Synthesis and Dienophilic Behavior of Enantiomerically Pure (Z)-3-p-Tolylsulfinylacrylonitriles

Article abstract of DOI:10.1021/jo9721002

The syntheses of enantiomerically pure (Z)-3-p-tolylsulfinylacrylonitrile (1b) and its 2-n-butyl (1a), 2-tert-butyl (1c), and 2-benzyl (1d) derivatives, by stereoselective hydrocyanation with Et₂AlCN of their corresponding alkynylsulfoxides, are described. Asymmetric Diels-Alder reactions of these dienophiles with cyclopentadiene are also reported, the most significant finding being their total π-facial diastereoselectivity, controlled by the sulfur configuration, which can be readily inverted by using BF₃ as a catalyst. The endo selectivity is very high for 1b under thermal and catalytic (ZnBr₂) conditions and complete in the presence of BF₃, whereas 1a and 1d only exhibit a complete endo selectivity in the presence of BF₃.

Full text of DOI:10.1021/jo9721002

3324
J . Org. Chem. 1998, 63, 3324-3332
Syn th esis a n d Dien op h ilic Beh a vior of En a n tiom er ica lly P u r e
(Z)-3-p-Tolylsu lfin yla cr ylon itr iles
J ose L. Garc´ıa Ruano,* Antonio Esteban Gamboa, Ana M. Mart´ın Castro, and
J esu´s H. Rodr´ıguez*
Dpto. de Qu´ımica Orga´nica, Universidad Auto´noma de Madrid, Cantoblanco, 28049-Madrid, Spain
M. Isabel Lo´pez-Solera
Dpto. de Qu´ımica Inorga´nica, Universidad Auto´noma de Madrid, Cantoblanco, 28049-Madrid, Spain
Received November 17, 1997
The syntheses of enantiomerically pure (Z)-3-p-tolylsulfinylacrylonitrile (1b) and its 2-n-butyl (1a ),
2-tert-butyl (1c), and 2-benzyl (1d ) derivatives, by stereoselective hydrocyanation with Et2AlCN of
their corresponding alkynylsulfoxides, are described. Asymmetric Diels-Alder reactions of these
dienophiles with cyclopentadiene are also reported, the most significant finding being their total
π-facial diastereoselectivity, controlled by the sulfur configuration, which can be readily inverted
by using BF3 as a catalyst. The endo selectivity is very high for 1b under thermal and catalytic
(ZnBr2) conditions and complete in the presence of BF3, whereas 1a and 1d only exhibit a complete
endo selectivity in the presence of BF3.
In tr od u ction
sulfinyl dienophiles in the synthesis of natural products),
it is due to the formation of mixtures of aryl vinyl
sulfoxide epimers at sulfur (when asymmetric oxidation
of chiral vinyl sulfides is required7) and/or (E)- and (Z)-
isomers (always observed from methods using Emmons-
Horner reactions8), the separation of which was required
previous to their use as dienophiles. The second problem
associated with the use of these dienophiles derives from
their moderate or low reactivity. To increase it, the most
usually adopted solution has been the use of sulfoxides
bearing aryl groups with higher electron-withdrawing
power than that of p-tolylsulfinyl (usually pyridyl deriva-
tives) and/or Lewis acids as catalysts (not always com-
patible with dienes or adducts), which, in their turn, are
essential to achieve an efficient control of the π-facial
selectivity in many cases.6 The control of the endo/exo
selectivity is more difficult. It is moderate with 2-sulfi-
nylacrylates9 and even lower with trans-3-sulfinyl-
acrylates,8a,10 which should be inferred from the endo-
director character of both groups (SOAr and CO2R). The
best results were obtained from cis-3-sulfinylacrylates,
which afforded endo adducts in a highly stereoselective
manner only when reactions with cyclopentadiene were
catalyzed by Et2AlCl.11
The use of activated vinyl sulfoxides as dienophiles in
asymmetric Diels-Alder reactions has gained wide at-
tention in recent years1 due to the ability of the sulfinyl
group to control the π-facial selectivity. The presence of
additional activating groups at vinyl sulfoxides is neces-
sary in order to increase their reactivity (unsubstituted
vinyl sulfoxides are very poor dienophiles) and restrict
the conformational mobility around the C-S bond. In
this sense, several groups have been added to sulfinyl
ethylenes, such as carbonyl,2 nitro,3 sulfonyl,4 and
sulfinyl.1g,5 Nevertheless, the most widely studied one
is doubtlessly the ester group,1b the contribution of
Koizumi in this field clearly being the most significant.6
One of the problems limiting the scope of these dieno-
philes is the lack of efficient methods for their syntheses.
In the case of 3-sulfinylacrylates (which are the most used
(1) (a) Carren˜o, M. C. Chem. Rev. 1995, 95, 1717. (b) Carretero, J .
C.; Garc´ıa Ruano, J . L.; Mart´ın Cabrejas, L. M. Tetrahedron: Asym-
metry 1997, 8, 2215 (and references cited). (c) Carren˜o, M. C.; Garc´ıa
Ruano, J . L.; Urbano, A.; Lo´pez-Solera, M. I. J . Org. Chem. 1997, 62,
976 (and references cited). (d) Yamakoshi, Y. N.; Ge, W.-Y.; Sugita, J .;
Okayama, K.; Takahashi, T.; Koizumi T. Heterocycles 1996, 42, 129
(and references cited). (e) Cecchet, E.; Di Furia, F.; Licini, G.; Modena,
G. Tetrahedron: Asymmetry 1996, 7, 369. (f) Hayes, P.; Dujardin, G.;
Maignan, C. Tetrahedron Lett. 1996, 21, 3687 (and references cited).
(g) Aggarwal, V. K.; Drabowicz, J .; Grainger, R. S.; Gu¨ltekin, Z.;
Lightowler, M.; Spargo, P. L. J . Org. Chem. 1995, 60, 4962 (and
references cited).
Since acrylonitriles are among the most widely used
dienophiles, it was surprising that the cyano group had
never been used as an activating moiety of vinyl sulfox-
(2) (a) Alcudia, F.; Llera, J . M.; Ordon˜ez, M. Tetrahedron Lett. 1995,
36, 4889. (b) Guessous, A.; Rouessac, F.; Maignan, C. Bull Soc. Chim.
Fr. 1986, 837. (c) De Lucchi, O.; Lucchini, V.; Marchioro, C.; Valle, G.;
Modena, G. J . Org. Chem. 1986, 51, 1457. (d) Brimble, M. A.; Davis,
B. R. Tetrahedron 1985, 41, 4965.
(3) Fuji, K.; Tanaka, K.; Abe, H.; Matsumoto, K.; Harayama, T.;
Ikeda, A.; Taga, T.; Miwa, Y.; Node, M. J . Org. Chem. 1994, 59, 2221.
(4) Lo´pez, R.; Carretero, J . C. Tetrahedron: Asymmetry 1991, 2, 93.
(5) (a) Arai, Y.; Kuwayama, S.; Takeuchi, Y.; Koizumi, T. Synth.
Commun. 1986, 16, 233. (b) De Lucchi, O.; Fabbri, D.; Lucchini, V.
Synlett 1991, 565. (c) Aggarwal, V. N.; Lightowler, M.; Lindell, S. D.
Synlett 1992, 730. (d) Katagiri, N.; Ise, S.; Watanabe, N.; Kaneko, C.
Chem. Pharm. Bull. 1990, 38, 3242. (e) Carretero, J . C.; Garc´ıa Ruano,
J . L.; Mart´ın Cabrejas, L. M. Tetrahedron: Asymmetry 1997, 8, 409.
(6) See Arai, Y.; Koizumi, T. Sulfur Rep. 1993, 15, 41 (and references
cited).
(7) Takayama, H.; Iyobe, A.; Koizumi, T. J . Chem. Soc., Chem.
Commun. 1986, 771. The use of sulfoxides bearing bornyl and isobornyl
moieties joined to the sulfur atom, which control the asymmetric
oxidation of thioethers into sulfoxides, allowed solution of this problem
(De Lucchi, O.; Lucchini, V.; Marchioro, C.; Valle, G.; Modena, G. J .
Org. Chem. 1986, 51, 1457), but these sulfoxides have never been used
in the synthesis of natural products.
(8) (a) Koizumi, T.; Hakamada, I.; Yoshii, E. Tetrahedron Lett. 1984,
25, 87. (b) Maignan, C.; Guessoues, A.; Rouessac, F. Tetrahedron Lett.
1984, 25, 1727.
(9) Arai, Y.; Kuwayama, S.; Takeuchi, Y.; Koizumi, T. Tetrahedron
Lett. 1984, 25, 6205.
(10) Proust, S. M.; Ridley, D. D. Aust. J . Chem. 1984, 37, 1677.
