant] allowed the separation of the two diene
epimers, with 3CS showing a slightly enhanced chromato-
graphic mobility with respect to 3CR.
(S,SS,Z)-3-[(2-Hyd r oxy-2-p h en yleth yl)su lfin yl]-1-m eth -
oxybu ta -1,3-d ien e (3CS): oil; [R]25D +100 (c ) 0.008, CHCl3);
1H NMR δ 7.4-7.3 (m, Ph), 6.16 (d, J 1,2 ) 6.8, H-1), 6.06 (s,
H2-4), 5.34 (dd, J vic ) 10.0, 1.7, CHCHAHB), 5.03 (d, H-2), 4.44
(SS,Z)-3-[(1S)-Isob or n eol-10-su lfin yl]-1-m et h oxybu t a -
1
1,3-d ien e (3AS): oil; [R]25 -34 (c ) 0.004, CHCl3); H NMR
D
δ 6.18 (d, J 1,2 ) 6.8, H-1), 6.01 and 5.99 (two s, H2-4), 5.04 (d,
H-2), 4.12 (dd, J 2′,3′ ) 7.8, 3.8, H-2′), 3.77 (s, OMe), 3.32 (ABd,
J 10′A,10′B ) 14.0, HA-10′), 2.51 (ABd, HB-10′), 2.4 (br s, OH), 1.9-
1.1 (m, H2-3′,5′,6′, H-4′), 1.10 (s, H3-8′), 0.81 (s, H3-9′); 13C NMR
δ 149.5 (C-1), 147.1 (C-3), 116.4 (C-4), 98.3 (C-2), 76.4 (C-2′),
61.0 (OMe), 53.8 (C-10′), 53.0 (C-1′), 50.2 (C-7′), 44.6 (C-4′),
39.7 (C-3′), 31.1 and 27.5 (C-5′,6′), 20.5 and 20.1 (C-8′,9′); FAB-
MS m/ z 285 (M + 1, 100), 135 (84), 75 (79).
Rea ction of (S,RS)-2-[(2-Cya n oeth yl)su lfin yl]-2-p h en -
yleth a n ol (7BR) w ith (E)-En yn e 9. The following products
were obtained by eluting first with toluene only (to remove
the excess enyne) then with toluene containing increasing
amounts of CH2Cl2.
(br s, OH), 3.73 (s, OMe), 3.27 (split ABd, J gem ) 13.7, J vic
)
10.0, CHCHAHB), 2.74 (split ABd, CHCHAHB); 13C NMR δ
149.8 (C-1), 145.5 (C-3), 142.3 (C-1′), 128.6 (C-2′,6′), 127.8 (C-
4′), 125.7 (C-3′,5′), 116.9 (C-4), 97.8 (C-2), 69.1 (CHOH), 60.8
(OMe), 57.3 (CHCH2); FAB-MS m/ z 253 (M + 1, 16), 138 (54),
137 (100).
(S,SS,E)-3-[(2-Hyd r oxy-1-p h en yleth yl)su lfin yl]-1-m eth -
oxybu ta -1,3-d ien e (2BS): oil; [R]25D +127 (c ) 0.004, CHCl3);
1H NMR δ 7.5-7.1 (m, Ph), 6.79 (d, J 1,2 ) 12.9, H-1), 5.45 and
5.29 (two s, H2-4), 5.36 (d, H-2), 4.7-4.1 (m, CH2CH), 4.0 (br
s, OH), 3.52 (s, OMe); 13C NMR δ 151.9 (C-1), 146.9 (C-3), 133.1
(C-1′), 128.9, 128.7, and 128.6 (C-2′,3′,4′,5′,6′), 114.1 (C-4), 96.5
(C-2), 68.8 (CH2CH), 64.6 (CH2CH), 56.6 (OMe); FAB-MS m/ z
253 (M + 1, 100), 121 (53), 83 (46). The minor epimer
(S,RS,E)-3-[(2-h yd r oxy-1-p h en yleth yl)su lfin yl]-1-m eth ox-
ybu ta -1,3-d ien e (2BR) was obtained in mixture with 2BS and
(S,RS,Z)-3-[(2-Hyd r oxy-2-p h en yleth yl)su lfin yl]-1-m eth -
oxybu ta -1,3-d ien e (3CR): oil; [R]25 -71 (c ) 0.002, CHCl3);
D
1H NMR δ 7.4-7.3 (m, Ph), 6.16 (d, J 1,2 ) 6.7, H-1), 5.94 and
5.92 (two s, H2-4), 5.41 (dd, J vic ) 9.6, 2.2, CHCHAHB), 5.04
(d, H-2), 4.27 (br s, OH), 3.72 (s, OMe), 3.06 (split ABd, J gem
)
13.2, J vic ) 2.2, CHCHAHB), 2.95 (split ABd, CHCHAHB); 13C
NMR δ 150.2 (C-1), 147.5 (C-3), 142.4 (C-1′), 128.6 (C-2′,6′),
128.0 (C-4′), 125.8 (C-3′,5′), 115.6 (C-4), 97.0 (C-2), 71.3
(CHOH), 60.9 (OMe), 60.5 (CHCH2); FAB-MS m/ z 253 (M +
1, 12), 138 (51), 137 (100).
