Remote stereocontrol by the sulfinyl group. Diels-Alder reaction of cyclopentadiene with substituted (S)-[2-(p-tolylsulfinyl)styrenes and (S)-[2-(p-tolylsulfinyl)phenyl] vinyl ketones

Article abstract of DOI:10.1016/j.tet.2012.03.112

The ability of a homochiral sulfinyl group at the dienophile to act as a remote stereocontrol inductor in the Diels-Alder reaction with cyclopentadiene has been evaluated. High pressure conditions were required for the reactions of (S)-2-(p-tolylsulfinyl)styrenes 3-5 (E-1,2-disubstituted double bond) and 6-8 (1,1-disubstituted double bond). A good facial selectivity and total endo selectivity were attained with 1,1-disubstitued dienophiles, though the 1,2-disubstituted ones afforded poorer results. In contrast, (S)-[2-(p-tolylsulfinyl)phenyl] vinyl ketones 9-11 reacted readily at low temperature (-40 °C) with complete endo selectivity and high facial selectivity in the presence of Yb(OTf)₃ as a chelating reagent of sulfinyl and carbonyl oxygen atoms. Concerning furan reactions, β-trifluoromethyl enone 14 afforded Diels-Alder adducts with high facial selectivity in the presence of the Lewis acid, but β-non-substituted enones 9 and 12 yielded products of furan conjugate addition to the double bond.

Full text of DOI:10.1016/j.tet.2012.03.112

Tetrahedron 68 (2012) 4129e4137
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Remote stereocontrol by the sulfinyl group. DielseAlder reaction
of cyclopentadiene with substituted (S)-[2-(p-tolylsulfinyl)styrenes
and (S)-[2-(p-tolylsulfinyl)phenyl] vinyl ketones
,
a
a
M. Carmen Maestro a , Jose Antonio Fernandez-Salas , Jose L. García Ruano ,
*
ꢀ
ꢀ
ꢀ
Oney O. Ramírez-Rodríguez a b, Ramiro Araya-Maturana b
Departamento de Química Organica (C-1), Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
,
a
ꢀ
ꢀ
b
ꢀ
Departamento de Química Organica y Físico-Química, Universidad de Chile, Casilla 233, Santiago 1, Chile
a r t i c l e i n f o
a b s t r a c t
Article history:
The ability of a homochiral sulfinyl group at the dienophile to act as a remote stereocontrol inductor in
the DielseAlder reaction with cyclopentadiene has been evaluated. High pressure conditions were re-
quired for the reactions of (S)-2-(p-tolylsulfinyl)styrenes 3e5 (E-1,2-disubstituted double bond) and 6e8
(1,1-disubstituted double bond). A good facial selectivity and total endo selectivity were attained with
1,1-disubstitued dienophiles, though the 1,2-disubstituted ones afforded poorer results. In contrast, (S)-
[2-(p-tolylsulfinyl)phenyl] vinyl ketones 9e11 reacted readily at low temperature (ꢀ40 ꢁC) with complete
endo selectivity and high facial selectivity in the presence of Yb(OTf)3 as a chelating reagent of sulfinyl
Received 23 January 2012
Received in revised form 22 March 2012
Accepted 28 March 2012
Available online 4 April 2012
Keywords:
Remote asymmetric induction
Homochiral sulfoxide
Asymmetric DielseAlder
Chiral styrene
and carbonyl oxygen atoms. Concerning furan reactions,
b-trifluoromethyl enone 14 afforded Diel-
seAlder adducts with high facial selectivity in the presence of the Lewis acid, but
enones 9 and 12 yielded products of furan conjugate addition to the double bond.
b-non-substituted
Ó 2012 Elsevier Ltd. All rights reserved.
Chiral enone
Furan conjugated addition
1. Introduction
reactions taking place at remote positions.7a We have mainly
studied 1,4-asymmetric induction processes controlled by the sul-
finyl group at the nucleophilic moiety,15,16 and we have observed
that these reactions proceed with an almost complete control of the
stereoselectivity. Besides, in the presence of Yb(OTf)3, an excellent
result was also obtained in 1,4-17 and 1,5-asymmetric induction
processes18 being the sulfur function at the electrophile, usually
a carbonyl compound. The efficiency of this catalyst seems to be
due to the formation of stable chelated species with the sulfinyl and
carbonyl oxygen atoms, which are highly reactive and show
a strong facial discrimination toward the attack of nucleophiles. On
the other hand, hetero DielseAlder reactions of oxygenated dienes
with (S)-2-[2-(p-tolylsulfinyl)phenyl]acetaldehyde (1) provided
sulfinyl dihydropyranones19 with a high level of trans selectivity in
the presence of Yb(OTf)3, according to a 2 step mechanism in-
volving the Mukaiyama’s type reaction where chelated species
formed from the aldehyde and the Lewis acid are acting as
electrophiles.
The generation of asymmetric centers with a high control of the
stereoselectivity constitutes an important goal in organic synthesis.
In this context, the DielseAlder reaction1 has always been consid-
ered as indispensable for the construction of cyclohexane frame-
works in a regio- and stereochemically defined manner, being
possible to control the absolute configuration of cycloadducts as it
has been exemplified by the use of chiral auxiliaries (bonded to the
dienophile2 or the diene3 moieties), chiral Lewis acid catalysts4 or
organocatalysts,5 and even with chiral solvents.6 Among the
asymmetric inductors profusely employed in DielseAlder reaction,
the sulfinyl group plays a preponderant role.7 On the other hand,
the application of modern synthetic techniques, as microwave ac-
tivation,8,9 sonication10 or high pressure,11 sometimes combined
with solvents as water,8b,10b,12 fluorous media,11b ionic liquid-
s8b,10a,13 or supercritical CO2,14 allows to increase the reaction rate
or to obtain better selectivities.
Some years ago we initiated a program to investigate the effi-
ciency of the sulfinyl group to control the stereoselectivity of
Taking into account our experience in asymmetric cycloaddition
reactions mediated by sulfoxides,7a,20,21 as well as in the use of the
sulfinyl group at 2-p-tolylsulfinylphenyl moiety as remote chiral
inducer of many nucleophilic additions16 we wondered the possi-
ble influence of this moiety on the stereoselectivity of the
* Corresponding author. E-mail address: carmen.maestro@uam.es (M.C.
Maestro).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.112

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M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
DielseAlder reactions of double bonds containing it,19,22 being 2-p-
tolylsulfinyl styrene (2) our model substrate. However, as this
compound is presumably a bad dienophile, we decided to in-
corporate EWG (electron withdrawing groups) to different posi-
tions of the double bond. In this sense, we have also studied 1,2-
disubstituted E-sulfinylstyrenes 3e5, and 1-acylstyrenes 6e8
(Scheme 1), differing in the relative position of the CO and SO
groups. Finally, sulfinylated vinyl arylketones 9e12 and 14, with the
arylsulfinyl group no directly joined to the dienophilic system,
complete the series of compounds whose behavior in their Diel-
seAlder reactions with cyclopentadiene have been studied and
described in this paper.
Scheme 2. Synthesis of (S)-[2-(p-tolylsulfinyl)]styrenes 3e5 and (S)-[2-(p-tol-
ylsulfinyl)phenyl] vinyl ketones.
Scheme 1. Dienophiles studied in this paper.
2. Results and discussion
The synthesis of compounds 223 and 6e818d had been pre-
viously reported. The (S)-2-p-tolylsulfiny benzaldehyde17 was used
as starting material for the rest of dienophiles considered in this
paper. Enantiomerically pure compounds 3 and 4 resulted by its
reaction with the corresponding diethyl phosphonate, whereas
nitroaldol reaction was used to synthesize 5 (see Scheme 2). Finally,
9e12 were prepared by reaction of the aldehyde with the corre-
sponding vinyl magnesium bromide and further oxidation of the
resulting diastereoisomeric mixtures of alcohols with MnO2 at rt
(Scheme 2).
Scheme 3. Synthesis of E-(S)-[2-(p-tolylsulfinyl)phenyl] trifluoromethylvinyl ketone.
A different approach, consisting in the aldolic condensation
under acidic conditions of the trifluoroacetaldehyde aminal24 with
the silylenolether derived from (S)-2-(p-tolylsulfinyl)phenyl-
ethanone25 13, was used to prepare the trifluoromethyl ketone 14
(Scheme 3).
Table 1
Reaction of sulfinylstyrenes 3, 4 and 5 with cyclopentadiene at 8.2 kbar
Reactions of the 2-p-tolylsulfinyl styrene 2 were unsuccessful in
all the studied conditions. Reactions of compounds 3e5 with
cyclopentadiene, performed under multiple conditions (reaction
time, temperature, and Yb(OTf)3 as Lewis acid), were also un-
successful. Thus we studied the influence of high pressure
conditions.11
Entry
Dienophile
Yb(OTf)3
(equiv)
Time (h)
Adduct
endo
A/B
Yield
(%)b
(endo/exo)a
Reactions of 3e5 were carried out in acetonitrile at room tem-
perature with 10 equiv of cyclopentadiene in a high pressure ap-
paratus at 8.2 kbar. The obtained results are depicted at Table 1.
In the absence of a Lewis acid, the cycloaddition of sulfi-
nylketone 3 needs two days to completion and proceeds with
good yield but very low stereoselectivity (endoeexo and facial).
The presence of Yb(OTf)3 as Lewis acid substantially increases the
reactivity (only 10 min were needed to completion) but has scarce
1
2
3
4
5
6
3
3
4
4
5
5
d
1
48
15 (67/33)
15 (40/60)
16 (70/30)
16 (70/30)
17 (100/0)
17 (100/0)
55/45
67/33
35/65
75/25
60/40
64/36
78
80
80
90
90
91
10 min
3þ3þ12c
3þ3þ12c
6,5
d
1
d
1
4
a
Measured by 1H NMR.
Global yield.
Cyclopentadiene (10 equiv) were added after each period.
b
c

M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
4131
positive influence on both types of selectivity, being the pre-
dominance of the exo adducts the most relevant feature of these
reactions. Similar behavior was observed in reactions with the
ester derivative 4 (Table 1, entries 3 and 4). The best stereo-
selective behavior was showed by the nitro functionalized dien-
ophile 5 (Table 1, entries 5 and 6), that exclusively affords endo
adducts, but with poor facial selectivity. Reactivity and sense of
the facial selectivity for endo adducts are not significantly in-
creased by the catalyst.
Separation of the endo and exo adducts was possible in all the
cases, as well as endo-15A and endo-15B. endo and exo adducts are
clearly differentiated by NOESY experiments and vicinal J values of
head-bridge protons. The classification as endo adducts of the two
inseparable major diastereoisomers of adduct 16 as well as those of
adduct 17, was effected by m-CPBA oxidation of the mixture of
sulfoxides into a mixture of the corresponding enantiomeric sul-
fones (undistinguished by 1H NMR). The absolute configuration for
the endo adducts was based in the unequivocal assignment of
compound endo-15A, performed by X-ray diffraction studies,26 and
the comparison of the chemical shifts of the olefinic protons of the
endo-15e17 adducts, resonating at lower field than those corre-
sponding to the endo A structures.
