Enantioselective synthesis of aryl sulfoxides via palladium-catalyzed arylation of sulfenate anions

Article abstract of DOI:10.1021/ol702343g

Arylation of various sulfenate anions generated from β-sulfinyl esters by retro-Michael reaction in the presence of palladium(0) and enantiopure ligands gave the corresponding aryl sulfoxides in enantio-enriched form. The Josiphos-type ligand (R)-(S)-PPF-

Full text of DOI:10.1021/ol702343g

ORGANIC
LETTERS
2007
Vol. 9, No. 26
5493-5496
Enantioselective Synthesis of Aryl
Sulfoxides via Palladium-Catalyzed
Arylation of Sulfenate Anions
Guillaume Maitro, Sophie Vogel, Mounel Sadaoui, Guillaume Prestat,
David Madec,* and Giovanni Poli*
UniVersite´ Pierre et Marie Curie-Paris 6, Laboratoire de Chimie Organique (UMR
CNRS 7611), Institut de Chimie Mole´culaire (FR 2769), Case 183, 4 Place Jussieu,
F-75252 Paris Cedex 05, France
gioVanni.poli@upmc.fr; madec@ccr.jussieu.fr
Received October 7, 2007
ABSTRACT
Arylation of various sulfenate anions generated from â-sulfinyl esters by retro-Michael reaction in the presence of palladium(0) and enantiopure
ligands gave the corresponding aryl sulfoxides in enantio-enriched form. The Josiphos-type ligand (R)-(S)-PPF-t-Bu2 turned out to be the best
ligand tested, allowing ee’s up to 83% in a predictable sense.
Enantiopure sulfoxides represent an important class of
compounds because of their usefulness as chiral auxiliaries
or as chiral ligands in asymmetric catalysis.1 Moreover, a
number of sulfoxides are known in the field of pharmaceuti-
cal and medicinal chemistry.2 As a consequence, the synthesis
of chiral nonracemic sulfoxides has been of high interest for
several decades.3 Two different methods are commonly
employed for the preparation of this type of compounds: (a)
the addition of organometallic nucleophiles, such as Grignard
reagents, to enantiopure sulfinates having a stereogenic sulfur
atom,4,5 and (b) the enzymatic or catalytic asymmetric
oxidation of unsymmetrical thioethers,6 such as the modified
Sharpless procedures described by Kagan or Modena’s
groups.7 Despite their value, these two methods suffer from
some limitations such as the use of a stoichiometric amount
of chiral auxiliary in the preparation of enantiopure sulfinate
precursors and high substrate-dependency of the asymmetric
oxidation.
On the other hand, palladium-catalyzed arylation represents
a primary synthetic tool to generate carbon-heteroatom
bonds.8 In particular, the use of sulfur-based nucleophiles9
(6) For selected recent examples, see: (a) Kowalski, P.; Mitka, K.;
Ossowska, K.; Kolarska, Z. Tetrahedron 2005, 61, 1933-1953. (b)
Kaczorowska, K.; Kolarska, Z.; Mitka, K.; Kowalski, P. Tetrahedron 2005,
61, 8315-8327. (c) Madec, D.; Mingoia, F.; Macovei, C.; Maitro, G.;
Giambastiani, G.; Poli, G. Eur. J. Org. Chem. 2005, 552-557. (d) Scarso,
A.; Strukul, G. AdV. Synth. Catal. 2005, 347, 1227-1234. (e) Drago, C.;
Caggiano, L.; Jackson, R. F. W. Angew. Chem., Int. Ed. 2005, 44, 7221-
7223. (f) Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2007, 129, 8940-
8941. (g) Yamagushi, T.; Matsumoto, K.; Saito, B.; Katsuki, T. Angew.
Chem., Int. Ed. 2007, 46, 4729-4731. (h) Sun, J.; Zhu, C.; Dai, Z.; Yang,
M.; Pan, Y.; Hu, H. J. Org. Chem. 2004, 69, 8500-8503. (i) del R´ıo, R.
E.; Wang, B.; Achab, S.; Bohe´, L. Org. Lett. 2007, 9, 2265-2268.
(7) (a) Pitchen, P.; Dunach, E.; Deshmukh, M. N.; Kagan, H. B. J. Am.
Chem. Soc. 1984, 106, 8188-8193. (b) Pitchen, P.; Kagan, H. B.
