Synthesis and Dienophilic Behavior of (S)-2-Cyano-3-(p-tolylsulfinyl)-1,4-benzoquinone

Article abstract of DOI:10.1021/jo035629+

Hydrocyanation of 2-(p-tolylsulfinyl)-1,4-benzoquinone (2) followed by oxidation with PhI(OAc)₂ gives 2-cyano-3-(p-tolylsulfinyl)-1,4-benzoquinone (1). The generation of 1 in the presence of cyclic and acyclic dienes affords the Diels-Alder add

Full text of DOI:10.1021/jo035629+

SCHEME 1
Syn th esis a n d Dien op h ilic Beh a vior of
(S)-2-Cya n o-3-(p-tolylsu lfin yl)-1,4-
ben zoqu in on e
J ose´ Luis Garc´ıa Ruano* and Carlos Alemparte
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias,
Universidad Auto´noma de Madrid,
Cantoblanco, 28049 Madrid, Spain
joseluis.garcia.ruano@uam.es
Received November 5, 2003
Abstr a ct: Hydrocyanation of 2-(p-tolylsulfinyl)-1,4-benzo-
quinone (2) followed by oxidation with PhI(OAc)2 gives
2-cyano-3-(p-tolylsulfinyl)-1,4-benzoquinone (1). The genera-
tion of 1 in the presence of cyclic and acyclic dienes affords
the Diels-Alder adducts with a complete chemo- (only
reaction with the sulfinyl-substituted double bond takes
place), regio- (controlled by the cyano group), and endo
selectivity (with respect to the quinone moiety), whereas the
π-facial selectivity is dependent on the structure of the diene.
The wide use of quinones as dienophiles1 contrasts with
their much lower applications in asymmetric Diels-Alder
reactions. In this field, some studies of limited scope
concerning the use of Ti,2 B,3 and other metal4 complexes
as chiral catalysts as well as other involving reactions
with some chiral dienes5 have been developed. The
attachment of a chiral auxiliary to the quinone skeleton
has also been investigated,6 the best results being
obtained with sulfinylquinones.7 The complete endo
selectivity and the high π-facial selectivity (strongly
influenced by the reaction conditions) and reactivity are
key features of the Diels-Alder reactions of these dieno-
philes.7 Nevertheless, two main limitations exist when
X ) H (Scheme 1), concerning the impossibility to obtain
adducts II with cyclic dienes and III with acyclic ones.
Thus, the reaction of 2-(p-tolylsulfinyl)-1,4-benzoquinone
with cyclic dienes affords with complete chemoselectivity
adducts I,8 rather than adducts II resulting from the
addition to the sulfinyl-substituted double bond. On the
other hand, adducts III derived from acyclic dienes are
very prone to desulfinylation and regenerate the quinonic
structure under the reaction conditions.8,9 Moreover,
many of these quinones undergo subsequent aromatiza-
tion, thus losing all the stereogenic centers created during
the Diels-Alder reaction (Scheme 1).
To increase the scope of these attractive dienophiles,
the search for sulfinylquinones able to evolve into types
II and III adducts is undoubtably interesting. We rea-
soned that the presence of an electron-withdrawing group
at C(3) could help to solve the above-mentioned problems.
First, it would increase the reactivity of the C(2)-C(3)
double bond, thus inverting the chemoselectivity and
giving rise therefore to adducts II instead of I. Besides,
desulfinylation from III would not be so favored, since
the quinone structure cannot be recovered. The good
results obtained in the Diels-Alder reactions of (Z)-p-
tolylsulfinylacrylonitriles10 and the easy introduction of
a cyano into multiple bonds made it the group of choice.
In this paper, we report the synthesis of (S)-2-cyano-3-
(p-tolylsulfinyl)-1,4-benzoquinone (1, X ) CN in Scheme
* Corresponding author.
(1) (a) Naruta, Y.; Maruyama, K. In The Chemistry of Quinonoid
Compounds; Patai, S., Rappoport, Z., Eds.; Wiley-Interscience: New
York, 1988; Vol. 2, p 241. (b) Finley, K. T. In Kirk-Othmer Encyclopedia
of Chemical Technology; Grayson, M., Eckroth, D., Eds.; Wiley-
Interscience: New York, 1982; Vol. 19, p 572.