(11) Arai, Y.; Hayashi, M.; Yamamoto, M.; Takayama, H.; Koizumi,
T. Chem. Lett. 1987, 185.
S0022-3263(97)02100-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/29/1998

Synthesis of (Z)-3-p-Tolylsulfinylacrylonitriles
J . Org. Chem., Vol. 63, No. 10, 1998 3325
Ta ble 1. Com p osition of Rea ction Mixtu r es Obta in ed by
Tr ea tm en t of 2a w ith Et2AlCN (2 equ iv) in Tolu en e
Sch em e 1
ides in asymmetric Diels-Alder reactions.12 Taking into
account that CN and CO2R groups are synthetic equiva-
lents and the synthesis of nitriles can be achieved by
methods different to those of esters, we decided to set
up the search of efficient methods to prepare optically
pure 3-sulfinylacrylonitriles and the study of their be-
havior as asymmetric dienophiles. In this sense, the
linear structure of the cyano group, as compared with
the trigonal structure of the CO2R group, suggested
significant differences in both π-facial and mainly endo/
exo selectivities (the steric interactions of these groups
with the sulfinyl one must be quite different) for the
evolution of sulfinylacrylates and sulfinylnitriles. Fi-
nally, despite that the reactivity of both types of dieno-
philes must be predictably similar, the influence of
different Lewis acids as catalysts could be different and
must also be investigated. In this paper we report the
highly stereocontrolled hydrocyanation of alkynyl sul-
foxides with Et2AlCN to afford (R,Z)-3-p-tolylsulfiny-
lacrylonitriles 1a -d (Scheme 1), as well as the behavior
of these compounds as dienophiles, which present clear
advantages with respect to sulfinyl esters, mainly due
to their ability to invert the π-facial selectivity, depending
on the Lewis acid used as the catalyst, and the interest-
ing behavior of the resulting sulfinylnitriles under acidic
hydrolysis conditions.
entry
T (°C)a
t (h)
2a
1a
1e
3
1
2
3
4
5
6
7
8
9
-78
-78
-78
-20
-20
-20
20
0.5
2
24
0.5
2
14
0.5
2
86
74
40
24
14
26
40
75
95
56
80
76
61
20
39
15
1
5
5
20
24
24
20
20
24
a
At 60 °C the formation of side products can be detected.
Ta ble 2. Com p osition of th e Rea ction Mixtu r es
Obta in ed by Tr ea tm en t of 2d a n d 2c w ith Et2AlCN (2
equ iv) in Tolu en e
Resu lts a n d Disccu ssion
sub-
Syn th esis of su lfin yla cr ylon itr iles. To achieve the
synthesis of the starting (Z)-sulfinyldienophiles 1a -d ,
we have investigated the reaction of 1-alkynyl sulfoxides
2a -d 13 with Et2AlCN (Tables 1 and 2). In previous
papers,14 we had demonstrated that the addition of this
hydrocyanating reagent to the carbonyl group of R-sulfi-
nyl ketones takes place with very high stereoselectivity,
presumably due to the association of the sulfinyl oxygen
with the metal as a previous step to the intramolecular
cyanide transfer. On the basis of this assumption, we
reasoned that a similar highly stereoselective addition
could take place on alkynyl sulfoxides, provided that the
species resulting from their association with Et2AlCN
were able to evolve through an intramolecular conjugated
addition.
entry strate T (°C) t (h)
1d
1c
1b
others
1
2
3
4
5
6
7
2d
2c
2c
2c
2c
2b
2b
-20
-20
+20
-78
-78
-20
-20
2
2
1
2
100(90)a
41(30)a
25
59 (55)a,b
75b
24
76c
24
2
66(60)a
complex mixture
34c
3e
(55)a
9d
a
In parentheses are the isolated yields after chromatography
of the crude reaction. Compound 4. c Starting 2c. Compound
b
d
5. e In minutes.
The results obtained in reactions of alkynyl sulfoxide
2a with Et2AlCN in toluene are collected in Table 1. As
we can see, an increase in the reaction time provokes the
oxidation of 1a into sulfone 3.15 As the temperature
became higher, the formation of (E)-sulfinyl derivative
1e could be detected and its proportion increased with
the temperature. Further experiences varying the amount
of reagent demonstrated that the use of 4, 6, or 8 equiv
of Et2AlCN gave the same results. Much lower reactivity
and selectivity were observed when the amount of
reagent was smaller than 2 equiv.
(12) Ono, T.; Tamaoka, T.; Yuasa, Y.; Matsuda, T.; Nokami, J .;
Wakabayashi, S. J . Am. Chem. Soc. 1984, 106, 7890. Trost, B. M.;
Mallarts, S. Tetrahedron Lett. 1993, 34, 8025. Hiroi, K.; Umemura,
M. Tetrahedron 1993, 49, 1831.
(13) The synthesis of optically pure 1-alkynyl p-tolyl sulfoxides 2a -d
was accomplished following the previously described procedure (Kosugi,
H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. J . Org. Chem.
1987, 52, 1078) consisting in the reaction of l-menthyl (S)-p-toluene-
sulfinate (Mioskowsky, C.; Solladie´, G. Tetrahedron 1980, 36, 227.
Solladie´, G. Synthesis 1981, 185) and the corresponding 1-alkynyl-
magnesium bromide in toluene. In our hands, the reaction temperature
had to be increased from -20 °C, as described, to 20 °C in order to get
good yields.
The best conditions found in the above experiences
(Table 1, entry 5) were successfully used to synthesize
1-alkynyl sulfoxide 1d (Table 2), which was obtained from
(14) (a) Garc´ıa Ruano, J . L.; Mart´ın Castro, A. M.; Rodr´ıguez, J . H.
Tetrahedron Lett. 1991, 32, 3195. (b) Garc´ıa Ruano, J . L.; Mart´ın
Castro, A. M.; Rodr´ıguez, J . H. J . Org. Chem. 1992, 57, 7235. (c)
Escribano, A.; Garc´ıa Ruano, J . L.; Mart´ın Castro, A. M.; Rodr´ıguez,
J . H. Tetrahedron 1994, 50, 7567.
(15) We had observed the oxidation of sulfoxides into sulfones during
hydrocyanation of â-sulfinylimines with Et2AlCN (unpublished results)
in those cases requiring long reaction times. The course of these
reactions is not clear.

3326 J . Org. Chem., Vol. 63, No. 10, 1998
Ruano et al.
Sch em e 2
2d and Et2AlCN (2 equiv) as the sole reaction product in
90% yield. When compound 2c reacted under identical
conditions (-20 °C, 2 h), 1c was obtained in moderate
yield (entry 2). The major product of this reaction was
(()-S-p-tolyl 3,3-dimethyl-2-cyanobutanethioate (4),16 the
proportion of which increased up to 75% when the
reaction was conducted at room temperature (entry 3).
Nevertheless, it was not detected when the reaction was
carried out at -78 °C (entries 4 and 5). Under these
conditions, compound 1c was the sole reaction product
(60% yield after 24 h).17 The formation of the sulfone
derived from 2c was not detected even after 5 days of
reaction.
The synthesis of (Z)-3-[(R)-p-tolylsulfinyl]propeneni-
trile 1b was accomplished by reaction of (R)-ethynyl
p-tolyl sulfoxide (2b) with Et2AlCN. When the reaction
was conducted at -20 °C for 2 h, a complex mixture of
compounds containing 1b in very low proportion (<5%)
was obtained. Better results were achieved at -20 °C
at shorter times (3 min), 1b being the major product (55%
isolated yield).18
This mechanistic proposal was supported by treatment
of the 1:1 complex 2b-MAD [methylbis(di-2,6-tert-butyl-
4-methylphenoxy)aluminum] with Et2AlCN. Under these
conditions, the association of the aluminum of the hy-
drocyanating reagent with the sulfinylic oxygen was
prevented, and the unaltered starting material 2b was
recovered.
Rea ction s w ith Cyclop en ta d ien e. Reactions of
dienophiles 1a and 1d with cyclopentadiene in refluxing
CH2Cl2 for several hours afforded mixtures of endo-6 and
exo-6 cycloadducts (Table 3, entries 1 and 4). Unaltered
1c could be recovered after 120 h under these conditions
(entry 3), whereas 1b only required 1 h to be completely
transformed into a major adduct, endo-6b (entry 2).
Addition of ZnBr2 improved the reactivity (1c remains
unaltered after 120 h, but at room temperature 1a , 1b,
and 1d required reaction times identical to those at reflux
in the absence of a catalyst), but it had scarce effect on
the π-facial selectivity (it remains complete with all the
dienophiles) and on the endo/exo selectivity (which
remains low with 1a and 1d and high with 1b) (entries
5, 6, and 8).
Reactions with TMSCN/18-crown-6 ether/KCN19 were
also studied, but the results obtained with the different
substrates were less satisfactory.20
The formation of (Z)-3-p-tolylsulfinylacrylonitriles as
the major hydrocyanation products could be rationalized
as indicated in Scheme 2, by assuming an intramolecular
cyanide transfer from the species resulting from associa-
tion of the sulfinyl oxygen with the reagent.
