Sulfoxides as stereochemical controllers in intermolecular Heck reactions

Article abstract of DOI:10.1002/1521-3765(20010917)7:18<3890::AID-CHEM3890>3.0.CO;2-Y

The study of a variety of substituted sulfoxides as chiral auxiliaries in intermolecular Heck reactions of sulfinyldihydrofurans and sulfinylcyclopentenes with different iodoarenes is reported. In the presence of [Pd(OAc)₂]/Ag₂CO

Full text of DOI:10.1002/1521-3765(20010917)7:18<3890::AID-CHEM3890>3.0.CO;2-Y

FULL PAPER
Sulfoxides as Stereochemical Controllers in Intermolecular Heck Reactions
Nuria Díaz Buezo, Juan Carlos de la Rosa, JuliaÂn Priego, IneÂs Alonso, and
Juan Carlos Carretero*[a]
Abstract: The study of a variety of substituted sulfoxides as chiral auxiliaries in
intermolecular Heck reactions of sulfinyldihydrofurans and sulfinylcyclopentenes
with different iodoarenes is reported. In the presence of [Pd(OAc)2]/Ag2CO3 and a
bidentate phosphine ligand, synthetically useful yields and asymmetric inductions
were obtained. By far the best diastereoselectivities were obtained by the use of the
palladium-coordinating o-(N,N-dimethylamino)phenylsulfinyl group. By final re-
moval of the chiral auxiliary, these sulfoxide-stereocontrolled asymmetric Heck
processes were applied to the enantioselective synthesis of 1-aryl-substituted and 1,3-
diaryl-substituted dihydrofurans and cyclopentenes.
Keywords: asymmetric synthesis
cyclopentenes dihydrofurans
Heck reaction ´ sulfoxides
´
´
´
mediated reactions.[6] Herein we report in detail on appropri-
ately substituted sulfoxides that act as efficient chiral auxil-
iaries in intermolecular asymmetric Heck reactions of cyclic
alkenes.[7]
Introduction
Since its discovery in the late 1960s, the palladium-catalyzed
arylation and alkenylation of olefins (the Heck reaction) has
become one of the most versatile and widely used metal-
catalyzed method for C C bond formation.[1] Among other
factors, the high versatility of this reaction relies on the
availability of the starting substrates (usually alkenes and
organic halides or triflates), its broad substrate generality, and
its high functional group compatibility. Currently, a very
important challenge to provide even more improvements in
the synthetic usefulness of this reaction is the development of
highly efficient asymmetric versions.[2] Most precedents of
asymmetric Heck reactions have been performed with the use
of catalytic amounts of enantiopure chiral ligands, specially
bidentate ligands, such as BINAP or (phosphinoaryl)oxazo-
lines.[2, 3]
Despite the inherent conceptual and practical appeal of an
approach based on chiral catalysts, it is surprising that the
alternative stoichiometric chiral auxiliary approach, presum-
ably less substrate-dependent, has been seldom considered.[4]
In this field, we reasoned that the amply demonstrated
capability of the sulfinyl group to act as an efficient stereo-
chemical controller in key traditional C C bond-forming
reactions,[5] such as Michael additions and Diels ± Alder
cycloadditions, could also be extended to transition metal
Results and Discussion
Synthesis and Heck reactions of sulfinyldihydrofurans and
sulfinylcyclopentenes: To explore the reactivity of cyclic a,b-
unsaturated sulfoxides in Heck reactions we undertook the
synthesis of a variety of racemic sulfinyldihydrofurans and
sulfinylcyclopentenes that have very different substituents at
the sulfur atom in terms of steric size, electronic character,
and potential palladium-coordinating properties (Scheme 1).
The arylsulfinyl dihydrofurans 1 ± 4 were readily prepared in
two steps from 2,3-dihydrofuran by sulfenylation with the
corresponding aryl methyl sulfoxide under Pummerer reac-
tion conditions[8] and further oxidation of the thioether (meta-
chloroperoxybenzoic acid (MCPBA)). To test a bulky alkyl
sulfoxide, the tert-butylsulfinyl dihydrofuran 5 was synthe-
sized from a-bromo-g-butyrolactone by initial nucleophilic
substitution with sodium tert-butyl thiolate, reduction of the
lactone to the hemiacetal moiety with diisobutylaluminum
hydride (DIBAL-H), and formal dehydration (Scheme 1).
Concerning the cyclopentene series, the p-tolylsulfinyl and
tert-butylsulfinyl cyclopentenes 6 and 7 were readily prepared
by direct sulfinylation of cyclopentenyllithium with methyl p-
tolylsulfinate or tert-butyl thiosulfinate,[9] respectively. Finally,
the potentially palladium-coordinating aminophenylsulfinyl
cyclopentene 8 was prepared in two steps by sulfenylation of
[a] Prof. J. C. Carretero, N. Díaz Buezo, J. C. de la Rosa, J. Priego
I. Alonso
Â
Departamento de Química Organica
Â
Facultad de Ciencias, Universidad Autonoma de Madrid
28049 Madrid (Spain)
Fax : (‡34)913973966
E-mail: juancarlos.carretero@uam.es
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Chem. Eur. J. 2001, 7, No. 18

3890±3900
DMF at 1008C, a clean reaction was observed with the use of
Ag2CO3 as the base. As a second and less determinant factor,
bidentate phosphine ligands, such as 1,3-bis(diphenylphos-
phanyl)propane (dppp) or 1,1'-bis(diphenylphosphanyl)ferro-
cene (dppf), tended to be somewhat more efficient than
monodentate ligands (PPh3, P(oTol)3, or AsPh3). Typical
optimized experimental conditions were: PhI (3 equiv),
[Pd(OAc)2] (10 mol%), dppp (10 mol%), Ag2CO3 (2 equiv)
in DMF at 1008C (Table 1).
Table 1. Heck reaction of a,b-unsaturated sulfoxides 1 ± 8 with iodoben-
zene.[a]
Sulfoxide
X
R
Product A:B ratio[b] Yield[%][c]
1
2
3
4
5
6
7
8
O
O
O
O
O
Ph
9
10
11
77:23
78:22
75:25
6:94
68
80
47
80
±
62
±
76
2, 4-Me2C6H3
o-(MeO)C6H4
o-(Me2N)C6H4 12
[d]
tBu
±
13
±
±
CH2 pTol
CH2 tBu
CH2 o-(Me2N)C6H4 14
60:40
[d]
±
8:92
[a] Reaction conditions: PhI (3 equiv), [Pd(OAc)2] (10 mol%), dppp
(10 mol%), Ag2CO3 (200 mol%), DMF, 1008C. [b] Determined by
1H NMR spectroscopy on the crude mixture. [c] In purified products after
flash chromatography. [d] Complex mixture of products.
Scheme 1. Synthesis of racemic sulfinyldihydrofurans and cyclopentenes
1 ± 8. a) 1) ArSOMe, (CF3CO)2O, CH2Cl2, 788C, 2) Et3N, 788C;
b) MCPBA, CH2Cl2, 788C; c) NaStBu, DMF, RT; d) DIBAL-H, THF,
788C; e) Ac2O, Et3N, DMAP, CH2Cl2, 08C; f) PhSeH, BF3 ´ Et2O,
CH2Cl2, 08C; g) 1) nBuLi, THF, 788C; 2) tBuSOStBu or pTolSOOMe,
THF, 788C; h) 1) nBuLi, THF, 788C; 2) Ar-S-S-Ar, THF, 788C.
DMAP ˆ 4-dimethylaminopyridine.
Under these conditions, except for the tert-butylsulfinyl
derivatives 5 and 7 which proved to be much less reactive and
afforded complex mixtures of products after long reaction
times, the rest of the substrates led to the corresponding Heck
products in reasonable to good yields (47 ± 80%). Taking into
account the usually scant reactivity of trisubstituted alkenes in
intermolecular Heck reactions,[11] note the efficiency of these
sulfinylated cycloalkenes as well as the absence of products
resulting in a final isomerization of the double bond.[12]
However, the most interesting outcome of these reactions is
the dependence of the stereoselectivity on the substitution at
the sulfoxide. The reaction of the aryl sulfoxides 1 ± 3 and 6
was uniformly and moderately stereoselective in favor of the
A isomer, regardless of the steric bulk of the sulfoxide. On the
contrary, the Heck reaction of the sulfoxides that contain a o-
(N,N-dimethylamino)phenyl group (4 and 8) occurred with
much higher stereoselectivity and, outstandingly, with oppo-
site stereocontrol (the B isomer was the major product).
To investigate the scope of the Heck arylations of optimal
sulfoxides 4 and 8, both electron-poor and electron-rich
iodoarenes were studied (entries 1 ± 9, Table 2). The reaction
is quite general and affords the corresponding Heck products
(12 ± 21) in moderate to good isolated yields (45 ± 86%).
Interestingly, these reactions led predominantly to the B
isomer, with observed A:B ratios ranging from 25:75 to 6:94.
The only exception to this general trend was the behavior of
the ortho-substituted iodoarene (entry 9, Table 2), which
afforded an equimolecular mixture of A and B isomers.
cyclopentenyl-lithium with the corresponding disulfide and
subsequent oxidation with MCPBA.
With the a,b-unsaturated sulfoxides 1 ± 8 in hand, we
studied their Heck reactions with excess iodobenzene.[10]
After extensive experimentation, we found that while com-
plex mixtures of sulfinylated and nonsulfinylated compounds
were obtained in the presence of common bases, such as Et3N,
diisopropylethylamine (DIPEA), proton sponge, or K2CO3 in
Abstract in Spanish: Se ha abordado el estudio de una amplia
Â
variedad de sulfoxidos como auxiliares quirales en reacciones
de Heck intermoleculares de sulfinildihidrofuranos y sulfinil-
ciclopentenos con yodoarenos. Elevados rendimientos e in-
Â
ducciones asimetricas apreciables se obtuvieron utilizando
[Pd(OAc)2] como catalizador, Ag2CO3 como base y una
fosfina bidentada como ligando. Con gran diferencia, las
mejores diastereoselectividades se obtuvieron utilizando un
Â
Â
sulfoxido con capacidad para coordinarse con el atomo de
paladio: el grupo o-(N,N-dimetilamino)fenilsulfinilo. Tras
Â
eliminacion final del auxiliar quiral, estas reacciones de Heck
Â
asimetricas controladas por el grupo sulfinilo se han aplicado a
la síntesis enantioselectiva de dihidrofuranos y ciclopentenos
1-aril y 1,3-diarilsustituidos.
Chem. Eur. J. 2001, 7, No. 18
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Table 2. Heck reaction of aminosulfoxides 4 and 8 with iodoarenes.[a]
Entry Sulfoxide
X
O
Ar
Ph
Product A:B ratio[b] Yield[%][c]
1
2
3
4
5
6
7
8
9
4
8
4
8
4
8
4
4
4
12
14
15
16
17
18
19
6:94
8:92
14:86
25:75
6:94
80
76
55
77
64
83
45
86
47
CH2 Ph
O
CH2 p-(MeO)C6H4
O
p-(MeO)C6H4
p-(NO2)C6H4
CH2 p-(NO2)C6H4
12:88
7:93
O
O
O
p-(CO2Me)C6H4
3-Me-4-MeO-C6H3 20
2,4-(MeO)2C6H3 21
15:85
50:50
[a] Reaction conditions as indicated in Table 1. [b] Determined by 1H NMR
spectroscopy on the crude mixture. [c] In purified products after flash
chromatography.
Scheme 2. Mechanistic hypothesis for the stereoselectivity of the Heck
reaction.
The configurational assignment of stereoisomers A and B
was first established by NMR studies (and later confirmed by
chemical correlations). In particular, the chemical shifts of H2
and H4 were found to be excellent diagnostic criteria (Fig-
ure 1). Thus, H4 appears to be significantly more deshielded
in isomers A than in isomers B (ddH4(A B) ˆ 0.1 ± 0.5 ppm,
CDCl3), whereas the opposite behavior is observed for H2
(ddH2(A B) ˆ 0.1 ± 0.5 ppm, CDCl3). These important spec-
troscopic effects might be explained on the basis of the highly
deshielding effect induced by the sulfinylic oxygen on its
hydrogen in 1,3-parallel relationship:[13] H4 in isomers A and
H2 in isomers B in their presumed most stable conformations
around the C S bond, thus avoiding important 1,3-parallel
interactions between substituents at sulfur and at C2 (Fig-
ure 1).
give complex C. Further insertion on the upper face of the
double bond and b-hydrogen elimination would explain the
formation of A as the major isomer. On the other hand, in the
case of the sulfoxides 4 and 8, the plausible coordination of
‡
[ArPdL2] to the dimethylamino moiety would lead to the
amino complex D[16], which would intramolecularly direct the
insertion of the aryl group on the bottom face of the double
bond to afford the isomer B after the final b-hydrogen
elimination step. In agreement with this proposal, the
pronounced drop of B stereoselectivity observed in the
reaction with the bulky ortho-substituted iodoarene (entry 9,
Table 2), compared to meta- and para-substituted substrates
(entries 1 ± 8), could be caused by the greater difficulty to
attain the required sterically congested p-complex D (see
Scheme 2) with palladium ± nitrogen coordination.