(2) (a) White, J . D.; Choi, Y. Helv. Chim. Acta 2002, 85, 4306. (b)
Breuning, M.; Corey, E. J . Org. Lett. 2001, 3, 1559. (c) White, J . D.;
Choi, Y. Org. Lett. 2000, 2, 2373. (d) Mikami, K.; Motoyama, Y.; Terada,
M. J . Am. Chem. Soc. 1994, 116, 2812. (e) Engler, T. A.; Letavic, M.
A.; Lynch, K. O., J r.; Takusagawa, F. J . Org. Chem. 1994, 59, 1179.
(f) Engler, T. A.; Letavic, M. A.; Takusagawa, F. Tetrahedron Lett.
1992, 33, 6731. (g) Mikami, K.; Terada, M.; Motoyama, Y.; Nakai, T.
Tetrahedron: Asymmetry 1991, 2, 643.
(3) (a) Ryu, D. H.; Corey, E. J . J . Am. Chem. Soc. 2003, 125, 6388.
(b) Ryu, D. H.; Lee, T. W.; Corey, E. J . J . Am. Chem. Soc. 2002, 124,
9992.
(4) Evans, D. A.; Wu, J . J . Am. Chem. Soc. 2003, 125, 10162.
(5) Recent references: (a) Huang, H.-L.; Liu, R.-S. J . Org. Chem.
2003, 68, 805. (b) Huang, H.-L.; Huang, H.-C.; Liu, R.-S. Tetrahedron
Lett. 2002, 43, 7983. (c) Guo, H.; Madhushaw, R. J .; Shen, F.-M.; Liu,
R.-S. Tetrahedron 2002, 58, 5627. (d) Pai, C.-C.; Liu, R.-S. Org. Lett.
2001, 3, 1295.
(7) For a review, see: (a) Garc´ıa Ruano J . L.; Cid de la Plata, B. In
Topics in Current Chemistry; Page, P. C. B., Ed.; Springer-Berlin, 1999;
Vol. 204, p 1. For recent references, see: (b) Carren˜o, M. C.; Garc´ıa
Cerrada, S.; Sanz Cuesta, M. J .; Urbano, A. J . Org. Chem. 2003, 68,
4315. (c) Carren˜o, M. C.; Garc´ıa Cerrada, S.; Urbano, A. Chem.
Commun. 2002, 1412. (d) Carren˜o, M. C.; Garc´ıa Cerrada, S.; Sanz
Cuesta, M. J .; Urbano, A. Chem. Commun. 2001, 1452. (e) Carren˜o,
M. C.; Garc´ıa Cerrada, S.; Urbano, A. J . Am. Chem. Soc. 2001, 123,
7929. (f) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Toledo, M. A. Chem. Eur.
J . 2000, 6, 288.
(8) (a) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Toledo, M. A.; Urbano,
A.; Remor, C. Z.; Stefani, V.; Fischer, J . J . Org. Chem. 1996, 61, 503.
(b) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. Tetrahedron Lett.
1989, 30, 4003.
(6) (a) Brimble, M. A.; Elliott, R. J .; McEwan, J . F. Aust. J . Chem.
2000, 53, 571. (b) Brimble, M. A.; McEwan, J . F.; Turner, P.
Tetrahedron: Asymmetry 1998, 9, 1239. (c) Brimble, M. A.; Duncalf,
L. J .; Reid, D. C. W.; Roberts, T. R. Tetrahedron 1998, 54, 5363. (d)
Beagley, B.; Curtis, A. D. M.; Pritchard, R. G.; Stoodley, R. G. J . Chem.
Soc, Perkin Trans. 1 1992, 1981.
(9) (a) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Remor, C. Z.; Urbano,
A. Tetrahedron: Asymmetry 2000, 11, 4279. (b) Carren˜o, M. C.; Garc´ıa
Ruano, J . L.; Remor, C. Z.; Urbano, A.; Fischer, J . Tetrahedron Lett.
1997, 38, 9077.
10.1021/jo035629+ CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/21/2004
J . Org. Chem. 2004, 69, 1405-1408
1405

SCHEME 2a
SCHEME 3
a
Reaction conditions: (a) Et2AlCN/THF or toluene; (b) (i)
TMSCN/BF3‚OEt2 (neat), (ii) NaOH (aq), (iii) HCl; (c) PhI(OAc)2/
acetone.
venient the in situ generation of 1 in the presence of the
diene.18 Although the ee could not be established at this
point (due to the low stability of 1), it was accurately
determined for the Diels-Alder adducts derived from 1
(vide infra).
