Palladium-catalyzed asymmetric addition of diarylphosphines to α,β-unsaturated sulfonic esters for the synthesis of chiral phosphine sulfonate compounds

Article abstract of DOI:10.1021/ol402351c

Highly stereoselective addition of diarylphosphines to α,β- unsaturated sulfonic esters catalyzed through a PCP pincer-Pd complex is developed to synthesize chiral phosphine sulfonic esters with excellent enantioselectivity (up to 99.5% ee). The transform

Full text of DOI:10.1021/ol402351c

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Palladium-Catalyzed Asymmetric Addition
of Diarylphosphines to r,β-Unsaturated
Sulfonic Esters for the Synthesis of Chiral
Phosphine Sulfonate Compounds
Junzhu Lu,‡ Jinxing Ye,‡ and Wei-Liang Duan*,†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 LingLing Road, Shanghai 200032, China,
and School of Pharmacy, East China University of Science and Technology,
130 Meilong Road, Shanghai 200237, China
wlduan@mail.sioc.ac.cn
Received August 15, 2013
ABSTRACT
Highly stereoselective addition of diarylphosphines to R,β-unsaturated sulfonic esters catalyzed through a PCP pincerÀPd complex is developed
to synthesize chiral phosphine sulfonic esters with excellent enantioselectivity (up to 99.5% ee). The transformation of the chiral adduct into a
useful palladium phosphine sulfonate complex is also demonstrated.
Phosphorus compounds are ligands that are widely used
in organometallic chemistry and catalysis.1 Introducing
another heteroatom, such as nitrogen, sulfur, or oxygen
atoms, into the ligand to form hybrid phosphorus ligands
can significantly extend the application fields of these
ligands.2 Phosphine sulfonates, as a new family member
of phosphorus bidentate ligands, has received considerable
attention in the past 10 years and has proven to be effective
in polymerization, hydroformylation, dehydrogenation,
and CÀH bond activation processes.3,4 However, the
synthesis and application of optically active phosphine
sulfonate has been seldom explored.5 The first optically
active phosphine sulfonate ligand was recently prepared
(4) For reviews on the use of phosphine sulfonate ligands in catalytic
reactions, see: (a) Nakamura, A.; Anselment, T. M.; Claverie, J.; Goodall,
B.; Jordan, R. F.; Mecking, S.; Rieger, B.; Sen, A.; van Leeuwen, P. W. N.
M.; Nozaki, K. Acc. Chem. Res. 2013, 46, 1438. (b) Nakamura, A.; Ito, S.;
Nozaki, K. Chem. Rev. 2009, 109, 5215. For leading examples in
polymerization, see: (c) Drent, E.; van Dijk, R.; van Ginkel, R.; van
Oort, B.; Pugh, R. I. Chem. Commun. 2002, 744. (d) Drent, E.; van Dijk,
R.; van Ginkel, R.; van Oort, B.; Pugh, R. I. Chem. Commun. 2002, 964.
(e) Kochi, T.; Noda, S.; Yoshimura, K.; Nozaki, K. J. Am. Chem. Soc.
2007, 129, 8948. (f) Weng, W.; Shen, Z.; Jordan, R. F. J. Am. Chem. Soc.
2007, 129, 15450. (g) Bettucci, L.; Bianchini, C.;Claver, C.; Garcia Suarez,
E. J.; Ruiz, A.; Meli, A.; Oberhauser, W. Dalton Trans. 2007, 5590. (h)
Liu, S.; Borkar, S.; Newsham, D.; Yennawar, H.; Sen, A. Organometallics
2007, 26, 210. (i) Vrela, J.; Lief, G. R.; Shen, Z.; Jordan, R. F. Organo-
metallics 2007, 26, 6624. (j) Nakamura, A.; Munakata, K.; Kochi, T.;
Nozaki, K. J. Am. Chem. Soc. 2008, 130, 8128. Heckreaction: (k) Schultz,
T.; Pfaltz, A. Synthesis 2005, 1005. Allylation: (l) Sundararaju, B.;
Achard, M.; Demersean, B.; Toupet, L.; Sharma, G. V. M; Bruneau, C.