Two main conclusions can be obtained from the results at
Table 2, the complete endo selectivity27 (with the sole exception
of enone 8 without Yb(OTf)3, entry 5) and the high facial se-
lectivity, both scarcely dependent of the presence of the Lewis
acid.
The results obtained from DielseAlder reaction of enones 9e12
with cyclopentadiene are depicted in Table 3. Contrasting with the
previously studied ketones, these enones are good dienophiles and
react with cyclopentadiene at atmospheric pressure, even at
-40 ꢁC. Complete endo selectivity was attained from 9e11, whereas
the exo adducts were also obtained in reactions, catalyzed or not,
from compound 12 (entries 10 and 11). In all the cases, very low
(ꢂ10%) facial selectivity was observed in the absence of Lewis acid
(Table 3, entries 1, 3, 6 and 10), but the presence of Yb(OTf)3 im-
proves it very much with monosubstitued (9) and (E)-di-
substituted (10) ketones (Table 3, entries 2 and 5), being the
influence less significant with (Z)-disubstituted (11) and gem-
disubstituted (12) ketones (entries 9 and 11). This improvement
suggests the formation of a stable chelate, with the Lewis acid
associated to the sulfinyl and carbonyl oxygen atoms, restricting
the conformational preferences of the dienophile and thus in-
creasing the stereoselectivity (see later).
We then studied the reactivity of the 1,1-disubstituted alkenes
6e8, with a presumably better relative arrangement of the carbonyl
and sulfinyl groups to become chelated by the Lewis acid [this
chelation had been proposed to explain the stereoselective re-
duction with NaBH4 in the presence of Yb(OTf)318d]. Reactions of
ketones 6 (R¼Me), 7 (R¼n-Pr) and 8 (R¼i-Pr) with cyclopentadiene
were unsuccessfully attempted in acetonitrile under thermal and
catalytic [Yb(OTf)3] conditions, making necessary the use of high
pressure conditions (8.2 kbar) to obtain the corresponding adducts.
The results for complete conversion of the dienophile are shown in
Table 2.
Table 3
DielseAlder cycloaddition of enones 9e12 with cyclopentadiene
Table 2
DielseAlder cycloaddition of enones 6, 7 and 8 with cyclopentadiene
Entry Dienophile Yb(OTf)3 equiv Time (h) Temp (ꢁC) endo A/Ba Yieldb (%)
1
2
3
4
5
6
7
8
9
9
d
1
ꢀ40
21 (55/45) 86c
1.2
d
10 min ꢀ40
21 (96/4)
22 (55/45)
22 (93/7)
22 (96/4)
23 (53/47)
23 (80/20)
94
d
83
85
d
d
equiv
10
10
10
11
11
11
11
12
12
12 days rt
1.2
1.2
d
23
72
ꢀ10
ꢀ40
14 days rt
3
36
48
14 days rt
96
1.2
1.2
1.2
d
rt
Entry
Dienophile
Yb(OTf)3
(equiv)
Time
(h)
Adduct
endo
Yieldb
(%)
A/Ba
ꢀ10
23 (85/15) 75
9
10
11
ꢀ40
23 (85/15)
d
24 (75/25)f 80c
d
1
2
3
4
5
6
6
6
7
7
8
8
d
1
3
6.5
3
6.5
3
6.5
18
18
19
19
20
20
86/14
93/7
90/10
90/10
83/17c
90/10
75
79
73
73
d
24 (50/50)d
1.2
ꢀ40e
d
Measured by 1H NMR.
Yield of the major A adduct.
Global yield.
A 40% of an exo adduct was obtained.
No reaction in 48 h at -78 ꢁC.
a
1
d
1
b
c
d
e
f
83
a
Measured by 1H NMR.
Yield of the major A adduct.
A 30% of an exo adduct was also obtained.
b
c
A 20% of an exo adduct was obtained.
The endo structure assigned to compounds 18e20 was based on
Configurational assignment of these adducts was also per-
the NOESY experiment carried out with adduct 18A, that suggest
the existence of n.O.e. effect between the R group and the head-
bridged hydrogen, only understandable with the acetyl group
placed at endo position. The assignment of the adducts as belonging
to the series A or B was effected by comparison of 1H NMR chemical
shifts of both olefinic protons, with closer values in adducts B than
in A ones. Finally, the absolute configuration, which is not un-
equivocal, was deduced from the mechanistic model proposed for
these reactions (see later).
formed by 1H NMR (see S. I.) and then, confirmed by X-ray dif-
fraction26 in the case of the adduct endo-21A.
The good results obtained in reactions of sulfinylenones 9e12
and cyclopentadiene, prompted us to study their reactions with
other less reactive dienes, as 1-methoxy-1,3-cyclohexadiene, furan,
2-methylfuran and 2,5-dimethylfuran. The first reactions were
performed with 1-methoxy-1,3-cyclohexadiene, with the aim of
determining their regioselectivity (see Table 4). Then, E-enone 10
reacted at rt with 5 equiv of the above diene, in the presence of

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M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
Table 4
DielseAlder cycloaddition of enones 10, 11 and 14 with 1-methoxy-1,3-
cyclohexadiene
Scheme 4. Conjugated addition reactions of furan to enones 9 and 12 in the presence
of Yb(OTf)3.
Entry Dienophile Time (h) Temp (ꢁC) Adduct (endo/exo)a Yieldb (%)
Reaction of the enone 14 with the symmetric 2,5-dimethylfuran
does not work, even under forced experimental conditions (reflux
with 10 equiv of the diene). Finally, the reaction of 14 with 2-
methylfuran at rt cleanly afforded a 80:20 diastereisomeric mix-
ture of the corresponding FriedeleCrafts alkylation products 30
(Scheme 5).
1
2
3
4
10
11
14
14
40
40
20
8
rt
rt
25 (75/25)
25 (75/25)
26 (70/30)d
26 (60/40)
70 (48)c
68
d
ꢀ30
rt
75
a
b
c
Measured by 1H NMR.
Global yield.
Yield of the major endo adduct.
d
A 40% of conversion was attained.
a stoichiometric quantity of ytterbium triflate as Lewis acid catalyst,
to yield a 75:25 diastereoisomeric mixture of the adducts 25, al-
though 40 h were necessary to complete the cycloaddition (Table 4,
entry 1). The obtained adducts were easily separated by flash-
column chromatography to afford
a 48% of the major di-
astereomer. Identical conditions were applied to the reaction of the
methoxy diene with the Z-enone 11 and, surprisingly, the same
adducts 25, also in 75:25 ratio, were obtained (Table 4, entry 2).
This result clearly indicated that an isomerisation from Z-enone 10
to E-enone 11 was occurring during the cycloaddition,28 which is
much easier for the E-isomer 10. Taking into account that ZeE
equilibration is not observed in reactions with cyclopentadiene, it
must be a consequence of the lower reactivity of the 1-methoxy-
1,3-cyclohexadiene, requiring higher temperatures and longer re-
action times (compare Tables 3and 4), and facilitated by the pres-
ence of the Lewis acid. The reaction of this diene with the more
reactive trifluoromethyl derivative 14, under the same experi-
mental conditions used with 10 and 11, yielded a 60:40 mixture of
the diastereoisomeric adducts 26 (Table 4, entry 4). Stereo-
selectivity was slighly larger by decreasing the temperature (a
70:30 diastereoisomeric mixture was obtained at ꢀ30 ꢁC, Table 4,
entry 3) though the conversion was only a 40% for a reaction time
of 20 h.
We must remark that the two adducts formed in the reactions of
methoxycyclohexadiene (both exhibiting the regiochemistry
expected from the orientation rules) result in its endo and exo ap-
proach to the less hindered face of the dienophile, whereas those
formed with cyclopentadiene are the result of the endo approach to
both diastereotopic faces.29
Reactions with the furan presented a special interest due to
the profuse applicability of the obtained adducts.30 However, it
is less reactive than the cyclopentadiene and its reactions with
10 and 11 were unfruitful. Reactions of furan with 9 and 12 at
room temperature in the presence of the Lewis acid exclusively
yielded the FriedeleCrafts alkylation products 27 and 2831
(Scheme 4).
Scheme 5. Reactions of trifluoromethyl substituted enone 14 with furan and 2-
methylfuran in the presence of Yb(OTf)3.
Results obtained in Table 1 indicate that the only influence of the
Lewis acid on the reaction course is related to the increase of re-
activity, which remains very low in any condition. The endo selec-
tivity observed in the absence of Lewis acid is a consequence of the
lower endo-directing character of the 2-p-tolylsulfinylphenyl group
with respect to that of the electron withdrawing one (W), which is
very large in the case of NO2. The association of the catalyst to the
substituents is not able to produce chelated species, probably due
to the long distance existing between the sulfinyl and the W group
adopting the trans arrangement (a in Scheme 6). In accordance
with the results observed in Table 2, indicating that the facial se-
lectivity is not modified by the presence of the Yb(OTf)3, we must
conclude that the evolution of the reaction through the chelated
species like b (Scheme 6) is highly improbable, despite the distance
between the sulfinyl and carbonyl oxygen atoms in compounds
6e8 would allow their formation. The instability of species b pro-
voked by the lost of conjugation and/or their low reactivity due to
the steric destabilization of the approaches of the cyclopentadiene
to both diastereotopic faces (the plane containing the CO group is
orthogonal to that of the double bond), would explain this fact. The
endo approach of the cyclopentadiene to the less hindered face of
the presumably most stable non-chelated conformation b0 (Scheme
6) would explain the formation of adducts endo-18Ae20A (Table 2)
as the major ones in these reactions. Finally, the chelated forms
from compounds 8e12 and 14 (R1, R2 y R3 have not been repre-
sented in Scheme 6) will adopt the chair-like conformation c with
the CO conjugated with the double bond, but orthogonal to the
The only cycloadduct obtained with furan resulted in its reaction
with the trifluoromethyl derivative 14 affording the DielseAlder
products with an excellent facial selectivity but only moderated
endo selectivity, as it was the case with methoxycyclohexadiene.
The easy separation of the reaction mixture allowed the prepara-
tion of the diastereomerically pure major component, endo-29A,32
in 60% yield (Scheme 5). Its structure was unequivocally assigned
by X-ray diffraction studies26 and resulted to be identical to that of
the major adducts obtained from 8e11 with cyclopentadiene.

M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
4133
aromatic ring. The lower face of the double bond will be hindered
by the sulfinyl group, and then, the favored approaches of cyclo-
pentadiene (Table 3) and furan (Scheme 5) will take place to the
upper face, affording essentially compounds endo-21Ae24A and
endo-29A, respectively.
syringe. The resulting solution was stirred for 12 h at room
temperature and then, the reaction mixture was hydrolyzed
(saturated NH4Cl), extracted (3x5 mL DCM), washed (saturated
NaCl), dried (MgSO4) and the solvent evaporated under reduced
pressure. The residue was purified by flash-column chroma-
tography. The eluent and the obtained yield in each case are
indicated below.