1) as well as its behavior as a dienophile in reactions with
cyclopentadiene and 1-methoxybutadiene.
The synthesis of dienophile 1 was achieved through a
two-step hydrocyanation-oxidation sequence starting
from sulfinylquinone 2.11 The efficiency of Et2AlCN in the
hydrocyanation of vinylsulfoxides12 prompted us to study
its reaction with 2. Surprisingly, when 2 was treated with
Et2AlCN in either THF or toluene, we observed the clean
addition of an ethyl group instead of the expected
cyanation (Scheme 2). Other hydrocyanating reagents13
such as TMSCN/KCN/18-C-6 or LiCN were also unsuc-
cessful. Finally, reaction of 2 with TMSCN in the pres-
ence of BF3‚OEt2 (40 mol %) and, importantly, under
solvent-free conditions yielded the expected compound 3
(Scheme 2) along with its O-silyl derivative, making a
basic workup necessary. After protonation and flash
chromatography, cyanohydroquinone 3 was isolated in
62% yield and >99% ee (HPLC).
Next, we turned our attention to the oxidation of
hydroquinone 3. When the most usual reagents (CAN,14
DDQ,15 and AgO/HNO316) were employed, decomposition
of the starting material occurred. The use of a hyperva-
lent iodine reagent,17 PhI(OAc)2, gave identically poor
results if the reaction was carried out in methanol.
However, by tuning the solvent to acetone the formation
of targeted quinone 1 could be observed, probably due to
the non-nucleophilic character of this solvent (Scheme
2). The instability of this compound in solution precludes
its chromatographic purification and makes more con-
When the reaction of hydroquinone 3 with PhI(OAc)2
was immediately followed by addition of cyclopentadiene,
a 57:43 mixture of two Diels-Alder adducts (4 and 5,
1
Scheme 3) was obtained. From their H NMR spectra it
was easily deduced that cycloaddition had taken place
to the sulfinyl-substituted double bond exclusively, show-
ing that the extra-activation by the cyano group com-
pletely inverts the chemoselectivity typically observed in
the reactions of quinone 2 with cyclopentadiene (see
Scheme 1). The oxidation of the sulfinyl group of 4 and 5
afforded enantiomeric sulfones, evidencing both adducts
result from the same endo or exo approach of the diene
from different faces of the tetrasubstituted double bond.
The enantiomeric purity (ee >99%) of the cycloadducts
was established by chiral HPLC and their endo stereo-
chemistry assumed on the basis of the well-established
strong endo-director character of the quinone ring.19
All the attempts to improve the diastereoselection by
changing the reaction conditions (solvent or temperature)
were fruitless, a poor π-facial selectivity being observed
in all cases. The best chemical yield was obtained when
PhI(OAc)2 was added over a mixture of hydroquinone 3
and cyclopentadiene in CH2Cl2 (65% overall yield (57:43
diastereomeric mixture) from 3, Scheme 3).
The poor π-facial selectivity observed can be due to the
existence of a similar population of both s-cis and s-trans
conformers (the absence of a preferred conformation
around the C-S bond must be a consequence of the
strong dipolar interactions of the sulfinyl with both CN
and CO groups destabilizing the s-cis and s-trans con-
formers, respectively). The preferred approach of the
diene, governed by steric grounds, would take place from
a different face in both conformations (that bearing the
lone electronic pair at sulfur),20 thus accounting for the
(10) (a) Garc´ıa Ruano, J . L.; Alemparte, C.; Mart´ın Castro, A. M.;
Adams, H.; Rodr´ıguez Ramos, J . H. J . Org. Chem. 2000, 65, 7938. (b)
Garc´ıa Ruano, J . L.; Esteban Gamboa, A.; Mart´ın Castro, A. M.;
Rodr´ıguez Ramos, J . H.; Lo´pez-Solera, M. I. J . Org. Chem. 1998, 63,
3324.
(11) (a) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Toledo, M. A.; Urbano,
A. Tetrahedron: Asymmetry 1997, 8, 913. (b) Carren˜o, M. C.; Garc´ıa
Ruano, J . L.; Urbano, A. Synthesis 1992, 651.
(12) Garc´ıa Ruano, J . L.; Cifuentes Garc´ıa, M.; Laso, N. M.; Mart´ın
Castro, A. M.; Rodr´ıguez Ramos, J . H. Angew. Chem., Int. Ed. 2001,
40, 2507.
