Copper(II)-bis(oxazoline) catalyzed asymmetric Diels-Alder reaction with α′-arylsulfonyl enones as dienophiles

Article abstract of DOI:10.1021/jo8009227

(Chemical Equation Presented) α′-Arylsulfonyl enones are efficient bidentate dienophiles for the Cu(II)-bis(oxazoline) catalyzed enantioselective Diels-Alder reaction with a number of dienes, affording the corresponding products with good to high enantiomeric excesses. The resulting products can be alkylated and the sulfone removed, so α′- arylsulfonyl enones can be regarded as surrogates of simple monodentate enones, which are poor dienophiles with this catalytic system.

Full text of DOI:10.1021/jo8009227

Copper(II)-Bis(oxazoline) Catalyzed Asymmetric
Diels-Alder Reaction with r′-Arylsulfonyl
Enones as Dienophiles
Santiago Barroso,† Gonzalo Blay,*,† Lina Al-Midfa,†
M. Carmen Mun˜oz,‡ and Jose´ R. Pedro*,†
Departament de Qu´ımica Orga`nica, Facultat de Qu´ımica,
UniVersitat de Vale`ncia, C/Dr. Moliner, 50, E-46100
Burjassot (Vale`ncia), Spain, and Departament de F´ısica
Aplicada, UniVersitat Polite`cnica de Vale`ncia,
E-46071 Vale`ncia, Spain
FIGURE 1. Examples of chelating dienophiles.
jose.r.pedro@uV.es; gonzalo.blay@uV.es
ReceiVed April 29, 2008
Diels-Alder reaction are normally categorized in two groups:
those that bind to the Lewis acid at one point (monodentate
dienophiles) and those that bind at two points (bidentate
dienophiles). Earlier studies with monodentate dienophiles have
focused mainly on the reaction of unsaturated aldehydes,3
especially with an R-substituent, and to a lesser extent on the
reaction of alkyl acrylates5 and quinones.6 The asymmetric
Diels-Alder reaction with ketone dienophiles has been only
recently reported, despite the prevalence of enantiopure ketones
in natural products.7 However, in most of the examples that
use acyclic enones as dienophiles the results are largely
dependent on the substituent attached to the carbonyl group,
which is poorly amenable to variation. Besides these mono-
dentate dienophiles, a number of effective bidentate dienophiles
have been reported. Thus, 3-alkenoyl-1,3-oxazolidin-2-ones (a)
have proven to be very efficient substrates with a large number
of metal-based catalysts and have become the standard test for
new catalyst development.8 Examples of other chelating dieno-
philes (Figure 1) include N-hydroxyacrylamides (b),9 R′-
hydroxyenones (c),10 unsaturated R-ketoesters (d),11 2-alkylidene-
R′-Arylsulfonyl enones are efficient bidentate dienophiles for
the Cu(II)-bis(oxazoline) catalyzed enantioselective Diels-
Alder reaction with a number of dienes, affording the
corresponding products with good to high enantiomeric
excesses. The resulting products can be alkylated and the
sulfone removed, so R′-arylsulfonyl enones can be regarded
as surrogates of simple monodentate enones, which are poor
dienophiles with this catalytic system.
(4) For some examples of asymmetric organocatalytic Diels-Alder reaction,
see: (a) Kano, T.; Tanaka, Y.; Maruoka, K. Org. Lett. 2006, 8, 2687–2689. (b)
Sakakura, A.; Suzuki, K.; Nakano, K.; Ishihara, K. Org. Lett. 2006, 8, 2229–
2232. (c) Nakashima, D.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 9626–
9627. (d) Wilson, R. M.; Jen, W. S.; Mac Millan, D. W. C. J. Am. Chem. Soc.
2005, 127, 11616–11617. (e) Kim, K. H.; Lee, K. S.; Lee, D.-W.; Ko, D.-H.;
Ha, D.-C. Tetrahedron Lett. 2005, 46, 5991–5994. (f) Lemay, M.; Ogilvie, W. W.