Tetrahedron Lett. 1984, 25, 1049-1052. (c) DiFuria, F.; Modena, G.;
Seraglia, R. Synthesis 1984, 325-326. (d) Brunel, J. M.; Duetsch, M.;
Kagan, H. B. J. Org. Chem. 1995, 60, 8086-8088. (e) Brunel, J. M.; Kagan,
H. B. Synlett 1996, 404-406. (d) Kagan, H. B. In Catalytic Asymmetric
Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New-York, 2000; Chapter
6c.
(1) Fernandez, I.; Khiar, N. Chem. ReV. 2003, 103, 3651-3705.
(2) For reviews, see: (a) Carreno˜, M. C. Chem. ReV. 1995, 95, 1717-
1760. (b) Legros, J.; Dehli, J. R.; Bolm, C. AdV. Synth. Catal. 2005, 347,
19-31. (c) Bentley, R. Chem. Soc. ReV. 2005, 34, 609-624.
(3) Khiar, N.; Fernandez, I.; Alcudia, A.; Alcudia, F. In AdVances in
Sulfur Chemistry; Rayner, C. M., Ed.; JAI Press, Inc: Stanford, 2000; Vol.
2, p 57.
(4) (a) Andersen, K. K. Tetrahedron Lett. 1962, 3, 93-95. (b) Andersen,
K. K.; Gafield, W.; Papanikolaou, N. E.; Foley, J. W.; Perkins, J. I. J. Am.
Chem. Soc. 1964, 86, 5637-5646. (c) Mioskowski, C.; Solladie´, G.
Tetrahedron 1980, 35, 227-236. (d) Solladie´, G.; Hutt, J.; Girardin, A.
Synthesis 1987, 173.
(5) For selected recent examples, see: (a) Khiar, N.; Araujo, C. S.;
Alcudia, F.; Ferna´ndez, I. J. Org. Chem. 2002, 67, 345-356. (b) Delouvrie´,
B.; Fensterbank, L.; Na´jera, F.; Malacria, M. Eur. J. Org. Chem. 2002,
3507-3525. (c) Ruano, J. L. G.; Alemparte, C.; Aranda, M. T.; Zarzuelo,
M. M. Org. Lett. 2003, 5, 75-78. (d) Lu, B. Z.; Jin, F.; Zhang, Y.; Wu,
X.; Wald, S. A.; Senanayake, C. H. Org. Lett. 2005, 7, 1465-1468.
10.1021/ol702343g CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/23/2007

such as sulfinates10 and thiolates11 allows an easy generation
of aryl sulfones and aryl sulfides, respectively. In this context,
we recently described the synthesis of aryl sulfoxides12 by
palladium-catalyzed arylation of sulfenate anions.13
This original coupling reaction has been successfully
achieved by generation of the desired sulfenate14 anion via
â-sulfinyl esters enolate elimination15 under specifically
developed biphasic conditions (Scheme 1).16
The coupling reaction between the in situ generated p-tolyl
sulfenate anion and p-iodoanisole was chosen as the model
reaction, using toluene/H2O biphasic conditions (Table 1).
Table 1. Optimization of Reaction Conditionsa
Scheme 1
temp yield
(°C)
% eec
entry
ligand
base
solvent
(%) b (config)
1
2
3
4
5
6
7
8
9
Xantphosd KOH
tol/H2O
tol/H2O
tol/H2O
tol/H2O
tol/H2O
tol/H2O
tol/H2O
tol/H2O
tol/H2O
tol/H2O
tol/H2O
70
70
70
70
70
70
70
70
70
70
70
110
84
0
42
13
55
0
0
0
54
30
0
Binape
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
(+)-Diopf
8 (R)
29 (R)
83 (R)
A
B
C
D
E
F
G
H
B
25 (S)
12 (S)
10
11
12
Cs2CO3 tol
83
73 (R)
a Reagents and reaction conditions: p-iodoanisole (1.2 equiv), â-sulfi-
nylester, Pd2dba3 (1 mol %), ligand (2 mol %), KOH (50% aqueous solution,
20 equiv), 1:1 toluene/H2O, 70 °C or Cs2CO3 (4 equiv), at reflux of toluene.
b Yields are given for isolated products. c Enantiomeric excess was deter-
mined by chiral supercritical fluid chromatography. d Xantphos: 4,5-
bis(phenylphosphino)-9,9-dimethylxanthene. e Binap: 2,2′-bis(diphenylphos-
From this result, we reasoned that, if suitable enantiopure
ligands were used for the coupling, the prostereogenic nature
of the sulfenate anion could disclose a new route toward
enantiomerically enriched aryl sulfoxides (Scheme 2).17 Yet,
f
phino-1,1′-binaphthyl. (+)-Diop: (+)-O-isopropylidene-trans-2,3-dihydroxy-
1,4-bis(diphenyl-phosphino)butane.