Once it had been demonstrated that the o-(dimethylami-
no)phenylsulfinyl group can act as an efficient stereochemical
controller in intermolecular diastereoselective Heck reac-
tions, and taking into account that the Heck products are new
examples of a,b-unsaturated sulfoxides, we envisaged the
possibility of the use of these compounds as substrates for a
second Heck reaction. Thus, the dihydrofurans 12B and 15B
and the cyclopentenes 14 (A:B ˆ 8:92) and 16 (A:B ˆ 20:80)
were treated with different iodoarenes (Ar2I) under quite
Figure 1. 1H NMR criteria for the stereochemical assignment of A and B
isomers. ddH4(A B) ˆ 0.1 ± 0.5 ppm, CDCl3; ddH2(A B) ˆ 0.1 ±
0.5 ppm, CDCl3.
similar
palladium-catalyzed
conditions
([Pd(OAc)2]
(10 mol%), dppp or dppf (10 mol%), Ag2CO3 (200 mol%),
DMF, 1008C), although longer reaction times were employed
(usually 20 ± 24 h instead of 1 ± 6 h) (Table 3).
As a mechanistic hypothesis, we speculate that the opposite
stereochemical behavior of the o-(dimethylamino)phenyl
sulfoxides 4 and 8, compared to the rest of aryl sulfoxides,
could be caused by the ability of the nitrogen to chelate the
palladium atom in the key p-alkenyl palladium complex, to
give in this case a chelation-controlled reaction[14] instead of a
sterically controlled process (Scheme 2). Thus, after oxidative
addition, the coordination of the intermediate cationic
Outstandingly, a single 1,3-diarylated stereoisomer F was
detected and isolated in all cases (products 22 ± 29, 50 ± 84%
yield after chromatographic purification). In full agreement
with these results, when the palladium-catalyzed reaction of 4
and 8 with excess iodobenzene was monitored by thin-layer
chromatography until disappearance of the corresponding
monosubstituted Heck products 12 and 14, the 1,3-diphenyl-
substituted dihydrofuran 22 and cyclopentene 25 were
isolated in 55% and 81% yield, respectively, as single isomers
(Scheme 3). The stereochemical assignment of the products F
‡
arylpalladium species [ArPdL2] with the double bond of
vinyl sulfoxides 1 ± 3 and 6 would preferably occur from the
least hindered face,[15] namely that opposite the R group, to
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Sulfoxide-Stereocontrolled Intermolecular Heck Reactions
3890±3900
Table 3. Second Heck reaction with iodoarenes.[a]
Kaganꢁs conditions[18] for enantioselective oxidation of sul-
fides and the oxidation with Davisꢁ chiral oxaziridine[19]
afforded (S)-4 with low or moderate optical purity (enantio-
meric excess (ee) ˆ 26% and 62%, respectively, measured by
1H NMR in the presence of [Pr(hfc)3] (hfc ˆ 3-(heptafluoro-
propylhydroxymethylene)-d-camphorate).
Entry Sulfoxide
X
Ar1
Ar2
Ph
Product Yield[%][b]
1[c]
2
12B
12B
12B
O
O
O
Ph
Ph
Ph
22
83
69
84[d]
75
80
78
70
50
p-(MeO)C6H4 23
p-(NO2)C6H4 24
Ph
3[c]
4
14B[e]
14B[e]
15B
CH2 Ph
CH2 Ph
O
O
25
5
6[c]
7
p-(MeO)C6H4 26
p-(MeO)C6H4 Ph 27
p-(MeO)C6H4 p-(MeO)C6H4 28
15B
8
16B[f]
CH2 p-(MeO)C6H4 Ph
29
Scheme 4. Attempts of enantioselective synthesis of 4 by asymmetric
oxidation.
[a] Reaction conditions as indicated in Table 1. [b] In pure product after flash
chromatography. [c] Reaction carried out in the presence of dppf instead of
dppp. [d] Conversion yield. [e] Sulfoxide 14 was used as a 8:92 mixture of A ‡
B isomers. [f] Sulfoxide 16 was used as a 20:80 mixture of A ‡ B isomers.
As a second alternative, we undertook the enantioselective
synthesis of 4 and 8 with enantiomerically pure sulfur
compounds as starting materials. Different synthetic ap-
proaches were developed for the preparation of (R)-4 and
(R)-8 (Scheme 5). In the case of (R)-4 the synthesis starts with
the readily available (S)-o-(N,N-dimethylamino)phenyl meth-
yl sulfoxide[20][(S)-30]. Its deprotonation with lithium diiso-
propylamide (LDA; Et2O, 788C) and further reaction with
ethylene oxide afforded the g-hydroxysulfoxide (S)-31
(72%). Subsequent treatment with LDA (2 equiv, THF,
788C) and addition of ethyl formate gave the hemiacetal
32 as a mixture of stereoisomers at C2 and C3 (80% yield).
Scheme 3. Double Heck reaction of a,b-unsaturated sulfoxides 4 and 8.
could not be unambiguously established by NMR methods,
but was rigorously proved by X-ray diffraction[17] in the case of
dihydrofuran 24 and cyclopentene 25. This excellent diaster-
eoselectivity could again be explained invoking a chelation
control exerted by the o-(dimethylamino)phenylsulfinyl
group (intermediate E), which in this case could be reinforced
by the steric effects associated with aryl substitution at the
initially formed stereogenic carbon. In agreement with the
critical importance of the Pd ± N coordination in the stereo-
chemical control of the Heck reaction of o-(dimethylamino)-
phenylsulfoxides, the Heck reaction of the phenylsulfinyl
dihydrofuran 9B with iodobenzene occurred with poor
stereoselectivity to afford a 2:1 mixture of the corresponding
1,3-diphenyl-substituted diastereomers.
Application in asymmetric synthesis: To apply these highly
diastereoselective sulfur-mediated Heck reactions in asym-
metric synthesis, three issues had to be addressed: 1) the
synthesis of the starting sulfoxides 4 and 8 in enantiomerically
pure form, 2) the confirmation that the Heck reactions take
place without previous racemization at the sulfur center, and
3) the final elimination of the chiral auxiliary.
As the most direct potential approach to the enantioselec-
tive synthesis of dihydrofuran 4, we studied first the asym-
metric oxidation of its thioether precursor (Scheme 4).
Unfortunately, both the treatment with [Ti(OiPr)4]/(R,R)-
diethyl tartrate ((R,R)-DET)/cumene hydroperoxide under
Scheme 5. Synthesis of enantiopure (R)-4 and (R)-8.
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FULL PAPER
Finally, dehydration of 32 with MsCl/Et3N gave the required
dihydrofuran (R)-4 in 77% yield and with very high optical
1
purity (ee > 96%, H NMR, [Pr(hfc)3]).
On the other hand, the enantiopure sulfinylcyclopentene
(R)-8 was readily prepared in two steps by application of
Kaganꢁs procedure for the synthesis of enantiopure sulfoxides
based on two successive sulfur-nucleophilic substitutions from
the commercially available sulfite 33.[21] The reaction of
enantiopure 33 with o-(N,N-dimethylamino)phenyllithium
(generated in situ by treatment of the corresponding iodide
with nBuLi) in diethyl ether at 788C, gave the sulfinate 34 as
the major product (61% yield). Unexpectedly, the reaction of
34 with cyclopentenyllithium afforded (R)-8 with an enantio-
meric excess of 88%; this indicates that a certain racemization
at sulfur had occurred. Interestingly, this loss of optical purity
was completely suppressed when the reaction was performed
with the Grignard reagent of 1-bromocyclopentene (THF,
RT), which led to the required cyclopentenylsulfoxide (R)-8
in high yield (85%) and enantiomeric purity (ee ˆ 96.6%,
HPLC, ChiralcelOD column).
Scheme 7. Synthesis of cyclopentenes (S)-37 and (S)-38.
(2S,4R)-2,4-diphenyltetrahydrofuran[23] ((2S,4R)-36, 90%,
1
ee > 96%, H NMR, [Pr(hfc)3]) by direct hydrogenation and
C S cleavage with Raney-Ni (EtOH, RT).
The application of (R)-4 and (R)-8 to the enantioselective
synthesis of aryl- and 1,3-diaryl-substituted dihydrofurans and
cyclopentenes is shown in Scheme 6 and Scheme 7, respec-
tively.
In a similar way, by controlling the progress of the Heck
reaction of (R)-8 with iodobenzene, either the monosubsti-
tuted Heck product 14 (A:B ˆ 8:92) or the disubstituted Heck
product 25 were isolated in very high optical purities (ee ˆ
97% for 25, HPLC, ChiralcelOD column). After some
experimentation,[24] we found that in these cases the most
suitable method for the cleavage of the chiral auxiliary was
the palladium-catalyzed reductive desulfurization in the
Ar
PhI
[Pd(OAc)2]
dppp
S
O
Zn act.
(R)-4
NH4Cl, THF
51%
Ag2CO3
DMF, 100 °C
77%
Ph
Ph
(2S, SR)-12B
O
O
presence of
a
bulky Grignard reagent[25] ([Pd(acac)2]
(R)-35
(5 mol%), iPrMgBr (300 mol%), THF). Thus, oxidation of
sulfoxides 14 to the corresponding sulfone (MCPBA) and
desulfonylation with [Pd(acac)2]/iPrMgBr gave (S)-3-phenyl-
cyclopentene[12e] [(S)-37] (55% yield, ee ˆ 90%, GC Cyclosilb
column). Under quite similar palladium-catalyzed reductive
conditions (3R,SR)-25 afforded (S)-1,3-diphenylcyclopentene
[(S)-38] (77%, ee ˆ 94%, HPLC, ChiralpakAS column)
(Scheme 7).
ee > 96%
PhI
Ag2CO3
Pd(OAc)2
83%
Ar
Ph
Ph
O
S
Raney Ni
EtOH
90%
Ph
(3R, SR)-22
Ph
O
O
(2S, 4R)-36
ee>96%
Ar = o-(Me2N)C6H4
Scheme 6. Synthesis of dihydrofuran (R)-35 and tetrahydrofuran (2S,4R)-
36.
Conclusions
We have shown that the sulfinyl group is able to act as a
stereochemical controller in intermolecular Heck arylations
and double Heck arylations of sulfinyl cycloalkenes. High
reactivities and synthetically useful diastereoselectivities were
achieved by the use of the potentially palladium chelating o-
(N,N-dimethylamino)phenylsulfinyl group. Interestingly, the
procedure based on the use of this unprecedented type of
palladium-coordinating aryl-substituted sulfoxide seems to be
very general with respect to both the alkene (cyclopentene or
dihydrofuran) and the substitution at the iodoarene. More-
over, as the enantiomerically pure sulfinylcycloalkenes 4 and
8 are readily available, and suitable methods for the final
removal of the sulfoxide have been developed, this overall
chiral auxiliary-based procedure constitutes an alternative to
the use of chiral bidentate ligands in asymmetric Heck
reactions.
Heck reaction of (R)-4 with iodobenzene under the
optimized reaction conditions and further chromatographic
purification afforded (2S,SR)-12B (77% yield; note: in the
nomenclature used in this paper the nonitalic S in the
stereochemical descriptor indicates the sulfur atom). Its
desulfinylation with activated powdered zinc[22] yielded the
known (R)-2-phenyl-2,5-dihydrofuran ((R)-35, ee > 96%),
whose optical rotation was identical to that previously
reported.[12e] It is worth noting that this chemical correlation
proves the stereochemical assignments previously established
by NMR and also demonstrates that sulfoxide (R)-4 is
configurationally stable under the experimental conditions
of the Heck reaction. On the other hand, the second Heck
reaction of (2S,SR)-12B with iodobenzene yielded (3R,SR)-22
(83%), which was transformed in one-step into enantiopure
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Sulfoxide-Stereocontrolled Intermolecular Heck Reactions
3890±3900
3-(tert-Butylsulfenyl)-4,5-dihydro-2-furanone: a-Bromo-g-butyrolactone
(1.0 g, 6.06 mmol) was added to a solution of sodium tert-butyltiolate
(747 mg, 6.70 mmol) in DMF (15 mL) at room temperature. The mixture
was stirred at room temperature for 12 h. The mixture was diluted with
Et2O (30 mL) and washed with H2O (2 Â 20 mL). The organic layer was
dried (MgSO4) and evaporated. The residue was purified by flash
chromatography (ethyl acetate/hexane 1:1) to afford the sulfenylfuranone
(537 mg, 51%). 1H NMR (200 MHz, CDCl3): d ˆ 4.30 (m, 2H), 3.55 (dd,
J ˆ 8.4, 6.0 Hz, 1H), 2.70 (m, 1H), 2.22 (m, 1H), 1.41 (s, 9H); 13C NMR
(75 MHz, CDCl3): d ˆ 176.4, 66.4, 44.4, 38.7, 32.4, 31.0.
Experimental Section
Melting points are uncorrected; 1H NMR were acquired at 200 or
300 MHz, 13C NMR were acquired at 50 or 75 MHz (indicated in each
case). Chemical shifts (d) are reported in ppm relative to CDCl3 (7.26 and
77.0 ppm). Mass spectra (MS) and high resolution mass spectra (HRMS)
were determined at an ionizing voltage of 70 eV. Reactions were usually
carried out under a dry argon atmosphere in anhydrous solvents. THF and
diethyl ether were distilled from sodium benzophenone under argon.