Org. Lett. 2005, 7, 4141–4144. (g) Huang, Y.; Unni, A. K.; Thadani, A. N.;
Rawal, V. H. Nature 2003, 424, 146. (h) Northrup, A. B.; Mac Millan, D. W. C.
J. Am. Chem. Soc. 2002, 124, 2458–2460.
The Diels-Alder (D-A) reaction is a powerful organic
transformation that constitutes a versatile method for the
synthesis of cyclohexene-containing building blocks of great
interest for the total synthesis of bioactive natural products.1
The opportunity to generate up to four stereogenic centers in a
stereocontrolled way has stimulated great interest in the
development of enantioselective procedures for this transforma-
tion.2–4 The use of chiral Lewis acids has been, by far, the most
used tactic for this purpose. The success of this approach
depends largely on the fitting of the structure of the Lewis acid
to the structure of the dienophile. The dienophiles used in the
(5) Ryu, D. H.; Lee, T. W.; Corey, E. J. J. Am. Chem. Soc. 2002, 124, 9992–
9993.
(6) (a) Jarvo, E. R.; Lawrence, B. M.; Jacobsen, E. N. Angew. Chem., Int.
Ed. 2005, 44, 6043–6046. (b) Ryu, D. H.; Zhou, G.; Corey, E. J. J. Am. Chem.
Soc. 2004, 126, 4800–4802. (c) Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc.
2003, 125, 6388–6390. (d) Breuning, M.; Corey, E. J. Org. Lett. 2001, 3, 1559–
1562.
† Universitat de Vale`ncia.
(7) (a) Singh, R. S.; Adachi, S.; Tanaka, F.; Yamauchi, T.; Inui, C.; Harada,
T. J. Org. Chem. 2008, 73, 212–218. (b) Liu, D.; Canales, E.; Corey, E. J. J. Am.
Chem. Soc. 2007, 129, 1498–1499. (c) Rickerby, J.; Vallet, M.; Bernardinelli,
G.; Viton, F.; Ku¨ndig, E. P. Chem. Eur. J. 2007, 13, 3354–3368. (d) Futatsugi,
K.; Yamamoto, H. Angew. Chem., Int. Ed. 2005, 44, 1484–1487. (e) Singh, R. S.;
Harada, T. Eur. J. Org. Chem. 2005, 3433–3435. (f) Zhou, G.; Hu, Q.-Y.; Corey,
E. J. Org. Lett. 2003, 5, 3979–3982. (g) Hawkins, J. M.; Nambu, M.; Loren, S.
Org. Lett. 2003, 5, 4293–4295.
‡ Universitat Polite`cnica de Vale`ncia.
(1) Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650–1667.
(2) For examples on the use of chiral auxiliaries, see:(a) Evans, D. A.;
Chapman, K. T.; Bisaha, J. J. Am. Chem. Soc. 1988, 110, 1238–1256. (b) Evans,
D. A.; Chapman, K. T.; Bisaha, J. J. Am. Chem. Soc. 1984, 106, 4261–4263. (c)
Oppolzer, W.; Chapuis, C.; Bernardinelli, G. HelV. Chim. Acta 1984, 67, 1397–
1401.
(3) For general reviews and accounts on catalytic asymmetric Diels-Alder
reactions, see: (a) Harada, T.; Kusukawa, T. Synlett 2007, 1823–1835. (b)
Cycloaddition Reactions in Organic Synthesis; Kobayashi, S., Jørgensen, K. A.
Eds.; Wiley-VCH: New York, 2002. (c) Lewis Acids in Organic Synthesis;
Yamamoto, H. Ed.; Wiley-VCH: New York, 2000; Vols. 1 and 2. (d) Evans,
D. A.; Johnson, J. S. In ComprehensiVe Asymmetric Catalysis; Jacobsen,
E. N.; Pfaltz, A.; Yamamoto, H. Eds.; Springer: Berlin, 1999; Vol. 3.
(8) (a) Evans, D. A.; Barnes, D. M.; Johnson, J. S.; Lectka, T.; von Matt, P.;
Miller, S. J.; Murry, J. A.; Norcross, R. D.; Shaughnessy, E. A.; Campos, K. R.