3.2.1. (S,E)-4-[2-(p-Tolylsulfinyl)phenyl]but-3-en-2-one (3). Compo-
und 3 obtained from 1 and diethyl (2-oxopropyl)-phosphonate.
Chromatography: n-hexane:AcOEt, 3:1. Yield: 77%; white solid; mp:
65e67 ꢁC; the ee was determined by HPLC (Chiralcel OD, 1.0 mL/
min, i-PrOH/hexane 30/70,
l
¼254 nm, tR¼(S) 8.1 (R) 9.1 min), 98%
ee; ½a 2D0
ꢃ
ꢀ391 (c 1, CHCl3); 1H NMR
d
8.06 (dd, J¼8.1, 1.51 Hz, 1H),
8.00 (d, J¼16.1 Hz,1H), 7.61e7.57 (m, 2H), 7.51e7.49 (m, 1H), 7.45 (d,
J¼8.15 Hz, 2H), 7.22 (d, J¼8.15 Hz, 2H), 6.55 (d, J¼16.1 Hz, 1H), 2.36
(s, 3H), 2.34 (s, 3H); 13C NMR
d 198.0, 145.0, 142.2, 141.8,137.5,133.3,
131.6, 131.3, 130.4, 130.3, 127.4, 125.6, 125.5, 27.9, 21.7. IR (KBr)
d
3055, 2875, 1672, 1610, 1465, 1398, 1277, 1084. MS (ESI) m/z: 337
[MþNa]þ (29), 285 [MþH]þ (100), 243 (23), 149 (92), 145 (26), 139
(22); Anal. Calcd for C17H16O2S: C, 71.80; H, 5.67; S, 11.28. Found: C,
71.35; H, 4.82; S, 11.11.
Scheme 6. Favored approach of cyclopentadiene to enones 6e12.
3.2.2. (S,E)-Ethyl 3-[2-(p-tolylsulfinyl)phenyl]acrylate (4). Compo-
und 4 was obtained from 1 and triethyl phosphonoacetate. Chro-
matography: n-hexane:AcOEt, 3:1. Yield: 70%; white solid; mp
98e100 ꢁC; the ee was determined by HPLC (Chiralcel OD, 1.0 mL/
In summary, we have demonstrated that a 2-p-tolylsulfinyl-
phenyl moiety at the dienophile is able to control the facial selec-
tivity of the DielseAlder reactions when the sulfinyl oxygen atom
can interact, via a chelation agent as the Yb(OTf)3, with another
electron withdrawing group present at the double bond.
min, i-PrOH/hexane 30/70,
l
¼254 nm, tR¼(S) 13.7 (R) 10.1 min), 98%
ee; ½a 2D0
ꢃ
ꢀ408 (c 1, CHCl3); 1H NMR
d
8.12 (d, J¼15.7 Hz, 1H),
8.10e8.07 (m, 1H), 7.55e7.61 (m, 2H); 7.48 (d, J¼8.1 Hz, 2H),
7.49e7.45 (m, 1H), 7.20 (d, J¼8.1 Hz, 2H), 6.31 (d, J¼15.7 Hz, 1H),
4.29 (q, J¼7.2 Hz, 1H), 4.28 (q, J¼7.1 Hz, 1H), 1.35 (t, J¼7.1 Hz, 3H);
3. Experimental section
3.1. General methods
13C NMR
d 166.3, 142.3, 142.1, 142.0, 138.8, 132.9, 131.4, 131.3, 130.4,
127.2, 125.7, 124.8, 122.1, 61.1, 21.7, 14.6. IR (KBr)
d 3956, 2981, 1714,
1637, 1466, 1316, 1277, 1181, 1035. MS (ESI) m/z: 337 [MþNa]þ (54),
315 [MþH]þ (46), 269 (88), 149 (31), 139 (100); Anal. Calcd
for C18H18O3S: C, 68.76; H, 5.77; S, 10.20. Found: C, 68.56; H, 5.92; S,
10.10.
Melting points were determined using a Gallenkamp apparatus
in open capillary tubes. The IR spectra were recorded on a Bruker
Vector 22 spectrometer and the frequencies are given in cmꢀ1
.
NMR spectra were acquired on a Brucker AC-300 instrument at
300 and 75.5 MHz for 1H and 13C NMR, respectively. Chemical
3.2.3. (S,E)-1-(2-Nitrovinyl)-2-(p-tolylsulfinyl)benzene (5). To a so-
lution of aldehyde 1 (1.02 mmol) and t-BuOH (4 mL) in THF (4 mL),
nitromethane (1.54 mmol) was added and the mixture was cooled
at 0 ꢁC. Then, t-BuOK (0.11 mmol) was added and the resulting
mixture was stirred for 12 h at rt. The mixture was diluted,
extracted (Et2O:AcOEt, 1:1), washed (saturated NaCl), dried
(MgSO4), the solvent evaporated under reduced pressure and the
residue purified by flash cromatography (DCM:AcOEt 10:1) before
the addition of dichloromethane (5 mL) and trifluoroacetic anhy-
dride (0.85 mmol) at -10 ꢁC. The resulting solution was allowed to
stir 2 min and then triethylamine (1.70 mmol) was dropwise added
over a period of 15 min The reaction mixture was stirred at ꢀ10 ꢁC
for an additional period of 30 min and the resulting mixture was
poured into dichlomethane and washed with saturated NH4Cl so-
lution. The aqueous layers were extracted with the same solvent,
the combined organic layers dried (MgSO4) and the solvent re-
moved under reduced pressure. The residue was purified by flash
cromatography using as eluent n-hexane:AcOEt, 2:1. Yield: 75%;
yellow solid; mp: 122e124 ꢁC; the ee was determined by HPLC
shifts (d) are reported in parts per million relative to residual
solvent signals (CHCl3, 7.26 ppm for 1H NMR, CDCl3, 77.0 ppm for
13C NMR spectra). 13C NMR spectra were acquired on a broad-band
decoupled mode. Optical rotations were measured on a Per-
kineElmer 241 polarimeter. Microanalyses were carried out on
a LECO CHNS-932. High resolution mass spectra were obtained by
ESIþ (MeoHþ0,1% formic acid) with a QSTAR (Applied Biosystems)
apparatus. Silica gel 60 (230e400 mesh ASTM) and DC-Alufolien
60 F254 were used for flash-column chromatography and ana-
lytical TLC, respectively. All reactions were carried out in anhy-
drous solvents. THF was dried with molecular sieves. iPr2NH was
distilled from KOH. Freshly distilled cyclopentadiene was always
used. Other commercially available starting materials were used
without purification. n-BuLi (2.5 M solution in hexanes) was
purchased from Aldrich. Reactions under high pressure conditions
were carried out using Unipress Equipment 101LV Synthesis of
compounds 1,17 2,23 6,18d 7,18d 8,18d and 1325 have been previously
described.
(Chiralcel IC, 0.8 mL/min, i-PrOH/hexane 30/70,
l
¼254 nm, tR¼(S)
3.2. Synthesis of styrenes 3e5
40.2 (R) 64.8 min), 98% ee; ½a D20
ꢃ
ꢀ274 (c 1, CHCl3); 1H NMR
d 8.49 (d,
J¼13.5 Hz, 1H), 8.15 (d, J¼7.9 Hz, 1H), 7.72e7.69 (m, 1H), 7.53e7.54
(m, 2H), 7.47 (d, J¼8.1 Hz, 2H). 7.36 (d, J¼13.5 Hz, 1H), 7.23 (d,
To a solution of NaH (4.17 mmol) in anhydrous THF (10 mL)
was added the corresponding phosphonate (4.17 mmol). The
resulting mixture was stirred for 30 min at rt under argon at-
mosphere. The solution was cooled at ꢀ78 ꢁC, and sulfinyl
aldehyde 1 (3.8 mmol) in THF anhydrous (5 mL) was added via
J¼8.1 Hz, 2H); 2.34 (s, 3H); 13C NMR
d 146.5, 142.6, 141.4, 139.2,
133.5, 132.9, 131.8, 130.6, 128.4, 128.1, 125.9, 125.7, 21.7. IR
(KBr)
d 3114, 2921, 1717, 1522, 1341, 1084, 1039, 960; MS (ESI) m/z:
310 [MþNa]þ (14), 288 [MþH]þ (85), 149 (100). Anal. Calcd

4134
M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
for C15H13NO3S: C, 63.98; H, 4.70; N, 4.66; S, 10.68. Found: C, 63.58;
H, 4.68; N, 4.73; S, 10.75.
129.7, 129.5, 125.8, 125.3, 21.3, 17.8; IR (NaCl) d 3056, 2924, 2361, 1652,
1450, 1328, 1198, 1062, 810, 763; MS (ESI) m/z: 569 [2MþH]þ (14), 285
[MþH]þ (100); Anal. Calcd for C17H16O2S: C, 71.80; H, 5.67; S, 11.28.
Found: C, 72.17; H, 5.96; S, 11.01.
3.3. Synthesis of sulfinyl a,b-unsaturated ketones 9e12 and 14
A vinyl magnesium bromide solution (3.3 mmol) in anhydrous
THF was added to aldehyde 1 (1.65 mmol) in anhydrous THF
(10 mL) at ꢀ78 ꢁC. The solution was stirred for 5 h at ꢀ78 ꢁC. Then,
the reaction mixture was hydrolyzed (saturated NH4Cl), extracted
(3ꢄ5 mL DCM), washed (saturated NaCl), dried (MgSO4) and the
solvent evaporated under reduced pressure. The obtained two
epimeric allylic alcohols were purified by flash-column chroma-
tography using as eluent DCM:AcOEt, 8:1. Then, MnO2 (16 mmol) in
DCM was added, and the reaction mixture was stirred for 36 h at rt,
and filtered through Celite. The filtrate was evaporated under re-
duced pressure and the residue was purified by flash-column
chromatography. The eluent and the obtained yield in each case
are indicated below.
3.3.5. (E,S)-4,4,4-Trifluoro-1-[2-(p-tolylsulfinyl)phenyl]but-2-en-1-
one (14). To a solution of HMDSLi (0.31 mmol, 1 M heptane) in
anhydrous THF (0.5 mL) under argon atmosphere was dropwise
added a solution of 13 (0.31 mmol) in anhydrous THF (2.5 mL). The
resulting mixture was stirred 20 min at rt. Then, TMSCl
(0.372 mmol) was added and the resulting solution was stirred 3 h.