Scheme 2
Preliminary experiments performed with Binap and Diop
ligands were disappointing. Indeed, with the former ligand
no sulfoxide was observed (entry 2), whereas Diop allowed
generation of the expected coupling product in a moderate
(42%) yield and a poor (8%) ee (entry 3). After the beginning
of our project, Hartwig and co-workers reported the pal-
ladium-catalyzed coupling reaction of aryl halides with thiols
using enantiopure Josiphos A as the ligand.11c Although in
Hartwig’s paper asymmetric catalysis was not addressed, this
result prompted us to test Josiphos-type ligands in our
coupling reactions.
such a strategy appeared non-obvious, as our previous study
demonstrated that achiral Xantphos was the only ligand able
to promote the coupling reaction.12
Encouragingly, use of Josiphos A as the ligand allowed
access to p-tolylsulfinyl anisole with 29% ee albeit with a
very poor yield (13%) (entry 4).
On the other hand, use of ligand B allowed generation of
the corresponding sulfoxide18 in 55% yield and a satisfactory
83% ee (entry 5). Replacement of Josiphos with the Josiphos-
type ligands C-E or Mandiphos-, Taniaphos-, and Walphos-
type ligands F-H, respectively (Figure 1), increased neither
the yield nor the enantioselectivity (entries 6-11). Finally,
optimized conditions were set with ligand B (Cs2CO3 as base
(8) Prim, D.; Campagne, J.-M.; Joseph, D.; Andrioletti, B. Tetrahedron
2002, 58, 2041-2075.
(9) Kondo, T.; Mitsudo, T.-A. Chem. ReV. 2000, 100, 3205-3220.
(10) (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M.; Bernini,
R. J. Org. Chem. 2004, 69, 5608-5614. (b) Cacchi, S.; Fabrizi, G.;
Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719-4721.
(11) For pioneering works, see: (a) Migita, T.; Shimizu, T.; Asami, Y.;
Shiobara, J.; Kato, Y.; Kosugi, M. Bull. Chem. Soc. Jpn. 1980, 53, 1385-
1389. (b) Foa`, M.; Santi, R.; Garavalia, F. J. Organomet. Chem. 1981, 206,
C29-C32. For more recent examples, see: (c) Ferna´ndez-Rodr´ıguez, M.
A.; Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 2180-2181. (d)
Ferna´ndez-Rodr´ıguez, M. A.; Shen, Q.; Hartwig, J. F. Chem. Eur. J. 2006,
12, 7582-7596. (e) Itoh, T.; Mase, T. J. Org. Chem. 2006, 71, 2203-
2206. (f) Moreau, X.; Campagne, J.-M.; Meyer, G.; Jutand, A. Eur. J. Org.
Chem. 2005, 3749-3760. (g) Mispelaere-Canivet, C.; Spindler, J.-F.; Perrio,
S.; Beslin, P. Tetrahedron 2005, 61, 5253-5259. (h) Itoh, T.; Mase, T.
Org. Lett. 2004, 6, 4587-4590. (i) Murata, M.; Buchwald, S. L. Tetrahedron
2004, 60, 7397-7403.
(13) For reviews on the chemistry of sulfenate anions, see: (a) O’Donnell,
J. S.; Schwan, A. L. J. Sulfur Chem. 2004, 25, 183-211. (b) Hogg, D. R.
Chemistry of Sulfenic Acids and Esters. The Chemistry of Sulfenic Acids
and their DeriVatiVes; Wiley-Interscience: Toronto, 1990; pp 361-402.
(c) Drabowicz, J.; Kielbasinski, P.; Mikolajczyk, M. The Chemistry of
Sulfenic Acids, Esters and their DeriVatiVes; Patai, S., Ed.; John Wiley &
Sons: New York, 1990; pp 351-429.