J. Am. Chem. Soc. 1999, 121, 7582–7594. (b) Evans, D. A.; Miller, S. J.; Lectka,
T.; von Matt, P. J. Am. Chem. Soc. 1999, 121, 7559–7553. (c) Evans, D. A.;
Miller, S. J.; Lectka, T. J. Am. Chem. Soc. 1993, 115, 6460–6461.
(9) (a) Corminboeuf, O.; Renaud, P. Org. Lett. 2002, 4, 1735–1738. (b)
Corminboeuf, O.; Renaud, P. Org. Lett. 2002, 4, 1731–1734.
10.1021/jo8009227 CCC: $40.75
Published on Web 07/23/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6389–6392 6389

SCHEME 1. Diels-Alder Reaction between
Cyclopentadiene (2) and Compounds 3
FIGURE 2. Structure of bis(oxazoline) ligands used in this study.
1,3-dicarbonyl compounds (e),12 acrylimides (f),13 or 2-acylimid-
azoles (g),14 which upon combination with the Lewis acid form
tight templates that give rise to highly ordered transition
structures responsible for the enantioselectivity. In some of these
cases, the resulting D-A product can be transformed into a ketone
upon removal of the bidentate template, normally with the use of
a nucleophilic organometallic reagent. Wada and co-worker have
introduced the use of R′-phenylsulfonyl enones (h) as heterodienes
in hetero-D-A reactions catalyzed by TADDOL-Ti(IV) com-
plexes.15 The ꢀ-sulfonyl ketone acts as a bidentate ligand for the
chiral titanium reagent. These authors have also described the
enantioselective D-A reaction of these substrates with cyclopen-
tadiene to afford the cycloadduct in high optical purity, although
no other diene was explored.16 Because ꢀ-sulfonyl ketones can be
alkylated17 and the sulfonyl group reductively removed,18 this kind
of dienophiles can be regarded as alkyl enone equivalents.
In connection with our recent research on enantioselective
catalytic D-A reactions19 we became interested in exploring
effective new catalysts and expanding the substrate scope for
the D-A reaction with R′-arylsulfonyl enones.
A screening of different BOX ligands and metal salts in
dichloromethane (DM) as solvent showed that the combination
of Cu(OTf)2 and (S)-PhBOX (1a) gave the best results, affording
the expected D-A product 4a with a 91:9 endo:exo ratio, 95%
ee (for the major endo product) and full conversion after 5 h at
0 °C (Table 1, entry 1). However, the (S)-t-BuBOX (1b), (R)-
InBOX (1c) and (S)-PhPyBOX (1d) ligands slowed down the
reaction and provided the corresponding product with lower
diastereo- and enantioselectivity (entries 2-4). From the other
metal salts tested, only zinc triflate afforded results similar to
those of copper triflate, although the reaction was considerably
slower and the product was obtained with slightly lower ee
(entry 7). Several solvents were also screened with the complex
1a-Cu(OTf)2. In all the cases the reaction took place with lower
stereoselectivity than in dichloromethane. Interestingly, toluene
gave a slightly better diastereoselectivity while it provided the
product with slightly lower ee (entry 9). By combining both
solvents it was possible to maximize both the diastereo- and
enantioselectivity of the reaction (entries 12-14).
Next, we studied the substrate scope of the reaction with
different R′-arylsulfonyl enones under the optimized condi-
tions. Both the substituent on the double bond and on the
arylsulfonyl group were amenable to variation; the results
are shown in Table 2.