(16) To explain the formation of racemic thioester 4, we assume the
process is an additive Pummerer reaction (see de Lucchi O.; Miotti
U.; Modena G. In Organic Reactions; Paquette, L., et al., Eds.; J ohn
Wiley & Sons: New York, 1991; Vol. 40, p 157). The equilibrium
between ylide A1 and R-methalated species A2 must be shifted toward
A1 due to unstabilizing steric interactions between one of the substit-
uents of the aluminum and the tert-butyl group. From A1 we postulate
the formation of B, the hydrolysis of which and further deprotonation
explain the formation of 5c.
The endo or exo stereochemistry of the obtained
adducts could be established from the value of the
coupling constants J 3,4 (3.2 Hz for the endo adducts and
ca. 0 Hz for the exo ones) and J 3,7 (2.3 Hz for the exo
adducts, as a consequence of the W planar arrangement
between H-3 and H-7; see the reaction shown in Table
3). The absolute configuration of substrates endo-6a and
exo-6a could be unequivocally determined by X-ray
studies (Supporting Information).
To explain the complete π-facial diastereoselectivity
observed for these reactions, it is necessary to assume
that the conformational equilibrium of dienophiles 1 is
completely shifted toward rotamer B depicted in Scheme
3, with the sulfinyl oxygen in an s-trans arrangement.
This preference must be a consequence of the strong
dipolar repulsion between the CN and SO groupings.21
The attack of the diene, governed by a steric approach
(19) Kunz, H.; Sager, W.; Pfrengle, W.; Schanzenbach, D. Tetrahe-
dron Lett. 1988, 29, 4397.
(20) Lower reactivity and sluggish reactions containing so far
unidentified decomposition products were the general characteristics
of these reactions. Under the best conditions, compound 2a yielded
1a (60% estimated yield) at 0 °C after 72 h, whereas 1b was obtained
from 2b (-78 °C, 46 h, 42% estimated yield by NMR), and 1c from 2c
(0 °C, 21 h, 62% estimated yield).
(21) To check this assumption, we carried out the cycloaddition of
1a in solvents of higher polarity, thus favoring the most polar s-cis
conformations. The obtained results indicate the formation of a mixture
containing four adducts, the proportion of the two new adducts being
higher with the increase in the solvent polarity (Table 3, entries 9 and
10).
(17) At low temperature (-78 °C), thioester 5c was detected only
after long reaction times.
(18) A decrease in the reaction temperature hinders the transforma-
tion of substrate 2b and favors the predominance of undesired
products.

Synthesis of (Z)-3-p-Tolylsulfinylacrylonitriles
J . Org. Chem., Vol. 63, No. 10, 1998 3327
Ta ble 3. Diels-Ald er Rea ction s of Dien op h iles 1a -1d w ith Cyclop en ta d ien e u n d er Th er m a l Con d ition s or in th e
P r esen ce of Zn Br 2
cycloaddition conditions
cat.
(2 equiv)
endo-6/exo-6/
endo-7/exo-7a
yield
(%)
entry
dienophile
solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
T (°C)
t (h)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1a
1b
1c
1d
1a
1a
50
50
50
50
20
20
20
20
50
50
72
1
120
20
70
1
120
20
48
36
48/52/0/0
>90/<10/0/0
89
78
45/55/0/0
45/55/0/0
>90/<10/0/0
91
82
75
ZnBr2
ZnBr2
ZnBr2
ZnBr2
CH2Cl2
MeOH
1:1 MeOH- H2O
58/42/0/0
42/48/6/4
36/45/13/6
81
71
72
10
a
Isomeric ratio as determined by 1H NMR analysis of the crude mixtures.
Sch em e 3
Sch em e 4
control, must take place from the less hindered diaste-
reotopic face of the dienophile (back face in Scheme 3)
adopting such a conformation.
The comparison of the results obtained from our
sulfinylnitriles with those from (Z)-3-p-tolylsulfinylacry-
lates8,22,23 suggests that the first ones are slightly more
reactive. Otherwise, the π-facial selectivity of reactions
of 1 is also higher than that of their corresponding esters,
but this does not mean a significant improvement be-
cause de are usually higher than 90% starting from
acrylates. Concerning the endo/exo selectivity, the be-
havior of nitriles and esters is quite similar. It is very
high for 1b, but substantially decreases for 1a and 1d .
The observed influence of the ZnBr2 as a catalyst of
cycloadditions of 1 (it increases the reactivity, slightly
modifies the endo/exo selectivity, but does not affect the
π-facial selectivity) suggests that it can associate with
nitrogen, oxygen, or both, but this association must not
modify the conformational preferences of the dienophiles.
A similar behavior was observed for reactions of (Z)-3-
sulfinylacrylates catalyzed by other Lewis acids.10 There-
fore, despite the wide use of these substrates as dieno-
philes in the asymmetric synthesis of many natural
products,7,24 there is not any known catalyst able to
reverse the sense of the π-facial selectivity of their
cycloadditions.
triles.25 This idea derived from the finding by our
research group that the hydrolysis of â-sulfinylnitriles
with BF3/NaI into â-sulfenylcarboxyamides26 or BF3/
MeOH into â-sulfinylcarboxyamides27 took place under
very mild conditions, presumably due to the formation
of a cyclic oxosulfonium intermediate (C, Scheme 4). On
the basis of this assumption we reasoned that compounds
1 could evolve into intermediates C′ in the presence of
(24) (a) Arai, Y.; Hyashi, Y.; Matatoshi, Y.; Takayama, H.; Koizumi,
T. Chem. Lett. 1987, 185. (b) Arai, Y.; Hayashi, Y.; Matatoshi, Y.;
Takayama, H.; Koizumi, T. J . Chem. Soc., Perkin Trans. 1 1988, 3133.
(c) Takayama, H.; Iyobe, A.; Koizumi, T. Chem. Pharm. Bull. 1987,
35, 433. (d) Takahashi, T.; Iyobe, A.; Arai, Y.; Koizumi, T. Synthesis
1989, 189. (e) Takahashi, T.; Katsubo, H.; Iyobe, A.; Namiki, T.;
Koizumi, T. J . Chem. Soc., Perkin Trans. 1 1990, 3065. (f) Takayama,
H.; Hayashi, K.; Takeuchi, Y.; Koizumi, T. Heterocycles 1986, 24, 2137.
(g) Takayama, H.; Hayashi, K.; Koizumi, T. Tetrahedron Lett. 1986,
27, 5509.
At this point we decided to study the influence of the
BF3 on the π-facial diastereoselectivity of our sulfinylni-
(22) Guessous, A.; Rouessac, F.; Maignan, C. Bull. Soc. Chim. Fr.
1986, 837.
(23) Brimble, M. A.; Davis, B. R. Tetrahedron 1985, 41, 4965.
(25) It had been unsuccessfully used with sulfinylacrylates (ref 10).

3328 J . Org. Chem., Vol. 63, No. 10, 1998
Ruano et al.
Sch em e 5
completely endo- and π-facial-selective manner, yielding
species D, which would be attacked by the nucleophile
(methanol) added during the workup of the reaction,
affording an intermediate sulfurane E, which evolves into
endo-8 adducts by further reaction with a second mol-
ecule of MeOH. To our knowledge, this is the first report
on a complete inversion of the configuration of sulfoxides
in acidic medium.31
Con clu sion
We have demonstrated that hydrocyanation of alkynyl
sulfoxides with Et2AlCN is highly stereoselective, thus
allowing the first synthesis of optically pure (Z)-3-p-
tolylsulfinylacrylonitrile (1b) as well as its 2-n-butyl (1a ),
2-tert-butyl (1c), and 2-benzyl (1d ) derivatives. The
dienophilic reactivity of these acrylonitriles is similar or
slightly higher than that of their corresponding acrylates.
The π-facial selectivity of their reactions with cyclopen-
tadiene is complete under thermal and catalytic ZnBr2
conditions, and it can be totally reversed in the presence
of BF3. The endo-selectivity is scarce for 2-substituted
derivatives, but very high for compound 1b. All the
reactions are completely endo-selective, when conducted
under BF3 catalysis, and yield sulfinyl carboxamides
(instead of the expected nitriles), due to the hydrolysis
of the cyano group, which takes place with concomitant
inversion of the configuration at sulfur.
BF3. The evolution of C′ would exhibit the π-facial
selectivity opposite to that observed under thermal
conditions [compare the spatial arrangement of the
substituents around the sulfur for conformation B (see
Scheme 3) and species C′].
Diels-Alder reactions of compounds 1, catalyzed by
BF3‚OEt2, were studied at -20 °C, because higher tem-
peratures determine the fast polymerization of the diene
(Scheme 5). Under these conditions, reactions of 1a and
1d were very slow and required long reaction times (15
days) to afford endo-8a (62%) and endo-8d (53%), respec-
tively, as sole adducts, after quenching the reaction
mixtures with methanol. Compound endo-8b was ob-
tained as a sole adduct (72% yield) by treatment of 1b
with BF3 in CH2Cl2 at reflux for 1 h, further reaction with
cyclopentadiene for 3 h at -20 °C, and final addition of
methanol.28
The spectroscopic study of compounds endo-8 revealed
that they are adducts containing p-tolylsulfinyl and
carboxamide groups (the latter presumably resulting
from hydrolysis of the cyano group), both in an endo
arrangement. The absolute configuration of these ad-
ducts has been established as follows: basic hydrolysis
(KOH/t-BuOH at reflux29) of nitrile endo-6a , the config-
uration of which had been unequivocally established by
X-ray diffraction (see above), led to the amide endo-8′a ,
which turned out to be an enantiomer of endo-8a .30 This
result allowed us to assign to the latter, and therefore to
all endo-8 adducts, the configuration depicted in Scheme
5.
Exp er im en ta l Section
Gen er a l Meth od s. All moisture sensitive reactions were
performed in flame-dried glassware equipped with rubber
septa under positive pressure of argon. Solvents were dried
according to literature procedures.32 Et2AlCN was used as a
commercially available 1.0 M solution in toluene. The cyclo-
pentadiene used in Diels-Alder cycloadditions was obtained
following the procedure described in the literature.33 ZnBr2
was flame-dried in the reaction flask before use. Flash
chromatography was carried out with silica gel 60 (230-400
mesh ASTM), and silica gel F254 plates were used for
preparative TLC. NMR spectra (Tables 4 and 5) were deter-
mined in CDCl3 solutions at 200.1 and 50.3 MHz for 1H and
13C NMR, respectively.
1-Alkynyl p-tolyl sulfoxides 2a -d were prepared following
the described procedure, with slight modification.13
(+)-(S)-1-Hexin yl p-tolyl su lfoxid e (2a ):13 [R]20D +89.7 (c
1
1.0, acetone); H NMR δ 7.68 and 7.35 (AA′BB′ system, 4H),
2.41 (s, 3H), 2.40 (t, 2H, J ) 7.0), 1.70-1.10 (m, 4H), 0.90 (t,
3H, J ) 7.0); 13C NMR δ 141.4, 140.6, 129.3 (2C), 124.2 (2C),
104.9, 77.7, 28.8, 21.1, 20.6, 18.6, 12.7.
(+)-(R)-Eth yn yl p-tolyl su lfoxid e (2b):13 [R]20D +220.1 (c
1.0, CHCl3); 1H NMR δ 7.71 and 7.36 (AA′BB′ system, 4H),
3.71 (s, 1H), 2.43 (s, 3H); 13C NMR δ 142.7, 140.6, 130.1 (2C),
125.0 (2C), 90.2, 81.6, 21.3.
The formation of endo-8 as the only adducts from
reactions of cyclopentadiene and 1 catalyzed by BF3 can
be explained as indicated in Scheme 4. The reaction of
intermediate C′ with the diene must take place in a
(+)-(S)-3,3-Dim eth yl-1-bu tyn yl p-Tolyl Su lfoxid e (2c).
Compound 2c (white solid) was obtained in 81% yield from
the reaction of 3,3-dimethyl-1-butynylmagnesium bromide and
l-menthyl (S)-p-toluenesulfinate. Reaction time 3.5 h. It was
crystallized from hexane: mp 71-72 °C; [R]20 +84.8 (c 0.23,
D
(26) Garc´ıa Ruano, J . L.; Mart´ın Castro, A. M.; Rodr´ıguez Ramos,
J . H. Tetrahedron Lett. 1996, 37, 4569.
(27) Garc´ıa Ruano, J . L.; Mart´ın Castro, A. M.; Rodr´ıguez, J . H.
Rubio Flamarique, A. C. Tetrahedron: Asymmetry 1997, 8, 3503.
(28) These conditions were not successful for 1a and 1d , which
yielded mixtures containing 8a and 8d in minor proportion. The
structure of the major compounds obtained in these reactions is
currently under investigation.
(29) Hall, J . H.; Gisler, M. J . Org. Chem. 1976, 41, 3769. Under
these conditions, sulfur configuration should not be affected.
(30) In this reaction compound 11 was also recovered (see Experi-
mental Section). It results from epimerization at C-R of the sulfinyl
group under basic reaction conditions.
(31) We are currently investigating the mechanistic proposal de-
picted in Scheme 4 to explain the inversion of the herein described
configuration, studying the scope of these hydrolysis reactions for other
â-sulfinyl nitriles and related substrates, and searching the proper
experimental conditions to get the complete inversion of the sulfoxides
in acidic medium. The results of this study will be published in due
course.
(32) Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification of
Laboratory Chemical, 2nd ed.; Pergamon Press: New York, 1980.
(33) Vogel A. I. Practical Organic Chemistry, 5th ed., Longman
Scientific and Technical: London, 1989; p 1122.

Synthesis of (Z)-3-p-Tolylsulfinylacrylonitriles
J . Org. Chem., Vol. 63, No. 10, 1998 3329
Ta ble 4. 1H NMR Da ta of Com p ou n d s 1a -e
δ (multiplicity, J in hertz)
dCH
6.76 (s)
b
compd
C6H4
CH3Ar
R
1a (R ) n-Bu)
1b (R ) H)
1c (R ) t-Bu)
1d (R ) Bn)
1ea (R ) n-Bu)
7.59 and 7.35
7.59 and 7.35
7.58 and 7.35
7.57 and 7.35
7.52 and 7.37
2.43 (s)
2.41 (s)
2.42 (s)
2.42 (s)
2.43 (s)
2.32 (t, 2H, 7.0), 1.70-1.20 (m, 4H), 0.89 (t, 3H, 7.0)
5.89 (d, 10.2)
7.10 (d, 10.2)
6.73 (s)
1.18 (s, 9H)
6.76 (s)
6.86 (s)
7.40-7.25 (m, 3H), 7.20-7.05 (m, 2H), 3.60 (s, 2H)
2.85-2.50 (m, 2H), 1.80-1.30 (m, 4H), 0.97 (t, 3H, 7.0)
a
b
E isomer. All are an AA′BB′ system.
Ta ble 5. 1H NMR Da ta of Ad d u cts 6 a n d 8
δ (multiplicity, J in hertz)
b
compd
C6H4
CH3Ar
H-1
H-3
H-4
H-5
H-6
H-7a and H-7b
R
endo-6a
7.80, 7.33 2.41 (s) 3.20-3.00 3.12
3.70-3.50 6.73 (dd,
6.55 (dd,
1.85-1.65 (m), 1.60-0.85 (m, 6H), 0.67
(R ) n-Bu)
endo-6b
(R ) H)
endo-6d
(R ) Bn)
(m)
(d, 3.2)
(m)
3.70-3.55 6.71 (dd,
(m) 2.7 & 5.9) 2.7 & 5.9) 1.45-1.25 (m)
6.38 (dd, 1.85-1.65
2.7 & 5.4) 3.2 & 5.4) (m, 2H)
3.2 & 5.4) 3.2 & 5.4) 1.65-1.50 (m) (t, 3H, 7.0)
7.79, 7.32 2.41 (s) 3.50-3.30 2.90 (dd,
6.52 (dd,
1.85-1.65 (m), 3.62 (dd, 1H, 3.2 & 8.6)
(m)
3.2 & 8.6)
7.77, 7.31 2.40 (s) 3.20-3.00 3.23
3.70-3.50 6.69 (dd,
7.35-7.15 (m, 3H), 7.10-6.90
(m, 2H), 2.59 & 2.30 (AB
system, 2H, 13.7)
(m)
(d, 3.2)
(m)
exo-6a
7.78, 7.34 2.41 (s) 3.40-3.20 2.34
3.70-3.50 6.32 (dd,
6.11 (dd,
2.32-2.20 (m), 1.20-1.00 (m, 6H), 0.73
(R ) n-Bu)
exo-6d
(m)
(d, 3.2)
(m)
3.2 & 5.4) 3.2 & 5.4) 1.90-1.70 (m) (t, 3H, 7.0)
7.65, 7.30 2.38 (s) 3.20-3.00 2.40
3.65-3.45 6.39 (dd,
6.27 (dd,
2.25-2.20 (m), 7.40-7.15 (m, 3H), 7.10-6.90
(R ) Bn)
(m)
(d, 2.1)
(m)
3.1 & 5.5) 3.1 & 5.5) 1.76-1,71 (m) (m, 2H), 2.41 & 1.93 (AB
system, 2H, 13.3)
endo-8a
(R ) n-Bu)
7.77, 7.25 2.37 (s) 2.90-2.70 3.13
3.60-3.40 6.68 (dd,
6.33 (dd,
1.90-1.40
5.66 (bs, 1H), 5.30 (bs, 1H),
1.90-1.40 (m, 4H), 1.05 (m,
2H, 7.0), 0.63 (t, 3H, 7.0)
(m)
(d, 3.2)
(m)
2.7 & 5.9) 2.7 & 5.4) (m, 2H)
endo-8b
(R ) H)a
endo-8d
(R ) Bn)
7.52, 7.18 2.25 (s) 2.20-3.00 2.98 (dd,
3.40-3.30 6.38 (dd,
6.12 (dd,
1.60-1.45 (m), 3.67 (dd, 1H, 3.3 & 8.7)
(m)
3.3 & 8.7)
(m)
2.9 & 5.4) 3.0 & 5.9) 1.45-1.30 (m)
7.49, 7.33 2.48 (s) 3.20-3.00 3.24(d, 2.7) 3.40-3.20 6.76 (dd,
6.31 (dd,
1.95-1.75 (m), 7.50-7.15 (m, 5H), 6.20 (bs,
(m)
(m)
2.7 & 5.4) 2.7 & 5.4) 1.75-1.60 (m) 1H), 5.40 (bs, 1H), 3.68
& 2.78 (AB system, 2H, 13.4)
a
b
Methanol-d4 as solvent. All are an AA′BB′ system.
1
CHCl3); H NMR δ 7.68 and 7.34 (AA′BB′ system, 4H), 2.43
crystallized from hexane: mp 86-87 °C; [R]20 +43.5 (c 0.7,
D
(s, 3H), 1.27 (s, 9H); 13C NMR δ 142.2, 141.5, 130.2 (2C), 125.3
(2C), 112.8, 78.0, 30.0 (3C), 28.6, 21.5. Anal. Calcd for C13H16
CHCl3); 1H NMR δ 7.73 and 7.35 (AA′BB′ system, 4H), 7.40-
7,10 (m, 5H,), 3.83 (s, 2H), 2.44 (s, 3H); 13C NMR δ 142.2, 140.9,
133.8, 130.0 (2C), 128.6 (2C), 127.8 (2C), 127.0, 125.0 (2C),
112.4, 80.1, 25.8, 21.3. Anal. Calcd for C16H14SO: C, 75.56;
H, 5.55; S, 12.60. Found: C, 75.06; H, 5.36; S, 12.44.
-
SO: C, 70.87; H, 7.32; S, 14.55. Found: C, 70.74; H, 7.02; S,
14.78.
(+)-(S)-3-P h en yl-1-p r op yn yl p-Tolyl Su lfoxid e (2d ).
Compound 2d (white solid) was obtained in 40% yield from
the reaction of 3-phenyl-1-propynylmagnesium bromide and
l-menthyl (S)-p-toluenesulfinate.34 Reaction time 3 h. It was
Hyd r ocya n a tion of 1-Alk yn yl Su lfoxid es in to â-Su lfi-
n yla cr ylon itr iles. (i) With Et2AlCN.14 A solution of 1-alky-
nyl p-tolyl sulfoxide in 4 mL of toluene was added into a
solution of 2 mmol of Et2AlCN in 3 mL of toluene, and the
mixture was stirred under argon; reaction times and temper-
atures are indicated in each case. The reaction mixture was
quenched with 5 mL of a saturated aqueous solution of
potassium sodium tartrate. The organic layer was diluted with
5 mL of CH2Cl2 and the mixture was stirred until there was
clean layer separation. The aqueous solution was extracted
with CH2Cl2 (3 × 10 mL). The combined organic layers were
dried over Na2SO4 and the solvent was evaporated. The crude
mixture was purified by flash chromatography using the eluent
indicated in each case.
(34) In this reaction the following products were also isolated: (-)-
(R)-[(E)-2-bromo-3-phenyl-1-propenyl] p-tolyl sulfoxide (9), (-)-(R)-[(Z)-
2-benzyl-5-phenyl-1-penten-3-ynyl] p-tolyl sulfoxide (10) (14%), and the
starting (-)-(S)-p-toluenesulfinate (13%). Compound 9 (white solid) was
crystallised from diethyl ether: mp 103-104 °C; [R]20D -196.8 (c 0.51,
CHCl3); 1H NMR δ 7.61 and 7.33 (AA′BB′ system, 4H), 7.40-7.25 (m,
3H), 7.25-7.10 (m, 2H), 6.60 (s, 1H), 3.84 (s, 2H), 2.43 (s, 3H); 13C
NMR δ 141.7, 140.7, 138.4, 135.6, 135.2, 130.1 (2C), 129.1 (2C), 128.7
(2C), 127.5, 124.1 (2C), 48.0, 21.4. Anal. Calcd for C16H15BrSO: C,
57.32; H, 4.51; S, 9.56. Found: C, 57.05; H, 4.32; S, 9.80. Compound
10 (white solid) was crystallized from hexane-EtOAc (1: 1): mp 66-
67 °C; [R]20 -528.7 (c 0.51, CHCl3); 1H NMR δ 7.54 and 7.32 (AA′BB′
D
system, 4H), 7.50-7.15 (m, 8H), 7.30-7.10 (m, 2H), 6.39 (s, 1H), 3.82
(s, 2H), 3.57 (s, 2H), 2.43 (s, 3H); 13C NMR δ 141.7, 141.5, 141.1, 136.2,
135.4, 133.4, 129.9 (2C), 129.1 (2C), 128.6 (4C), 127.8 (2C), 127.0, 126.7,
123.9 (2C), 99.3, 78.9, 43.7, 25.9, 21.3. Anal. Calcd for C25H22SO: C,
81.04; H, 5.98; S, 8.51. Found: C, 80.51; H, 5.75; S, 8.47.
(ii) With TMSCN/18-Cr ow n -6 Eth er /KCN.19 A solution
of 1 mmol of 1-alkynyl p-tolyl sulfoxide in 10.2 mL of CH2Cl2
was added into a solution of 26.8 mg (0.1 mmol) of 18-crown-6
ether and 7.8 mg (0.12 mmol) of KCN in 4 mL of CH2Cl2. The

3330 J . Org. Chem., Vol. 63, No. 10, 1998
Ruano et al.
mixture was cooled at the temperature indicated in each case
and 248 mg (2.5 mmol) of TMSCN was added. The solution
was stirred at this temperature for the corresponding time.
After hydrolysis with 10 mL of water, the crude product was
extracted with CH2Cl2 (3 × 10 mL), dried over Na2SO4, and
concentrated. The reaction mixture was purified by flash
chromatography; the eluent is indicated in each case.
(2C), 122.6, 115.6, 55.2, 35.7, 27.7 (3C), 21.2. Anal. Calcd for
C14H17NOS: C, 67.98; H, 6.93; N, 5.66; S, 12.96. Found: C,
67.97; H, 6.36; N, 5.58; S, 13.43.
(-)-(R,R,Z)-1,2-Bis(p -t olylsu lfin yl)et h en e (5). Com-
pound 5 was obtained as a byproduct of hydrocyanation of 2b
with Et2AlCN or with TMSCN/18-crown-6 ether/KCN. When
the reaction was carried out with Et2AlCN at -78 °C for 24 h,
5 (27% yield) and 1b (26% yield) were isolated after flash
chromatography (3:2 EtOAc-hexane) of the reaction mixture.
(-)-(R,Z)-2-n -Bu tyl-3-(p-tolylsu lfin yl)pr open en itr ile (1a).
Compound 1a was prepared by hydrocyanation of 2a with Et2-
AlCN (2 h, -20 °C, 85% yield) or with TMSCN/18-crown-6
ether/KCN (72 h, 0 °C, 60% yield). In both cases, chromatog-
raphy of the reaction mixtures (1:3 EtOAc-hexane) afforded
Compound 5 was crystallized from hexane-EtOAc (2:3): mp
1
86-87 °C; [R]20 -904.8 (c 0.56, CHCl3); H NMR δ 7.64 and
D
7.30 (AA′BB′ system, 8H), 6.73 (s, 2H), 2.42 (s, 3H); 13C NMR
δ 144.1 (2C), 142.3 (2C), 139.7 (2C), 130.4 (4C), 124.8 (4C),
21.4 (2C). Anal. Calcd for C16H16O2S2: C, 63.13; H, 5.30; S,
21.06. Found: C, 62.99; H, 5.00; S, 20.85.
pure 1a as a yellow oil: [R]20 -340.0 (c 1.0, CHCl3); 1H NMR
D
δ 7.59 and 7.35 (AA′BB′ system, 4H), 6.76 (s, 1H), 2.43 (s, 3H),
2.32 (t, 2H, J ) 7.0), 1.70-1.20 (m, 4H), 0.89 (t, 3H, J ) 7.0);
13C NMR δ 150.4, 142.4, 139.4, 130.3 (2C), 123.9 (2C), 122.3,
114.7, 34.5, 29.0, 21.4, 21.3, 13.3. HRMS exact mass calcd for
Diels-Ald er Cycloa d d ition s of â-Su lfin yla cr ylon itr iles
w ith Cyclop en ta d ien e. Meth od i: Th er m a l Con d ition s.
To a stirred solution of â-sulfinylacrylonitrile (1 mmol) in CH2-
Cl2 (3.75 mL), in the presence of some hydroquinone crystals,
freshly distilled cyclopentadiene (675 µL, 8 mmol) was added
at room temperature. When the addition was completed, the
reaction mixture was heated at reflux for the time indicated
in each case. The crude mixture was concentrated and purified
by flash chromatography (the eluent is indicated in each case).
Meth od ii: In th e P r esen ce of Zn Br 2. To a solution of
ZnBr2 (450.4 mg, 2 mmol) in THF (0.5 mL), under argon at
room temperature, was added a solution of â-sulfinylacryloni-
trile (1 mmol) in CH2Cl2 (3.7 mL). The mixture was stirred
for 1 h and then freshly distilled cyclopentadiene (675.4 µL, 8
mmol) was added. The reaction mixture was stirred at room
temperature for the time indicated in each case, poured into
water (4 mL), and extracted with CH2Cl2 (3 × 4 mL). The
organic layer was dried over Na2SO4 and concentrated. The
crude product was purified by flash chromatography with the
eluent indicated in each case.
Meth od iii: In th e P r esen ce of BF3‚OEt2. Meth od iii.A.
BF3‚OEt2 (148 µL, 1.2 mmol) was added, under argon at room
temperature, to a solution of â-sulfinylacrylonitrile (1 mmol)
in CH2Cl2 (10 mL), and the mixture was stirred for 2.5 h. Then
it was cooled at -20 °C and freshly distilled cyclopentadiene
(675.4 µL, 8 mmol) was added. The reaction mixture was
stirred at -20 °C for the time indicated in each case and then
decomposed by treatment with methanol (10 mL) for 1.5 h at
room temperature. The resulting mixture was poured into
water (5 mL) and extracted with CH2Cl2 (3 × 15 mL). The
organic layer was dried over Na2SO4 and concentrated. The
crude product was purified by flash chromatography with the
eluent indicated in each case.
C
14H17NOS (M+) 247.1031, found 247.1031.
(-)-(R,Z)-3-(p-Tolylsu lfin yl)p r op en en itr ile (1b). Com-
pound 1b was prepared by hydrocyanation of 2b with Et2AlCN
(3 min, -20 °C, 55% yield) or with TMSCN/18-crown-6 ether/
KCN (46 h, -78 °C, 30% yield). In both cases, chromatography
of the reaction mixtures (3:2 EtOAc-hexane) afforded pure
1b as a white solid. It was crystallized from hexane-EtOAc
(2:1): mp 112-113 °C; [R]20D -441.8 (c 0.69, CHCl3); 1H NMR
δ 7.59 and 7.35 (AA′BB′ system, 4H), 7.10 (d, 1H, J ) 10.2),
5.89 (d, 1H, J ) 10.2), 2.41 (s, 3H); 13C NMR δ 157.7, 142.9,
138.4, 130.4 (2C), 124.1 (2C), 113.1, 104.1, 21.3. Anal. Calcd
for C10H9NOS: C, 62.80; H, 4.74; N, 7.32; S, 16.76. Found:
C, 62.64; H, 4.64; N, 7.17; S, 17.03.
(-)-(R,Z)-2-t-Bu tyl-3-(p-tolylsu lfin yl)pr open en itr ile (1c).
Compound 1c was prepared by hydrocyanation of 2c with Et2-
AlCN (48 h, -78 °C, 60% yield) and ii) with TMSCN/18-
crown-6 ether/KCN (21 h, 0 °C, 62% yield). In both cases,
chromatography of the reaction mixtures (1:1 EtOAc-hexane)
afforded pure 1c as a white solid. It was crystallized from
hexane-EtOAc (6:1): mp 131-132 °C; [R]20 -234.6 (c 0.41,
D
1
CHCl3); H NMR δ 7.58 and 7.35 (AA′BB′ system, 4H), 6.73
(s, 1H), 2.42 (s, 3H), 1.18 (s, 9H); 13C NMR δ 147.7, 142.4,
139.4, 132.5, 130.4 (2C), 123.9 (2C), 114.1, 36.8, 27.9 (3C), 21.4.
Anal. Calcd for C14H17NOS: C, 67.98; H, 6.93; N, 5.66; S, 12.96.
Found: C, 67.94; H, 6.51; N, 5.88; S, 13.03.
(-)-(R,Z)-2-Ben zyl-3-(p-tolylsu lfin yl)pr open en itr ile (1d).
Compound 1d was prepared by hydrocyanation of 2d with Et2-
AlCN (2 h, -20 °C, 90% yield). Chromatography of the
reaction mixture (1:4 EtOAc-hexane) afforded pure 1d as a
white solid. It was crystallized from EtOAc-hexane (1:6): mp
1
88-89 °C; [R]20 -336.9 (c 0.80, CHCl3); H NMR δ 7.57 and
D
7.35 (AA′BB′ system, 4H), 7.40-7.25 (m, 3H), 7.20-7.05 (m,
2H), 6.76 (s, 1H), 3.60 (s, 2H), 2.42 (s, 3H); 13C NMR δ 151.5,
142.6, 139.3, 133.5, 130.4 (2C), 129.1 (2C), 129.0 (2C), 127.9,
Meth od iii.B. The experimental procedure was identical
to that reported in method A except that in this case the
mixture of â-sulfinylacrylonitrile and BF3‚OEt2 was heated at
reflux of CH2Cl2 for 1 h before addition of cyclopentadiene.
(+)-(1S ,2S ,3S ,4R ,(S )R )-2-n -Bu t yl-3-(p -t olylsu lfin yl)-
bicyclo[2.2.1]h ep t-5-en e-2-ca r bon itr ile (en d o-6a ). Com-
pound endo-6a was obtained as a white solid from 1a by
following method i [Table 3, entry 1, 42% isolated yield after
chromatographic purification (1:5 EtOAc-CH2Cl2)] or method
ii [Table 3, entry 5, 40% isolated yield after chromatographic
purification (1:5 EtOAc-CH2Cl2)]. It was crystallized from
124.1 (2C), 121.3, 114.7, 40.8, 21.4. Anal. Calcd for C17H15
-
NOS: C, 72.57; H, 5.37; N, 4.98; S, 11.39. Found: C, 72.10;
H, 5.20; N, 5.08; S, 11.32.
(-)-(R,E)-2-n -Bu tyl-3-(p-tolylsu lfin yl)pr open en itr ile (1e).
Compound 1e was obtained as a white solid by hydrocyanation
of 2a with Et2AlCN. When the reaction was carried out at
room temperature, after 2 h 1e (16% yield) and 1a (70% yield)
were isolated after flash chromatography (1:3 EtOAc-hexane)
of the reaction mixture. Compound 1e was crystallized from
hexane-diethyl ether (1:1): mp 59-60 °C; [R]20D -67.0 (c 0.64,
EtOAc-hexane (1:2): mp 115-116 °C; [R]20 +34.9 (c 0.91,
D
1
CHCl3); H NMR δ 7.80 and 7.33 (AA′BB′ system, 4H), 6.73
1
CHCl3); H NMR δ 7.52 and 7.37 (AA′BB′ system, 4H), 6.86
(dd, 1H, J ) 3.2 and 5.4), 6.55 (dd, 1H, J ) 3.2 and 5.4), 3.70-
3.50 (m, 1H), 3.12 (d, 1H, J ) 3.2), 3.20-3.00 (m, 1H), 2.41 (s,
3H), 1.85-1.65 (m, 1H), 1.65-1.50 (m, 1H), 1.60-0.85 (m, 6H),
0.67 (t, 3H, J ) 7.0); 13C NMR δ 142.9, 140.1, 138.0, 136.9,
130.0 (2C), 126.5 (2C), 120.8, 76.5, 51.7, 46.2, 44.9, 44.6, 38.4,
27.1, 22.4, 21.1, 13.6. Anal. Calcd for C19H23NOS: C, 72.80;
H, 7.40; N, 4.47; S, 10.23. Found: C, 72.72; H, 7.25; N, 4.38;
S, 10.80.
(-)-(1R ,2S ,3S ,4S ,(S)R )-2-n -Bu t yl-3-(p -t olylsu lfin yl)-
b icyclo[2.2.1]h ep t -5-en e-2-ca r b on it r ile (exo-6a ). Com-
pound exo-6a was obtained as a white solid starting from 1a
by following method i [Table 3, entry 1, 47% isolated yield after
chromatographic purification (1:5 EtOAc-CH2Cl2)] or method
ii [Table 3, entry 5, 42% isolated yield after chromatographic
(s, 1H), 2.85-2.50 (m, 2H), 2.43 (s, 3H), 1.80-1.30 (m, 4H),
0.97 (t, 3H, J ) 7.0); 13C NMR δ 149.9, 142.3, 138.7, 130.1
(2C), 123.9 (2C), 123.0, 115.9, 29.9, 29.5, 21.4, 21.0, 13.2. Anal.
Calcd for C14H17NOS: C, 67.98; H, 6.93; N, 5.66; S, 12.96.
Found: C, 67.83; H, 6.71; N, 5.79; S, 12.98.
(()-p-Tolyl 3,3-dim eth yl-2-cyan obu tan eth ioate (4). Com-
pound 4 was obtained as a white solid in the hydrocyanation
of 2c with Et2AlCN. When the reaction was carried out at
-20 °C for 2 h, 4 (55% yield) and 1c (30% yield) were isolated
after flash chromatography (1:1 EtOAc-hexane) of the reac-
tion mixture. Compound 4 was crystallized from hexane: mp
59-60 °C; 1H NMR δ 7.35 and 7.15 (m, 4H), 3.48 (s, 1H), 2.37
(s, 3H), 1.20 (s, 9H); 13C NMR δ 189.3, 140.5, 134.1 (2C), 130.1

Synthesis of (Z)-3-p-Tolylsulfinylacrylonitriles
J . Org. Chem., Vol. 63, No. 10, 1998 3331
purification (1:5 EtOAc-CH2Cl2)]. It was crystallized from
EtOAc-hexane (1:2): mp 120-121 °C; [R]20 -208.4° (c 0.59,
D
EtOAc-hexane (1:2): mp 154-155 °C; [R]20 -54.3 (c 0.90,
CHCl3); 1H NMR δ 7.65 and 7.30 (AA′BB′ system, 4H), 7.40-
7.15 (m, 3H), 7.10-6.90 (m, 2H), 6.39 (dd, 1H, J ) 3.1 and
5.5), 6.27 (dd, 1H, J ) 3.1 and 5.5), 3.65-3.45 (m, 1H), 3.20-
3.00 (m, 1H), 2.41 and 1.93 (AB system, 2H, J ) 13.3), 2.38
(s, 3H), 2.40 (d, 1H, J ) 2.1), 2.23 (m, 1H), 1.74 (m, 1H); 13C
NMR δ 142.4, 140.1, 138.7, 134.9, 134.8, 130.0 (2C), 129.6 (2C),
128.5 (2C), 127.4, 125.6 (2C), 121.7, 72.9, 52.4, 47.0, 46.9, 43.9,
42.6, 21.4. Anal. Calcd for C22H21NOS: C, 76.05; H, 6.09; N,
4.03; S, 9.23. Found: C, 76.22; H, 5.98; N, 4.07; S, 9.66.
(-)-(1R,2R,3R,4S,(S)S)-2-n -Bu t yl-3-(p -t olylsu lfin yl)-
bicyclo[2.2.1]h ep t-5-en e-2-ca r boxa m id e (en d o-8a ). Ad-
duct endo-8a was obtained as a white solid starting from 1a
in the presence of BF3‚OEt2 by following method iii.A [reaction
time 360 h; 62% isolated yield after chromatographic purifica-
tion (6:1 CH2Cl2-MeOH)]. It was crystallized from CH2Cl2:
D
1
CHCl3); H NMR δ 7.78 and 7.34 (AA′BB′ system, 4H), 6.32
(dd, 1H, J ) 3.2 and 5.4), 6.11 (dd, 1H, J ) 3.2 and 5.4), 3.70-
3.50 (m, 1H), 3.40-3.20 (m, 1H), 2.41 (s, 3H), 2.34 (d, 1H, J )
3.2), 2.32-2.20 (m, 1H), 1.90-1.70 (m, 1H) 1.20-1.00 (m, 6H),
0.73 (t, 3H, J ) 7.0); 13C NMR δ 142.7, 140.1, 138.3, 134.5,
130.0 (2C), 126.2 (2C), 122.2, 73.8, 52.8, 46.6, 45.3, 44.4, 37.3,
27.4, 22.3, 21.5, 13.6. Anal. Calcd for C19H23NOS: C, 72.80;
H, 7.40; N, 4.47; S, 10.23. Found: C, 72.59; H, 7.16; N, 4.52;
S, 10.72.
(1R,2R,3R,4S,(S)R) a n d (1S,2R,3R,4R,(S)R)-2-n -Bu tyl-
3-(p -t o ly ls u lfin y l)b ic y c lo [2.2.1]h e p t -5-e n e -2-c a r b o -
n itr ile (en d o-7a + exo-7a ). A mixture of diastereomers endo-
7a + exo-7a was obtained as a white solid starting from 1a
under thermal conditions (method i) as a result of a change in
the reaction solvent: (a) by using MeOH (Table 3, entry 9),
from 95 mg (0.385 mmol) of 1a were obtained 48.2 mg (0.154
mmol) of a mixture of adducts exo-6a , endo-7a , and exo-7a ,
(83:10:7) and 37.4 mg (0.119 mmol) of endo-6a after chromato-
graphic purification (1:20 acetone-CH2Cl2); (b) by using MeOH
+ H2O (1:1) (Table 3, entry 10), from 100 mg (0.405 mmol) of
1a were obtained 10 mg (0.032 mmol) of a mixture of adducts
endo-7a and exo-7a (51:49), 44 mg (0.140 mmol) of exo-6a , and
38 mg (0.121 mmol) of endo-6a after chromatographic purifica-
mp 205-206 °C; [R]20 -28.9 (c 0.27, CHCl3);1H NMR δ 7.77
D
and 7.25 (AA′BB′ system, 4H), 6.68 (dd, 1H, J ) 2.7 and 5.9),
6.33 (dd, 1H, J ) 2.7 and 5.4), 5.66 (bs, 1H), 5.30 (bs, 1H),
3.60-3.40 (m, 1H), 3.13 (d, 1H, J ) 3.2), 2.90-2.70 (m, 1H),
2.37 (s, 3H), 1.90-1.40 (m, 6H), 1.05 (m, 2H), 0.63 (t, 3H, J )
7.0); 13C NMR δ 175.3, 143.8, 140.8, 136.7 (2C), 129.1 (2C),
126.5 (2C), 79.5, 60.9, 54.2, 46.3, 46.2, 41.5, 29.6, 27.2, 21.3,
13.7. Anal. Calcd for C19H25NO2S: C, 68.85; H, 7.60; N, 4.23;
S, 9.67. Found: C, 68.63; H, 7.13; N, 4.15; S, 9.69.
tion (2:3 EtOAc-hexane). Data corresponding to a 74:26
(-)-(1R,2R,3R,4S,(S)S)-3-(p-Tolylsu lfin yl]bicyclo[2.2.1]-
h ep t-5-en e-2-ca r boxa m id e (en d o-8b). Adduct endo-8b was
obtained as a white solid from 1b in the presence of BF3.OEt2
by following method iii.B [reaction time 3 h; 72% isolated yield
after chromatographic purification (12:1 CH2Cl2-MeOH)]. It
1
mixture of endo-7a /exo-7a : [R]20 +263.8 (c 0.09, CHCl3); H
D
NMR δ 7.65 and 7.37 (AA′BB′ system, 8H), 6.54 (dd, 1H, J )
3.2 and 5.9), 6.28 (dd, 1H, J ) 2.7 and 5.4), 6.20-6.00 (m, 2H)
3.45-3.30 (m, 1H), 3.30-3.10 (m, 1H), 2.95 (d, 1H, J ) 3.2),
2.44 (m, 7H), 2.40-2.25 (m, 2H), 2.28 (d, 1H, J ) 3.2), 2.20-
2.10 (m, 16H), 0.96 (t, 6H, J ) 7.0); 13C NMR δ 142.6, 142.7,
140.2 (2C), 138.1, 137.7, 135.1, 134.5, 130.1 (4C), 125.8 (2C),
125.3 (2C), 122.0, 120.7, 79.4, 75.8, 52.5, 51.3, 47.9, 47.5, 47.3,
46.2, 46.1, 45.5, 39.9, 38.7, 28.0, 27.7, 22.6, 22.5, 21.5 (2C),
13.8 (2C).
was crystallized from CH2Cl2-MeOH (20:1): mp 226-227 °C;
1
[R]20 -20.6 (c 0.12, CHCl3); H NMR δ 7.52 and 7.18 (AA′BB′
D
system, 4H), 6.38 (dd, 1H, J ) 2.9 and 5.4), 6.12 (dd, 1H, J )
3.0 and 5.9), 3.67 (dd, 1H, J ) 3.3 and 8.7), 3.40-3.30 (m, 1H),
3.20-3.00 (m, 1H), 2.98 (dd, 1H, J ) 3,3 and 8.7), 2.25 (s, 3H),
1.60-1.45 (m, 1H), 1.45-1.30 (m, 1H); 13C NMR δ 175.4, 143.6,
141.6, 138.0, 135.1, 130.8 (2C), 128.2 (2C), 72.1, 50.3, 50.1, 49.4,
48.2, 21.3. Anal. Calcd for C15H17NO2S: C, 65.43; H, 6.22; N,
5.09; S, 11.64. Found: C, 64.91; H, 5.93; N, 4.91; S, 11.53.