(12) (a) Maitro, G.; Vogel, S.; Prestat, G.; Madec, D.; Poli, G. Org. Lett.
2006, 8, 5951-5954. See also: (b) Colobert, F.; Ballesteros-Garrido, R.;
Leroux, F. R.; Ballesteros, R.; Bele´n, A. Tetrahedron Lett. 2007, 48, 6896-
6899.
5494
Org. Lett., Vol. 9, No. 26, 2007

Table 2. Scope of the Reactiona
Figure 1. Enantiopure ligands tested.
at reflux of toluene), which led to the desired sulfoxide in
83% yield, with only limited % ee erosion (entry 12).
With the optimized reaction conditions in hand, the scope
and limitations of this enantioselective transformation were
investigated by treating the â-sulfinyl esters 1a-c with a
variety of substituted aryl iodides (Table 2). p-Tolyl sulfenate
precursor 1a reacted with p- and m-iodoanisoles to afford
the corresponding isomeric sulfoxides 2a or 3a19 in 83% or
90% yields and in 73% or 68% ee’s, respectively (entries 1
and 2). On the other hand, starting from o-iodoanisole, the
coupling product 4a was isolated in 78% yield in racemic
form (entry 3). p-Iodonitrobenzene gave the sulfoxide 5a in
67% yield and 66% ee (entry 4), whereas an excellent
coupling yield (98%) and an interesting 80% ee were
(14) For examples reporting the use of sulfenate anions as precursors of
sulfoxides, sulfenic acids, sulfenate esters and thiols, see: (a) Katritzky,
A. R.; Takahashi, I.; Marson, C. M. J. Org. Chem. 1986, 51, 4914-4920.
(b) O’Donnell, J. S.; Schwan, A. L. Tetrahedron Lett. 2003, 44, 6293-
6296. (c) Maezaki, N.; Yoshigami, R.; Maeda, J.; Tanaka, T. Org. Lett.
2001, 3, 3627-3629. (d) Maezaki, N.; Yagi, S.; Ohsawa, S.; Ohishi, H.;
Tanaka, T. Tetrahedron 2003, 59, 9895-9906. (e) Maezaki, N.; Yagi, S.;
Yoshigami, R.; Maeda, J.; Suzuki, T.; Ohsawa, S.; Tsukamoto, K.; Tanaka,
T. J. Org. Chem. 2003, 68, 5550-5558. (f) Maezaki, N.; Yagi, S.; Maeda,
J.; Yoshigami, R.; Tanaka, T. Heterocycles 2004, 62, 263-277. (g)
Sandrinelli, F.; Perrio, S.; Beslin, P. J. Org. Chem. 1997, 62, 8626-8627.
(h) Sandrinelli, F.; Perrio, S.; Beslin, P. Org. Lett. 1999, 1, 1177-1180. (i)
Sandrinelli, F.; Perrio, S.; Averbuch-Pouchot, M.-T. Org. Lett. 2002, 4,
3619-3622. (j) Sandrinelli, F.; Fontaine, G.; Perrio, S.; Beslin, P. J. Org.
Chem. 2004, 69, 6916-6919. (k) Aversa, M. C.; Bonaccorsi, P.; Faggi, C.;
Lamanna, G.; Menichetti, S. Tetrahedron 2005, 61, 11902-11909. (l)
Martin, C.; Sandrinelli, F.; Perrio, C.; Perrio, S.; Lasne, M.-C. J. Org. Chem.
2006, 71, 210-214. (m) Davis, F. A. J. Org. Chem. 2006, 71, 8993-9003.
(n) Goto, K.; Keiichi, S.; Furukawa, S.; Miyasaka, S.; Takahashi, Y.;
Kawashima, T. Chem. Lett. 2006, 35, 862-863. (o) Boudou, C.; Berges,
M.; Sagnes, C.; Sopkova-de Oliveira, Santos, J.; Perrio, S.; Metzner, P. J.