CH2Cl2 and ethyl formate were distilled from P2O5. Flash column
chromatography was performed on silica gel (Merck-60, 230 ± 400 mesh).
3-(tert-Butylsulfinyl)-4,5-dihydro-2-furanone: Oxidation of the previously
obtained sulfenylfuranone (500 mg, 2.87 mmol) with MCPBA as described
for the synthesis of sulfoxides 1 ± 4 afforded the corresponding sulfinylfur-
anone (544 mg, 99%). M.p. 82 ± 838C; 1H NMR (200 MHz, CDCl3): d ˆ
4.44 (t, J ˆ 7.0 Hz, 2H), 3.61 (dd, J ˆ 10.2, 5.9 Hz, 1H), 3.00 (m, 1H), 2.36
Synthesis of (Æ)-4-arylsulfinyl-2,3-dihydrofurans 1 ± 4: Trifluoroacetic
anhydride (9.9 mL, 70 mmol) was added to a solution of methyl aryl
sulfoxide (14.0 g, 76 mmol) in dry CH2Cl2 (120 mL) at 788C, and the
solution was stirred for 15 min. 2,3-Dihydrofuran (5.3 g, 70 mmol) was
added to this mixture and the reaction was stirred at 788C for 15 min.
Triethylamine (35 mL) was added at the same temperature, the mixture
was slowly warmed to room temperature and stirred for 24 h. The reaction
mixture was poured into water, the organic layer was separated, and the
aqueous layer was extracted with CH2Cl2 (2 Â 100 mL). The combined
organic layers were dried (Na2SO4) and the solvent was evaporated. The
residue was purified by flash chromatography (ethyl acetate/hexane 1:20)
to afford the corresponding sulfenyldihydrofuran (10.9 g, 65%).
(m, 1H), 1.35 (s, 9H); 13C NMR (75 MHz, CDCl3): d ˆ 174.4, 68.1, 55.7,
‡
53.2, 23.0, 19.3; MS (EI): m/z (%): 134 ([M
tBu], 25), 86 (33), 57 (tBu,
100); elemental analysis calcd (%) for C8H14O3S: C 50.50, H 7.42, S 16.85;
found: C 50.84, H 7.38, S 17.34.
4-(tert-Butylsulfinyl)-2,3-dihydrofuran (5): DIBAL-H in hexane (1m,
3.4 mL, 3.4 mmol) was added to a solution of the previously obtained
sulfinylfuranone (430 mg, 2.26 mmol) in THF (6 mL) at 788C under an
Ar atmosphere. After the mixture had been stirred for 1 h, HCl was added
(10%, 10 mL). The organic layer was separated and the aqueous layer was
extracted with EtOAc (2 Â 15 mL). The combined organic layers were
dried (Na2SO4) and the solvent was evaporated to afford the corresponding
mixture of hemiacetals (347 mg, 80%).
A solution of MCPBA (23 mmol) in CH2Cl2 was added dropwise to a
cooled solution ( 788C) of the sulfenyldihydrofuran (5.0 g, 23 mmol) in
CH2Cl2 (75 mL). The reaction was monitored by TLC until the starting
sulfide had disappeared. A saturated solution of Na2SO3 (10 mL), followed
by a saturated solution of NaHCO3 (30 mL) were added. The organic layer
was separated and the aqueous layer was extracted with CH2Cl2 (2 Â
100 mL). The combined organic layers were dried (Na2SO4) and the
solvent was evaporated. The residue was purified by flash chromatography.
Ac2O (340 mL, 3.60 mmol), Et3N (750 mL, 5.4 mmol), and 4-(N,N-dimethyl-
amino)pyridine (catalytic amount) were added to a solution of these
hemiacetals (347 mg, 80%) in dry CH2Cl2 (10 mL) at 08C. The mixture was
stirred at room temperature for 1 h. NH4Cl (15 mL) was added, the organic
layer was separated, and the aqueous layer was extracted with CH2Cl2 (2 Â
10 mL). The combined organic layers were dried (Na2SO4) and the solvent
evaporated to afford a mixture of acetates (359 mg, 85%).
4-(Phenylsulfinyl)-2,3-dihydrofuran (1): Yield 69%; m.p. 57 ± 588C;
1H NMR (200 MHz, CDCl3): d ˆ 7.61 ± 7.39 (m, 5H), 7.09 (t, J ˆ 1.6 Hz,
1H), 4.60 ± 4.36 (m, 2H), 2.94 (dddd, J ˆ 14.0, 9.7, 8.1, 2.1 Hz, 1H), 2.20
(dddd, J ˆ 14.0, 10.7, 9.1, 1.6 Hz, 1H); 13C NMR (50 MHz, CDCl3): d ˆ
153.2, 141.6, 128.8, 127.6, 122.9, 117.9, 71.1, 23.1; MS (EI): m/z (%): 194
Benzeneselenol (262 mL, 2.13 mmol) was added to a solution of these
acetates (359 mg, 1.53 mmol) in dry CH2Cl2 (15 mL) cooled at 788C
under an Ar atmosphere. The mixture was stirred at 08C for 16 h. NaOH
(1m, 10 mL) was added, the organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (2 Â 10 mL). The combined organic layers
were dried (Na2SO4), and the solvent was evaporated to afford a mixture of
selenides.
‡
([M ], 8), 178 (5), 146 (100), 117 (44), 77 (33); elemental analysis calcd (%)
for C10H10O2S: C 61.83, H 5.19, S 16.50; found: C 61.67, H 4.98, S 16.42.
4-[(2,4-Dimethyl)phenylsulfinyl]-2,3-dihydrofuran (2): Yield 40%; m.p.
51 ± 528C; 1H NMR (200 MHz, CDCl3): d ˆ 7.82 (d, J ˆ 8.0 Hz, 1H), 7.22 (d,
J ˆ 8.0 Hz, 1H), 7.00 (s, 1H), 7.00 (t, J ˆ 1.7 Hz, 1H), 4.58 ± 4.36 (m, 2H),
2.93 (dddd, J ˆ 14.0, 11.1, 7.5, 1.7 Hz, 1H), 2.36 (s, 3H), 2.26 (s, 3H), 2.15
(dddd, J ˆ 14.0, 11.0, 9.1, 1.8 Hz, 1H); 13C NMR (50 MHz, CDCl3): d ˆ
153.2, 141.7, 137.1, 134.2, 131.6, 127.4, 124.3, 118.0, 72.5, 24.9, 21.1, 17.9; MS
A solution of MCPBA (1.50 mmol) in CH2Cl2 was added to a solution of
this mixture of selenides in CH2Cl2 (10 mL) at 788C. After 1 h, solutions
of saturated Na2SO3 (10 mL) and saturated NaHCO3 (20 mL) were added.
The organic layer was separated and the aqueous layer was extracted with
CH2Cl2 (2 Â 20 mL). The combined organic layers were dried (Na2SO4) and
the solvent was evaporated. The residue was purified by flash chromatog-
raphy (AcOEt) to afford 5 (115 mg, 40% from the acetates). 1H NMR
(200 MHz, CDCl3): d ˆ 6.86 (t, J ˆ 1.8 Hz, 1H), 4.58 (dt, J ˆ 8.2, 1.7 Hz,
2H), 3.08 (dddd, J ˆ 14.0, 10.2, 8.6, 1.7 Hz, 1H), 2.84 (dddd, J ˆ 14.2, 11.0,
9.1, 2.0 Hz, 1H), 1.28 (s, 9H).
‡
(EI): m/z (%): 222 ([M ], 10), 205 (13), 174 (100), 105 (29), 91 (35), 77 (33);
elemental analysis calcd (%) for C12H14O2S: C 64.84, H 6.35, S 14.42; found:
C 64.22, H 6.21, S 14.45.
4-(2-Methoxyphenylsulfinyl)-2,3-dihydrofuran (3): Yield 44%; m.p. 121 ±
1238C; 1H NMR (200 MHz, CDCl3): d ˆ 7.84 (dd, J ˆ 7.8, 1.8 Hz, 1H), 7.41
(dt, J ˆ 8.1, 2.5 Hz, 1H), 7.15 (dt, J ˆ 7.5, 0.9 Hz, 1H), 7.00 (t, J ˆ 1.7 Hz,
1H), 6.90 (dd, J ˆ 8.4, 0.8 Hz, 1H), 4.5 ± 4.38 (m, 2H), 3.83 (s, 3H), 2.91
(dddd, J ˆ 15.6, 12.3, 7.7, 1.7 Hz, 1H), 2.20 (dddd, J ˆ 15.7, 11.3, 9.6, 1.7 Hz,
1H); 13C NMR (50 MHz, CDCl3): d ˆ 155.2, 152.6, 131.8, 129.6, 125.5,
1-(p-Tolylsulfinyl)cyclopentene (6): nBuLi (2.5m, 1.42 mL, 3.40 mmol) was
added to a solution of 1-bromocyclopentene (0.50 g, 3.40 mmol) in THF
(10 mL) at 788C. After the mixture had been stirred for 1.5 h at 788C, a
solution of methyl p-toluenesulfinate (0.91 g, 3.09 mmol) in THF (10 mL)
was added and the reaction mixture was kept at 788C for 1 h and was then
poured into water. The organic layer was separated and the aqueous layer
was extracted with ethyl acetate (2 Â 10 mL). The combined organic layers
were dried (Na2SO4) and the solvent was evaporated. The residue was
purified by flash chromatography (ethyl acetate/hexane 1:1) to afford 6
(0.46 g, 72%). 1H NMR (300 MHz, CDCl3): d ˆ 7.44 and 7.25 (AA'BB'
system, m, 4H), 6.51 (s, 1H), 2.47 (m, 2H), 2.37(s, 3H), 2.08 (m, 2H), 1.91
(m, 2H); 13C NMR (75 MHz, CDCl3): d ˆ 147.7, 141.0, 139.3, 137.8, 129.7,
‡
121.0, 117.9, 110.7, 72.2, 55.6, 24.9; MS (EI): m/z (%): 224 ([M ], 6), 208 (8),
176 (100), 147 (11), 108 (11), 77 (21); elemental analysis calcd (%) for
C11H12O3S: C 58.91, H 5.39, S 14.29; found: C 58.43, H 5.12, S 14.34.
4-[2-(N,N-dimethylamino)phenylsulfinyl]-2,3-dihydrofuran (4): Yield
60%; 1H NMR (200 MHz, CDCl3): d ˆ 7.91 (dd, J ˆ 7.8, 1.8 Hz, 1H), 7.41
(dt, J ˆ 7.6, 1.7 Hz, 1H), 7.25 (dt, J ˆ 7.3, 1.4 Hz, 1H), 7.13 (dd, J ˆ 8.0,
1.3 Hz, 1H), 7.00 (t, J ˆ 1.9 Hz, 1H), 4.55 ± 4.33 (m, 2H), 2.86 (dddd, J ˆ
13.9, 11.0, 7.5, 2.0 Hz, 1H), 2.69 (s, 6H), 2.10 (dddd, J ˆ 13.9, 11.1, 9.4,
2.0 Hz, 1H); 13C NMR (50 MHz, CDCl3): d ˆ 152.7, 151.01, 136.3, 131.4,
‡
124.5, 32.8, 27.9, 22.9, 21.3; MS (EI): m/z (%): 206 ([M ], 31), 190 (14), 157
‡
125.6, 123.9, 120.0, 118.3, 72.2, 44.7, 25.2; MS (EI): m/z (%): 237 ([M ], 9),
(39), 143 (100), 123 (75), 84 (56), 65 (47).
220 (95), 150 (100), 136 (36), 91 (40), 77 (39); HRMS (EI): m/z calcd for
C12H15NO2S: 237.0828; found: 237.0823; elemental analysis calcd (%) for
C12H15NO2S: C 60.73, H 6.37, N 5.90, S 13.51; found: C 60.29, H 6.60, N 5.85,
S 13.85.
1-(tert-Butylsulfinyl)cyclopentene (7): nBuLi (2.5m, 1.42 mL, 3.40 mmol)
was added to a solution of 1-bromocyclopentene (0.50 g, 3.40 mmol) in
THF (10 mL) at 788C. After the mixture had been stirred for 1.5 h at
788C,
a
solution of (Æ)-tert-butyl-tert-butanethiosulfinate (0.44 g,
Synthesis of 4-(tert-butylsulfinyl)-2,3-dihydrofuran (5)
3.09 mmol) in THF (10 mL) was added, and the reaction was kept at
Chem. Eur. J. 2001, 7, No. 18
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0718-3895 $ 17.50+.50/0
3895

J. C. Carretero et al.
FULL PAPER
788C for 1 h. The reaction mixture was poured into water. The organic
layer was separated, and the aqueous layer was extracted with ethyl acetate
(2 Â 10 mL). The combined organic layers were dried (Na2SO4) and the
solvent was evaporated. The residue was purified by flash chromatography
d ˆ 155.6, 147.2, 139.4, 132.5, 131.8, 129.5, 128.5, 128.4, 127.1, 125.4, 121.7,
110.6, 86.0, 75.0, 55.4.