Because metal complexes with bis(oxazoline) (BOX)20
ligands have found successful application in a large number of
enantioselective reactions with bidentate substrates, we decided
to explore this kind of ligand in our research (Figure 2). Also,
while our work was near to completion, Kim et al. reported a
catalytic enantioselective Mukaiyama-Michael reaction of
2-(trimethylsilyloxy)furan with R′-phenylsulfonyl enones cata-
lyzed by Cu-BOX complexes.21
In general, variations on the arylsulfonyl group had little effect
on the reaction outcome (entries 1-3), although the p-
chlorophenylsulfonyl enone 3c gave the product with the best
ee. The reaction was also successful with tosylsulfonyl enones
bearing different substitution on the ꢀ-carbon of the double
bond. Thus high enantiomeric excesses (above 95%) and good
diastereoselectivities were obtained with ꢀ-aryl-substituted
compounds, regardless of the electronic features of the aryl
p-substituent (entries 4-6). The dienophile also tolerates a
methyl group attached to the double bond (entry 8) and even a
bulky tert-butyl group (entry 10), although in this case the
reaction had to be carried out at room temperature. Compound
3g, which has a monosubstituted double bond, reacted rapidly
to give the D-A product 4g with good diastereo- and enanti-
oselectivity (96%) but with low yield. The high reactivity of
these enones probably gave rise to side reactions that lowered
the yield (entry 7). A second conjugated double bond as in
dienone 3j was also tolerated (entry 11). Compound 3k, which
bears a methyl group attached to the R-carbon of the double
bond, reacted with cyclopentadiene to give the corresponding
D-A product with high enantioselectivity, although as a 1:1
diastereomeric mixture (entry 12). The reaction could even be
performed with a trisubstituted alkene 3l with good results (entry
13). Also, the amount of catalyst could be reduced as low as
The reaction between compound 3a (R1 ) Ph, R2 ) H, R3
) Me) and cyclopentadiene (2) was used for the optimization
of the reaction conditions (Scheme 1, Table 1).
(10) Palomo, C.; Oiarbide, M.; Garc´ıa, J. M.; Gonza´lez, A.; Arceo, E. J. Am.
Chem. Soc. 2003, 125, 13942–13493.
(11) Zhou, J.; Tang, Y. Org. Biomol. Chem. 2004, 2, 429–433.
(12) Yamauchi, M.; Aoki, T.; Li, M.-Z.; Honda, Y. Tetrahedron: Asymmetry
2001, 12, 3113–3118.
(13) Sibi, M. P.; Ma, Z.; Itoh, K.; Prabagaran, N.; Jasperse, C. P. Org. Lett.
2005, 7, 2349–2352.
(14) (a) Evans, D. A.; Fandrick, K. R.; Song, H. J.; Scheidt, K. A.; Xu, R.
J. Am. Chem. Soc. 2007, 129, 10029–10041. (b) Boersma, A. J.; Feringa, B. L.;
Roelfes, G. Org. Lett. 2007, 9, 3647–3650. (c) Ishihara, K.; Fushimi, M. Org.
Lett. 2006, 8, 1921–1924.
(15) (a) Wada, E.; Yasuoka, H.; Kanemasa, S. Chem. Lett. 1994, 1637–1640.
(b) Wada, E.; Pei, W.; Yasuoka, H.; Chin, U.; Kanemasa, S. Tetrahedron 1996,
52, 1205–1220.
(16) Wada, E.; Pei, W.; Kanemasa, S. Chem. Lett. 1994, 2345–2348.
(17) Nenajdenko, V. G.; Krasovskiy, A. L.; Balenkova, E. S. Tetrahedron
2007, 63, 12481–12539.
(18) Najera, C.; Yus, M. Tetrahedron 1999, 55, 10547–10658.
(19) (a) Barroso, S.; Blay, G.; Pedro, J. R. Org. Lett. 2007, 9, 1983–1986.
(b) Barroso, S.; Blay, G.; Cardona, L.; Pedro, J. R. Synlett 2007, 2659–2661.
(20) For a review on BOX catalyzed reactions, see: (a) Desimoni, G.; Faita,
G.; Jørgensen, K. A. Chem. ReV. 2006, 106, 3561–3651.
(21) Yang, H.; Kim, S. Synlett 2008, 555–560.
6390 J. Org. Chem. Vol. 73, No. 16, 2008

TABLE 1. Screening of Ligands, Metal Salts and Solvents for the Diels-Alder reaction of 3a (R1 ) Ph, R2 ) H, R3 ) Me) and
cyclopentadiene (2) according to Scheme 1a
entry
MX
L
solvent
DM
DM
DM
DM
DM
DM
DM
t (h)
conv (%)b
endo:exob
ee endo (%)c
1
2
3
4
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(SbF6)2
Mg(OTf)2
Zn(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
1a
1b
1c
1d
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
5
70
70
24
22
24
20
24
20
20
5
100
29
94
9
100
64
100
20
84
91:9
76:24
89:11
82:18
86:14
80:20
87:13
79:21
95:5
76:24
80:20
93:7
94:6
95:5
95
-7d
42
-34d
56
5
6e
7
73
93
69
8e
9
THF
Tol
91
10
11
12
13
14f
MeCN
MeNO2
DM/Tol (1:1)
DM/Tol (1:2)
DM/Tol (1:1)
10
-8d
61
100
100
100
100
4
3
24
95
94
96
a 3a (0.25 mmol), 2 (1.8 mmol), MX (0.025 mmol), L (0.025 mmol), solvent (1.6 mL), 0 °C, unless otherwise stated. b Determined by 1H NMR.
c Determined by HPLC. d The opposite enantiomer was obtained. e Room temperature. f -20 °C.
TABLE 2. Diels-Alder Reaction of Compounds 3 and
corresponding cyclohexanone 4p with high ee and good yield
(67% after hydrolysis of the trimethylsilyl enol ether).
The absolute stereochemistry of endo-4d (Table 2, entry 4)
was elucidated by X-ray crystallographic analysis (see Sup-
porting Information), and for the rest of the products it was
assigned on the assumption of a uniform reaction mechanism.
To explain the stereochemical course of the reaction, we propose
two possible models similar to those reported previously for
other Cu(II)-BOX catalyzed reactions in which the dienophile
would coordinate the Cu(II) atom in a bidentate fashion through
the carbonyl and sulfone oxygen atoms (Figure 3). In the first
model, this would lead to a distorted square planar complex (i)
in which the R-si face of the double bond in the s-trans
conformation of the enone would be available for the endo
approach of the diene.21 Alternatively, a species with tetrahedral
geometry (ii) and the enone having the s-cis conformation would
account for the same stereochemical outcome.22 Although the
square planar geometry is normally more favorable for the Cu(II)
complexes, in this case the tetrahedral complex could be
stabilized by a π-π interaction between the enone double bond
and the phenyl group of the bis(oxazoline).23,24
Cyclopentadiene (2) According to Scheme 1a
entry 3
R1
R2 R3 t (h) 4, yield (%)b endo:exoc ee (%)d
1
2
3
4
5
6
7
8
a
b
c
d
e
f
g
h
h
i
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
Me
OMe
Cl
Me
Me
Me
Me
Me
Me
Me
4
2
0.7
5
1
4a,97
4b,92
4c,96
4d,95
4e,93
4f,90
4g,50
4h,93
4h,85
4i,99
4j,86
4k,65
4l,93
93:7
93:7
93:7
96:4
92:8
90:10
92:8
92:8
92:8
43:57
94:6
95/nd
95/nd
97/98
95/nd
95/94
95/95
96/nd
91/nd
92/nd
90/83
92/nd
94/90
96/88
4-MeOC6H4
4-BrC6H4
4-NO2C6H4
H
Me
Me
t-Bu
PhCH)CH-
H
Me
1
0.1
0.3
5
9e
10f
11
12
13f
5
j
k
l
Me 24
Me Me
Me Me
0.3
9
49:51
50:50
a 3 (0.25 mmol), 2 (1.8 mmol), Cu(OTf)2 (0.025 mmol), 1a(0.025
mmol), 1:1 DM/Tol (1.6 mL), 0 °C unless if otherwise stated. b Isolated
product after flash chromatography. c Determined by 1H NMR.
d Determined by HPLC. e 3h (1.0 mmol), 2 (6.0 mmol), Cu(OTf)2
(0.025 mmol), 1a (0.025 mmol), 1:1 DM/Tol (6.0 mL), 0 °C. f Room
temperature.
Scheme 2 shows some examples of transformation of the
Diels-Alder product 4h. The active methylene of the ketosul-
fones can be alkylated with a variety of alkylating agents and
the sulfone group reductively removed to provide the corre-
sponding ketones 6 and 8, with good yields for the two steps
and without loss of optical purity.
In summary, we have shown that R′-arylsulfonyl enones are
efficient dienophiles for the asymmetric Cu(II)-BOX catalyzed
Diels-Alder reaction with reactive dienes. The success of the
reaction lies in the bidentate character of these compounds that
allows for a two binding point coordination with the catalyst.
Because the resulting products can be alkylated and the sulfone
group removed, the R′-aryl sulfonyl enones can be used as
bidentate surrogates of simple monodentate enones in enanti-
oselective Cu-BOX catalyzed D-A reactions.
FIGURE 3. Stereochemical models for the Diels-Alder reaction.
2.5 mol % and the reaction scaled up at least four times without
noticeable effect on the yield and stereoselectivity (Table 2, entry
9).
Finally, we tested the reaction with other dienes using
compounds 3g and 3h as dienophiles (Table 3). 1,3-Cyclohexa-
diene and 3g gave the expected product 4m (entry 1) with high
enantioselectivity (96% ee) as only one diastereomer (endo:
exo >99:1). Compound 3g reacted with isoprene to give
compound 4n with high regioselectivity and moderate ee (entry
2), similar to that obtained in the reaction with 2,3-dimethylb-
utadiene (entry 3). Significantly, the more reactive 2-trimeth-
ylsilyloxy-1,3-butadiene reacted with compound 3h to give the
(22) (a) Pandey, M. K.; Bisai, A.; Singh, V. K. Tetrahedron Lett. 2006, 47,
897–900. (b) Rasappan, R.; Hager, M.; Gissibi, A.; Reiser, O. Org. Lett. 2006,
8, 6099–6102. (c) Zhao, J.-L.; Liu, L.; Sui, Y.; Liu, Y.-L.; Wang, D.; Chen,
Y.-J. Org. Lett. 2006, 8, 6127–6130.
(23) The metal geometry in the Ph-BOX-Cu(II) complexes is controversial;
see: (a) Thourhauge, J.; Roberson, M.; Hazell, R. G.; Jørgensen; K, A. Chem.
Eur. J. 2002, 8, 1888–1898. (b) Evans, D. A.; Johnson, J. S.; Olhava, E. J. J. Am.
Chem. Soc. 2000, 122, 1635–1649.
(24) For mechanistics aspects of the D-A reaction, see: (a) Spino, C.; Pesant,
M.; Dory, Y. Angew. Chem., Int. Ed. 1998, 37, 3262–3265.
J. Org. Chem. Vol. 73, No. 16, 2008 6391

TABLE 3. Diels-Alder Reaction of Some Dienes with Compounds 3g and 3ja
entry
diene
3
t (h)
4, yield (%)b
isomeric ratio
ee (%)c
1
2
3
4
1,3-cyclohexadiene
3g
3g
3g
3h
8
21
24
0.5
4m, 45
4n, 35
4o, 56
4p, 67f
>99:1d
96/nd
79/69
76
2-methyl-1,3-butadiene (isoprene)
2,3-dimethyl-1,4-butadiene
2-trimethylsilyloxy-1,4-butadiene
96:4e
92f
a 3 (0.25 mmol), diene (1.8 mmol), Cu(OTf)2 (0.025 mmol), 1a (0.025 mmol), 1:1 DM/Tol (1.6 mL), 0 °C. b Isolated product after flash
chromatography. c Determined by HPLC. d endo/exo. e 1,4-/1,3- regioisomers. f Yield and ee after hydrolysis
SCHEME 2. Modification of the Diels-Alder Products
major endo (2S,3S)-(+) tR ) 17.6 min, minor endo (2R,3R)-(-)
tR ) 22.5 min. endo-4a (ee 95%, de 94%): mp 120-123 °C;
[R]25 +121.7 (c 0.9, CHCl3); H NMR (300 MHz, CDCl3) δ
1
D
7.68 (2H, d, J ) 8.3 Hz), 7.31 (4H, m), 7.21 (3H, m), 6.36 (1H,
dd, J ) 3.2 Hz, J ) 5.6 Hz), 5.92 (1H, dd, J ) 2.7 Hz, J ) 5.7
Hz), 4.31 (1H, d, J ) 13.7 Hz), 4.07 (1H, d, J ) 13.7 Hz), 3.44
(1H, dd, J ) 3.4 Hz, J ) 5.0 Hz), 3.39 (1H, s), 3.10 (1H, dd,
J ) 1.3 Hz, J ) 4.9 Hz), 2.99 (1H, d, J ) 1.5 Hz), 2.43 (3H,
s), 1.85 (1H, d, J ) 8.7 Hz), 1.60 (1H, ddd, J ) 1.6 Hz, J ) 3.3
Hz, J ) 8.7 Hz); 13C NMR (75.5 MHz, CDCl3) δ 198.0 (s),
145.2 (s), 143.1 (s), 139.5 (d), 135.7 (s), 132.7 (d), 129.8 (d),
128.5 (d), 128.3 (d), 127.4 (d), 126.2 (d), 65.8 (t), 60.9 (d), 49.0
(d), 47.4 (t), 46.5 (d), 45.6 (d), 21.6 (q); MS(FAB) m/z (%):
367 (M++1, 4), 301 (100), 155 (24); HRMS 367.1371,
C22H23O3S required 367.1362. exo-4a (significant peaks, taken
from an endo/exo mixture): 1H NMR (300 MHz, CDCl3) δ 6.01
(1H, dd, J ) 2.9 Hz, J ) 5.6 Hz), 4.22 (1H, d, J ) 13.6 Hz),
3.54 (1H, dd, J ) 3.4 Hz, J ) 5.7 Hz), 3.15 (1H, d, J ) 1.3
Hz), 1.49 (1H, ddd, J ) 1.6 Hz, J ) 3.3 Hz, J ) 8.8 Hz); 13C
NMR (75.5 MHz, CDCl3) δ 199.4 (s), 141.9 (s), 136.4 (d), 136.3
(d), 128.2 (d), 127.86 (d), 126.6 (d), 66.6 (t), 59.6 (d), 49.3 (d),
47.6 (t), 47.3 (d), 46.3 (d).
Acknowledgment. Financial support from the Ministerio de
Educacio´n y Ciencia and FEDER (CTQ 2006-14199) is grate-
fully acknowledged. S.B. thanks the Universitat de Vale`ncia
for a predoctoral grant (V segles program).
Experimental Section25
Procedure for Catalytic Enantioselective D-A Reaction.
Cu(OTf)2 (9.0 mg, 0.025 mmol) contained in a dry Schlenk tube
was heated at 90 °C under vacuum for 1 h. After this time (S)-
PhBOX 1a (8.4 mg, 0.025 mmol), dichloromethane (0.8 mL),
and toluene (0.8 mL) were added under nitrogen atmosphere,
and the mixture was stirred for 1 h at room temperature. Then,
the R′-arylsulfonyl enone 3a (75.0 mg, 0.25 mmol) was added,
and the mixture was stirred for 0.5 h. After this time, the solution
was cooled to 0 °C and freshly distilled cyclopentadiene (2, 0.15
mL, 1.8 mmol) was added. After 4 h, the reaction mixture was
concentrated under reduced pressure, and the residue was
chromatographed on silica gel eluting with hexane-EtOAc (9:
1) to give 4a (89.0 mg, 97%). Assay of enantiomeric excess:
chiral HPLC analysis (Chiralpak AD-H, 15% isopropanol-85%
hexane, 1.0 mL/min); exo (both enantiomers) tR ) 15.8 min,
Supporting Information Available: General experimental
methods, characterization data for all new compounds, copies
of 1H and 13C NMR spectra and chromatograms for compounds
3, 4, 6, and 8 and synthetic intermediates for compounds 3,
ORTEP plot and crystallographic information file (CIF) for
compound 4d. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO8009227
(25) For a description of the general experimental methods, see Supporting
Information.
6392 J. Org. Chem. Vol. 73, No. 16, 2008