Org. Chem. 2007, 72, 5403-5406. (p) Foucoin, F.; Caupene, C.; Santos
J.-F.; Sopkova-de Oliveira Santos, J.; Perrio, S.; Metzner, P. Synthesis 2007,
1315-1324.
a Reagents and reaction conditions: aryl iodide (1.2 equiv), â-sulfiny-
lester, Pd2dba3 (1 mol %), ligand B (2 mol %), Cs2CO3 (4 equiv) at reflux
of toluene. b Yields are given for isolated products. c Enantiomeric excess
was determined by chiral supercritical fluid chromatography. Absolute
configuration was determined by comparison of [R]D with literature values.
d ee% was determined by comparison of [R]D.
obtained using p-iodotrifluoromethyl benzene as the substrate
(entry 5).20 Reaction of 2-iodothiophene produced the
corresponding coupling product 7a21 in 85% yield and 49%
ee (entry 6). Starting from the â-sulfinylester 1b (R )
2-naphthyl), reaction with p-iodoanisole and p-iodotoluene
afforded the corresponding 2-naphthylsulfoxides 2b or 3b22
(15) Caupe`ne, C.; Boudou, C.; Perrio, S.; Metzner, P. J. Org. Chem.
2005, 70, 2812-2815.
(16) (a) Madec, D.; Prestat, G.; Martini, E.; Fristrup, P.; Poli, G.; Norrby,
P.-O. Org. Lett. 2005, 7, 995-998. (b) Maitro, G.; Prestat, G.; Madec, D.;
Poli, G. Synlett 2006, 1055-1058. (c) Maitro, G.; Prestat, G.; Madec, D.;
Poli, G. J. Org. Chem. 2006, 71, 7449-7454.
(17) For pioneering works concerning the use of sulfenate anions in
enantioselective approaches, see: (a) Reference 11. (b) Kobayashi, M.;
Manabe, K.; Umemura, K.; Matsuyama, H. Sulfur Lett. 1987, 6, 19-24.
(c) Drabowicz, J.; Lyzwa, P.; Mikolajczyk, M. Phosphorus Sulfur 1983,
16, 267-270.
(18) Garcia Ruano, J. L.; Alemparte, C.; Aranda, M. T.; Zarzuelo, M.
M. Org. Lett. 2003, 5, 75-78.
(19) Saeva, F. D.; Rayner, D. R.; Mislow, K. J. Am. Chem. Soc. 1968,
90, 4176-4178.
(20) Rayner, D. R.; Gordon, A. J.; Mislow, K. J. Am. Chem. Soc. 1968,
90, 4854-4860.
(21) Girodier, L.; Maignan, C.; Rouessac, F. Tetrahedron: Asymmetry
1992, 3, 857-858.
(22) Mislow, K.; Axelrod, M.; Rayner, D. R.; Gotthardt, H.; Coyne, L.
M.; Hammond, G. S. J. Am. Chem. Soc. 1965, 87, 4958-4959.
Org. Lett., Vol. 9, No. 26, 2007
5495

in 75% or 93% yields and in 72% or 65% ee’s, respectively
(entries 7 and 8). Finally, benzylsulfenate precursor 1c gave
the aryl benzylsulfoxides 2c23 or 3c24 in 67% or 71% yields
and 40% or 47% ee’s, respectively (entries 9 and 10). It is
noteworthy for predictive assignment that ligand B constantly
favors sulfur-carbon bond formation via the pro-S sulfenate
anion lone pair (Scheme 2).
In conclusion, we have reported the first asymmetric
transition-metal-catalyzed arylation of sulfenate anions,
thereby disclosing a new synthetic route toward enantio-
merically enriched aryl sulfoxides. The Josiphos-type ligand
B turned out to be the best ligand tested, allowing ee’s up
to 83% and in a predictable sense. Studies to elucidate the
details of reaction mechanism as well as the origin of the
enantioselectivity are currently in progress.
Acknowledgment. We dedicate this paper in memory of
Dr. Charles Mioskowski. CNRS and UPMC are acknowl-
edged for financial support. The sponsorship of COST Action
D40 “Innovative Catalysis: New Processes and Selectivities”
is kindly acknowledged.
Supporting Information Available: General procedures
and spectroscopic data for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
(23) Donnoli, M. I.; Superchi, S.; Rosini, C. J. Org. Chem. 1998, 63,
9392-9395.
(24) Kelly, P.; Lawrence, S. E.; Maguire, A. R. Eur. J. Org. Chem. 2006,
4500-4509.
OL702343G
5496
Org. Lett., Vol. 9, No. 26, 2007