After this time the solvent was directly removed. To a solution
of the residue in dry DCM (2.5 mL) at 0 ꢁC under argon
atmosphere was added 1,1-bis(dimethylamino)-2,2,2-trifluoro-
ethane (0.23 mmol) and BF3.OEt2 (0.23 mmol). The resulting solu-
tion was stirred for 3 h at room temperature and then, the reaction
mixture was quenched (saturated NaHCO3), extracted (3ꢄ5 mL
DCM), washed (saturated NaCl), dried (MgSO4) and the solvent
evaporated under reduced pressure. The residue was purified by
flash-column chromatography: AcOEt-n-hexane 1:1. Yield: 65%;
white solid; mp: 102e104 ꢁC; the ee was determined by HPLC
3.3.1. (S)-1-[2-(p-Tolylsulfinyl)phenyl]prop-2-en-1-one (9). Compo-
und 9 was obtained from 1 and vinyl magnesium bromide. Chro-
matography: DCM:AcOEt, 5:1. Yield: 82%; yellow solid; mp:
(Chiralcel IC, 0.8 mL/min, i-PrOH/hexane 30/70,
l
¼254 nm, tR¼(S)
98e100 ꢁC; ½a 2D0
ꢃ
ꢀ270 (c 1, CHCl3); 1H NMR
d
8.49 (d, J¼7.2 Hz, 1H),
24.7 (R) 27.6 min), 98% ee; ½a D20
ꢃ
ꢀ228 (c 0.96, CHCl3); 1H NMR
d 8.59
7.85e7.79 (m, 2H), 7.66 (d, J¼8.3 Hz, 2H), 7.60e7.55 (m, 1H), 7.18 (d,
J¼7.9 Hz, 2H), 7.04 (dd, J¼17.1, 10.6 Hz, 1H), 6.35 (dd, J¼17.1, 1.3 Hz,
(dd, J¼7.9, 1.1 Hz, 1H), 7.94e7.86 (m, 2H), 7.68e7.61 (m, 3H), 7.40
(dq, J¼15.6, 1.9 Hz, 1H), 7.26e7.17 (m, 2H), 6.72 (dq, J¼15.6, 6.5 Hz,
1H), 5.97 (dd, J¼10.6, 1.2 Hz, 1H), 2.32 (s, 3H); 13C NMR
d
190.7,
1H), 2.33 (s, 3H); 13C NMR
d 187.4, 149.9, 143.2, 141.4, 134.6, 133.2,
149.4, 143.8, 141.3, 134.9, 133.9, 132.7, 132.2, 130.5, 130.1, 129.9,
131.7,131.2,130.5 (c),130.4,130.1,129.7,126.7,125.9, 21.33; IR (NaCl)
126.7, 125.8, 21.7; IR (KBr)
d
3060, 2922, 2360, 1658, 1606, 1402,
d 3090, 2924, 1736, 1680, 1303, 1277, 1211, 1019, 863; MS (ESI) m/z:
1260, 1029, 1015, 750; MS (ESI) m/z: 293 [2MþNa]þ (13), 271
[MþH]þ (100), 179 (48), 149 (38); Anal. Calcd for C16H14O2S: C,
71.08; H, 5.22; S, 11.86. Found: C, 70.77; H, 5.32; S, 11.79.
699 [2MþNa]þ (98), 361 [MþNa]þ (90), 339 [MþH]þ (100); HRMS
m/z calcd for C17H14F3O2S [MþHþ]: 339.0661, found: 339.0655.
Anal. Calcd for C17H13F3O2S: C, 60.35; H, 3.90; S, 9.48. Found: C,
60.12; H, 4.10; S, 9.34.
3.3.2. (E,S)-1-[2-(p-Tolylsulfinyl)phenyl]but-2-en-1-one (10). Comp-
ound 10 was obtained from 1 and (E)-prop-1-en-1-yl magnesium
bromide. Chromatography: DCM:AcOEt 7:1. Yield: 82%. Yellow
3.4. DielseAlder reaction under high pressure conditions.
General procedure
solid; ½a 2D0
ꢃ
ꢀ259 (c 1.1, CHCl3). 1H NMR
d 8.45e8.42 (m, 1H),
7.80e7.75 (m, 2H), 7.67e7.64 (m, 2H), 7.58e7.52 (m, 1H), 7.19e7.16
(m, 2H), 6.97 (dq, J¼15.4, 7.0 Hz, 1H), 6.76 (dq, J¼15.4, 1.4 Hz, 1H),
A solution of the corresponding dienophile (0.1 mmol) and
Yb(OTf)3 (0.11 mmol) in CH3CN (1.8 mL) was stirred at rt for 45 min.
Then, freshly distilled cyclopentadiene (10 mmol) was added and
the resulting solution was placed in a Teflon ampoule. The ampoule
was placed in the high pressure apparatus and compressed up to
the indicated pressure for the indicated time. Following de-
compression, the mixture was hydrolyzed (saturated NH4Cl),
extracted (3ꢄ5 mL DCM), washed (saturated NaCl), dried (MgSO4)
and the solvent evaporated under reduced pressure. The residue
was purified by flash-column chromatography. The eluent and the
obtained yield in each case are indicated below.
2.32 (s, 3H), 1.97 (dd, J¼7.0, 1.5 Hz, 3H).13C NMR
d 190.19, 148.6,
143.6, 140.9, 135.4, 133.1, 130.1, 129.6, 129.3, 127.9, 126.3, 125.4, 21.4,
18.8. IR (KBr) d 3060, 2919, 2361, 1663, 1617, 1439, 1300, 1224, 1022,
920, 810, 764. MS (ESI) m/z: 285 [MþH]þ (100), 227 (10). Anal. Calcd
for C17H16O2S: C, 71.80; H, 5.67; S, 11.28. Found: C, 71.83; H, 5.74; S,
11.13.
3.3.3. (Z,S)-1-[2-(p-Tolylsulfinyl)phenyl]but-2-en-1-one (11). Comp-
ound 11 was obtained from 1 and (Z)-prop-1-en-1-yl magnesium
bromide followed by the oxidation with MnO2. Chromatography:
DCM:AcOEt, 7:1. Yield: 85%; yellow oil; ½a D20
ꢃ
ꢀ236 (c 0.9, CHCl3); 1H
3.4.1. 1-{(1S,2R,3R,4R)-3-[2-((S)-p-Tolylsulfinyl)phenyl]bicyclo[2.2.1]
hept-5-en-2-yl}ethanone (endo-15A). Compound endo-15A was
obtained as major diastereomer from 3 in absence of Yb(OTf)3.
Chromatography: Et2O:n-hexane, 3:2. Yield: 20%; white solid; mp:
NMR
d
8.5 (dd, J¼1.0, 8.0 Hz, 1H), 7.85e7.75 (m, 2H), 7.70e7.66 (m,
2H), 7.54 (dt, J¼7.5, 1.2 Hz, 1H), 7.18e7.15 (m, 2H), 6.72 (dq, J¼1.8,
11.5 Hz, 1H), 6.46 (dq, J¼11.5, 7.2 Hz, 1H), 2.33 (s, 3H), 2.07 (dd,
J¼7.2, 1.8 Hz, 3H); 13C NMR
d
191.7, 149.2, 146.0, 144.26, 141.1, 136.3,
113e115 ꢁC; ½a 2D0
ꢃ
ꢀ213 (c 0.55, CHCl3); 1H NMR
d 8.02e7.99 (m, 1H),
133.6, 130.4, 129.9, 129.8, 126.8, 125.6, 125.3, 21.7, 16.6; IR (NaCl)
7.59e7.57 (m, 2H), 7.43e7.40 (m, 2H), 7.36e7.33 (m, 1H), 7.26e7.23
(m, 2H), 6.48 (dd, J¼5.7, 3.1 Hz,1H), 6.06 (dd, J¼2.0, 5.7 Hz,1H), 3.55
(br s, 1H), 3.37 (br s, 1H), 3.36 (br s, 1H), 2.94 (br s, 1H), 2.34 (s, 3H),
1.90 (s, 3H), 1.80 (d, J¼9.0 Hz, 1H), 1.53 (dd, J¼8.9, 1.7 Hz, 1H); 13C
d
3060, 2919, 1659, 1610, 1435, 1230, 1007, 918, 809, 760; MS
(ESI) m/z: 569 [2MþH]þ (10), 285 [MþH]þ (100); Anal. Calcd for
C17H16O2S: C, 71.80; H, 5.67; S, 11.28. Found: C, 72.17; H, 5.96;
S, 11.01.
NMR
d 206.9, 144.9, 141.8, 141.5, 140.9, 138.9, 133.6, 131.0, 130.0,
127.8, 126.0, 125.7, 125.5, 57.3, 52.0, 46.2, 46.1, 42.0, 28.7, 21.4. IR
3.3.4. (S)-2-Methyl-1-[2-(p-tolylsulfinyl)phenyl]prop-2-en-1-one (12).
Compound 12 was obtained from 1 and prop-1-en-2-yl magnesium
bromide followed by the oxidation with MnO2. Chromatography:
(NaCl) d 3056, 2973, 1707, 1594, 1440, 1331,1082,1031. MS (ESI) m/z:
753 [2MþNa]þ (15), 351 [MþH]þ (100). HRMS m/z calcd for
C22H23O2S [MþH]þ: 351.1413, found: 351.1399.
DCM:AcOEt, 7:1. Yield: 79%; colorless oil; ½a D20
ꢃ
ꢀ94 (c 1.2, CHCl3). 1H
NMR
d
8.20 (d, J¼7.4 Hz, 1H), 7.70e7.62 (m, 3H), 7.52e7.43 (m, 2H),
3.4.2. 1-{(1S,2S,3S,4R)-3-[2-((S)-p-Tolylsulfinyl)phenyl]bicyclo[2.2.1]
hept-5-en-2-yl}ethanone (exo-15A). Compound exo-15A was
obtained as major diastereomer from 3 in presence of Yb(OTf)3.
7.21e7.19 (m, 2H), 5.95 (s, 1H), 5.50 (s, 1H), 2.33 (s, 3H), 2.03 (s, 3H);
13C NMR
196.9, 147.4, 144.1, 142.7, 141.1, 136.6, 132.1, 129.9, 129.7,
d

M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
4135
Chromatography: Et2O:n-hexane, 3:2. Yield: 35%; colorless oil.
1081, 1041, 1025, 756. MS (ESI) m/z: 721 [2MþNa]þ (41), 701
[2MþH]þ (23), 351 [MþH]þ (100), 285 (79), 307 (57). HRMS m/z
calcd for C22H23O2S [MþH]þ: 351.1413, found: 351.1412.