1
Isomer B (2S*,SR*): H NMR (200 MHz, CDCl3)(significant signals): d ˆ
7.62 (dd, J ˆ 9.5, 1.7 Hz, 1H), 6.67 (dd, J ˆ 8.5, 0.7 Hz, 1H), 6.56 (q, J ˆ
1.7 Hz, 1H), 5.78 (ddd, J ˆ 5.8, 3.9, 2.0 Hz, 1H), 3.69 (s, 3H); 13C NMR
(50 MHz, CDCl3) (significant signals): d ˆ 148.0, 138.8, 133.2, 127.4, 125.9,
1
(ethyl acetate/hexane 1:1) to afford 7 (0.26 g, 67%). H NMR (300 MHz,
CDCl3): d ˆ 6.33 (m, 1H), 2.52 (m, 4H), 2.01(m, 2H), 1.20 (s, 9H);
13C NMR (75 MHz, CDCl3): d ˆ 144.4, 139.2, 55.3, 32.6, 31.6, 23.9, 23.4; MS
‡
121.4, 110.5, 86.7; MS(EI) (m/z): 300 ([M ], 7), 283 (96), 252 (31), 144 (35),
‡
(EI): m/z (%): 172 ([M ], 0.6), 116 (97), 86 (49), 84 (75), 67 (100), 57 (65).
115 (100), 91 (32), 77 (74); HRMS (EI): m/z calcd for C17H16O3S: 300.0820;
1-[2-(N,N-Dimethylamino)phenylsulfinyl]cyclopentene (8): nBuLi (2.5m,
5.7 mL, 14.22 mmol) was added to a solution of 1-bromocyclopentene
(2.41 g, 16.41 mmol) in THF (120 mL) at 788C. After the mixture had
been stirred for 1.5 h at 788C, a solution of 2-(N,N-dimethylamino)-
phenyl disulfide (3.37 g, 10.94 mmol) in THF (220 mL) was added and the
reaction was kept at 788C for 1 h. The reaction mixture was poured into
water. The organic layer was separated and the aqueous layer was extracted
with CH2Cl2 (2 Â 100 mL). The combined organic layers were dried
(Na2SO4) and the solvent was evaporated. Oxidation of the resulting
sulfenyl cyclopentene with MCPBA, as described for the synthesis of
sulfoxide 7, afforded 8 (1.75 g, 68%). M.p. 52 ± 538C; 1H NMR (200 MHz,
CDCl3): d ˆ 7.85 (dd, J ˆ 1.6, 7.5 Hz, 1H), 7.40 (dt, J ˆ 1.6, 7.5 Hz, 1H), 7.23
(dt, J ˆ 1.1, 7.53 Hz, 1H), 7.11 (dd, J ˆ 1.1, 7.0 Hz, 1H), 6.47 (m, 1H), 2.69 (s,
6H), 2.45 (m, 3H), 1.98 (m, 3H); 13C NMR (75 MHz, CDCl3): d ˆ 151.6,
146.9, 137.2, 131.4 (2C), 125.6, 124.2, 120.0, 44.9, 32.9, 28.4, 23.1; elemental
analysis calcd (%) for C13H17NOS: C 66.34, H 7.28, N 5.95, S 13.63; found: C
66.43, H 7.05, N 5.71, S 13.49.
found: 300.0821.
3-[2-(N,N-Dimethylamino)phenylsulfinyl]-2-phenyl-2,5-dihydrofuran (12):
Eluent: ethyl acetate/hexane (1:2). Yield 80%.
Isomer B (2S*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.70 (dd, J ˆ 7.8,
1.7 Hz, 1H), 7.40 (dt, J ˆ 7.6, 1.6 Hz, 1H), 7.30 ± 7.13 (m, 6H), 7.03 (dd, J ˆ
7.9, 1.1 Hz, 1H), 6.30 (q, J ˆ 2.0 Hz, 1H), 5.76 (ddd, J ˆ 5.9, 4.3, 2.1 Hz, 1H),
4.92 (ddd, J ˆ 14.5, 5.4, 1.6 Hz, 1H), 4.77 (ddd, J ˆ 14.5, 5.4, 1.6 Hz, 1H),
2.56 (s, 6H); 13C NMR (75 MHz, CDCl3): d ˆ 151.3, 146.4, 138.9, 135.2,
132.7, 131.9, 128.3, 128.1, 127.2, 126.2, 123.8, 119.6, 86.7, 74.6, 44.4; MS (EI):
‡
m/z (%): 313 ([M ], 4), 296 (79), 190 (47), 150 (100), 120 (21), 91 (51), 77
(53); elemental analysis calcd (%) for C18H19NO2S: C 68.98, H 6.11, N 4.47,
S 10.23; found: C 68.97, H 6.34, N 4.33, S 10.68. (2S,SR)-12B (obtained from
(R)-4): [a]2D5
(R)-2,2,2-trifluoro-1-(9-antryl)ethanol).
ˆ
162.5 (c ˆ 1.0, CHCl3) (ee ꢀ 96%, determined by 1H NMR,
Isomer A (2R*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.69 (dd, J ˆ 8.1,
1.6 Hz, 1H), 7.38 (dt, J ˆ 7.5, 1.8 Hz, 1H), 7.33 ± 7.18 (m, 5H), 7.12 (dt, J ˆ
7.5, 1.1 Hz, 1H), 7.05 (dd, J ˆ 8.1, 1.1 Hz, 1H), 6.82 (q, J ˆ 1.6 Hz, 1H), 5.57
(ddd, J ˆ 5.9, 3.8, 2.1 Hz, 1H), 4.95 (ddd, J ˆ 14.0, 5.4, 1.6 Hz, 1H), 4.80
(ddd, J ˆ 14.0, 3.2, 1.6 Hz, 1H), 2.57 (s, 6H); 13C NMR (75 MHz, CDCl3):
d ˆ 151.6, 148.2, 139.3, 136.2, 132.2, 131.5, 128.6, 128.4, 127.2, 125.7, 124.3,
119.6, 86.3, 75.0, 44.9; elemental analysis calcd (%) for C18H19NO2S: C
68.98, H 6.11, N 4.47, S 10.23; found: C 68.79, H 6.06, N 4.38, S 9.96.
General procedure for the Heck reactions of sulfinyldihydrofurans and
cyclopentenes with iodoarenes: In a two-necked round-bottom flask were
sequentially added at room temperature the corresponding a,b-unsatu-
rated sulfoxide (2.2 mmol), iodoarene (6.6 mmol), silver carbonate
(4.4 mmol), palladium acetate (0.22 mmol), dppp (or dppf) (0.22 mmol),
and dry DMF (50 mL). The reaction mixture was degassed and stirred
vigorously at 1008C under argon. The reaction was monitored by TLC until
the starting sulfoxide had disappeared (2 ± 48 h). The mixture was then
cooled to room temperature, diluted with diethyl ether (50 mL), and
washed with water (2 Â 30 mL). The organic layer was dried (MgSO4) and
evaporated. The residue was analyzed by 1H NMR spectroscopy to
determine the A:B ratio and was purified by flash chromatography (the
eluents and yields are indicated below for each case).
2-(p-Tolylsulfinyl)-3-phenyl-1-cyclopentene (13): Eluent: ethyl acetate/
hexane (2:1). Yield 62%.
Isomer A (3R*,SR*): 1H NMR (300 MHz, CDCl3): d ˆ 7.32 ± 7.12 (m, 6H),
7.07 ± 6.99 (m, 3H), 7.30 ± 7.13 (m, 5H), 6.79 (m, 1H), 3.48 (m, 1H),2.87 ±
2.44 (m, 3H), 2.38 (s, 3H), 2.09 ± 1.84 (m, 2H); 13C NMR (75 MHz,
CDCl3)(mixture A ‡ B): d ˆ 151.1, 150.8, 142.5, 142.4, 141.8, 139.3, 138.3,
138.0, 135.6, 135.3, 129.8, 129.5, 128.6, 128.3, 127.6, 127.4, 126.7, 126.4, 125.4,
125.2, 50.1, 50.0, 36.0, 25.2, 31.7, 31.5, 21.4, 21.3; MS (EI): m/z (%): 282
2-Phenyl-3-(phenylsulfinyl)-2,5-dihydrofuran (9): Eluent: ethyl acetate/
hexane (1:1). Yield 68%.
‡
([M ], 54), 266 (71), 234 (76), 141 (88), 128 (95), 115 (100), 91 (94), 65 (53).
Isomer B (3S*,SR*): 1H NMR (300 MHz, CDCl3) (significant signals): d ˆ
Isomer A (2R*,SR*): M.p. 79 ± 808C; 1H NMR (200 MHz, CDCl3): d ˆ
7.51 ± 7.13 (m, 10H), 6.87 (q, J ˆ 1.8 Hz, 1H), 5.27 (ddd, J ˆ 5.8, 3.9, 2.0 Hz,
1H), 5.06 (ddd, J ˆ 14.3, 5.9, 1.8 Hz, 1H), 4.85 (ddd, J ˆ 14.3, 4.0, 1.8 Hz,
1H); 13C NMR: (75 MHz): d ˆ 147.9, 141.2, 138.5, 131.7, 130.9, 129.2, 128.8,
128.5, 127.3, 125.1, 86.0, 75.5; elemental analysis calcd (%) for C16H1402S: C
71.11, H 5.18, S 11.85; found: C 70.92, H 5.37, S 11.88
6.38 (m, 1H), 4.03 (m, 1H).
2-[2-(N,N-Dimethylamino)phenylsulfinyl]-3-phenyl-1-cyclopentene (14):
Eluent: ethyl acetate/CH2Cl2 (1:8). Yield 76%.
Isomer B (3R*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.72 (dd, J ˆ 1.6,
8.0 Hz, 1H), 7.37 (dt, J ˆ 1.6, 7.53 Hz, 1H), 7.00 ± 7.25 (m, 7H), 6.10 (m, 1H),
4.09 (m, 1H), 2.36 ± 2.72 (m, 9H), 1.98 (m, 1H); 13C NMR (75 MHz,
CDCl3): d ˆ 151.5, 150.0, 142.8, 137.9, 136.3, 131.5, 128.1, 127.5, 127.1, 126.4,
1
Isomer B (2S*,SR*): H NMR (200 MHz, CDCl3)(significant signals): d ˆ
6.54 (q, J ˆ 1.9 Hz, 1H), 5.80 (ddd, J ˆ 5.9, 4.3, 2.1 Hz, 1H); 13C NMR
(50 MHz, CDCl3): d ˆ 147.5, 141.6, 138.5, 132.6, 131.1, 128.7, 128.4, 128.2,
‡
123.7, 119.3, 50.2, 44.5, 35.3, 31.4; MS (EI): m/z (%): 311 ([M ], 9), 294
‡
127.0, 124.8, 86.3, 74.8; MS (EI): m/z: 270 ([M ], 2), 253 (100), 144 (31), 125
(100), 176 (17), 152 (43), 143 (34), 120 (17), 91 (41), 77 (25); HRMS (EI):
m/z calcd for C19H21NOS: 311.1343; found: 311.1341. (3R,SR)-14B (de ˆ
84%) (obtained from (R)-8): [a]2D5 ˆ ‡143.3 (c ˆ 1, CHCl3).
(9), 115 (77), 105 (29), 91 (27), 77 (35).
3-(2,4-Dimethylphenylsulfinyl)-2-phenyl-2,5-dihydrofuran (10): Eluent:
ethyl acetate/hexane (1:4). Yield 80%.
1
Isomer A (3S*,SR*): H NMR (200 MHz, CDCl3) (significant signal): d ˆ
6.81 (m, 1H); 13C NMR (75 MHz, CDCl3): d ˆ 152.2, 150.7, 143.0, 137.2,
1
Isomer A (2R*,SR*): H NMR (200 MHz, CDCl3): d ˆ 7.51 (d, J ˆ 8.1 Hz,
136.2, 131.7, 128.2, 127.5, 127.1, 125.9, 123.5, 119.0, 49.7, 44.7, 35.8, 31.4.
1H), 7.35 ± 7.05 (m, 6H), 6.97 (brs, 1H), 6.89 (q, J ˆ 1.9 Hz, 1H), 5.21 (ddd,
J ˆ 5.8, 3.9, 1.9 Hz, 1H), 5.04 (ddd, J ˆ 14.1, 5.6, 1.7 Hz, 1H), 4.89 (ddd, J ˆ
14.1, 3.8, 1.7 Hz, 1H), 2.37 (s, 3H), 2.10 (s, 3H).
3-[2-(N,N-dimethylamino)phenylsulfinyl]-2-(4-methoxyphenyl)-2,5-dihy-
drofuran (15): Eluent: ethyl acetate/hexane (2:3). Yield 55%.
Isomer B (2S*,SR*): 1H NMR (200 MHz, CDCl3) (significant signals): d ˆ
Isomer B (2S*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.68 (dd, J ˆ 7.7,
1.6 Hz, 1H), 7.39 (dt, J ˆ 7.6, 1.6 Hz, 1H), 7.21 ± 7.02 (m, 5H), 6.80 (d, J ˆ
8.6 Hz, 1H), 6.31 (q, J ˆ 1.7 Hz, 1H), 5.67 (ddd, J ˆ 5.9, 4.1, 2.0 Hz, 1H),
4.87 (ddd, J ˆ 14.6, 5.8, 1.7 Hz, 1H), 4.70 (ddd, J ˆ 14.6, 4.1, 1.9 Hz, 1H),
3.79 (s, 3H), 2.60 (s, 6H); 13C NMR (50 MHz, CDCl3): d ˆ 159.7, 151.4,
146.3, 135.4, 133.1, 131.9, 131.1, 128.8, 126.4, 123.9, 119.6, 113.5, 86.4, 74.4,
6.30 (q, J ˆ 1.8 Hz, 1H), 5.82 (ddd, J ˆ 5.9, 3.9, 1.7 Hz, 1H). Mixture A ‡ B;
‡
MS (EI): m/z (%): 298 ([M ], 11), 281 (97), 154 (17), 144 (32), 137 (43), 105
(100), 91 (78), 77 (68); HRMS (EI): m/z calcd for C18H18O2S: 298.1027;
found: 298.1029.
3-(2-Methoxyphenylsulfinyl)-2-phenyl-2,5-dihydrofuran (11): Eluent: ethyl
acetate/hexane (1:2). Yield 47%.
‡
55.2, 44.6; MS (EI): m/z (%): 343 ([M ], 7), 326 (94), 190 (44), 176 (18), 150
(100), 120 (9), 107 (7), 91 (34).
Isomer A (2R*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.57 (dd, J ˆ 8.1,
1.6 Hz, 1H), 7.36 (dt, J ˆ 8.6, 1.6 Hz, 1H), 7.30 ± 7.13 (m, 5H), 7.01 (dt, J ˆ
7.6, 0.9 Hz, 1H), 6.84 (q, J ˆ 1.7 Hz, 1H), 6.80 (dd, J ˆ 7.1, 0.7 Hz, 1H), 5.65
(ddd, J ˆ 5.5, 3.4, 1.8 Hz, 1H), 4.97 (ddd, J ˆ 14.4, 5.8, 1.7 Hz, 1H), 4.81
(ddd, J ˆ 14.2, 3.4, 1.8 Hz, 1H), 3.71 (s, 3H); 13C NMR (75 MHz, CDCl3):
Isomer A (2R*,SR*): 1H NMR (200 MHz, CDCl3) significant signals: d ˆ
6.80 (q, J ˆ 1.8 Hz, 1H), 5.55 (ddd, J ˆ 5.6, 3.6, 1.9 Hz, 1H), 3.79 (s, 3H),
2.56 (s, 6H); 13C NMR (75 MHz, CDCl3): d ˆ 159.7, 151.6, 148.1, 136.1,
132.0, 131.4, 128.5, 128.4, 127.3, 125.6, 124.1, 119.5, 113.6, 85.8, 55.2, 44.9.
3896
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0718-3896 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 18

Sulfoxide-Stereocontrolled Intermolecular Heck Reactions
3890±3900
2-[2-(N,N-dimethylamino)phenylsulfinyl]-3-(4-methoxyphenyl)-1-cyclo-
pentene (16): Eluent: ethyl acetate/CH2Cl2 (1:8). Yield 77%.
Isomer A (2R*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.66 (dd, J ˆ 7.7,
1.6 Hz, 1H), 7.36 (dt, J ˆ 7.6, 1.6 Hz, 1H), 7.10 (dt, J ˆ 7.6, 1.2 Hz, 1H),
7.10 ± 7.00 (m, 2H), 6.92 (d, J ˆ 2.1 Hz, 1H), 6.80 (q, J ˆ 1.7 Hz, 1H), 6.72 (d,
J ˆ 8.3 Hz, 1H), 5.53 (ddd, J ˆ 5.6, 3.4, 1.8 Hz, 1H), 4.93 (ddd, J ˆ 14.3, 5.8,
1.8, 1H), 4.75 (ddd, J ˆ 14.2, 3.6, 1.7 Hz, 1H), 3.80 (s, 3H), 2.60 (s, 6H), 2.15
(s, 3H); 13C NMR (50 MHz, CDCl3): d ˆ 158.0, 151.7, 148.1, 136.3, 132.0,
131.3, 130.9, 129.5, 126.6, 125.9, 125.7, 124.1, 119.5, 109.6, 86.0, 74.7, 55.3,
44.9, 16.2; HRMS (EI): m/z calcd for C20H23NO3S: 357.1399; found:
357.1392.
Isomer B (3R*,SR*): 1H NMR (200 MHz): d ˆ 7.73 (dd, J ˆ 1.6, 8.1 Hz,
1H), 7.40 (dt, J ˆ 1.6, 8.1 Hz, 1H), 7.18 (dt, J ˆ 1.6, 8.1 Hz, 1H), 7.08 ± 7.00
(m, 3H), 6.80 ± 6.72 (m, 2H), 6.07 (q, J ˆ 2.15 Hz, 1H), 4.05 (m, 1H), 3.79 (s,
3H), 2.62 (s, 6H), 2.35 ± 2.60 (m, 3H), 1.90 (m, 1H); 13C NMR (75 MHz):
d ˆ 158.2, 151.5, 150.2, 137.8, 136.5, 135.0, 131.5, 128.6, 126.6, 123.9, 119.4,
‡
113.6, 55.2, 49.6, 44.7, 35.4, 31.4; MS (EI): m/z (%): 341 ([M ], 8), 324 (83),
176 (20), 152 (81), 150 (100), 120 (15), 91 (38), 77 (27); HRMS (EI): m/z
3-[2-(N,N-dimethylamino)phenylsulfinyl]-2-(2,4-dimethoxyphenyl)-2,5-di-
hydrofuran (21): Eluent: ethyl acetate/hexane (2:3). Yield 47%.
calcd for C20H23NO2S: 341.1449; found: 341.1458.
1
Isomer A (3S*,SR*): H NMR (200 MHz, CDCl3) (significant signal): d ˆ
Isomer B (2S*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.65 (dd, J ˆ 7.8,
1.7 Hz, 1H), 7.35 (dt, J ˆ 7.6, 1.6 Hz, 1H), 7.11 (dt, J ˆ 7.5, 1.1 Hz, 1H), 7.04
(d, J ˆ 8.2 Hz, 1H), 7.01 (dd, J ˆ 8.1, 1.0 Hz, 1H), 6.37 (m, 2H), 6.10 (ddd,
J ˆ 5.8, 3.8, 1.9 Hz, 1H), 4.81 (ddd, J ˆ 14.5, 5.7, 1.7 Hz, 1H), 4.71 (ddd, J ˆ
14.4, 3.8, 1.8 Hz, 1H), 3.80 (s, 3H) 3.70 (s, 3H), 2.61 (s, 6H); 13C NMR
(75 MHz, CDCl3): d ˆ 161.0, 158.3, 151.5, 145.8, 135.6, 133.8, 131.7, 129.6,
126.3, 123.8, 119.6, 104.0, 98.2, 80.7, 74.1, 55.3, 55.2, 44.7; MS (EI): m/z (%):
6.47 (m, 1H); 13C NMR (75 MHz, CDCl3): d ˆ 151.4, 146.7, 138.5, 137.9,
132.2, 129.3, 126.4, 125.0, 124.6, 120.7, 119.9, 114.5, 55.9, 45.6, 33.6, 29.2,
23.9.
3-[2-(N,N-dimethylamino)phenylsulfinyl]-2-(4-nitrophenyl)-2,5-dihydro-
furan (17): Eluent: ethyl acetate/hexane (1:2). Yield 64%.
Isomer B (2S*,SR*): M.p. 120 ± 1218C; 1H NMR (200 MHz, CDCl3): d ˆ
8.13 (d, J ˆ 8.8 Hz, 2H), 7.62 (dd, J ˆ 7.7, 1.6 Hz, 1H), 7.43 (dt, J ˆ 7.6,
1.6 Hz, 1H), 7.30 (d, J ˆ 8.9 Hz, 2H), 7.19 (dt, J ˆ 7.6, 1.1 Hz, 1H), 7.10 (dd,
J ˆ 8.0, 0.9 Hz, 1H), 6.55 (q, J ˆ 1.9 Hz, 1H), 5.67 (ddd, J ˆ 5.8, 3.8, 1.8 Hz,
1H), 4.98 (ddd, J ˆ 14.9, 5.9, 1.6 Hz, 1H), 4.82 (ddd, J ˆ 14.8, 3.9, 1.7 Hz,
1H), 2.61 (s, 6H); 13C NMR (75 MHz, CDCl3): d ˆ 151.4, 147.8, 146.4, 145.4,
135.0, 134.5, 132.3, 128.2, 126.4, 124.1, 123.4, 119.8, 85.6, 75.2, 44.7; MS (EI):
‡
373 ([M ], 4), 356 (58), 205 (40), 190 (36), 165 (49), 150 (100), 136 (22), 120
(19), 91 (31), 77 (25); HRMS (EI): m/z calcd for C20H23NO4S: 373.1348;
found: 373.1351.
Isomer A (2R*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.71 (dd, J ˆ 7.9,
1.6 Hz, 1H), 7.37 (d, J ˆ 7.5, 1.7 Hz, 1H), 7.22 (d, J ˆ 8.2 Hz, 1H), 7.13 (dt,
J ˆ 7.6, 1.1 Hz, 1H), 7.04 (dt, J ˆ 8.0, 1.0 Hz, 1H), 6.80 (q, J ˆ 1.9 Hz, 1H),
6.45 (dd, J ˆ 8.4, 2.4 Hz, 1H), 6.38 (d, J ˆ 2.4 Hz, 1H), 5.91 (ddd, J ˆ 5.5,
3.3, 2.1 Hz, 1H), 4.85 (ddd, J ˆ 14.0, 7.5, 1.7 Hz, 1H), 4.72 (ddd, J ˆ 14.0, 3.3,
1.6 Hz, 1H), 3.81 (s, 3H), 3.71 (s, 3H), 2.50 (s, 6H); 13C NMR (75 MHz,
CDCl3): d ˆ 160.9, 158.2, 151.4, 146.7, 136.1, 131.7, 130.1, 129.3, 125.1, 124.3,
119.7, 119.4, 103.7, 98.2, 80.4, 74.2, 55.1, 55.0, 44.4; HRMS (EI): m/z calcd
for C20H23NO4S: 373.1348; found: 373.1341.
‡
m/z (%): 358 ([M ], 4), 341 (100), 190 (48), 150 (97), 120 (22), 91 (43);
elemental analysis calcd (%) for C18H18N2O4S: C 60.32, H 5.06, N 7.82, S
8.95; found: C 60.15, H 5.03, N 7.62, S 8.98.
2-[2-(N,N-dimethylamino)phenylsulfinyl]-3-(4-nitrophenyl)-1-cyclopen-
tene (18): Eluent: ethyl acetate/CH2Cl2 (1:8). Yield 83%.
Isomer B (3R*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 8.06 (m, 2H), 7.62
(dd, J ˆ 1.6, 7.5 Hz, 1H), 7.40 (dt, J ˆ 1.6, 7.5 Hz, 1H), 7.24 ± 7.12 (m, 3H),
7.04 (dd, J ˆ 1.6, 7.5 Hz, 1H), 6.48 (q, J ˆ 2.1 Hz, 1H), 3.97 (m, 1H), 2.63 (s,
6H), 2.72 ± 2.48 (m, 3H), 1.88 (m, 1H); 13C NMR (75 MHz, CDCl3)
(mixture A ‡ B): d ˆ 151.4, 151.2, 151.0, 150.8, 148.1, 146.5, 140.7, 139.1,
135.7, 131.7, 131.6, 128.3, 127.8, 127.6, 126.0, 125.4, 123.8, 123.7, 123.3, 123.1,
119.5, 119.2, 49.8, 44.6, 44.5, 35.2, 35.0, 31.6, 31.5; MS (EI): m/z (%): 356
(3R*,SR*)-4-[2-(N,N-dimethylamino)phenylsulfinyl]-3,5-diphenyl-2,3-di-
hydrofuran (22): Eluent: ethyl acetate/hexane (1:4). Yield 83%; m.p. 112 ±
1138C; 1H NMR (200 MHz, CDCl3): d ˆ 8.04 (m, 2H), 7.61 (dd, J ˆ 7.8,
1.9 Hz, 1H), 7.56 ± 7.47 (m, 3H), 7.42 (dd, J ˆ 7.5, 1.9 Hz, 1H), 7.32 ± 7.06 (m,
7H), 4.61 (dd, J ˆ 10.2, 9.1 Hz, 1H), 4.30 (dd, J ˆ 9.1, 6.2 Hz, 1H), 3.61 (dd,
J ˆ 10.3, 6.2 Hz, 1H), 2.50 (s, 6H); 13C NMR (75 MHz, CDCl3): d ˆ 165.1,
150.6, 142.1, 136.5, 131.1, 130.6, 129.0, 128.6, 128.3, 127.6, 127.0, 126.5, 123.3,
‡
([M ], 3), 340 (41), 339 (96), 176 (23), 152 (24), 150 (100), 91 (40), 77 (73);
‡
HRMS (EI): m/z calcd for C19H20N2O2S: 356.1210; found: 356.1194.
119.5, 114.5, 78.9, 49.4, 44.4; MS (EI): m/z (%): 389 ([M ], 11), 372 (65), 152
1
(73), 120 (12), 77 (61); elemental analysis calcd (%) for C24H23NO2S: C
Isomer A (3S*,SR*): H NMR (200 MHz, CDCl3) (significant signal): d ˆ
74.01, H 5.96, N 3.60, S 8.22; found: C 73.74, H 5.88, N 3.28, S 8.49. (3R,SR)-
6.70 (m, 1H).
22 (obtained from (2S,SR)-12B): [a]D25
ˆ
118 (c ˆ 1.0, CHCl3).
3-[2-(N,N-dimethylamino)phenylsulfinyl]-2-(4-methoxycarbonylphenyl)-
2,5-dihydrofuran (19): Eluent: ethyl acetate/hexane (1:1). Yield 45%.
(3R*,SR*)-4-[2-(N,N-dimethylamino)phenylsulfinyl]-3-(4-methoxyphenyl)-
5-phenyl-2,3-dihydrofuran (23): Eluent: ethyl acetate/hexane (1:4). Yield
69%; 1H NMR (200 MHz, CDCl3): d ˆ 8.01 (m, 2H), 7.58 (dd, J ˆ 7.5,
1.6 Hz, 1H), 7.53 ± 7.45 (m, 3H), 7.41 (dd, J ˆ 7.5, 1.6 Hz, 1H), 7.15 (t, J ˆ
7.5 Hz, 2H), 7.05 (d, J ˆ 8.6 Hz, 2H), 6.80 (d, J ˆ 8.6 Hz, 2H), 4.58 (dd, J ˆ
10.3, 8.9 Hz, 1H), 4.26 (dd, J ˆ 9.1, 6.4 Hz, 1H), 3.79 (s, 3H), 3.56 (dd, J ˆ
10.2, 6.3 Hz, 1H), 2.48 (s, 6H); 13C NMR (75 MHz, CDCl3): d ˆ 165.0,
158.6, 150.6, 136.5, 134.2, 131.1, 130.6, 129.1, 128.6, 128.3, 126.6, 123.3, 119.5,
114.6, 113.7, 79.0, 55.1, 48.8, 44.2.
Isomer B (2S*,SR*): 1H NMR (200 MHz, CDCl3): d ˆ 7.95 (d, J ˆ 8.2 Hz,
2H), 7.66 (dd, J ˆ 7.8, 1.7 Hz, 1H), 7.40 (dt, J ˆ 7.6, 1.7 Hz, 1H), 7.25 (d, J ˆ
8.3 Hz, 2H), 7.17 (dt, J ˆ 7.5, 1.1 Hz, 1H), 7.02 (dd, J ˆ 7.7, 1.1 Hz, 1H), 6.35
(q, J ˆ 1.8 Hz, 1H), 5.75 (ddd, J ˆ 5.9, 3.8, 1.6 Hz, 1H), 4.94 (ddd, J ˆ 14.6,
5.9, 1.7 Hz, 1H), 4.79 (ddd, J ˆ 14.6, 4.0, 1.8 Hz, 1H), 3.91 (s, 3H), 2.55 (s,
6H); 13C NMR (75 MHz, CDCl3): d ˆ 174.7, 151.4, 146.3, 144.2, 135.3, 133.3,
132.2, 130.1, 129.5, 127.3, 126.4, 124.0, 119.7, 86.3, 75.0, 52.1, 44.6; MS (EI):
‡
m/z (%): 371 ([M ], 2), 354 (49), 203 (6), 190 (31), 150 (100), 136 (30), 120
(3R*,SR*)-4-[2-(N,N-dimethylamino)phenylsulfinyl]-3-(4-nitrophenyl)-5-
phenyl-2,3-dihydrofuran (24): Eluent: ethyl acetate/hexane (1:4). Yield
46% (84% in converted yield); m.p. 119 ± 1218C; 1H NMR (200 MHz,
CDCl3): d ˆ 8.12 (d, J ˆ 8.1 Hz, 2H), 8.04 ± 7.99 (m, 2H), 7.58 (dt, J ˆ 7.6,
1.7 Hz, 1H), 7.58 ± 7.49 (m, 3H), 7.45 (dt, J ˆ 7.5, 1.6 Hz, 1H), 7.28 (d, J ˆ
8.6 Hz, 2H), 7.17 (t, J ˆ 7.4 Hz, 2H), 4.64 (dd, J ˆ 9.6, 9.4 Hz, 1H), 4.28 (dd,
J ˆ 9.3, 5.6 Hz, 1H), 3.71 (dd, J ˆ 10.2, 5.7 Hz, 1H), 2.47 (s, 6H); 13C NMR
(50 MHz, CDCl3): d ˆ 165.3, 150.7, 149.8, 146.9, 136.3, 131.4, 131.0, 128.5,
128.3, 126.1, 123.6, 123.4, 119.8, 114.0, 78.0, 49.0, 44.1; MS (EI): m/z (%):
(17), 91 (26); HRMS (EI): m/z calcd for C20H21NO4S: 371.1191; found:
371.1185; elemental analysis calcd (%) for C20 H21NO4S: C 64.67, H 5.70, N
3.77, S 8.63; found: C 64.34, H 6.04, N 3.75, S 8.25.
Isomer A (2R*,SR*): 1H NMR (200 MHz, CDCl3) (significant signals): d ˆ
6.82 (q, J ˆ 1.8 Hz, 1H), 5.65 (ddd, J ˆ 5.6, 3.4, 1.9 Hz, 1H), 3.91 (s, 3H),
2.60 (s, 6H).
3-[2-(N,N-dimethylamino)phenylsulfinyl]-2-(4-methoxy-3-methylphenyl)-
2,5-dihydrofuran (20): Eluent: ethyl acetate/hexane (1:3). Yield 86%.
‡
434 ([M ], 8), 417 (66), 150 (62), 120 (15), 105 (100), 77 (63); elemental
analysis calcd (%) for C24H22N2O4S: C 66.34, H 5.10, N 6.45, S 7.38; found:
C 66.03, H 4.90, N 6.24, S 7.00.
Isomer B (2S*,SR*): M.p. 80 ± 838C; 1H NMR (200 MHz, CDCl3): d ˆ 7.71
(dd, J ˆ 7.8, 1.7 Hz, 1H), 7.38 (dt, J ˆ 7.6, 1.7 Hz, 1H), 7.20 (dt, J ˆ 7.5,
0.9 Hz, 1H), 7.04 ± 6.98 (m, 2H), 6.87 (d, J ˆ 2.0 Hz, 1H), 6.71 (d, J ˆ
8.3 Hz, 1H), 6.30 (q, J ˆ 1.8 Hz, 1H), 5.68 (ddd, J ˆ 5.8, 4.1, 2.0 Hz, 1H),
4.88 (ddd, J ˆ 14.5, 5.8, 1.7 Hz, 1H), 4.72 (ddd, J ˆ 14.6, 4.1, 1.8 Hz, 1H),
3.81 (s, 3H), 2.61 (s, 6H), 2.14 (s, 3H); 13C NMR (50 MHz, CDCl3): d ˆ
157.8, 151.5, 146.4, 135.4, 132.7, 131.9, 130.4, 129.7, 126.4, 126.2, 123.8, 119.5,
Crystal structure data for C24H22N2O4S [(3R*,SR*)-24]: Crystal size 0.15 Â
0.50  0.30 mm, monoclinic, space group C2/c, a ˆ 35.163(3), b ˆ 6.7788(5),
c ˆ 22.205(2) Š, b ˆ 124.160(5)8, Vˆ 4379.8(6) Š3, Z ˆ 8, 1calcd
ˆ
3
1
1.318 Mgm
,
m ˆ 1.590mm
,
2qmax ˆ 114.268, CuKa radiation, l ˆ
‡
109.3, 86.5, 74.2, 55.2, 44.6, 16.2; MS (EI): m/z (%): 357 ([M ], 5), 340 (56),
1.54178 Š, 2q/w scans, Tˆ 296 K, absorption correction: none, 2942
reflections collected, 2459 independent. Refinement on F 2 for 2942
reflections and 283 parameters gave R1 ˆ 0.0521 and wR2 ˆ 0.1384 for
I > 2s(I)m Residual electron density 0.268 < D1 < 0.259 eŠ 3. S, O, N,
190 (34), 150 (100), 91 (39), 77 (27); elemental analysis calcd (%) for
C20H23NO3S: C 67.20, H 6.49, N 3.92, S 8.97; found: C 67.19, H 6.67, N 3.60, S
8.80.
Chem. Eur. J. 2001, 7, No. 18
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0718-3897 $ 17.50+.50/0
3897

J. C. Carretero et al.
FULL PAPER
and
C
atoms were refined with anisotropic thermal displacements
layer was separated, and the aqueous layer was extracted with CH2Cl2 (2 Â
50 mL). The combined organic layers were dried (Na2SO4) and the solvent
was evaporated. The residue was purified by flash chromatography (ethyl
parameters and the H atoms with isotropic parameters. The structure was
solved and refined with SHELX-97.[26]
acetate/hexane 1:1) to afford (S)-30 (1.28 g, 77%). [a]D25
ˆ
250.3 (c ˆ 1,
(3R*,SR*)-2-[2-(N,N-Dimethylamino)phenylsulfinyl]-1,3-diphenyl-1-cy-
clopentene (25): Eluent: ethyl acetate/hexane (1:6). Yield 75%; m.p. 160 ±
161 8C; 1H NMR (200 MHz, CDCl3): d ˆ 7.78 (dd, J ˆ 8.1 Hz, 2H), 7.52 ±
7.35 (m, 5H), 7.27 ± 7.15 (m, 4H), 7.12 ± 6.98 (m, 3H), 3.47 (m, 1H), 2.95 (m,
2H), 2.47 (s, 6H), 2.32 (m, 1H), 1.83 (m, 1H); 13C NMR (75 MHz, CDCl3):
d ˆ 155.7, 150.8, 143.7, 140.1, 136.7, 135.4, 131.0, 128.7, 128.4, 128.3, 127.9,
127.7, 126.7, 126.3, 123.5, 119.3, 52.3, 44.2, 36.5, 34.7; MS (EI): m/z (%): 387
CHCl3) (ee ꢀ 96%, 1H NMR, (R)-2,2,2-trifluoro-1-(9-antryl)ethanol);
1H NMR (200 MHz, CDCl3): d ˆ 7.88 (dd, J ˆ 9.7, 2.1 Hz, 1H), 7.43 (dt,
J ˆ 7.5, 1.6 Hz, 1H), 7.28 (dt, J ˆ 7.5, 2.2 Hz, 1H), 7.14 (dd, J ˆ 9.1, 1.1 Hz,
1H), 2.76 (s, 3H), 2.71 (s, 6H); 13C NMR (75 MHz, CDCl3): d ˆ 149.8,
139.6, 130.8, 123.8, 123.2, 119.3, 43.9, 41.1.
(S)-3-[2-(N,N-dimethylamino)phenylsulfinyl]-1-propanol [(S)-31]: LDA in
THF (0.5m, 6.2 mL, 3.09 mmol) at 788C under argon was added to a
solution of (S)-30 (472 mg, 2.58 mmol) in dry diethyl ether (16 mL). The
solution was stirred for 30 min and then ethylene oxide (5 mL) was added
at 788C. The reaction mixture was slowly warmed to 108C and then
kept at this temperature for 1 h. Saturated NH4Cl solution (25 mL) was
added, the organic layer was separated, and the aqueous layer was
extracted with CH2Cl2 (2 Â 50 mL). The combined organic layers were
dried (Na2SO4) and evaporated. The residue was purified by flash
‡
([M ], 6), 370 (100), 266 (6), 233 (17), 217 (39), 150 (62), 120 (10), 91 (55),
77 (23); elemental analysis calcd (%) for C25H25NOS: C 77.49, H 6.51, N
3.62, S 8.26; found: C 77.24, H 6.47, N 3.23, S 7.89. (3R,SR)-25 (obtained
from (R)-8): [a]2D5 ˆ ‡204.2 (c ˆ 1.0, CHCl3); HPLC: ee ˆ 97.7% (Chir-
1
alcelOD column; hexane/2-propanol 90:10; 0.5 mLmin
,
220 nm;
(3R,SR)-25 ˆ 10.3 min, (3S,SS)-25 ˆ 6.9 min).
Crystal structure data for C25H25NOS [(3R,SR)-25]: Crystal size 0.17 Â
0.25  0.25 mm, monoclinic, space group P21, a ˆ 8.431(2), b ˆ 14.141(3),
chromatography (ethyl acetate) to give (S)-31 (420 mg, 72%). [aD25
ˆ
c ˆ 8.867(2) Š,
b ˆ 102.19(2)8,
Vˆ 1033.3(4) Š3,
Z ˆ 2,
1calcd
ˆ
301.5 (c ˆ 1.0, CHCl3); 1H NMR (200 MHz, CDCl3): d ˆ 7.82 (dd, J ˆ
7.5, 1.6 Hz, 1H), 7.43 (dt, J ˆ 7.5, 1.6 Hz, 1H), 7.28 (dt, J ˆ 7.5, 1.1 Hz, 1H),
7.15 (dd, J ˆ 8.1, 1.1 Hz, 1H), 3.66 (brt, J ˆ 5.4 Hz, 2H), 3.40 (brs, 1H, OH),
3.20 (m, 1H), 3.00 (m, 1H), 2.69 (s, 6H), 1.87 (m, 2H); 13C NMR (50 MHz,
CDCl3): d ˆ 150.2, 136.5, 131.0, 124.4, 123.9, 119.6, 60.1, 50.6, 44.1, 25.0; MS
3
1
1.245 Mgm
,
m ˆ 1.492mm
,
2qmax ˆ 114.288, CuKa radiation, l ˆ
1.54178 Š, 2q/w scans, Tˆ 296 K, absorption correction: none, 1595
reflections collected, 1583 independent. Refinement on F 2 for 1595
reflections and 254 parameters gave R1 ˆ 0.0328 and wR2 ˆ 0.1055 for
I > 2s(I)m. Absolute structure parameter (Flack) ˆ 0.01(2). Residual
electron density 0.185 < D1 < 0.273 eŠ 3. S, O, N and C atoms were
refined with anisotropic thermal displacements parameters and the H
atoms with isotropic parameters. The structure was solved and refined with
SHELX-97.[26]
‡
(FAB): m/z (%): 228 ([M ‡1], 100).
(R)-4-[2-(N,N-dimethylamino)phenylsulfinyl]-2,3-dihydrofuran [(R)-4]:
(S)-31 (400 mg, 1.76 mmol) was dissolved in THF (12 mL), the solution
was cooled to 788C under argon, and LDA in THF (0.5m, 10.6 mL,
5.29 mmol) was added. After 30 min at 788C, ethyl formate (570 mL,
7.05 mmol) was added, and the reaction mixture was stirred at this
temperature for 2 h. A saturated aqueous solution of NH4Cl (30 mL) was
added, the reaction mixture was extracted with CH2Cl2 (3 Â 50 mL), and
the combined organic layers were dried (Na2SO4) and evaporated. The
residue was purified by flash chromatography (ethyl acetate/CH2Cl2 1:2) to
give the lactols 32 as a mixture of stereoisomers (358 mg, 80%). This
mixture of lactols (328 mg, 1.29 mmol) was dissolved in CH2Cl2 (14 mL).
The solution was cooled at 08C under argon and MsCl (200 mL, 2.57 mmol)
and Et3N (720 mL, 5.16 mmol) were sequentially added. The reaction
mixture was stirred at 08C for 1 h. Saturated aqueous NH4Cl (30 mL) was
added, the organic layer was separated, and the aqueous layer was
extracted with CH2Cl2 (2 Â 50 mL). The combined organic layers were
dried (Na2SO4) and evaporated. The residue was purified by flash
(3R*,SR*)-2-[2-(N,N-dimethylamino)phenylsulfinyl]-3-(4-methoxyphenyl)-
1-phenyl-1-cyclopentene (26): Eluent: ethyl acetate/hexane (1:4). Yield
80%; 1H NMR (200 MHz, CDCl3): d ˆ 7.81 ± 7.70 (m, 2H), 7.52 ± 7.35 (m,
5H), 7.09 (m, 2H), 6.93 (m, 2H), 6.77 (m, 2H), 3.79 (s, 3H), 3.42 (tq, J ˆ 2.1,
5.4 Hz, 1H), 2.92 (tq, J ˆ 2.1, 6.5 Hz, 2H), 2.44 (s, 6H), 2.26 (m, 1H), 1.78
(m, 1H); 13C NMR (75 MHz, CDCl3): d ˆ 158.0, 155.5, 150.7, 140.0, 136.5,
135.7, 135.3, 130.9, 128.6, 128.2 (2C), 128.1, 126.7, 123.4, 119.3, 113.2, 55.0,
51.4, 44.1, 36.3, 34.7; MS (EI): m/z (%): 417 ([M ], 33), 400 (100), 263 (26),
247 (78), 152 (34), 150 (72), 121 (29), 91 (48), 77(29); HRMS (EI): m/z calcd
for C26H27NO2S: 417.1751; found: 417.1762.
‡
(3R*,SR*)-4-[2-(N,N-dimethylamino)phenylsulfinyl]-5-(4-methoxyphenyl)-
3-phenyl-2,3-dihydrofuran (27): Eluent: ethyl acetate/hexane (1:2). Yield
78%; 1H NMR (200 MHz, CDCl3): d ˆ 7.99 (d, J ˆ 8.9 Hz, 2H), 7.60 (dd,
J ˆ 8.2, 1.8 Hz, 1H), 7.41 (dt, J ˆ 7.6, 1.7 Hz, 1H), 7.31 ± 7.06 (m, 7H), 7.00 (d,
J ˆ 9.0 Hz, 2H), 4.57 (dd, J ˆ 10.1, 9.1 Hz, 1H), 4.28 (dd, J ˆ 9.0, 5.9 Hz,
1H), 3.88 (s, 3H), 3.57 (dd, J ˆ 10.2, 5.9 Hz, 1H), 2.51 (s, 6H); 13C NMR
(75 MHz, CDCl3): d ˆ 165.1, 161.5, 150.6, 142.4, 136.5, 131.1, 130.3, 128.3,
127.6, 127.0, 126.6, 123.3, 121.5, 119.5, 113.7, 112.9, 78.7, 55.3, 49.5, 44.2.
chromatography (ethyl acetate/hexane 1:1) to give (R)-4 (215 mg, 77%).
1
[a]2D5
ˆ
221.7 (c ˆ 0.95, CHCl3) (ee ꢀ 96%, H NMR, [Pr(hfc)3]).
(2S,SS)-1,1-Diphenyl-1,2-dihydroxypropyl-2-O-[2-(N,N-dimethylamino)-
phenyl sulfinate (34): nBuLi (2.5m, 2.2 mL, 5.47 mmol) was added under
argon to a solution of N,N-dimethyl-2-iodoaniline (1.26 g, 5.11 mmol) in
dry Et2O (63 mL), cooled at 788C. This solution was slowly added to a
solution of sulfite 33 (1.0 g, 3.65 mmol) in Et2O/THF (13:1, 14 mL). The
reaction was monitored by TLC until 33 had disappeared. The mixture was
poured into water, the organic layer was separated, and the aqueous layer
was extracted with Et2O (3 Â 10 mL). The combined organic layers were
dried (MgSO4) and the solvent was evaporated. The residue was purified by
flash chromatography (ethyl acetate/hexane 1:7) to afford (2S,SS)-34
(3R*,SR*)-4-[2-(N,N-dimethylamino)phenylsulfinyl]-3,5-bis-(4-methoxy-
phenyl)-2,3-dihydrofuran (28): Eluent: ethyl acetate/hexane (1:4). Yield
70%; 1H NMR (200 MHz, CDCl3): d ˆ 7.99 (d, J ˆ 9.0 Hz, 2H), 7.60 (dd,
J ˆ 7.9, 1.8 Hz, 1H), 7.40 (dt, J ˆ 7.6, 1.7 Hz, 1H), 7.17 (t, J ˆ 7.6 Hz, 2H),
7.00 (d, J ˆ 8.8 Hz, 2H), 6.99 (d, J ˆ 8.6 Hz, 2H), 6.79 (d, J ˆ 8.7 Hz, 2H),
4.54 (dd, J ˆ 10.2, 9.1 Hz, 1H), 4.23 (dd, J ˆ 9.1, 6.0 Hz, 1H), 3.89 (s, 3H),
3.78 (s, 3H), 3.53 (dd, J ˆ 10.1, 6.1 Hz, 1H), 2.51 (s, 6H); 13C NMR
(75 MHz, CDCl3): d ˆ 164.9, 161.4, 158.5, 150.6, 136.6, 134.5, 131.0, 130.3,
128.6, 126.7, 123.2, 121.6, 119.5, 113.7, 113.0, 78.8, 55.3, 55.1, 48.8, 44.2.
(870 mg, 61%). [a]D25
ˆ
141.8 (c ˆ 1, CHCl3); 1H NMR (200 MHz,
CDCl3): d ˆ 7.95 (dd, J ˆ 1.6, 8.0 Hz, 1H), 7.53 ± 7.08 (m, 14H), 5.15 (q,
J ˆ 5.9 Hz, 1H), 2.50 (s, 6H), 1.46 (d, J ˆ 5.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d ˆ 151.9, 144.6, 143.2, 140.0, 133.1, 129.9, 127.8, 127.7, 127.2, 126.8,
(3R*,SR*)-2-[2-(N,N-dimethylamino)phenylsulfinyl]-1-(4-methoxyphenyl)-
3-phenyl-1-cyclopentene (29): Eluent: ethyl acetate/hexane (1:4). Yield
50%; 1H NMR (200 MHz, CDCl3): d ˆ 7.78 ± 7.72 (m, 2H), 7.46 ± 7.33 (m,
2H), 7.27 ± 7.14 (m, 3H), 7.12 ± 7.05 (m, 2H), 6.95 ± 7.04 (m, 4H), 3.88 (s,
3H), 3.45 (tq, J ˆ 1.1, 5.4 Hz, 1H), 2.92 (tc, J ˆ 1.6, 6.5 Hz, 2H), 2.48 (s, 6H),
2.26 (m, 1H), 1.79 (m, 1H); 13C NMR (75 MHz, CDCl3): d ˆ 160.0, 155.2,
150.7, 143.8, 138.4, 136.6, 130.9, 129.8, 127.8, 127.6, 126.7, 126.4, 126.2, 123.4,
119.3, 113.5, 55.2, 52.2, 44.2, 36.3, 34.5; MS (EI): m/z (%): 417 ([M ], 22),
400 (100), 263 (33), 247 (76), 152 (33), 150 (83), 121 (26), 91 (49), 77(27);
HRMS (EI): m/z calcd for C26H27NO2S: 417.1762; found: 417.1744.
‡
124.6, 124.4, 83.4, 80.5, 45.5, 18.4; MS (EI): m/z (%): 395 ([M ], 9), 183 (52),
169 (50), 152 (19), 136 (19), 120 (29), 105 (100), 91 (10), 77 (69); HRMS
(EI): m/z calcd for C23H24NO3S: 395.1521; found: 395.1537.
(R)-1-[2-(N,N-dimethylamino)phenylsulfinyl]-1-cyclopentene
[(R)-8]:
The sulfinate (2S,SS)-34 (200 mg, 0.51 mmol) in THF (15 mL) was slowly
added under argon to a solution of 1-cyclopentenylmagnesium bromide
(1.16 mmol) in THF (8 mL) at room temperature. The reaction was stirred
at room temperature for 1 h. The mixture was poured into water, the
organic layer was separated, and the aqueous layer was extracted with Et2O
(3 Â 10 mL). The combined organic layers were dried (MgSO4), and the
solvent was evaporated. The residue was purified by flash chromatography
(ethyl acetate/hexane 1:5) to afford (R)-8 (102 mg, 85%). [a]2D5 ˆ ‡190
(c ˆ 1, CHCl3); HPLC: ee ˆ 96.6% (ChiralcelOD column; hexane/2-
‡
(S)-2-(N,N-dimethylamino)phenyl methyl sulfoxide [(S)-30]: 1,2:5,6-Di-O-
isopropylidene-a-d-glucofuranosyl( )-(S)-methanesulfinate[20]
9.1 mmol) in toluene (30 mL) was added to a solution of o-(Me2N)C6H4-
MgI (27.3 mmol, 3 equiv) in diethyl ether (30 mL) at 08C. The mixture was
stirred for 1 h at 08C. Saturated NH4Cl (100 mL) was added, the organic
(2.93 g,
3898
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Chem. Eur. J. 2001, 7, No. 18

Sulfoxide-Stereocontrolled Intermolecular Heck Reactions
3890±3900
1
propanol 97:3; 0.5 mLmin
27.1 min)
,
l ˆ 254 nm; (R)-8 ˆ 25.1 min; (S)-8 ˆ
Org. Synth. 1996, 3, 447; d) W. Cabri, I. Candiani, Acc. Chem. Res.
1995, 28, 2; e) A. de Meijere, F. E. Meyer, Angew. Chem. 1994, 106,
2473; Angew. Chem. Int. Ed. Engl. 1994, 33, 2379.
(R)-2-Phenyl-2,5-dihydrofuran [(R)-35]:[12e] Activated zinc (1.30 g) and
saturated aqueous NH4Cl solution (5 mL) were added to a solution of
(2S,SR)-12B (106 mg, 0.34 mmol) in THF (5 mL). The mixture was stirred
vigorously at room temperature under argon. The progress of the reaction
was monitored by TLC. CH2Cl2 (20 mL) was added after 4 h. The organic
layer was separated and washed with saturated aqueous NaHCO3 (20 mL),
dried (Na2SO4), and evaporated. Flash chromatography (ethyl acetate/
hexane 1:10) of the residue gave (R)-35 (25 mg, 51%). [a]2D5 ˆ ‡282.0 (c ˆ
0.50, CHCl3) (ee ꢀ 96%, 1H NMR, [Pr(hfc)3]); 1H NMR (300 MHz,
CDCl3): d ˆ 7.23 ± 7.39 (m, 5H), 6.03 (ddt, J ˆ 6.0, 2.2, 1.6 Hz, 1H), 5.88
(ddt, J ˆ 6.0, 2.4, 1.6 Hz, 1H), 5.76 ± 5.82 (m, 1H), 4.87 (ddt, J ˆ 12.9, 6.1,
1.6 Hz, 1H), 4.76 (dddd, J ˆ 12.9, 4.1, 2.4, 1.6 Hz, 1H).
[2] For reviews on the asymmetric Heck reaction, see: a) M. Shibasaki,
E. M. Vogl, J. Organomet. Chem. 1999, 576, 1; b) M. Shibasaki, C. D. J.
Boden, A. Kojima, Tetrahedron 1997, 53, 7371; c) P. J. Guiry, A. J.
Hennessy, J. P. Cahill, Top. Catal. 1997, 4, 311.
[3] For some recent references, see: a) D. Flubacher, G. Helmchen,
Tetrahedron Lett. 1999, 40, 3867; b) J. C. Namyslo, D. E. Kaufmann,
Synlett 1999, 804; c) F. Miyazaki, K. Uotsu, M. Shibasaki, Tetrahedron
1998, 54, 13073; d) A. Kojima, T. Takemoto, M. Sodeoka, M.
Shibasaki, Synthesis 1998, 581.
[4] R. Grigg, M. J. R. Dorrty, J. F. Malone, Tetrahedron Lett. 1990, 31,
3075.
[5] a) J. L. García Ruano, B. Cid de la Plata, Top. Curr. Chem. 1999, 204,
1; b) M. C. Aversa, A. Barattucci, P. Bonaccorsi, P. Gianneto,
(2S,4R)-2,4-Diphenyltetrahydrofuran [(2S,4R)-36]:[23]
A
solution of
(3R,SR)-22 (130 mg, 0.33 mmol) in EtOH (5 mL) was added at 08C to a
suspension of Raney-Ni in EtOH (5 mL) and under a hydrogen atmos-
phere (1 atm). The reaction was monitored by TLC. After 20 h at 08C the
reaction was filtered over celite and the solvent was evaporated. The
residue was purified by flash chromatography (ethyl acetate/hexane 1:30)
Ä
Tetrahedron: Asymmetry 1997, 8, 1339; c) C. Carreno, Chem. Rev.
1995, 95, 1717.
[6] For the use of sulfoxides as chiral auxiliaries in Pauson ± Khand
reactions, see: J. Adrio, J. C. Carretero, J. Am. Chem. Soc. 1999, 121,
7411.
[7] Previous communications: a) J. C. de la Rosa, N. Díaz Buezo, J. C.
Carretero, Tetrahedron Lett. 2000, 41, 4107; b) N. Díaz Buezo, I.
Alonso, J. C. Carretero, J. Am. Chem. Soc. 1998, 120, 7129. For
to give (2S,4R)-36 (68 mg, 90%). [a]D25
ˆ
52.4 (c ˆ 1.40, CHCl3) (ee ꢀ
96%, 1H NMR, [Pr(hfc)3]); 1H NMR (300 MHz, CDCl3): d ˆ 7.47 ± 7.20
(m, 10H), 5.08 (dd, J ˆ 10.2, 5.7 Hz, 1H), 4.37 (t, J ˆ 8.4 Hz, 1H), 4.03 (t,
J ˆ 8.4 Hz, 1H), 3.65 (m, 1H), 2.77 (m, 1H), 2.02 (q, J ˆ 10.5 Hz, 1H).
Ä
intramolecular processes, see: c) N. Díaz Buezo, O. García Mancheno,
(S)-3-Phenyl-1-cyclopentene [(S)-37]:[12e] MCPBA (70%, 181 mg,
0.72 mmol) in CH2Cl2 (7 mL) was added to a solution of 14A,B (8:92)
(150 mg, 0.48 mmol) in CH2Cl2 (10 mL). The mixture was stirred vigorously
at 258C. After 4 h, saturated Na2SO3 (20 mL) and saturated aqueous
NaHCO3 (20 mL) were added. The organic layer was separated and the
aqueous layer was extracted with CH2Cl2. The combined organic layers
were dried (Na2SO4) and the solvent was evaporated. The residue was
dissolved in THF (10 mL), degassed, and cooled at 258C under argon.
Then [Pd(acac)2] (4.86, 0.02 mmol) (acac ˆ acetylacetonate) and iPrMgBr
(0.9m, 1.26 mL, 1.11 mmol) were added successively. After the mixture had
been stirred for 2 h at 258C, saturated aqueous NH4Cl (2 mL) was added.
The mixture was extracted with CH2Cl2 (2 Â 5 mL) and the combined
organic layers were dried (Na2SO4) and evaporated. The residue was
purified by flash chromatography (hexane) to give (S)-32 (69 mg, 55%).
J. C. Carretero, Org. Lett. 2000, 2, 1451.
[8] S. Jain, K. Shukla, A. Mukhopadhyay, S. N. Suryawanshi, D. S.
Bhakuni, Synth. Commun. 1990, 20, 1315.
[9] J. Priego, J. C. Carretero, Synlett 1999, 1603.
[10] Incomplete reactions were always observed with an equimolecular
amount of iodobenzene. On the other hand, other electrophiles, such
as bromobenzene and phenyltriflate, were also used in these Heck
reactions. However, these electrophiles were much less reactive than
iodobenzene; they gave low conversions and therefore very poor
yields of Heck products.
[11] a) B. C. Soderberg in Comprehensive Organometallic Chemistry II,
Vol. 3 (Eds.: E. W. Abel, F. G. A. Stone, G. Wilkinson), Pergamon,
Oxford, 1995, p. 241 ± 297. See also: b) S. O. Hillers, O. Reiser, Synlett
1995, 153.
[12] Dihydrofurans and cyclopentenes are very prone to undergo double-
bond isomerization in Heck reactions. For some asymmetric Heck
reactions of dihydrofurans and cyclopentenes, see, for instance:
a) S. R. Gilbertson, Z. Fu, D. Xie, Tetrahedron Lett. 2001, 42, 365;
b) A. J. Hennessy, Y. M. Malone, P. J. Guiry, Tetrahedron Lett. 2000,
41, 2261; c) Y. Hashimoto, Y. Horie, M. Hayashi, K. Saigo, Tetrahe-
dron: Asymmetry 2000, 11, 2205; d) C. G. Hartung, K. Köhler, M.
Beller, Org. Lett. 1999, 1, 709; e) O. Loiseleur, M. Hayashi, N.
Schmees, A. Pfaltz, Synthesis 1997, 1338; f) K. K. Hii, T. D. W.
Claridge, J. M. Brown, Angew. Chem. 1997, 109, 1033; Angew. Chem.
Int. Ed. Engl. 1997, 36, 984; g) S. Hillers, S. Sartori, O. Reiser, J. Am.
Chem. Soc. 1996, 118, 2087; h) O. Loiseleur, P. Meier, P. A. Pfaltz,
Angew. Chem. 1996, 108, 218; Angew. Chem. Int. Ed. Engl. 1996, 35,
200.
[a]2D5
ˆ
190 (c ˆ 1, CHCl3) (ee ˆ 90%, GC, Cyclosib column); 1H NMR
(200 MHz, CDCl3): d ˆ 7.28 (m, 2H), 7.18 (m, 3H), 5.94 (dq, J ˆ 2.2, 5.7 Hz,
1H), 5.77 (dq, J ˆ 2.2, 5.7 Hz, 1H), 3.89 (m, 1H), 2.44 (m, 3H), 1.73 (m, 1H).
(S)-1,3-Diphenylcyclopentene [(S)-38]: [Pd(acac)2] (2.80 mg, 0.01 mmol)
and iPrMgBr (0.9m, 750 mL, 0.66 mmol) were added to a solution of 25
(83 mg, 0.22 mmol) in THF (5 mL), degassed at room temperature under
argon. The mixture was stirred for 1.5 h at room temperature and saturated
aqueous NH4Cl (2 mL) was added. The mixture was extracted with CH2Cl2
(2 Â 10 mL) and the combined organic layers were dried (Na2SO4) and the
solvent was evaporated. The residue was purified by flash chromatography
(hexane) to give (S)-38 (37 mg, 77%). [a]2D5 ˆ ‡ 204 (c ˆ 1, CHCl3); HPLC:
ee ˆ 94% (Chiralpak AS column; hexane; 0.3 mLmin 1, l ˆ 254 nm; (S)-
38 ˆ 16.3 min, (R)-38 ˆ 18.1 min); 1H NMR (200 MHz, CDCl3): d ˆ 7.50
(m, 2H), 7.40 ± 7.12 (m, 8H), 6.23 (q, J ˆ 2.0 Hz, 1H), 4.08 (tq, J ˆ 4.1,
8.9 Hz, 1H), 2.84 (m, 2H), 2.57 (tq, J ˆ 4.5, 8.5 Hz, 1H), 1.92 (tq, J ˆ 6.9,
9.3 Hz, 1H); 13C NMR (75 MHz, CDCl3): d ˆ 146.4, 136.3, 129.3, 128.5,
128.4, 128.1, 127.8, 127.3, 126.2, 125.8, 51.9, 34.1, 33.1; MS (EI): m/z (%): 220
[13] R. Lett, A. Marquet, Tetrahedron 1974, 30, 3379.
[14] For Pd ± N coordinated complexes in Heck reactions of acyclic
nitrogen-containing vinyl ethers, see: a) M. Larhed, C. Andersson,
A. Hallberg, Tetrahedron 1994, 50, 285; b) C. Andersson, J. Larsson,
A. Hallberg, J. Org. Chem. 1990, 55, 5757; c) K. Olofsson, H. Sahlin,
M. Larhed, A. Hallberg, J. Org. Chem. 2001, 66, 544.
‡
([M ], 92), 143 (36), 91 (44), 77 (19).
[15] For conformational studies in a,b-unsaturated sulfoxides, see: a) L. F.
Tietze, A. Schuffenhauer, P. R. Schreiner, J. Am. Chem. Soc. 1998, 120,
7952; b) I. Arai, H. Takayama, T. Koizumi, Tetrahedron Lett. 1987, 28,
3689.
[16] Taking into account that the best diastereoselectivities in the Heck
arylations of alkenes 4 and 8 were obtained in the presence of
bidentate phosphines, the participation of pentacoordinate palladium
intermediates, instead of the tetracoordinate complex D, cannot be
ruled out. For asymmetric Heck reactions that involve five-coordinate
palladium intermediates, see: a) A. Ashimori, B. Bachand, L. E.
Overman, D. J. Poon, J. Am. Chem. Soc. 1998, 120, 6477; b) A.
Ashimori, B. Bachand, M. A. Calter, S. P. Govek, L. E. Overman, D. J.
Poon, J. Am. Chem. Soc. 1998, 120, 6488.
Acknowledgements
Â
Financial support of this work by the Ministerio de Educacion y Cultura
(DGES, project PB96 ± 0021), Ministerio de Ciencia Tecnología
(BQU2000 ± 0226) and Comunidad de Madrid (project 07B/28/1999) is
gratefully acknowledged. J.P. and N.D. thank the Ministerio de Educacion y
Cultura for a predoctoral fellowship.
y
Â
[1] Recent reviews: a) I. P. Beletskaya, A. V. Cheprakov, Chem. Rev.
2000, 100, 3009; b) S. Bräse, A. de Meijere in Metal-catalyzed Cross-
coupling Reactions (Eds.: F. Diederich, P. J. Stang), Wiley-VCH,
Weinheim, 1998, Chapt. 3; c) S. E. Gibson, R. J. Middleton, Contemp.
Chem. Eur. J. 2001, 7, No. 18
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0947-6539/01/0718-3899 $ 17.50+.50/0
3899

J. C. Carretero et al.
FULL PAPER
[17] Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Center as supplementary publication nos.
CCDC-160841 ((Æ)-24) and CCDC ± 149387 ((3R,SR)-25). Copies of
the data can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-336-033;
e-mail: deposit@ccdc.cam.ac.uk).
[18] J.-M. Brunel, P. Diter, M. Duetsch, H. B. Kagan, J. Org. Chem. 1995,
60, 8086.
[19] F. A., Davis, R. T. Reddy, W. Han, P. J. Carroll, J. Am. Chem. Soc.
1992, 114, 1428.
[21] F. Rebiere, O. Samuel, L. Ricard, H. B. Kagan, J. Org. Chem. 1991, 56,
5991.
[22] R. A. Holton, D. J. Crouse, A. D. Williams, R. M. Kennedy, J. Org.
Chem. 1987, 52, 2317.
Â
[23] A. D. Rodríguez, O. M. Cobar, O. L. Padilla, J. Nat. Prod. 1997, 60,
915.
[24] Unlike the case of the sulfinyldihydrofurans, the reaction of sulfinyl-
cyclopentane 14 with activated zinc gave exclusively the correspond-
ing thioether instead of the C S cleavage product.
[25] M. Julia, J. L. Fabre, Tetrahedron Lett. 1983, 24, 4311.
[26] G. M. Sheldrick, SHELX-97, University of Göttingen, Göttingen
(Germany), 1998.
Â
[20] (S)-30 was prepared following the DAG methodology: I. Fernandez,
N. Khiar, J. M. Llera, F. Alcudia, J. Org. Chem. 1992, 57, 6789.
Received: April 2, 2001 [F3167]
3900
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Chem. Eur. J. 2001, 7, No. 18