1
identified by H NMR: δ 7.5-7.1 (m, Ph), 6.72 (d, J 1,2 ) 12.9,
H-1), 5.32 and 5.07 (two s, H2-4), 5.21 (d, H-2), 4.7-4.1 (m,
CH2CH), 4.0 (br s, OH), 3.57 (s, OMe).
Gen er a l P r oced u r e for DA Cycloa d d ition s of Dien es
2AR, 2AS, 3AR, 2BS, a n d 2CS w ith Meth yl Acr yla te. Some
experimental conditions are reported in Table 2. When the
cycloaddition was performed without solvent the diene/dieno-
phile ratio was 1:35, while for reactions performed in CH2Cl2
(2 mL for 0.53 mmol of diene) the ratio was 1:6. In catalyzed
cycloadditions, the Lewis acid was always added to the solution
of diene and methyl acrylate in a diene/catalyst ratio of 1:0.8
(for more details, see the Supporting Information). The
reaction mixture was stirred until the diene totally disap-
peared, as verified by TLC monitoring. The crude mixture was
column chromatographed, eluting with petrol/EtOAc (80:20),
after evaporation under vacuum of the solvent, if present. The
fractions containing cycloadducts were combined and analyzed
by 1H NMR (Table 2) using CDCl3 for adducts 15AR-18AR,
CD3CN for adducts 15BS-18BS, and C6D6 for 15CS-18CS.
Further column chromatography was performed on the mix-
ture of adducts 15AR-18AR allowing the separation of the four
diastereomeric cycloadducts.
Rea ction of (S,RS)-2-[(2-Cya n oeth yl)su lfin yl]-2-p h en -
yleth a n ol (7BR) w ith (Z)-En yn e 10. The following products
were obtained by eluting first with toluene only (to remove
the excess enyne) and then with toluene containing increasing
amounts of CH2Cl2.
(S,SS,Z)-3-[(2-Hyd r oxy-1-p h en yleth yl)su lfin yl]-1-m eth -
oxybu ta -1,3-d ien e (3BS): oil; [R]25D +119 (c ) 0.003, CHCl3);
1H NMR δ 7.4-7.3 (m, Ph), 6.27 (d, J 1,2 ) 6.8, H-1), 5.97 and
5.54 (two s, H2-4), 5.03 (d, H-2), 4.54 (split ABd, J gem ) 12.4,
J vic ) 8.0, CHAHBCH), 4.16 (split ABd, J vic ) 3.4, CHAHBCH),
4.01 (dd, CHAHBCH), 4.2 (br s, OH), 3.72 (s, OMe); 13C NMR
δ 151.7 (C-1), 146.0 (C-3), 132.0 (C-1′), 129.2, 129.1 and 128.4
(C-2′,3′,4′,5′,6′), 118.4 (C-4), 95.0 (C-2), 67.6 (CH2CH), 64.0
(CH2CH), 61.0 (OMe); FAB-MS m/ z 253 (M + 1, 100), 121 (98),
83 (46). The minor epimer (S,RS,Z)-3-[(2-h yd r oxy-1-p h en -
yleth yl)su lfin yl]-1-m eth oxybu ta -1,3-d ien e (3BR) was ob-
tained in mixture with 3BS and identified by 1H NMR: δ 7.4-
7.3 (m, Ph), 6.10 (d, J 1,2 ) 6.7, H-1), 5.63 and 5.26 (two s, H2-
4), 4.81 (d, H-2), 4.6-3.9 (m, CH2CH), 4.2 (br s, OH), 3.71 (s,
OMe).