Angew. Chem., Int. Ed. 2010, 49, 2782. Dehydrogenation: (m) Sundararaju,
B.; Tang, Z.; Achard, M.; Sharma, G. V. M; Toupet, L.; Bruneau, C. Adv.
Synth. Catal. 2010, 352, 3141. (n) Yuan, K.; Jiang, F.; Sahli, Z.; Achard, M.;
Roisnel, T.; Bruneau, C. Angew. Chem., Int. Ed. 2012, 51, 8876. CÀH
activation: (o) Sundararaju, B.; Achard, M.; Sharma, G. V. M.; Bruneau,
C. J. Am. Chem. Soc. 2011, 133, 10340. (p) Boudiar, T.; Sahli, Z.;
Sundararaju, B.; Achard, M.; Kabouche, Z.; Doucet, H.; Bruneau, C.
J. Org. Chem. 2012, 77, 3674.
† Shanghai Institute of Organic Chemistry, CAS.
‡ East China University of Science and Technology.
(1) (a) Phosphorus Ligands in Asymmetric Catalysis: Synthesis and
€
Applications; Borner, A., Ed.; Wiley-VCH: Weinheim, 2008; Vols. 1À3. (b)
Phosphorus(III) Ligands in Homogeneous Catalysis; Kamer, P. C. J., van
Leeuwen, P. W. N. M., Ed.; John Wiley & Sons: Chichester, 2012.
(2) For reviews on hybrid phosphine ligands, see: (a) Wassenaar, J.;
Reek, J. N. H. Org. Biomol. Chem. 2011, 9, 1704. (b) Dieguez, M.;
Pamies, O. Isr. J. Chem. 2012, 52, 572.
(3) For early application of phosphine sulfonates in catalysis, see:
Aqueous-Phase Organometallic Catalysis; Cornils, B., Herrmann, W. A.,
Ed.; Wiley-VCH: Weinheim, 2002.
r
10.1021/ol402351c
XXXX American Chemical Society

through chiral HPLC resolution of the racemates and
applied in an asymmetric polymerization reaction by
Nozaki et al.5a Therefore, the development of efficient
methods to provide an array of optically active phosphine
sulfonates is highly desirable. We wondered, as part of
our ongoing interest in the synthesis of chiral phosphorus
compounds,6 if the asymmetric addition of phosphorus
nucleophiles to R,β-unsaturated sulfonic esters could be a
direct approach to provide chiral phosphine sulfonates
(eq 1).7,8 In this context, we report the first highly enantio-
selective synthesis of chiral phosphine sulfonate com-
pounds through the Pd-catalyzed asymmetric addition of
diarylphosphines to R,β-unsaturated sulfonic esters.
Table 1. Palladium-Catalyzed Addition of Diphenylphosphine
to R,β-Unsaturated Sulfonyl Compounds 1
sulfonyl
temp
time
(h)
yield
(%)a
ee
(%)b
entry
compound
solvent
(°C)
1
1a
1b
1c
1d
1e
1f
toluene
toluene
toluene
t-AmOH
t-AmOH
toluene
toluene
t-AmOH
t-AmOH
THF
rt
24
12
12
12
36
24
4
NR
55
À
2
rt
95
83
À
3
rt
91
4
rt
NR
NR
NR
85
R,β-Unsaturated sulfonyl compounds are good acceptors
of various carbon nucleophiles in asymmetric addition
5
rt
À
6
rt
À
7
1g
1g
1c
1c
1c
1c
1c
1c
rt
43
60
56
52
45
95
97
97
8
rt
2
88
(5) For examples of synthesis and application of the chiral phosphine
sulfonate ligand, see: (a) Nakamura, A.; Kageyama, T.; Goto, H.;
Carrow, B. P.; Ito, S.; Nozaki, K. J. Am. Chem. Soc. 2012, 134, 12366.
(b) Jiang, F.; Yuan, K.; Achard, M.; Bruneau, C. Chem.;Eur. J. 2013,
19, 10343.