½
a 2D0
ꢃ
ꢀ559 (c 1.0, CHCl3); 1H NMR
d 8.20e8.19 (m, 1H), 7.55e7.52 (m,
2H), 7.49e7.43 (m, 2H), 7.40e7.37 (m, 1H), 7.26e7.23 (m, 2H), 6.06
(dd, J¼5.5, 3.1 Hz, 1H), 6.01 (dd, J¼5.5, 2.7 Hz, 1H), 3.27 (br s, 1H),
3.24 (dd, J¼8.2, 3.4 Hz, 1H), 3.17 (dd, J¼4.9, 1.5 Hz, 1H), 2.37 (s, 3H),
2.14 (s, 3H), 2.13 (br s, 1H), 1.85 (d, J¼8.9 Hz, 1H), 1.46 (dd, J¼8.9,
3.4.6. 1-{(1S,2S,4S)-2-[2-((S)-p-Tolylsulfinyl)phenyl]bicyclo[2.2.1]
hept-5-en-2-yl}butan-1-one (endo-19A). Compound endo-19A was
obtained as major diastereomer from 7. Chromatography: Et2O:n-
1.5 Hz, 1H); 13C NMR
d 207.1, 143.7, 142.3, 141.8, 141.6, 138.2, 134.4,
130.9, 130.0, 127.5, 127.2, 126.5, 124.7, 60.8, 49.2, 46.8, 46.2, 41.6,
hexane, 3:1. Yield: 73%; colorless oil; ½a D20
ꢃ
ꢀ334 (c 0.95, CHCl3). 1H
29.6, 21.5; IR (NaCl)
d
3059, 2978, 1706, 1594, 1441, 1331, 1083, 1060.
NMR
d
7.83 (dd, J¼1.5, 7.8 Hz, 1H), 7.70 (d, J¼7.1 Hz, 1H), 7.50 (dt,
MS (ESI) m/z: 753 [2MþNa]þ (8), 373[MþNa]þ (10), 351 [MþH]þ
(100); HRMS m/z calcd for C22H23O2S [MþH]þ: 351.1379, found:
351.1396.
J¼7.3, 1.5 Hz, 1H), 7.40 (dt, J¼7.8, 1.3 Hz, 1H), 7.36e7.34 (m, 2H),
7.22e7.19 (m, 2H), 6.42 (dd, J¼5.7, 3.1 Hz, 1H), 5.82 (dd, J¼5.7,
3.0 Hz, 1H), 3.78 (br s, 1H), 3.12e3.06 (m, 2H), 2.35 (s, 3H),
2.36e2.25 (m, 1H), 2.12 (ddd, J¼18.1, 8.8, 5.3 Hz, 1H), 1.85e1.73 (m,
1H), 1.63e1.61 (m, 1H), 1.36e1.31 (m, 1H), 1.15e1.12 (m, 1H),
3.4.3. (1S,2R,3R,4R)- and (1R,2S,3S,4S) Ethyl 3-[2-((S)-p-tolylsulfinyl)
phenyl]bicyclo[2.2.1]hept-5-ene-2-carboxylate (endo-16A)þ(endo-
16B). Compounds endo-16A and endo-16B were obtained as
a 75:25 diastereoisomers mixture from 4. Chromatography: Et2O:n-
0.89e0.88 (m, 1H), 0.72 (t, J¼7.4 Hz, 3H). 13C NMR
d 208.1, 147.4,
143.8, 141.8,141.2,141.0,131.9,130.8, 129.7,129.0, 128.5, 126.7, 125.9,
64.5, 50.0, 48.2, 44.5, 41.8, 39.7, 21.3, 16.7, 13.6. IR (NaCl)
d 3061,
hexane 3:2. Yield: 65%; colorless oil; 1H NMR
d
7.93e7.85 (m, 1H),
2968, 2873, 1708, 1463, 1337, 1114, 1082, 1046, 1030, 810. MS (ESI)
m/z: 779 [2MþNa]þ (58), 757 [2MþH]þ (86), 401 [MþNa]þ (26),
379 [MþH]þ (100); HRMS m/z calcd for C24H27O2S [MþHþ]:
379.1692, found: 379.1710.
7.58e7.54 (m, 2H), 7.42e7.33 (m, 3H) 7.24e7.21 (m, 2H), 6.53 (dd,
J¼5.6, 3.1 Hz, 1H, A), 6.44 (dd, J¼5.6, 3.3 Hz, 1H, B), 6.13 (dd, J¼2.7,
5.6 Hz, 1H, A), 5.89 (dd, J¼5.5, 2.8 Hz, 1H, B), 4.25 (dd, J¼5.2, 3.4 Hz,
1H, B), 4.10e3.88 (m, 2H), 3.60 (dd, J¼5.0 1.4 Hz, 1H, A), 3.37 (br s,
1H, A), 3.33e3.30 (m, 1H), 3.19 (br s,1H, B), 3.00 (br s,1H, A), 2.56
(dd, J¼1.5, 5.2 Hz, 1H, B), 2.34 (s, 3H), 1,91 (d, J¼8.8 Hz, 1H, B), 1.78
(d, J¼8.9 Hz, 1H, A), 1.56e1.49 (m, 1H), 1.14 (t, J¼7.0 Hz, 3H, A), 0.89
3.4.7. 2-Methyl-1-{(1S,2S,4S)-2-[2-((S)-p-tolylsulfinyl)phenyl]bicyclo
[2.2.1]hept-5-en-2-yl}propan-1-one (endo-20A). Compound endo-
20A was obtained as major diastereomer from 8 in the presence of
Yb(OTf)3. Chromatography: Et2O:n-hexane, 2:1. Yield: 83%; white
(t, J¼7.2 Hz, 3H, B); 13C NMR
d 174.46, 173.42, 144.6, 142.3, 142.0,
141.2,140.6,139.0, 137.0,135.6, 134.4, 131.1,130.6, 129.9, 129.8,127.9,
127.8, 126.7, 125.9, 125.7, 125.4, 125.3, 124.8, 60.7, 60.5, 60.4, 52.1,
50.0, 49.3, 48.8, 48.6, 48.4, 46.5, 46.0, 44.34, 43.7, 21.3, 14.2. IR
solid; 118e120 ꢁC.
d
½
a 2D0
ꢃ
ꢀ114 (c¼0.9, chloroform). 1H NMR
7.80e7.74 (m, 1H), 7.53e7.50 (m, 2H), 7.46 (dt, J¼7.9, 1.5 Hz, 1H),
7.37 (dt, J¼7.9, 1.4 Hz, 1H), 6.42 (dd, J¼5.7, 3.1 Hz, 1H), 5.90 (dd,
J¼5.5, 2.9 Hz, 1H), 3.9 (br s, 1H), 3.16e3.14 (m, 2H), 2.89 (sept,
J¼6.7 Hz, 1H), 2.36 (s, 3H), 2.30 (dd, J¼12.0, 3.8 Hz, 1H), 0.99 (d,
(NaCl)
d 3060, 2957, 2925, 2807, 1727, 1594, 1464, 1377, 1262, 1182,
1083, 1057, 1030. MS (ESI) m/z: 783 [2MþNa]þ (27), 381 [MþH]þ
(100). HRMS m/z calcd for C23H25O3S [MþH]þ: 381.1518, found:
381.1507.
J¼6.6 Hz, 3H), 0.21 (d, J¼6.8 Hz, 3H). 13C NMR
d 212.6, 148.4, 142.9,
141.9, 141.3, 140.5, 131.8, 131.1, 129.6, 129.4, 128.1, 126.8, 126.1, 65.6,
49.6, 48.1, 44.3, 40.4, 37.1, 21.4, 21.1, 19.7. IR (KBr)
d 3063, 2974,
3.4.4. (1R,4S,5R,6S)- and (1S,4R,5S,6R)-5-Nitro-6-[2-((S)-p-tol-
ylsulfinyl)phenyl]bicyclo[2.2.1]hept-2-ene (endo-17A)þ(endo-17B).
Compounds endo-17A and endo-17B were obtained, in the absence
of Yb(OTf)3, as a 60:40 diastereoisomeric mixture from 5. Chro-
matography: Et2O:n-hexane, 3:2. Yield: 90%; colorless oil; 1H NMR
2872, 1704, 1463, 1339, 1081, 1045, 1031, 813. MS (ESI) m/z: 779
[2MþNa]þ (100), 757 [2MþH]þ (47), 401 [MþNa]þ (20), 379
[MþH]þ (53); HRMS m/z calcd for C24H27O2S [MþHþ]: 379.1692,
found: 379.1710.
d
8.23 (dd, J¼7.8, 1.53 Hz, 1H, B), 8.01e7.98 (m, 1H, A), 7.52e7.46
(m, 5H), 7.28e7.24 (m, 2H), 6.74 (dd, J¼5.7, 3.2 Hz 1H, A), 6.31 (dd,
J¼5.8, 3.2 Hz, 1H, B), 6.12 (dd, J¼5.7, 2.7 Hz, 1H, A),6.06 (dd, J¼5.8,
2.7 Hz, 1H, B), 5.35 (t, J¼4.1 Hz, 1H, A), 5.19 (t, J¼4.1 Hz, 1H, B), 3.87
(dd, J¼4.1, 2.4 Hz, 1H, A), 3.68 (br s, 1H, A), 3.60 (br s, 1H, B), 3.56
(dd, J¼4.1, 2.4 Hz, 1H, B), 3.09 (br s, 1H, A), 2.39 (s, 3H, B), 2.35 (s,
3H, A),2.14 (s, 1H, B), 1.93 (d, J¼9.6 Hz, 1H, B), 1.91 (d, J¼9.6 Hz, 1H,
3.5. Reaction of enones 9e12 and 14 under atmospheric
pressure. General procedure
A solution of the corresponding enone (0.1 mmol) and Yb(OTf)3
in CH3CN (1.8 mL) was stirred at rt for 45 min The solution was
cooled at the corresponding temperature and then the diene
(5e10 mmol) was added. After the indicated time, the mixture was
hydrolyzed (saturated NH4Cl), extracted (3ꢄ5 mL DCM), washed
(saturated NaCl), dried (MgSO4) and the solvent evaporated under
reduced pressure. The residue was purified by flash-column chro-
matography. The eluent used and the obtained yield in each case
are indicated below.
A), 1.71 (dd, J¼9.6, 2.3 Hz, 1H); 13C NMR
d 144.8, 142.6, 141.9, 140.8,
140.7, 138.4, 132.9, 132.7, 131.4, 131.2, 130.1, 128.6, 128.2, 127.2,
126.2, 126.1, 125.6, 125.5, 125.4, 91.2 (B), 88.9 (A), 51.9, 49.7, 48.1,
48.0, 45.5, 45.4, 45.0, 44.5, 21.5, 21.4; IR (NaCl)
d 3061, 2989, 1574,
1335, 1059, 1015, 810, 756. MS (ESI) m/z: 729 [2MþNa]þ (12), 707
[MþH]þ (14), 376 [MþNa]þ (15), 354 [Mþ1]þ (100); Anal. Calcd for
C20H19NO3S: C, 67.97; H, 5.42; N, 3.96; S, 9.07. Found: C, 67.71; H,
5.59; N, 3.84; S, 8.78.