Rea ction of (S)-2-[(2-Cya n oeth yl)su lfin yl]-1-p h en yl-
eth a n ol (7C) w ith (E)-En yn e 9. The mixture of dienes 2C
was obtained by eluting first with toluene to remove the excess
enyne and then with petrol containing increasing amounts of
EtOAc. Further column chromatography [benzene/2-propanol
(98:2) as eluant] allowed the separation of the two diene
epimers, with 2CS showing a slightly enhanced chromato-
graphic mobility with respect to 2CR.
(3R,4R,RS)-1-[(1S)-Isobor n eol-10-su lfin yl]-3-m eth oxy-
4-(m eth oxyca r bon yl)cycloh exen e (15AR): mp 112-114 °C;
1
[R]25 +130 (c ) 0.008, CHCl3); H NMR δ 6.71 (d, J 2,3 ) 4.4,
D
H-2), 4.20 (t, J 3,4 ) 4.4, H-3), 4.12 (dd, J 2′,3′ ) 8.2, 4.1, H-2′),
3.97 (br s, OH), 3.76 (s, 3-OMe), 3.42 (s, 4-COOMe), 3.14 (ABd,
J 10′A,10′B ) 12.9, HA-10′), 2.71 (ddd, J 4,5 ) 11.8, 3.3, H-4), 2.43
(ABq, HB-10′), 2.4-0.9 (m, H2-3′,5,5′,6,6′, H-4′), 1.08 (s, H3-
8′), 0.83 (s, H3-9′); 13C NMR δ 172.3 (CO), 146.4 (C-1), 126.3
(C-2), 77.0 (C-2′), 72.5 (C-3), 57.8 (3-OMe), 53.4 (C-10′), 51.8
(COOMe), 51.4 (C-1′), 48.3 (C-7′), 45.1 and 44.7 (C-4,4′), 38.4
(C-3′), 30.8 and 27.1 (C-5′,6′), 22.5 (C-6), 20.5 and 19.9 (C-8′,9′),
19.4 (C-5); FAB-MS m/ z 371 (M + 1, 100), 217 (16), 135 (59).
Anal. Calcd for C19H30O5S: C, 61.59; H, 8.16. Found: C, 61.60;
H, 8.13.
(S,SS,E)-3-[(2-Hyd r oxy-2-p h en yleth yl)su lfin yl]-1-m eth -
oxybu ta -1,3-d ien e (2CS): oil; [R]25 +83 (c ) 0.001, CHCl3);
D
1H NMR δ 7.4-7.3 (m, Ph), 6.84 (d, J 1,2 ) 13.1, H-1), 5.80 and
5.72 (two s, H2-4), 5.45 (d, H-2), 5.33 (dd, J vic ) 10.1, 2.1,
CHCHAHB), 3.97 (br s, OH), 3.64 (s, OMe), 3.26 (split ABd,
J gem ) 13.7, J vic ) 10.1, CHCHAHB), 2.79 (split ABd, CHCHAHB);
13C NMR δ 151.3 (C-1), 146.3 (C-3), 142.0 (C-1′), 128.6
(C-2′,4′,6′), 125.7 (C-3′,5′), 113.4 (C-4), 97.6 (C-2), 68.9 (CHOH),
58.4 (CHCH2), 56.8 (OMe).
(3S,4S,RS)-1-[(1S)-Isobor n eol-10-su lfin yl]-3-m eth oxy-4-
(m eth oxyca r bon yl)cycloh exen e (16AR): mp 193-195 °C;
1
[R]25 -138 (c ) 0.004, CHCl3); H NMR δ 6.72 (d, J 2,3 ) 4.4,
D
H-2), 4.19 (t, J 3,4 ) 4.4, H-3), 4.11 (ddd, J 2′,3′ ) 7.8, 3.8, J 2′,OH
) 3.8, H-2′), 3.97 (d, OH), 3.76 (s, 3-OMe), 3.43 (s, 4-COOMe),
3.24 (ABd, J 10′A,10′B ) 13.1, HA-10′), 2.65 (ddd, J 4,5 ) 12.7, 3.7,
H-4), 2.39 (ABq, HB-10′), 2.5-1.2 (m, H2-3′,5,5′,6,6′, H-4′), 1.09
(s, H3-8′), 0.83 (s, H3-9′). Anal. Calcd for C19H30O5S: C, 61.59;
H, 8.16. Found: C, 61.80; H, 8.10.
(S,RS,E)-3-[(2-Hyd r oxy-2-p h en yleth yl)su lfin yl]-1-m eth -
oxybu ta -1,3-d ien e (2CR): oil; [R]25 -58 (c ) 0.002, CHCl3);
D
1H NMR δ 7.4-7.3 (m, Ph), 6.85 (d, J 1,2 ) 13.1, H-1), 5.70 and
5.59 (two s, H2-4), 5.43 (d, H-2), 5.39 (dd, J vic ) 8.8, 3.5,
CHCH2), 4.18 (br s, OH), 3.63 (s, OMe), 3.08 (split ABd, J gem
(3R,4S,RS)-1-[(1S)-Isobor n eol-10-su lfin yl]-3-m eth oxy-4-
(m eth oxyca r bon yl)cycloh exen e (17AR): mp 68-69 °C;
) 13.5, J vic ) 8.8, CHCHAHB), 3.03 (split ABd, CHCHAHB); 13
C
NMR δ 151.5 (C-1), 148.0 (C-3), 142.0 (C-1′), 128.7 (C-2′,6′),
[R]25 -223 (c ) 0.013, CHCl3); 1H NMR δ 6.55 (br s, H-2),
D

4384 J . Org. Chem., Vol. 62, No. 13, 1997
Aversa et al.
4.30 (dd, J 2,3 ) 1.9, J 3,4 ) 8.1, H-3), 4.10 (m, H-2′), 3.76 (s,
3-OMe), 3.45 (s, 4-COOMe), 3.27 (ABd, J 10′A,10′B ) 13.0, HA-
10′), 2.66 (ddd, J 4,5 ) 11.4, 3.3, H-4), 2.35 (ABq, HB-10′), 2.3-
1.2 (m, H2-3′,5,5′,6,6′, H-4′), 1.09 (s, H3-8′), 0.83 (s, H3-9′). Anal.
Calcd for C19H30O5S: C, 61.59; H, 8.16. Found: C, 61.87; H,
8.06.
(3S,4R,RS)-1-[(1S)-Isobor n eol-10-su lfin yl]-3-m eth oxy-4-
(m eth oxyca r bon yl)cycloh exen e (18AR): mp 73-74 °C;
[R]25D +35 (c ) 0.013, CHCl3); 1H NMR δ 6.55 (br s, H-2), 4.29
(dd, J 2,3 ) 1.9, J 3,4 ) 8.0, H-3), 4.10 (m, H-2′), 3.75 (s, 3-OMe),
3.46 (s, 4-COOMe), 3.20 (ABd, J 10′A,10′B ) 13.0, HA-10′), 2.73
(ddd, J 4,5 ) 11.3, 3.3, H-4), 2.37 (ABq, HB-10′), 2.3-1.2 (m, H2-
3′,5,5′,6,6′, H-4′), 1.09 (s, H3-8′), 0.83 (s, H3-9′); 13C NMR δ 174.0
(CO), 144.3 (C-1), 127.7 (C-2), 77.0 (C-2′), 76.0 (C-3), 57.1 (3-
OMe), 53.8 (C-10′), 52.1 (COOMe), 51.5 (C-1′), 48.8 (C-7′), 45.6
and 45.1 (C-4,4′), 38.4 (C-3′), 30.9 and 27.2 (C-5′,6′), 24.5 (C-
6), 21.7 (C-5), 20.5 and 19.9 (C-8′,9′). Anal. Calcd for
C19H30O5S: C, 61.59; H, 8.16. Found: C, 61.49; H, 8.11.