9
rt
12
18
18
24
8
87
10
11
12
13
14
rt
89
CH2Cl2
toluene
toluene
toluene
rt
90
À30
À60
À78
91
(6) (a) Feng, J.-J.; Chen, X.-F.; Shi, M.; Duan, W.-L. J. Am. Chem.
Soc. 2010, 132, 5562. (b) Du, D.; Duan, W.-L. Chem. Commun. 2011, 47,
11101. (c) Chen, Y.-R.; Duan, W.-L. Org. Lett. 2011, 13, 5824. (d) Feng,
J.-J.; Huang, M.; Lin, Z.-Q.; Duan, W.-L. Adv. Synth. Catal. 2012, 354,
3122.
89
24
78
a Isolated yield. b Determined by HPLC with hexane/2-propanol.
(7) For reviews on catalytic asymmetric synthesis of chiral phos-
phanes, see: (a) Glueck, D. S. Synlett 2007, 2627. (b) Glueck, D. S.
Chem.;Eur. J. 2008, 14, 7108. (c) Harvey, J. S.; Gouverneur, V. Chem.
Commun. 2010, 7477. (d) Zhao, D.; Wang, R. Chem. Soc. Rev. 2012, 41,
2095. For leading examples, see: (e) Kovacik, I.; Wicht, D. K.; Grewal,
N. S.; Glueck, D. S.; Incarvito, C. D.; Guzei, I. A.; Rheingold, A. L.
Organometallics 2000, 19, 950. (f) Scriban, C.; Kovacik, I.; Glueck, D. S.
Organometallics 2005, 24, 4871. (g) Sadow, A. D.; Haller, I.; Fadini, L.;
Togni, A. J. Am. Chem. Soc. 2004, 126, 14704. (h) Sadow, A. D.; Togni,
A. J. Am. Chem. Soc. 2005, 127, 17012. (i) Butti, P.; Rochat, R.; Sadow,
A. D.; Togni, A. Angew. Chem., Int. Ed. 2008, 47, 4878. (j) Moncarz,
J. R.; Laritcheva, N. F.; Glueck, D. S. J. Am. Chem. Soc. 2002, 124,
13356. (k) Blank, N. F.; Moncarz, J. R.; Brunker, T. J.; Scriban, C.;
Anderson, B. J.; Amir, O.; Glueck, D. S.; Zakharov, L. N.; Golen, J. A.;
Incarvito, C. D.; Rheingold, A. L. J. Am. Chem. Soc. 2007, 129, 6847. (l)
Chan, V. S.; Bergman, R. G.; Toste, F. D. J. Am. Chem. Soc. 2007, 129,
15122. (m) Chan, V. S.; Stewart, I. C.; Bergman, R. G.; Toste, F. D.
J. Am. Chem. Soc. 2006, 128, 2786. (n) Scriban, C.; Glueck, D. S. J. Am.
Chem. Soc. 2006, 128, 2788. (o) Chan, V. S.; Chiu, M.; Bergman, R. G.;
Toste, F. D. J. Am. Chem. Soc. 2009, 131, 6021. (p) Hong, L.; Sun, W.;
Liu, C.; Zhao, D.; Wang, R. Chem. Commun. 2010, 2856. (q) Sun, W.;
Hong, L.; Liu, C.; Wang, R. Org. Lett. 2010, 12, 3914.
reactions.9 Most examples are limited to alkenyl 2-pyridyl
sulfones for the transition-metal catalyzed processes
because of the unique reactivity of the compounds de-
rived from the coordination of a nitrogen atom to metal
catalysts.9b,c R,β-Unsaturated sulfonic esters must be
used as electrophilic acceptors to realize our proposed
reaction. The only example of asymmetric nucleophilic
addition to R,β-unsaturated sulfonic esters was pioneered
by Hayashi/Nishimura and co-workers very recently.10
First, we examined the reactions of a series of R,β-
unsaturated sulfonyl compounds with diphenylphosphine
in the presence of a bisphosphino (Pincer) palladium
(9) For a review, see: (a) Nielsen, M.; Jacobsen, C. B.; Holub, N.;
~
(8) For catalytic asymmetric 1,4-addition of substituted phosphines or
phosphine oxides to electron-deficient alkenes, see: (a) Carlone, A.;
Bartoli, G.; Bosco, M.; Sambri, L.; Melchiorre, P. Angew. Chem., Int.