(13) (a) Nagata, W.; Yoshioka, M. Org. React. 1977, 25, 255. (b)
Friedrich, K.; Wallenfels, K. In The Chemistry of the Cyano Group;
Rappoport, Z., Ed.; Wiley-Interscience: New York, 1970; p 68.
(14) J acob, P., III; Callery, P. S.; Shulgin, A. T.; Castagnoli, N., J r.
J . Org. Chem. 1976, 41, 3627.
(18) Although the purification process is not always reproducible
we could isolate a small amount of the pure quinone 1 by crystallization
in acetone. The high specific rotation measured, [R] +1433 (c 0.26,
acetone), suggested a high ee.
(15) Becker, H.-D. J . Org. Chem. 1965, 30, 982.
(16) (a) Luly, J . R.; Rapoport, H. J . Org. Chem. 1981, 46, 2745. (b)
Syper, L.; Kloc, K.; Mlochowski, J .; Szulc, Z. Synthesis 1979, 521. (c)
Snyder, C. D.; Rapoport, H. J . Am. Chem. Soc. 1974, 96, 8046. (d) Boldt,
P. Chem. Ber. 1967, 100, 1270.
(19) The endo stereochemistry of the major adduct obtained in the
reactions of 1 with 1-methoxybutadiene, whose structure was deter-
mined by X-ray diffraction (vide infra), also supports this assumption.
Additionally, the sulfinyl and cyano groups in a Z arrangement do not
have a very strong endo-directing character (see ref 10).
(17) Moriarty, R. M.; Prakash, O. Org. React. 2001, 57, 327.
1406 J . Org. Chem., Vol. 69, No. 4, 2004

TABLE 1. Rea ction s of th e Qu in on e 1 w ith
1-Meth oxybu ta d ien e u n d er Differ en t Con d ition s
SCHEME 4
entry
solvent
T (°C)
8/9a
eeb (%)
1
2
3
4
CH2Cl2
CH2Cl2
acetone
CH2Cl2
rt
0
0
-30
86/14
88/12
79/21
92/8
85
92
88
92
a
1
By integration on the H NMR spectrum of the crude reaction
b
mixture. Enantiomeric excess of 8 determined by HPLC.
observed low facial selectivity (Scheme 3). According to
this explanation, the formation of a chelated species by
coordinating the sulfinyl and carbonyl oxygens with a
metal atom appeared as a possible solution to improve
the selectivity (it would favor the s-trans conformer).
Unfortunately, the instability of the quinone in the
presence of Lewis acids (ZnBr2, Eu(fod)3, or Me2AlCl)
made this strategy fail. We then tried to differentiate
more efficiently the faces of 1 by its transformation into
the rigid sulfimide 6, supposedly achievable by treatment
SCHEME 5
21
of 3 with HBF4 or BF3‚OEt2 followed by oxidation of
the resulting hydroquinone (Scheme 4). However, under
such conditions 3 evolved into the achiral sulfide 7.22
1-Methoxybutadiene was chosen as a model of acyclic
diene. When we carried out its cycloaddition reaction with
the cyanoquinone 1 under the optimal conditions found
for cyclopentadiene, two compounds 8 and 9 were formed
in an 86:14 ratio (entry 1, Table 1). As expected, none of
the reaction products undergo aromatization. The struc-
ture of the major one was unambiguously established by
X-ray analysis23 as the adduct resulting from the endo
addition of the diene to the si face of the dienophile.
Compound 9 is a diene lacking the sulfinyl group, which
must be formed by elimination of p-TolSOH from the
corresponding Diels-Alder adduct. We concluded that 9
did not proceed from 8 since treatment of the latter under
thermal, acidic or basic conditions did not afford 9 in any
1
case. The regiochemistry was easily assigned from its H
NMR spectroscopic data and the results previously
obtained from cyclopentadiene (only the two endo adducts
were formed) suggested 9 must be derived from the other
endo adduct.
These results indicate that the regioselectivity of the
reaction is complete (it is controlled by the cyano group)
as well as the endo selectivity (with respect to the
quinone ring). The π-facial selectivity is much higher
than that observed in the reaction with cyclopentadiene
(84% vs 14% de). Taking into account that the confor-
mational equilibrium of the dienophile is the same in
both cases, interactions altering the energy of the differ-
ent transition states must be invoked to explain this
different behavior. In the cycloadditions with cyclopen-
tadiene a steric interaction between the methylene bridge
of the diene and the sulfinyl oxygen of the dienophile in
the s-cis conformation could be responsible for the
destabilization of the transition state corresponding to
the endo-si addition (Scheme 5). This interaction is
neither present on the endo-re addition (as it takes place
on the s-trans conformer) nor with the acyclic diene due
to the lack of methylene bridge. To explain the influence
of the solvent polarity on the facial selectivity of reactions
with 1-methoxybutadiene (compare entries 2 and 3 in
Table 1) the existence of electrostatic repulsions desta-
bilizing the endo-re approach, caused by the proximity
of three negatively charged atoms (Scheme 5), can be
invoked. This repulsion would be lower for the endo-si
addition and would not exist in reactions with nonpolar-
ized dienes (such as cyclopentadiene).
(20) Arai, Y.; Takayama, H.; Koizumi, T. Tetrahedron Lett. 1987,
28, 3689.
(21) Garc´ıa Ruano, J . L.; Esteban Gamboa, A.; Gonza´lez Gutie´rrez,
L.; Mart´ın Castro, A. M.; Rodr´ıguez Ramos, J . H.; Yuste, F. Org. Lett.
2000, 2, 733.
(22) This transformation could take place through the following
mechanism:
(23) The authors have deposited atomic coordinates for 8 with the
Cambridge Crystallographic Data Centre (Deposit No. 223619). The
coordinates can be obtained, on request, from the Director, Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
U.K.
J . Org. Chem, Vol. 69, No. 4, 2004 1407

Gen er a l P r oced u r e for On e-P ot Hyd r oqu in on e Oxid a -
tion /Diels-Ald er Rea ction . To a mixture of 3 (55 mg, 0.20
mmol) and the diene (0.26 mmol) in 1 mL of CH2Cl2 was added
PhI(OAc)2 (71 mg, 0.22 mmol). After 20-40 min, the solvent was
removed and the crude mixture purified by flash chromatogra-
phy.
The enantiomeric excess of compound 8 obtained under
the conditions of entry 1 (Table 1) is 85%. This loss of
optical purity may be attributed to the lack of configu-
rational stability of quinone 1. It has been previously
described24 that (Z)-sulfinylacrylonitriles containing two
additional electron-withdrawing groups present a low
racemization barrier. This has been explained by assum-
ing delocalization of the lone electronic pair at sulfur to
the double bond when this is highly electron-deficient.
In our case, the observed ee must be compromised by the
relative rates of the racemization and the Diels-Alder
reaction. The higher reactivity of cyclopentadiene com-
pared to 1-methoxybutadiene accounts for the lower ee
measured in the cycloadducts derived from the latter
diene. The enantiomeric excess is slightly improved when
the temperature decreases25 (entries 2 and 4, Table 1),
which also enhances the facial selectivity. Under optimal
conditions (entry 4), the adduct 8 could be isolated in 71%
yield and 92% ee, after flash chromatography.
In summary, we have demonstrated that the introduc-
tion of a cyano group at C(3) of 2(-p-tolylsulfinyl)-
benzoquinone meets with change of chemoselectivity in
the Diels-Alder reactions with cyclopentadiene and
prevent the aromatization of the cycloadducts resulting
from acyclic dienes. The problems derived from the low
chemical and configurational stability of 1 can be mini-
mized by its in situ generation in the presence of the
diene. Regio- and endo-selectivity of the cycloadditions
were found to be complete in all cases. The π-facial
selectivity was dependent on the nature of the diene.
(1R,2S,7S,8S)-3,6-Dioxo-7-[(S)-p -t olylsu lfin yl]t r icyclo-
[6.2.1.02,7]u n d eca -4,9-d ien e-2-ca r bon itr ile (4). Oxidation of
3 followed by Diels-Alder reaction with cyclopentadiene at room
temperature in CH2Cl2 afforded 4 in 37% yield after flash
chromatography (1:4 acetone-hexane). The enantiomeric excess
was found to be >99% (HPLC, Chiralpak AD, i-PrOH/hexane
(30:70), 1.0 mL/min, 230 nm; 4 tR ) 11.0 min, ent-4 tR ) 9.2
min): [R]20D -329 (c 0.94, CHCl3); mp 107-108 °C (yellow solid;
HRMS (FAB) 338.0860 (M + 1)
+ (C19H16NO3S requires 338.0851);
MS (FAB) 338 (18) (M + 1)+, 307 (30), 155 (30), 154 (100), 138
(36), 137 (64), 136 (72), 91 (18), 77 (27); 1H NMR (CDCl3) δ 7.72
and 7.29 (AA′BB′ system, 4H), 6.28 (dd, 1H, J ) 3.1, 5.5 Hz),
6.26 and 6.00 (AB system, 2H, J ) 10.4 Hz), 6.12 (dd, 1H, J )
3.0, 5.6 Hz), 4.20 (m, 1H), 4.05 (m, 1H), 2.46 (d, 1H, J ) 10.1
Hz), 2.38 (s, 3H), 1.88 (dt, 1H, J ) 10.8, 1.6 Hz).
(1S,2R,7R,8R)-3,6-Dioxo-7-[(S)-p -t olylsu lfin yl]t r icyclo-
[6.2.1.02,7]u n d eca -4,9-d ien e-2-ca r bon itr ile (5). Oxidation of
3 followed by Diels-Alder reaction with cyclopentadiene at room
temperature in CH2Cl2 afforded 5 in 28% yield after flash
chromatography (1:4 acetone-hexane). The enantiomeric excess
was found to be >99% (HPLC, Chiralpak AD, i-PrOH/hexane
(30:70), 1.0 mL/min, 230 nm; 5 tR ) 9.3 min, ent-5 tR ) 10.4
min): [R]20D +539 (c 0.68, CHCl3); mp 113-114 °C (yellow solid);
HRMS (FAB) 338.0840 (M + 1)+ (C19H16NO3S requires 338.0851);
MS (FAB) 338 (24) (M + 1)+, 272 (39), 139 (79), 95 (47), 91 (50),
81 (69), 73 (51), 69 (64), 57 (72), 55 (100); 1H NMR (CDCl3) δ
7.49 and 7.41 (AA′BB′ system, 4H), 6.77 and 6.68 (AB system,
2H, J ) 10.4 Hz), 6.16 (dd, 1H, J ) 2.9, 5.6 Hz), 6.01 (dd, 1H, J
) 3.2, 5.5 Hz), 4.06 (m, 1H), 3.12 (m, 1H), 2.49 (s, 3H), 2.33 (d,
1H, J ) 10.2), 1.80 (dt, 1H, J ) 10.2, 1.7 Hz).
(4a S,5R,8a R)-1,4,4a ,5,8,8a -Hexa h yd r o-5-m eth oxy-1,4-d i-
oxo-8a -[(S)-p -t olylsu lfin yl]-1,4-n a p h t h a len e-4a -ca r b on i-
tr ile (8). Oxidation of 3 followed by Diels-Alder reaction with
1-methoxybutadiene at -30 °C in CH2Cl2 afforded 8 in 71% yield
after flash chromatography (1:4 acetone-hexane). The enantio-
meric excess was found to be 92% (HPLC, Chiralpak AD,
i-PrOH/hexane (30:70), 1.0 mL/min, 230 nm; 8 tR ) 10.4 min,
Exp er im en ta l Section
(S)-3,6-Dih yd r oxy-2-(p-tolylsu lfin yl)ben zon itr ile (3). To
a mixture of TMSCN (3.1 mL, 23.2 mmol) and 2 (1.9 g, 7.72
mmol) under argon at 0 °C was added BF3‚OEt2 (392 µL, 3.1
mmol). It was stirred for 1 h at rt. Then, 15 mL of CH2Cl2 and
10 mL of 10% NaOH were added. After being stirred for 5 min,
the aqueous layer was acidified by addition of concentrated HCl
and extracted with CH2Cl2 (3 × 15 mL). The organic layers were
dried (Na2SO4), and the solvent was removed. Chromatographic
purification (1:2 AcOEt-hexane) afforded 3 (1.31 g, 62%). The
enantiomeric excess was found to be >99% (HPLC, Chiralpak
AS, i-PrOH/hexane (30:70), 1.0 mL/min, 211 nm; (S)-3 tR ) 9.7
min, (R)-3 tR ) 19.6 min): [R]20D -116 (c 1.0, acetone); mp 136-
137 °C (yellow solid); HRMS (EI) 273.0454, M+ (C14H11NO3S
requires 273.0460); IR (film) 3262, 2925, 2226, 1594, 1461, 1278,
1080 cm-1; MS (EI) 273 (80) M+, 257 (85), 225 (20), 139 (43), 92
ent-8 tR ) 14.3 min): [R]20 -220 (c 1.0, CHCl3) for ee ) 88%;
D
mp 122-123 °C (yellow solid); HRMS (FAB) 356.0968 (M + 1)+
(C19H18NO4S requires 356.0957); MS (FAB) 356 (28) (M + 1)+,
217 (53), 216 (53), 154 (41), 139 (64), 136 (51), 107 (58), 95 (63),
91 (54), 81 (100), 55 (93); 1H NMR (CDCl3) δ 7.30 and 7.25
(AA′BB′ system, 4H), 7.09 and 6.64 (AB system, 2H, J ) 10.4
Hz), 6.05 (m, 2H), 4.20 (m, 1H), 3.14 (s, 3H), 3.09 (ddd, 1H, J )
1.5, 4.1, 19.5 Hz), 2.59 (m, 1H), 2.39 (s, 3H).
(4a S,5S)-1,4,4a ,5-Tet r a h yd r o-5-m et h oxy-1,4-d ioxo-1,4-
n a p h th a len e-4a -ca r bon itr ile (9). Oxidation of 3 followed by
Diels-Alder reaction with 1-methoxybutadiene at 0 °C in
acetone afforded 9 in 21% yield and 88% ee after flash chroma-
1
(99.9), 91 (100), 77 (47), 65 (47);. H NMR (CD3COCD3) δ 10.63
(bs, 1H), 9.92 (bs, 1H), 7.81 and 7.47 (AA′BB′ system, 4H), 7.13
and 7.05 (AB system, 2H, J ) 9.1 Hz), 2.41 (s, 3H); 13C NMR
(CD3COCD3) δ 155.4, 153.2, 144.1, 140.8, 131.2 (2C), 126.6, 126.1
tography (1:4 acetone-hexane): [R]20 +442 (c 0.3, CHCl3) for
D
ee ) 88%; mp 112-114 °C (yellow solid); HRMS (FAB) 216.0659
(M + 1)+ (C12H10NO3 requires 216.0661); MS (FAB) 216 (10) (M
(2C), 125.0, 121.8, 113.8, 96.2, 21.3. Anal. Calcd for C14H11
NO3S: C, 61.52; H, 4.06; N, 5.12; S, 11.73. Found: C, 61.49; H,
4.15; N, 5.12; S, 12.02.
-
1
+ 1)+, 155 (32), 154 (100), 137 (74), 136 (80); H NMR (CDCl3)
δ 7.37 (d, 1H, J ) 5.4 Hz), 7.07 and 6.94 (AB system, 2H, J )
10.6 Hz), 6.72 (dd, 1H, J ) 5.0, 9.5 Hz), 6.61 (dd, 1H, J ) 5.4,
9.5 Hz), 4.42 (d, 1H, J ) 5.0 Hz), 3.34 (s, 3H).
(S)-3,6-Dioxo-2-(p -t olylsu lfin yl)cycloh exa -1,4-d ien e-1-
ca r bon itr ile (1). To a solution of 3 (55 mg, 0.20 mmol) in 500
µL of acetone was added PhI(OAc)2 (71 mg, 0.22 mmol). A pure
precipitate of 1 was filtered off: [R]20 +1433 (c 0.26, acetone);
Ack n ow led gm en t. We thank CAICYT (Grant No.
BQU2003-04012) for financial support. C.A. thanks
Ministerio de Educacio´n, Cultura y Deportes, for a
grant.
D
1H NMR (CD3COCD3) 7.80 and 7.43 (AA′BB′ system, 4H), 7.08
and 7.01 (AB system, 2H, J ) 9.3 Hz), 2.41 (s, 3H); IR (film)
2925, 2232, 1667, 1594, 1454, 1237, 1140, 812 cm-1
.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
(24) Yuste, F.; Ortiz, B.; Pe´rez, J . I.; Rodr´ıguez-Herna´ndez, A.;
Sa´nchez-Obrego´n, R.; Walls, F.; Garc´ıa Ruano, J . L. Tetrahedron 2002,
58, 2613.
(25) The racemization rate decreases when the temperature becomes
lower. However, this also slows the Diels-Alder reaction, thus impos-
ing a limit in the enhancement of the ee.
and 13C NMR spectra of compounds 1, 3-5, 8, and 9 and
ORTEP structure of compound 8. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O035629+
1408 J . Org. Chem., Vol. 69, No. 4, 2004