(3S,4S,SS)-1-[[(S)-2-Hyd r oxy-1-p h en yleth yl]su lfin yl]-3-
hexene 20A (140 mg, 78%), which did not need any purifica-
tion: mp 91-93 °C; [R]25 +70 (c ) 0.012, CHCl3); 1H NMR δ
D
7.08 (br d, J 2,3 ) 4.4, H-2), 4.23 (t, J 3,4 ) 4.4, H-3), 4.16 (dd,
J 2′,3′ ) 8.0, 4.1, H-2′), 3.76 (s, 3-OMe), 3.45 (s, 4-COOMe), 3.40
(ABd, J 10′A,10′B ) 13.5, HA-10′), 2.81 (ABd, HB-10′), 2.7-1.1 (m,
H2-3′,5,5′,6,6′, H-4,4′), 1.07 (s, H3-8′), 0.82 (s, H3-9′); 13C NMR
δ 172.0 (CO), 143.6 (C-1), 134.4 (C-2), 76.3 (C-2′), 72.5 (C-3),
58.2 (3-OMe), 51.9 (COOMe), 51.4 (C-10′), 50.7 (C-1′), 49.2 (C-
7′), 44.2 and 43.5 (C-4,4′), 39.0 (C-3′), 30.4 and 27.5 (C-5′,6′),
23.7 (C-6), 20.6 and 19.9 (C-8′,9′), 19.2 (C-5). Anal. Calcd for
C19H30O6S: C, 59.04; H, 7.82. Found: C, 58.96; H, 7.79.
(3S,4S)-1-[(1S)-Isob or n eol-10-su lfon yl]-3-m et h oxy-4-
(m eth oxyca r bon yl)cycloh exen e (21A). 21A was obtained
(80%) by m-CPBA oxidation of the adduct 16AS, as reported
above: oil; [R]25 -120 (c ) 0.005, CHCl3); 1H NMR δ 7.06 (br
D
d, J 2,3 ) 4.1, H-2), 4.23 (t, J 3,4 ) 4.1, H-3), 4.16 (dd, J 2′,3′ ) 7.9,
4.1, H-2′), 3.76 (s, 3-OMe), 3.45 (s, 4-COOMe), 3.34 (ABd,
J 10′A,10′B ) 13.4, HA-10′), 2.82 (ABd, HB-10′), 2.7-1.1 (m, H2-
3′,5,5′,6,6′, H-4,4′), 1.07 (s, H3-8′) 0.82 (s, H3-9′); 13C NMR δ
172.0 (CO), 143.8 (C-1), 134.2 (C-2), 76.2 (C-2′), 72.5 (C-3), 58.2
(3-OMe), 51.9 (COOMe), 51.5 (C-10′), 50.8 (C-1′), 49.3 (C-7′),
44.2 and 43.5 (C-4,4′), 39.1 (C-3′), 30.5 and 27.5 (C-5′,6′), 23.6
(C-6), 20.5 and 19.9 (C-8′,9′), 19.2 (C-5). Anal. Calcd for
C19H30O6S: C, 59.04; H, 7.82. Found: C, 59.01; H, 7.77.
m -CP BA Oxid a tion of Dien e 2AR a n d DA Cycloa d d i-
tion of th e Obta in ed (E)-3-[(1S)-Isobor n eol-10-su lfon yl]-
1-m eth oxybu ta -1,3-d ien e (19A) to Meth yl Acr yla te in
CH2Cl2 a n d in th e P r esen ce of Zn Cl2. The sulfonyl diene
19A was obtained in almost quantitative yield by m-CPBA
oxidation of diene 2AR, following the procedure reported above
and submitted, without isolation,29 to DA cycloaddition: thus,
ZnCl2 (57 mg, 0.42 mmol) was added to a solution of diene
19A (159 mg, 0.53 mmol) and methyl acrylate (0.28 mL, 3.1
mmol) in CH2Cl2 (2 mL) under stirring at room temperature.
The reaction mixture was stirred further on, until the diene
totally disappeared, as verified by TLC monitoring. After
evaporation of the solvent under vacuum, the crude mixture
was column chromatographed, eluting with petrol/EtOAc (80:
20), and the mixture of adducts analyzed by 1H NMR: the
endo/ exo ratio, established from the relative intensities of the
vinyl proton signals (multiplets at δ 7.1 for endo and 6.9 ppm
for exo adducts), was 10:1, the two endo adducts 20A and 21A
being present in equal amounts.
m eth oxy-4-(m eth oxyca r bon yl)cycloh exen e (16BS): oil;
1
[R]25 +200 (c ) 0.001, CHCl3); H NMR (CD3CN) δ 7.4-7.3
D
(5H, Ph), 6.25 (dd, J 2,3 ) 4.6, J long range 1.1, H-2),27 4.22 (split
ABd, J 1′,2′ ) 5.6, J 2′A,2′B ) 11.7, HA-2′), 4.11 (split ABd, HB-2′),
4.01 (t, J 3,4 ) 4.6, H-3), 3.96 (t, H-1′), 3.63 (s, 3-OMe), 3.04 (s,
COOMe), 2.62 (ddd, J 4,5 ) 13.5, 3.6, H-4), 2.8-1.9 (m, H2-5,6);
13C NMR δ 172.3 (CO), 145.6 (C-1), 132.4, 129.1, 129.0 and
128.8 (Ph), 128.5 (C-2), 72.0 (C-3), 68.4 (CHSO), 64.6 (CH2-
OH), 57.2 (3-OMe), 51.8 (COOMe), 44.4 (C-4), 21.9 (C-6), 19.1
(C-5); FAB-MS m/ z 339 (M + 1, 7), 137 (100), 77 (54). Anal.
Calcd for C17H22O5S: C, 60.33; H, 6.56. Found: C, 60.39; H,
6.48.
(3S,4S,SS)-1-[[(S)-2-Hyd r oxy-2-p h en yleth yl]su lfin yl]-3-
m eth oxy-4-(m eth oxyca r bon yl)cycloh exen e (16CS): oil;
1
[R]25 +53 (c ) 0.002, CHCl3); H NMR (C6D6) δ 7.4-7.1 (m,
D
Ph), 6.81 (dd, J 2,3 ) 4.5, J long range ) 1.6, H-2), 5.29 (dd, J 1′A,2′
)
10.2, J 1′B,2′ ) 1.8, H-2′),28 3.85 (t, J 3,4 ) 4.3, H-3), 3.40 (s,
3-OMe), 3.03 (s, COOMe), 2.77 (split ABd, J 1′A,1′B ) 13.7, HA-
1′), 2.24 (split ABd, HB-1′), 2.12 (ddd, J 4,5 ) 12.8, 2.9, H-4),
2.0-1.2 (m, H2-5,6); 13C NMR δ 172.2 (CO), 144.8 (C-1), 141.8,
128.8, 128.2 and 125.6 (Ph), 127.4 (C-2), 72.3 (C-3), 69.0
(CHOH), 57.7 (3-OMe), 56.8 (CH2SO), 51.8 (COOMe), 45.0 (C-
4), 22.8 (C-6), 19.4 (C-5); FAB-MS m/z 339 (M + 1, 5), 137 (83),
77 (100). Anal. Calcd for C17H22O5S: C, 60.33; H, 6.56.
Found: C, 60.25; H, 6.48.
Ack n ow led gm en t . Financial support from the
MURST of Italy is gratefully acknowledged. We also
would like to thank Dr. S. M. A. J afari for sharing
preliminary results.
(3S,4S,SS)-1-[(1S)-Isobor n eol-10-su lfin yl]-3-m eth oxy-4-
(m eth oxyca r bon yl)cycloh exen e (16AS): mp 120-122 °C;
1
[R]25 +80 (c ) 0.005, CHCl3); H NMR δ 6.80 (d, J 2,3 ) 4.0,
D
H-2), 4.22 (t, J 3,4 ) 4.0, H-3), 4.02 (m, H-2′), 3.74 (s, 3-OMe),
3.43 (s, 4-COOMe), 3.45 (ABd, J 10′A,10′B ) 13.5, HA-10′), 2.81
(ddd, J 4,5 ) 11.5, 4.0, H-4), 2.73 (ABq, HB-10′), 2.5-1.1 (m, H2-
3′,5,5′,6,6′, H-4′), 1.07 (s, H3-8′), 0.85 (s, H3-9′); 13C NMR δ 172.4
(CO), 144.3 (C-1), 129.0 (C-2), 75.8 (C-2′), 72.8 (C-3), 57.9 (3-
OMe), 51.9 (COOMe), 51.5 (C-1′), 51.1 (C-10′), 49.2 (C-7′), 44.5
and 44.1 (C-4,4′), 40.8 (C-3′), 31.2 and 27.4 (C-5′,6′), 21.7 (C-
6), 20.4 and 20.2 (C-8′,9′), 19.7 (C-5); FAB-MS m/z 372 (M +
2, 22), 371 (M + 1, 100), 353 (12). Anal. Calcd for C19H30O5S:
C, 61.59; H, 8.16. Found: C, 61.75; H, 8.16.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure and spectral characterization for 1-sulfinyl-1,3-buta-
dienes 4AR and 5AR, IR data of compounds 1B, 1C, 2A, 2BS,
3A, 3BS, 6, 7, 12-14, 15AR, 16BS, 16CS, 20A, and 21A,
detailed procedures for DA reactions of dienes 2AR, 2AS, 2BS,
1
2CS, and 3AR and related extended Table 2, and copies of H
and 13C NMR spectra of dienes 2AR, 2AS, 2BS, 2CR, 2CS, 3AR,
3AS, 3BS, 3CR, 3CS, 4AR, and 5AR (29 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.
(3R,4R)-1-[(1S)-Isob or n eol-10-su lfon yl]-3-m et h oxy-4-
(m eth oxyca r bon yl)cycloh exen e (20A). m-CPBA carefully
dried over P2O5 (99 mg 80%, 0.46 mmol) was dissolved in CH2-
Cl2 (4.25 mL) and slowly added to a solution of an equimolar
amount of the adduct 15AR in CH2Cl2 (4.25 mL) at room
temperature. When oxidation appeared complete by TLC
(after 1 h about), anhydrous KF (140 mg) was added and the
mixture stirred overnight. After filtration, the evaporation of
the solvent under reduced pressure gave the sulfonylcyclo-
J O962286P
(29) NMR characterization of sulfonyl diene 19A: δ 7.06 (d, J 1,2
12.7, H-1), 6.00 and 5.75 (two s, H2-4), 5.58 (d, H-2), 4.19 (ddd, J 2′,3′
8.1, 4.0 Hz, J 2′,OH ) 4.0 Hz, H-2′), 3.70 (s, OMe), 3.36 (ABd, J 10′A,10′B
)
)
)
13.5 Hz, HA-10′), 2.87 (ABd, HB-10′), 3.31 (d, OH), 1.8-0.8 (m, H2-
3′,5′,6′, H-4′), 1.06 (s, H3-8′), 0.81 (s, H3-9′), 153.4 (C-1), 146.0 (C-3),
120.1 (C-4), 96.7 (C-2), 76.3 (C-2′), 57.0 (OMe), 52.1 (C-10′), 51.7 (C-
1′), 50.0 (C-7′), 44.1 (C-4′), 39.0 (C-3′), 30.3 and 27.5 (C-5′,6′), 20.5 and
19.8 (C-8′,9′).
(27) H-2 Multiplets of minor adducts appear at δ 6.16 (15BS), 5.98
(17BS), and 6.07 (18BS).
(28) H-2′ Multiplets of minor adducts appear at δ 5.35 (15CS), 5.53
(17CS), and 5.43 (18CS).