Ed. 2007, 46, 4504. (b) Ibrahem, I.; Rios, R.; Vesely, J.; Hammar, P.;
Paixao, M. W.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2010, 49, 2668.
For selected examples of asymmetric nucleophilic addition to R,β-
ꢀ
unsaturated sulfonyl compounds, see: (b) Mauleon, P.; Carretero,
ꢀ
J. C. Org. Lett. 2004, 6, 3195. (c) Mauleon, P.; Carretero, J. C. Chem.
ꢀ
Eriksson, L.; Himo, F.; Cordova, A. Angew. Chem., Int. Ed. 2007, 46,
ꢀ
Commun. 2005, 4961. (d) Mauleon, P.; Alonso, I.; Rivero, M. R.;
4507. (c) Bartoli, G.; Bosco, M.; Carlone, A.; Locatelli, M.; Mazzanti, A.;
Sambri, L.; Melchiorre, P. Chem. Commun. 2007, 722. (d) Fu, X.; Jiang,
Z.; Tan, C.-H. Chem. Commun. 2007, 5058. (e) Ibrahem, I.; Hammar, P.;
Carretero, J. C. J. Org. Chem. 2007, 72, 9924. (e) Desrosiers, J. N.;
Bechara, W. S.; Charette, A. B. Org. Lett. 2008, 10, 2315. (f) Bos, P. H.;
Minnaard, A. J.; Feringa, B. L. Org. Lett. 2008, 10, 4219. (g) Llamas, T.;
ꢀ
Vesely, J.; Rios, R.; Eriksso, L.; Cordova, A. Adv. Synth. Catal. 2008, 350,
ꢀ
Arrayas, R. G.; Carretero, J. C. Angew. Chem., Int. Ed. 2007, 46, 3329.
1875. (f) Zhao, D.; Mao, L.; Yang, D.; Wang, R. J. Org. Chem. 2010, 75,
6756. (g) Wen, S.; Li, L.; Wu, H.; Yu, F.; Liang, X.; Ye, J. Chem. Commun.
2010, 4806. (h) Huang, Y.; Pullarkat, S. A.; Li, L.; Leung, P.-H. Chem.
Commun. 2010, 6950. (i) Russo, A.; Lattanzi, A. Eur. J. Org. Chem. 2010,
6736. (g) Luo, X.; Zhou, Z.; Li, X.; Liang, X.; Ye, J. RSC Adv. 2011, 1,
698. (k) Yang, M.-J.; Liu, Y.-J.; Gong, J.-F.; Song, M.-P. Organometallics
2011, 30, 3793. (l) Huang, Y.; Chew, R. J.; Li, Y.; Pullarkat, S. A.; Leung,
P.-H. Org. Lett. 2011, 13, 5862. (m) Huang, Y.; Pullarkat, S. A.; Li, Y.;
Leung, P.-H. Inorg. Chem. 2012, 51, 2533. (n) Zhao, D.; Wang, L.; Yang,
D.; Zhang, Y.; Wang, R. Chem.;Asian. J. 2012, 7, 881. (o) Huang, Y.;
Pullarkat, S. A.; Teong, S.; Chew, R. J.; Li, Y.; Leung, P.-H. Organome-
tallics 2012, 31, 4871. (p) Huang, Y.; Pullarkat, S. A.; Chew, R. J.; Li, Y.;
Leung, P.-H. J. Org. Chem. 2012, 77, 6894. (q) Hatano, M.; Horibe, T.;
Ishihara, K. Angew. Chem., Int. Ed. 2013, 52, 4549.
(h) Desrosiers, J.-N.; Charette, A. B. Angew. Chem., Int. Ed. 2007, 46,
5955. (i) Moure, A. L.; Arrayas, R. G.; Carretero, J. C. Chem. Commun.