3.5.1. (1S,2S,4S)-Bicyclo[2.2.1]hept-5-en-2-yl[2-((S)-p-tolylsulfinyl)
phenyl]methanone (endo-21A). Compound endo-21A was obtained
as major diastereomer from 9 and cyclopentadiene. Chromatogra-
phy: Et2O:n-hexane 3:1. Yield: 94%; white solid; mp: 99e101 ꢁC;
3.4.5. 1-{(1S,2S,4S)-2-(2-((S)-p-Tolylsulfinyl)phenyl)bicyclo[2.2.1]
hept-5-en-2-yl}ethanone (endo-18A). Compound endo-18A was
obtained as major diastereomer from 6. Chromatography: Et2O:n-
½
a 2D0
ꢃ
ꢀ250 (c 0.4, CHCl3). 1H NMR
d
8.54 (dd, J¼7.9, 1.2 Hz, 1H), 8.03
hexane, 3:2. Yield: 79%; colorless oil; ½a D20
ꢃ
ꢀ344 (c 1.8, CHCl3). 1H
(dd, J¼7.9, 1.2 Hz, 1H), 7.81 (dt, J¼7.3, 1.3 Hz, 1H), 7.59 (dt, J¼7.6,
1.2 Hz, 1H), 7.55e7.52 (m, 2H), 7.15e7.13 (m, 2H), 5.97 (dd, J¼5.6,
3.1 Hz, 1H), 5.05 (dd, J¼5.6, 2.8 Hz, 1H), 3.77 (dt, J¼9.0, 4.1 Hz, 1H),
3.11 (br s, 1H), 2.90 (br s,1H), 2.31 (s, 3H), 1.93 (ddd, J¼11.7, 9.0,
3.7 Hz, 1H), 1.50 (dd, J¼11.7, 4.1 Hz, 1H), 1.39 (d, J¼1.4 Hz, 2H); 13C
NMR
d
7.76 (dd, J¼7.9, 1.5 Hz, 1H), 7.69 (d, J¼7.8 Hz, 1H), 7.50 (dt,
J¼7.3, 1.5 Hz, 1H), 7.42e7.34 (m, 3H), 7.23e7.20 (m, 2H), 6.44 (dd,
J¼5.7, 3.1 Hz, 1H), 5.89 (dd, J¼5.7, 2.9 Hz, 1H), 3.76 (br s, 1H),
3.07e3.03 (m, 2H), 2.35 (s, 3H), 2.14 (dd, J¼11.9, 3.7 Hz, 1H), 1.83 (s,
3H), 1.69e1.67 (m, 2H). 13C NMR
d
206.8, 147.9, 143.9, 142.3, 141.5,
NMR d 200.2, 148.8, 143.8, 140.8, 137.1, 134.1, 133.3, 131.5, 130.0,
141.4, 132.4, 131.1, 130.1, 129.6, 129.1, 126.9, 125.9, 65.2, 49.9, 48.6,
44.9, 39.7, 27.8, 21.7. IR (NaCl) 3059, 2975, 2868, 1709, 1464, 1221,
129.9, 129.3, 126.9, 125.2, 49.8, 47.6, 47.2, 42.8, 31.0, 29.1, 21.3; IR
(NaCl) 2975, 2833, 1672, 1585, 1337, 1218, 1023, 810, 757; MS (ESI)
d
d

4136
M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
m/z: 673 [MþNa]þ (18), 337 [MþH]þ (100). Anal. Calcd for
48.8, 47.5, 47.1, 46.8, 46.4, 46.1, 46.1, 29.7, 29.2, 28.6, 25.4, 21.3, 20.4,
19.9; MS (ESI) m/z: 471 [MþNa]þ (100), 449 [MþH]þ (50). HRMS m/
z calcd for C24H24F3O3S [MþH]þ: 449.1392, found: 449.1397.
C21H20O2S: C, 74.97; H, 5.99; S, 9.53. Found: C, 75.22; H, 6.11; S, 9.54.
3.5.2. [(1S,2S,3R,4R)-3-Methylbicyclo[2.2.1]hept-5-en-2-yl][2-((S)-p-
tolylsulfinyl)phenyl]methanone (endo-22A). Compound endo-22A
was obtained as major diastereomer from 10 and cyclopentadiene.
Chromatography: Et2O:n-hexane, 2:1. Yield: 85%; colorless oil;
3.5.6. (S)-3-(Furan-2-yl)-1-[2-(p-tolylsulfinyl)phenyl]propan-1-one
(27). Compound 27 was obtained from 9 and furan. Chromatog-
raphy: Et2O:n-hexane, 3:1. Yield: 69%; white solid; 1H RMN
d 8.56
½
a 2D0
ꢃ
ꢀ318 (c 0.4, CHCl3); 1H NMR
d
8.54 (dd, J¼7.9, 1.2 Hz, 1H),
(dd, J¼1.1, 7.9 Hz, 1H), 7.90 (dd, J¼7.8, 1.2 Hz, 1H), 7.84 (dt, J¼7.6,
1.3 Hz,1H), 7.63e7.55 (m, 3H), 7.29e7.25 (m,1H), 7.18e7.05 (m, 2H),
6.20 (dd, J¼3.2, 1.9 Hz, 1H), 5.95 (dd, J¼3.2, 0.8 Hz, 1H), 3.35e3.16
8.03e8.00 (m, 1H), 7.85e7.79 (m, 1H), 7.60 (dt, J¼7.6, 1.3 Hz, 1H),
7.52e7.49 (m, 2H), 7.15e7.13 (m, 2H), 6.07 (dd, J¼5.6, 3.1 Hz, 1H),
4.83 (dd, J¼5.6, 2.8 Hz, 1H), 3.28 (t, J¼3.8 Hz, 1H), 2.99 (br s, 1H),
2.48 (br s, 1H), 2.30 (s, 3H), 2.01 (ddt, J¼6.8, 3.8, 1.5 Hz, 1H), 1.67 (d,
J¼8.6 Hz, 1H), 1.38 (dd, J¼8.6, 1.6 Hz, 1H), 1.13 (d, J¼7.0 Hz, 3H); 13C
(m, 2H), 3.03e2.98 (m, 2H), 2.32 (s, 3H); 13C RMN
d 198.3, 154.0,
148.8, 143.8, 141.2, 140.6, 133.8, 133.8, 130.23, 128.7, 129.5, 126.7,
125.3, 110.3, 105.6, 37.4, 22.4, 21.4; MS (ESI) m/z: 361 [MþNa]þ (17),
407 [MþH]þ (100); HRMS m/z calcd C20H18O3S [MþHþ]: 339.1049,
found: 339.1045.
NMR
d 200.2, 148.7, 143.8, 140.9, 138.4, 134.3, 133.2, 131.1, 130.1,
130.0, 129.3, 127.0, 125.3, 56.2, 49.3, 48.6, 46.7, 35.7, 21.3, 20.7; IR
(NaCl) d 2963, 2868, 1668,1586,1436,1218,1062,1017, 808, 759; MS
(ESI) m/z: 723 [2MþNa]þ (19), 701 [2MþH]þ (32), 351 [MþH]þ
(100), 285 (50); HRMS m/z calcd for C22H23O2S [MþH]þ: 351.1315,
found: 351.1303.
3.5.7. (R)- and (S)-3-(Furan-2-yl)-2-methyl-1-[2-((S)-p-tolylsulfinyl)
phenyl]propan-1-one (28). Compound 28 was obtained as
a 60(A):40(B) epimers mixture from 12 and furan. Chromatography:
Et2O:n-hexane, 3:1. Global yield: 64%; 1H RMN
d
8.55 (dd, J¼7.8,
3.5.3. [(1S,2S,3S,4R)-3-Methylbicyclo[2.2.1]hept-5-en-2-yl][2-((S)-p-
tolylsulfinyl)phenyl]methanone (endo-23A). Compound endo-23A
was obtained as major diastereomer from 11 and cyclopentadiene.
Chromatography: Et2O:n-hexane, 3:1. Yield: 75%; colorless oil;
1.2 Hz, 1H), 7.82 (dd, J¼7.8, 1.1 Hz, 1H), 7.77 (dt, J¼7.6, 1.3 Hz, 1H),
7.65e7.52 (m, 3H), 7.30e7.26 (m, 1H), 7.20e7.08 (m, 2H), 6.21 (dd,
J¼3.2, 1.9 Hz, 1H, B), 6.15 (dd, J¼3.1, 1.9 Hz, 1H, A), 5.98 (dd, J¼3.2,
0.7 Hz, 1H, B), 5.77 (dd, J¼3.2, 0.7 Hz,1H, A), 3.35e3.16 (m, 2H), 3.04
(dd, J¼14.8, 6.6 Hz, 1H, B), 2.95 (dd, J¼15.2, 6.6 Hz, 1H, A), 2.72 (dd,
J¼15.0, 7.2 Hz, 1H, B), 2.62 (dd, J¼15.1, 7.4 Hz, 1H, A), 2.33 (s, 3H, A),
2.32 (s, 3H, B), 1.19 (d, J¼7.0 Hz, 3H, A), 0.96 (d, J¼6.9 Hz, 3H, B).
½
a 2D0
ꢃ
ꢀ191 (c 0.7, CHCl3). 1H NMR (300 MHz, CDCl3)
8.55 (dd, J¼8.0,
d
1.2 Hz, 1H), 7.94 (dd, J¼8.0, 1.0 Hz, 1H), 7.82 (dt, J¼7.8, 1.2 Hz, 1H),
7.61e7.56 (m, 1H), 7.49e7.46 (m, 2H), 7.09e7.06 (m, 2H), 6.48 (dd,
J¼5.6, 3.0 Hz, 1H), 5.83 (dd, J¼5.5, 2.8 Hz, 1H), 3.79 (dd, J¼10.0,
2.8 Hz,1H), 3.03 (br s,1H), 2.77e2.70 (m,1H), 2.68 (br s, 1H), 2.28 (s,
3H), 1.46 (dt, J¼8.4, 1.7 Hz, 1H), 1.19 (m, 1H), 0.02 (d, J¼6.9 Hz, 3H);
3.5.8. (1S,2S,3S,4R)-[2-((S)-p-Tolylsulfinyl)phenyl]{3-(trifluorome-
thyl)-7-oxabicyclo[2.2.1]hept-5-en-2-yl}methanone
(endo-29A).
13C NMR
d
201.4, 149.1, 143.7, 140.6, 137.0, 135.1, 133.3, 132.3, 130.0,
Compound endo-29A was obtained as major diastereomer from 14
and furan. Chromatography: Et2O:n-hexane, 3:1. Yield: 60%; white
129.9, 129.1, 127.0, 125.0, 52.4, 49.0, 48.9, 46.4, 39.1, 21.2, 15.4; IR
(NaCl)
d
3059, 2962, 2925, 1670, 1437, 1211, 1081, 1062, 1024, 807;
solid; mp: 108e110 ꢁC; ½a D20
ꢃ
ꢀ239 (c 0.45, CHCl3). 1H NMR
d 8.68 (dd,
MS (ESI) m/z: 723 [2MþNa]þ (10), 701 [2MþH]þ (37), 351 [MþH]þ
(100), 285 (33); HRMS m/z calcd for C22H23O2S [MþH]þ: 351.1413,
found: 351.1303.
J¼7.9, 1.1 Hz, 1H), 8.15 (d, J¼7.1 Hz, 1H), 7.97 (t, J¼7.5 Hz, 1H), 7.72 (dt,
J¼7.5, 0.9 Hz, 1H), 7.45e7.42 (m, 2H), 7.17e7.14 (m, 2H), 6.21 (dd,
J¼5.3, 1.7 Hz, 1H), 5.11e5.09 (m, 2H), 4.74 (dd, J¼5.8, 1.2 Hz, 1H) 4.04
(t, J¼4.4 Hz, 1H), 2.96 (dq, J¼9.6, 4.3 Hz, 1H), 2.32 (s, 3H); 13C NMR
3.5.4. (1R,2S,3R,4R)-1-Methoxy-3-methylbicyclo[2.2.2]oct-5-en-2-
yl-{2-[(S)-p-tolylsulfinyl]phenyl}methanone (endo-25A). Compound
endo-25A was obtained as major diastereomer from 10 or 11 and 1-
methoxycyclohexadiene. Chromatography: n-hexane:AcOEt 3:1.
d 193.3, 149.9, 143.4, 141.4, 136.1, 134.5, 132.5, 132.3, 130.6,130.5,129.3,
127.7, 125.9, 80.3, 79.5, 49.2, 45.2 (c), 21.3; IR (NaCl)
d 3083, 3061,
2921, 1677, 1334, 1284, 1271, 1141, 1082, 845; MS (ESI) m/z: 835
[2MþNa]þ (90), 813 [2MþH]þ (15), 407 [MþH]þ (37), 361 (100);
HRMS m/z calcd for C21H18F3O3S [MþH]þ: 407.0923, found: 407.0925.
Yield: 48%; colorless oil; ½a D20
ꢃ
ꢀ217 (c 1.2, CHCl3). 1H NMR (300 MHz,
CDCl3)
d
8.36 (d, J¼7.7 Hz, 1H), 8.06 (d, J¼7.7 Hz, 1H), 7.73 (t,
J¼7.5 Hz, 1H), 7.62e7.53 (m, 3H), 7.14 (d, J¼8.3 Hz, 2H), 6.41 (dd,
J¼6.6, 8.8 Hz, 1H), 3.25 (d, J¼6.5 Hz, 1H), 3.00 (s, 3H), 2.31 (s, 3H),
2.29e2.26 (s, 1H), 2.00e1.88 (m, 2H), 1.71e1.57 (m, 2H), 1.55e1.45
3.5.9. (R)- and (S)-4,4,4-Trifluoro-3-(5-methylfuran-2-yl)-1-(2-[(S)-
p-tolylsulfinyl]phenyl)butan-1-one (30). Compounds 30 were
obtained from 14 and 2-methylfuran as an inseparable 80:20 di-
astereomers mixture. Chromatography: n-hexane:AcOEt 3:1.
Global yield: 83%; colorless oil; 1H NMR (300 MHz, CDCl3)
(m, 1H), 1.01 (d, J¼7.0 Hz, 3H); 13C NMR
d 202.5, 148.1, 143.8, 140.4,
137.1, 134.1, 132.9, 130.8, 130.5, 130.0, 129.3, 126.4, 125.0, 81.4, 58.4,
51.0, 39.4, 36.1, 29.8, 21.2, 19.3, 18.8; MS (ESI) m/z: 789 [2MþNa]þ
(11), 417 [MþNa]þ (19), 395 [MþH]þ (52), 137 (100); HRMS m/z
calcd for C24H27O3S [MþH]þ: 395.1675, found: 395.1681.
d
8.56e8.55 (m,1H), 7.94 (d, J¼7.6 Hz,1H), 7.85 (t, J¼7.5 Hz,1H), 7.60
(t, J¼7.6 Hz, 1H), 7.50 (d, J¼8.3 Hz, 2H), 7.16 (d, J¼7.9 Hz, 2H, minor),
7.06 (d, J¼8.2 Hz, 2H, major), 6.18 (d, J¼3.1 Hz, 1H, minor), 6.06 (d,
J¼3.1 Hz, 1H, major), 5.89e5.88 (m, 1H, minor), 5.83e5.82 (m, 1H,
major), 4.28e4.16 (m, 1H), 3.67 (dd, J¼9.3, 17.4 Hz, 1H, minor), 3.60
(dd, J¼9.3, 17.6 Hz, 1H, major), 3.40 (dd, J¼4.2, 17.6 Hz, 1H, major),
3.27 (dd, J¼3.9, 17.4 Hz, 1H, minor) 2.32 (s, 3H, minor), 2.29 (s, 3H,
3.5.5. (1R,2S,3R,4R)-
and
(1S,2S,3R,4S)-1-Methoxy-3-(tri-
fluoromethyl)bicyclo[2.2.2]oct-5-en-2-yl-{2-[(S)-p-tolylsulfinyl]phe-
nyl}methanone (endo-26A)þ(exo-26A). Compounds endo-26A and
exo-26A were obtained as 60:40 diastereomers mixture from 14
and 1-methoxycyclohexadiene. Chromatography: n-hexane:AcOEt
major), 2.22 (s, 3H, minor), 2.16 (s, 3H, major). 13C NMR
d (major)
194.9, 152.3, 149.5, 144.9, 143.5, 140.8, 134.3, 133.1, 130.3, 129.7,
129.5, 129.4, 126.5, 126.4, 125.3, 110.27, 106.5, 38.6 (c), 36.4, 29.7,
21.3, 13.4; (ESI) m/z: 863 [2MþNa]þ (26), 841 [2MþH]þ (21), 443
[MþNa]þ (100), 421 [MþH]þ (71); HRMS m/z calcd for C22H20F3O3S
[MþH]þ: 421.1079, found: 421.1076.
3:1. Global yield: 75%; colorless oil. 1H NMR
d 8.41 (m, 1H),
8.08e8.03 (m, 1H), 7.78e7.71 (m, 1H), 7.56e7.44 (m, 3H), 7.09e7.06
(m, 2H), 6.35e6.30 (m,1H), 6.18e6.13 (m, 1H, exo), 5.72 (d, J¼8.7 Hz,
1H, endo), 3.76 (d, J¼7.1 Hz, 1H, endo), 3.54 (d, J¼7.1 Hz, 1H, exo),
2.83 (s, 3H, exo), 2.82 (s, 3H, endo), 2.84e2.80 (m, 1H), 2.24 (s, 3H,
endo), 2.23 (s, 3H, exo), 2.02e1.94 (m, 1H), 1.77e1.43 (m, 4H); 13C
Acknowledgements
NMR
d 200.0, 199.36, 148.3, 148.2, 143.8, 143.7, 140.7, 140.6, 135.5,
135.5,134.2, 133.5,133.4,132.9, 131.7, 131.6, 131.4, 131.2, 130.0, 129.9,
129.3, 129.2, 26.9, 126.9, 125.3, 125.1, 51.2, 80.7, 51.33, 51.1, 49.7,
Financial support of this work by the Spanish Government
ꢀ
(grant CTQ2009-12168) and Comunidad Autonoma de Madrid

M.C. Maestro et al. / Tetrahedron 68 (2012) 4129e4137
4137
Angew. Chem., Int. Ed. 2008, 47, 6576; (e) Pichon, N.; Harrison-Marchand, A.;
Toupet, L.; Maddaluno, J. J. Org. Chem. 2006, 71, 1892.
(AVANCAT S2009/PPQ1634) is gratefully acknowledged. J. A. F.-S.
ꢀ
thanks Comunidad Autonoma de Madrid (AVANCAT S2009/
12. Pan, C.; Wang, Z. Coord. Chem. Rev. 2008, 252, 736.
PPQ1634) for a predoctoral contract.
€
13. Vidis, A.; Kusters, E.; Sedelmeier, G.; Dyson, P. J. J. Phys. Org. Chem. 2008, 21, 264.
14. Oakes, R. S.; Heppenstall, T. J.; Shezad, N.; Clifford, A. A.; Rayner, C. M. Chem.
Commun. 1999, 1459.
15. For a review see: (a) García Ruano, J. L.; Martín-Castro, A. M. Heteroat. Chem.
2007, 18, 537 (and references cited therein).
Supplementary data
NMR spectra (1H, 13C) of compounds 3, 4, 5, 9, 10, 11, 12, 14, endo-
15A, exo-15A, endo-16Aþendo-16B, endo-17Aþendo-17B, endo-18A,
endo-19A, endo-20A, endo-21A, endo-22A, endo-23A, endo-25,
endo-26þexo-26, 27, endo-29A and 30 and X-ray ORTEP of com-
pounds endo-15A, endo-21A and endo-29A. Supplementary data
related to this article can be found online at doi:10.1016/
j.tet.2012.03.112.
16. (a) Garcia Ruano, J. L.; Torrente, E.; Martin-Castro, A. M. J. Org. Chem. 2011, 76,
ꢀ
3597; (b) García Ruano, J. L.; Marcos, V.; Aleman, J. Angew. Chem., Int. Ed. 2008,
47, 6836; (c) Garcia Ruano, J. L.; Schoepping, C.; Alvarado, C.; Aleman, J. Chem.
dEur. J. 2010, 16, 8968; (d) Arroyo, Y.; Sanz-Tejedor, M. A.; Alonso, I.; Garcia-
Ruano, J. L. Org. Lett. 2011, 13, 4534; (e) Garcia Ruano, J. L.; Parra, A.; Alonso, I.;
Fustero, S.; del Pozo, C.; Arroyo, Y.; Sanz-Tejedor, A. Chem.dEur. J. 2011, 17, 6142.
ꢀ
17. García Ruano, J. L.; Martín-Castro, A. M.; Tato, F.; Cardenas, D. J. Tetrahedron:
Asymmetry 2005, 16, 1963.
ꢀ
ꢀ~
18. (a) García Ruano, J. L.; Fernandez-Ibanez, M. A.; Maestro, M. C.; Rodríguez-
ꢀ
ꢀ
Fernandez, M. M. J. Org. Chem. 2005, 70, 1796; (b) García Ruano, J. L.; Fernandez-
ꢀ~
ꢀ
ꢀ~
Ibanez, M. A.; Maestro, M. C.; Rodriguez-Fernandez, M. M. Tetrahedron 2006, 62,
References and notes
ꢀ
1245; (c) García Ruano, J. L.; Fernandez-Ibanez, M. A.; Maestro, M. C. Tetrahe-
ꢀ
ꢀ~
dron 2006, 62, 12297; (d) García Ruano, J. L.; Fernandez-Ibanez, M. A.;
ꢀ
ꢀ
ꢀ
ꢀ
Fernandez-Salas, J. A.; Maestro, M. C.; Marquez-Lopez, P.; Rodríguez-Fernandez,
1. DielseAlder reaction reviews: (a) Fringuelli, F.; Taticchi, A. The DielseAlder Re-
action: Selected Practical Methods; John Wiley & Sons: Chichester, UK, 2002; (b)
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Pellisier, H. Tetrahedron 2009, 65, 2839.
M. M. J. Org. Chem. 2009, 74, 1200.
ꢀ
ꢀ~
19. García Ruano, J. L.; Fernandez-Ibanez, M. A.; Maestro, M. C. J. Org. Chem. 2006,
71, 7683.
20. Recent results of 1,3-dipolar cycloaddition to sulfinyl dipolarophiles: (a) Cruz
Cruz, D.; Yuste, F.; Martín, M. R.; Tito, A.; García Ruano, J. L. J. Org. Chem. 2009,
2. For review see: (a) Gnas, Y.; Glorius, F. Synthesis 2006, 1899; (b) Lait, S. M.;
Rankic, D. A.; Keay, B. A. Chem. Rev. 2007, 107, 767 For recent references see: (c)
Liu, X.; Snyder, J. K. J. Org. Chem. 2008, 73, 2935; (d) Sarotti, A. M.; Spanevello,
~
74, 3820; (b) García Ruano, J. L.; Nunez, A., Jr.; Martín, M. R.; Fraile, A. J. Org.
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Chem. 2008, 73, 9366; (c) García Ruano, J. L.; Fraile, A.; Martín, M. R.; Gonzalez,
R. A.; Suarez, A. G. Tetrahedron 2009, 65, 3502; (e) Broeker, J.; Knollmueller, M.;
G.; Fajardo, C. J. Org. Chem. 2008, 73, 8484.
Gaertner, P. Tetrahedron: Asymmetry 2009, 20, 273; (f) Lam, Y.; Cheong, P. H.-Y.;
Blasco Mata, J. M.; Stanway, S. J.; Gouverneur, V.; Houk, K. N. J. Am. Chem. Soc.
2009, 131, 1947; (g) Henderson, J. R.; Parvez, M.; Keay, B. A. Org. Lett. 2009, 11,
3178; (h) Henderson, J. R.; Chesterman, J. P.; Parvez, M.; Keay, B. A. J. Org. Chem.
2010, 75, 988.
21. (a) Garcia Ruano, J. L.; Cid de la Plata, B. In Topics in Current Chemistry; Page, P.
G. B., Ed.; Springer: Berlin, 1999; vol. 204; p 1; (b) Garcia Ruano, J. L.; Martín
Castro, A. M.; Rodríguez Ramos, J. H. Heteroat. Chem. 2002, 13, 453; (c) Garcia
Ruano, J. L.; Alemparte, C. J. Org. Chem. 2004, 69, 1405 and references cited
~
therein; (d) Arribas, C.; Carreno, M. C.; García Ruano, J. L.; Rodríguez, J. F.;
3. (a) Trost, B. M.; O’Krongly, D.; Belletire, J. L. J. Am. Chem. Soc. 1980, 102, 7595; (b)
Monbaliu, J.-C.; Robiette, R.; Peeters, D.; Marchand-Brynaert, J. Tetrahedron Lett.
Santos, M.; Sanz-Tejedor, M. A. Org. Lett. 2000, 2, 3165; (e) Garcia Ruano, J. L.;
€
€
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€
Gonzalez Gutierrez, L.; Martín Castro, A. M.; Yuste, F. Tetrahedron: Asymmetry
2009, 50, 1314; (c) Agopcan, S.; Celebi-Olcum; Ucısık, M. N.; Sanyal, A.;
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2002, 13, 2003; (f) Aranda, M. T.; Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.;
Aviyente, V. Org. Biomol. Chem. 2011, 9, 8079; (d) Fernandez de la Pradilla, R.;
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Carreno, M. C.; Cid, M. B.; García Ruano, J. L. Tetrahedron: Asymmetry 2000, 11,
Tortosa, M.; Castellanos, E.; Viso, A.; Baile, R. J. Org. Chem. 2010, 75, 1517.
4. For reviews see: (a) Harada, T.; Kusukawa, T. Synlett 2007, 1823; (b) Mellah, M.;
Voituriez, A.; Schulz, E. Chem. Rev. 2007, 107, 5133; (c) Pellisier, H. Tetrahedron
2007, 63, 1297; (d) Corey, E. J. Angew. Chem. Int. Ed. 2002, 41, 1650; (e) Kagan, H.
B.; Riant, O. Chem. Rev. 1992, 92, 1007 Selected recent references: (f) Boersma,
A. J.; Feringa, B. L.; Roelfes, G. Org. Lett. 2007, 9, 3647; (g) Harada, S.; Toudou, N.;
Hiraoka, S.; Nishida, A. Tetrahedron Lett. 2009, 50, 5652; (h) Mukherjee, S.;
Corey, E. J. Org. Lett. 2010, 12, 632.
5. Reviews in asymmetric organocatalysis: (a) Pellisier, H. Tetrahedron 2007, 63,
9267; (b) Notz, W.; Tanaka, F.; Barbas, C. F., III. Acc. Chem. Res. 2004, 37, 580
Selected references: (c) Northrup, A. B.; MacMillan, D. W. C. J. Am. Chem. Soc.
2002, 124, 2458; (d) Karsten, J.; Jorgensen, K. L. Angew. Chem., Int. Ed. 2003, 42,
1498; (e) Hayashi, Y.; Samanta, S.; Gotoh, H.; Ishikawa, H. Angew. Chem., Int. Ed.
2008, 47, 6634 and references cited therein; (f) Li, Q.; Wong, W.-Y.; Chan, W.-H.;
Lee, A. W. M. Adv. Synth. Catal. 2010, 352, 2142.
1217.
22. For other DielseAlder reactions of substrates containing remote sulfinyl groups
see: (a) Arai, Y.; Masuda, T.; Masaki, Y. J. Chem. Soc., Perkin Trans. 1 1999, 2165;
(b) Arai, Y.; Masuda, T.; Masaki, Y. Chem. Pharm. Bull. 1998, 46, 1078.
23. García Ruano, J. L.; Aleman, J.; Aranda, M. T.; Arevalo, M. J.; Padwa, A. Org. Lett.
2005, 7, 19.
24. Xu, Y.; Dolbier, W. R., Jr. J. Organomet. Chem. 2000, 65, 2134.
25. Garcia Ruano, J. L.; Martin-Castro, Ana, M.; Tato, F.; Pastor, C. J. J. Org. Chem.
2005, 70, 7346.
26. CCDC 862077, CCDC 862078 and CCDC 862079 contain the supplementary
crystallographic data of compounds endo-15A, endo-21A and endo-29A, re-
spectively. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
27. Complete endo selectivity has been also described for the reaction of 3-
phenylbut-3-en-2-one with cyclopentadiene in the presence of Me2AlCl. See:
Davies, H. M. L.; Dai, X. J. Org. Chem. 2005, 70, 6680.
6. (a) Winkel, A.; Reddy, P. V. G.; Wilhelm, R. Synthesis 2008, 999; (b) Nguyen Van
Buu, O.; Aupoix, A.; Vo-Thanh, G. Tetrahedron 2009, 65, 2260.
28. In order to prove the transformation of Z-enone 11 in E-enone 10 under the
reaction conditions, a 1:1 mixture of Yb(OTf)3 and compound 11 in acetonitrile
was maintained under stirring at room temperature for 20 h. Then, both E and
Z isomers 10 and 11 in 1:2 ratio, respectively, appeared at the resulting mixture
(1H NMR).
7. For a recent review of the sulfinyl group as chiral auxiliary in DielseAlder re-
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action see: (a) García Ruano, J. L.; Aleman, J.; Cid, M. B.; Fernandez-Ibanez, M.
A.; Maestro, M. C.; Martín, M. R.; Martín Castro, A. M. In Organosulfur Chemistry
in Asymmetric Synthesis; Toru, T., Bolm, C., Eds.; Wiley-VCH: Weinheim, 2008;
p 55; For a recent reference see: (b) Lanfranchi, D. A.; Bour, C.; Hanquet, G. Eur. J.
Org. Chem. 2011, 2818 For a review about the sulfinyl group as ligand in
29. To ascertain this result, besides the 1H NMR analysis of the reaction mixtures,
we have carried out a careful oxidation of the 60:40 mixture of adducts ob-
tained from the trifluoromethyl dienophile 14 and 1-methoxy-1,3-cyclo-
hexadiene, to transform the sulfinyl group into sulfone moiety. The formation
of a 60:40 mixture of the corresponding diastereoisomeric sulfones indicated
that the facial selectivity produced by the sulfinyl group is complete but the
DielseAlder reaction occurred with low endoeexo selectivity.
ꢀ
asymmetric catalysis see: (c) Fernandez, I.; Khiar, N. In Organosulfur Chemistry
in Asymmetric Synthesis; Toru, T., Bolm, C., Eds.; Wiley-VCH: Weinheim, 2008;
p
265; (d) Senanayake, C. H.; Han, Z.; Krishnamurthy, D. In Organosulfur
Chemistry in Asymmetric Synthesis; Toru, T., Bolm, C., Eds.; Wiley-VCH: Wein-
heim, 2008; p 233.
8. (a) Kappe, C. O. Chem. Soc. Rev. 2008, 37, 1127; (b) Chen, I.-O.; Young, J.-N.; Yu, S.
J. Tetrahedron 2004, 60, 11903.
30. (a) Leroy, J.; Fischer, N.; Wakselman, C. J. Chem. Soc., Perkin Trans. 11990, 1, 1281;
(b) Benjamin, N. M.; Martin, S. F. Org. Lett. 2011, 13, 450.
9. Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563.
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31. DielseAlder cycloadditions and FriedeleCrafts alkylation of furan derivatives
with non aromatic ketones catalyzed by chiral Lewis acids have been recently
reported: (a) Singh, R. S.; Adachi, S.; Tanaka, F.; Yamauchi, T.; Inui, C.; Harada, T.
J. Organomet. Chem. 2008, 73, 212; (b) Adachi, S.; Tanaka, F.; Watanabe, K.;
Harada, T. Org. Lett. 2009, 11, 5206.
32. Reaction of the dienophile with similar structure than 14, but lacking of the
sulfinyl group, afforded the adduct with exo configuration as the major one.
See: Leuger, J.; Blond, G.; Frohlich, R.; Billard, T.; Haufe, G.; Langlois, B. R. J.
Organomet. Chem. 2006, 71, 2735.
10. (a) Bravo, J. L.; Lopez, I.; Cintas, P.; Silvero, G.; Arevalo, M. J. Ultrason. Sonochem.
2006, 13, 408; (b) Timko, M. T.; Allen, A. J.; Danheiser, R. L.; Steinfeld, J. I.; Smith,
K. A.; Tester, J. W. Ind. Eng. Chem. Res. 2006, 45, 1594; (c) Cella, R.; Stefani, H. A.
Tetrahedron 2009, 65, 2619.
11. (a) Jenner, G. Tetrahedron Lett. 2002, 58, 5185; (b) Jenner, G.; Gacem, B. J. Phys.
Org. Chem. 2003, 16, 265 (and references cited therein). For recent articles on
synthesis via DielseAlder reaction under high pressure conditions see: (c)
Minuti, L.; Ballerini, E. J. Org. Chem. 2011, 76, 5392 (and references cited
therein); (d) Waalboer, D. C. J.; Schaapman, M. C.; van Delft, F. L.; Rutjes, F. P. J. T.