(+)-(1R ,2R ,3R ,4S ,(S)S )-2-Be n zyl-3-(p -t olylsu lfin yl)-
bicyclo[2.2.1]h ep t-5-en e-2-ca r boxa m id e (en d o-8d ). Ad-
duct endo-8d was obtained as a white solid starting from 1d
in the presence of BF3‚OEt2 by following method iii.A [reaction
time 360 h; 53% isolated yield after chromatographic purifica-
tion (20:1 CH2Cl2-MeOH)]. It was crystallized from CH2Cl2:
(+)-(1S,2S,3S,4R,(S)R)-3-(p-Tolylsu lfin yl)bicyclo[2.2.1]-
h ep t-5-en e-2-ca r bon itr ile (en d o-6b). Compound endo-6b
was obtained from 1b as a white solid after chromatographic
purification (EtOAc) following method i (Table 3, entry 2, 78%
isolated yield), method ii (Table 3, entry 6, 75% isolated yield),
or method iii.A (reaction time 1 h, 80% isolated yield). It was
crystallized from EtOAc-hexane (1:2): mp 140-141 °C; [R]20
D
+6.2 (c 0.32, CHCl3); 1H NMR δ 7.79 and 7.32 (AA′BB′ system,
4H), 6.71 (dd, 1H, J ) 2.7 and 5.9), 6.52 (dd, 1H, J ) 2.7 and
5.9), 3.55-3.70 (m, 1H), 3.62 (dd, 1H, J ) 3.2 and 8.6), 3.50-
3.30 (m, 1H), 2.90 (dd, 1H, J ) 3.2 and 8.6), 2.41 (s, 3H), 1.85-
1.65 (m, 1H), 1.45-1.25 (m, 1H); 13C NMR δ 142.4, 139.3, 136.1
(2C), 129.7 (2C), 125.9 (2C), 118.4, 67.9, 47.3, 47.0, 45.5, 29.7,
21.2. Anal. Calcd for C15H15NOS: C, 70.01; H, 5.87; N, 5.44;
S, 12.46. Found: C, 69.93; H, 5.55; N, 5.28; S, 12.54.
mp 209-210 °C; [R]20 +15.0 (c 0.10, CHCl3); 1H NMR δ 7.49
D
and 7.33 (AA′BB′ system, 4H), 7.50-7.15 (m, 5H), 6.76 (dd,
1H, J ) 2.7 and 5.4), 6.31 (dd, 1H, J ) 2.7 and 5.4), 6.20 (bs,
1H), 5.40 (bs, 1H), 3.68 and 2.78 (AB system, 2H, J ) 13.4),
3.40-3.20 (m, 1H), 3.24 (d, 1H, J ) 2.7), 3.20-3.00 (m, 1H),
2.48 (s, 3H), 1.95-1.75 (m, 1H), 1.75-1.60 (m, 1H); 13C NMR
δ 175.0, 141.8, 140.9, 137.5, 137.2, 135.6, 130.2 (2C), 129.5
(2C), 128.5 (2C), 127.1, 125.2 (2C), 77.2, 61.7, 52.1, 46.7, 46.2,
45.0, 21.4.
(-)-(1S ,2S ,3S ,4R ,(S)R )-2-Be n zyl-3-(p -t olylsu lfin yl)-
bicyclo[2.2.1]h ep t-5-en e-2-ca r bon itr ile (en d o-6d ). Com-
pound endo-6d was obtained as a white solid from 1d by
following method i [Table 3, entry 4, 39% isolated yield after
chromatographic purification (1:2 EtOAc-hexane)] or method
ii [Table 3, entry 8, 53% isolated yield after chromatographic
purification (1:1 EtOAc-hexane)]. It was crystallized from
Hyd r olysis of Ca r bon itr ile en d o-6a in to Ca r boxa m -
id e.29 To a stirred solution of 60 mg (0.192 mmol) of adduct
endo-6a in 1 mL of t-BuOH was added 200 mg of finely
powdered KOH. The reaction mixture was stirred at reflux
for 16 h, cooled at room temperature, and poured into 2 mL of
aqueous NaCl solution. The mixture was extracted with CH2-
Cl2 (3 × 2 mL). The organic layer was dried over Na2SO4 and
CaCl2 and then concentrated. The crude product was purified
by flash chromatography (12:1 CH2Cl2-MeOH) to give 20 mg
(0.060 mmol, 32%) of (+)-(1S,2S,3S,4R,(S)R)-2-n-butyl-3-(p-
tolylsulfinyl)bicyclo[2.2.1]hept-5-ene-2-carboxamide (endo-8′a )
EtOAc-hexane (1:2): mp 140-141 °C; [R]20 -122.5 (c 0.70,
D
CHCl3); 1H NMR δ 7.77 and 7.31 (AA′BB′ system), 7.35-7.15
(m, 3H), 7.10-6.90 (m, 2H), 6.69 (dd, 1H, J ) 2.7 and 5.4),
6.38 (dd, 1H, J ) 3.2 and 5.4), 3.70-3.50 (m, 1H), 3.23 (d, 1H),
3.20-3.00 (m, 1H), 2.59 and 2.30 (AB system, 2H, J ) 13.7),
2.40 (s, 3H), 1.85-1.65 (m, 1H); 13C NMR δ 142.7, 140.2, 137.8,
137.2, 134.1, 130.0 (2C), 128.4 (4C), 127.5, 126.2 (2C), 120.4,
76.3, 50.2, 46.1, 45.7, 44.6, 43.7, 21.4. Anal. Calcd for C22H21
-
[spectroscopic data are coincident with those of endo-8a : [R]20
D
NOS: C, 76.05; H, 6.09; N, 4.03; S, 9.23. Found: C, 76.14; H,
5.63; N, 3.92; S, 9.64.
+30.4 (c 0.27, CHCl3)] and 27.6 mg (0.083 mmol, 44%) of (+)-
(1S,2S,3R,4R,(S)R)-2-n-butyl-3-(p-tolylsulfinyl)bicyclo[2.2.1]-
hept-5-ene-2-carboxamide (11) which was crystallized from
(-)-(1R ,2S ,3S ,4S ,(S )R )-2-Be n zyl-3-(p -t olylsu lfin yl)-
b icyclo[2.2.1]h ep t -5-en e-2-ca r b on it r ile (exo-6d ). Com-
pound exo-6d was obtained as a white solid from 1d by
following method i [Table 3, entry 4, 42% isolated yield after
chromatographic purification (1:2 EtOAc-hexane)] or method
ii [Table 3, entry 8, 38% isolated yield after chromatographic
purification (1:1 EtOAc-hexane)]. It was crystallized from
hexane: mp 203-205 °C; [R]20 +149.4 (c 0.20, CHCl3); 1H
D
NMR 7.66 and 7.37 (AA′BB′ system, 4H), 7.42 (bs, 1H), 6.42
(dd, J ) 3.0 and 5.5), 5.87 (dd, J ) 3.2 and 5.5), 5.21 (bs, 1H),
3.25-3.23 (m, 1H), 2.87 (d, 1H, J ) 2.0), 2.77-2.62 (m, 1H),
2.46 (s, 3H), 2.20-2.10 (m, 1H), 2.15-1.90 (m, 1H), 1.85-1.79
(m, 1H), 1.70-1.10 (m, 5H), 0.96 (t, 3H, J ) 7.0); 13C NMR

3332 J . Org. Chem., Vol. 63, No. 10, 1998
Ruano et al.
176.9, 142.9, 140.6, 139.0, 134.9, 130.1 (2C), 125.6 (2C), 77.0,
59.1, 47.1, 44.6, 44.0, 33.1, 27.5, 23.1, 21.4, 13.9. Anal. Calcd
for C19H25NO2S: C, 68.85; H, 7.60; N, 4.23; S, 9.67. Found:
C, 68.35; H, 7.46; N, 4.12; S, 9.50.
Su p p or tin g In for m a tion Ava ila ble: IR and MS data of
compounds 1, 2, and 4-11. X-ray diagram and data of
compounds endo-6a and exo-6a (6 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.
Ack n ow led gm en t. We thank Direccio´n General de
Investigacio´n Cient´ıfica y Te´cnica (DGICYT) for finan-
cial support (Grants PB-93/257 and PB-95/210). One of
us (A.M.M.C.) is grateful to the Royal Society of London
for a fellowship.
J O9721002