2011, 47, 4701.
(10) Nishimura, T.; Takiguchi, Y.; Hayashi, T. J. Am. Chem. Soc.
2012, 134, 9086.
(11) For reviews on pincer metal complexes, see: (a) Albrecht, M.;
van Koten, G. Angew. Chem., Int. Ed. 2001, 40, 3750. (b) Selander, N.;
ꢀ
Szabo, K. J. Chem. Rev. 2011, 111, 2048. For synthesis and application
of the chiral PCPÀPdCl complex, see: (c) Longmire, J. M.; Zhang, X.
Tetrahedron Lett. 1997, 38, 1725. (d) Longmire, J. M.; Zhang, X.; Shang,
M. Organometallics 1998, 17, 4374.
(12) Due to the oxygen sensitivity of phosphine, the 1,4-adducts were
oxidized to the corresponding phosphine oxides for analysis.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 2. Palladium-Catalyzed Asymmetric Addition of
Diarylphosphines to R,β-Unsaturated Sulfonic Esters
Scheme 1. Synthesis of a Chiral Palladium Phosphine Sulfonate
Complex Based on the Obtained Adduct
yield
ee
entry
R1
R2
Ar
(%)a (%)b,c
1
Ph
p-MeOC6H4
CH(CF3)2
CH(CF3)2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
88
91
92
86
88
87
90
92
72
88
60
79
94
85
92
88
92
89
92
90
97
97
97
96
94
95
93
97
94
96
85
93
99.5
95
97
94
91
93
96
96
2
3
p-(t-Bu)C6H4 CH(CF3)2
4
m-MeC6H4
p-FC6H4
CH(CF3)2
CH(CF3)2
CH(CF3)2
CH(CF3)2
CH(CF3)2
CH2CF3
CH2CF3
CH2CF3
CH2CF3
CH2CF3
5
6
p-BrC6H4
m-BrC6H4
2-naphthyl
3-pyridinyl
2-thienyl
7
8
9d
10d
11d,e cyclohexyl
12d
13d
i-butyl
Ph
14d,f Ph
4-NO2C6H4 Ph
p-(t-Bu)C6H4 4-NO2C6H4 Ph
15d
16d
17d
18d
19
m-MeC6H4
p-FC6H4
p-BrC6H4
Ph
4-NO2C6H4 Ph
4-NO2C6H4 Ph
4-NO2C6H4 Ph
CH(CF3)2
CH(CF3)2
p-MeOC6H4
p-ClC6H4
Figure 1. X-ray structure of the palladium phosphine sulfonate
with the thermal ellipsoids drawn at the 50% probability level.
20
Ph
a Isolated yields. b Determined by HPLC with hexane/2-propanol.
c The absolute configurations of products were determined to be R by
X-ray crystal diffraction of the adduct in entry 1 (see Supporting
Information for details). d 5 mol % cat. (S,S)-4 was used. e The reaction
was conducted at rt. f The adduct was isolated as the trivalent phosphine
without oxidation.
sulfonic esters 1 that contain electron-donating or -with-
drawing groups on the aromatic ring, such as methoxy,
halide, and alkyl moieties, can be coupled with diphenyl-
phosphine, which uniformly form chiral phosphine oxides
in high yields and with excellent stereoselectivity (86À97%
yield, 93À97% ee; Table 2, entries 1À8). Notably, the
heteroatom-containing substrates that have a strong co-
ordination ability to transition metals, such as 2-thienyl
and 3-pyridinyl moieties, were tolerated under the current
catalytic system (72À88% yield, 94À96% ee; Table 2,
entries 9 and 10). In addition to the aromatic ring, alkyl
substituted groups at the β-position of the sulfonic esters,
such as cyclohexyl and isobutyl moieties, could also be
employed as acceptors for this phosphorus addition
reaction (60À79% yield, 86À93% ee; entries 11 and 12).
Moreover, various 4-nitrophenyl sulfonic esters are also
suitable reaction partners besides polyfluoroalkyl sulfonic
esters to extend the applicability of the current protocols
(88À92% yield, 91À97% ee; entries 14À18). For the
phosphorus nucleophilic component, substituted phos-
phines that bear electron-rich or -poor groups can be
effectively added to 1c to obtain excellent yields and enan-
tioselectivity (90À92% yield, 96% ee; entries 19 and 20).
To illustrate the utility of the current method, the
obtained phosphorus compound was converted into a chi-
ral palladium phosphine sulfonate complex (Scheme 1).
Thus, the optically active phosphine sulfonic ester
(Table 2, entry 14) was hydrolyzed to obtain a sulfonic
acid. The acid then reacted with a palladacycle salt and
catalyst.6a,11,12 The ethyl sulfonic ester 1a did not show
any reactivity toward the phosphorus addition (Table 1,
entry 1). Trifluoroethyl and hexafluoroisopropyl were
introduced into the sulfonic esters instead of an ethyl
group to increase the electrophilicity of the esters, and
the reactions were examined. The reaction proceeded
smoothly with moderate to high yields and good enan-
tioselectivity (entries 2 and 3). A similar phenomenon
was also observed for phenyl-, 2-pyridyl-, and methyl-
substituted sulfonyl compounds (entries 4À6). The intro-
duction of a trifluoromethyl group into the sulfonyl accep-
tors significantly increased the reactivity of the compounds
to achieve the desired product with moderate enantioselec-
tivity (88% yield, 60% ee; entry 8). The screening solvent
indicated that toluene is better than dichloromethane,
THF, and tert-amyl alcohol (entries 9À11). Finally, low-
ering the temperature to À60 °C increased the enantioselec-
tivity of the adduct to 97% ee with an 89% yield (entry 13).
The scope of substrates was examined under optimized
conditions, and the results are shown in Table 2. Various
(13) CCDC 944780, 944781 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 2. Proposed Catalytic Cycle for the Pd-Catalyzed Ad-
dition of Diarylphosphines to R,β-Unsaturated Sulfonic Esters
Scheme 3. Proposed Stereochemical Pathway (partial groups in
(S,S)-4 are omitted for clarity)
yielded a Pd complex of phosphine sulfonate (Scheme 1,
Figure 1)13 which may act as a possible catalyst in asym-
metric reactions.4,5
atom of the Pd catalyst. This reaction affords the product
with the (R)-configuration.
The proposed catalytic cycle for the current process is
illustrated in Scheme 2. First, transphosphination occurs
between the diarylphosphine and the pincerÀPdOAc,
which affords a palladium phosphido intermediate.6a
Then, the nucleophilic phosphorus addition to the β-
position of the sulfonic ester 1 generates a palladium
phosphine complex that bears a pendant anion.7f Finally,
the reaction of this Pd intermediate with HOAc releases
product 3 and regenerates active catalyst 4. The tentative
stereochemical pathway for the formation of (R)-product
is shown in Scheme 3. The spatial orientations of the
phenyl rings on the phosphorus atoms are different from
one another because of the existence of two chiral methyl
groups at the benzylic position of catalyst (S,S)-4. There-
fore, a chiral environment is established around the palla-
dium atom. The R,β-unsaturated sulfonic ester 1 reaches
the palladium phosphido intermediate with its R-Re face
preferentially to avoid the unfavorable steric interactions
between the substituent at the β-position of sulfonic esters
and the phenyl groups that protrude from the phosphorus
In summary, we have reported the pincer palladium-
catalyzed enantioselective addition of diarylphosphines to
R,β-unsaturated sulfonic esters for preparing chiral phos-
phorus sulfonyl compounds in high yields and excellent
enantiomeric excess under mild conditions. The investiga-
tion of optically active phosphine sulfonyl compounds,
such as bidentate ligands, toward transition metals, and
the application of these compounds as a catalyst in asym-
metric processes are currently under study.
Acknowledgment. We thank the National Basic Re-
search Program of China (973 Program 2010CB833300),
NSFC (20902099, 21172238), and SIOC for financial
support.
Supporting Information Available. Experimental pro-
cedures and characterization of the products. This mate-
rial is available free of charge via the Internet at http://
pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX