C 1-symmetric dicyclopentadienes as new chiral diene ligands for asymmetric rhodium-catalyzed arylation of N-tosylarylimines

Article abstract of DOI:10.1021/ol101531r

Monosubstituted C₁-symmetric dicyclopentadienes as a new class of diene ligands have been developed for asymmetric arylation of N-tosylarylimines in excellent yields (98-99%) with high enantioselectivities (90-96%). The preparation of these diene ligands relied on an efficient lipase-catalyzed resolution as the key step.

Full text of DOI:10.1021/ol101531r

ORGANIC
LETTERS
2010
Vol. 12, No. 17
3820-3823
C1-Symmetric Dicyclopentadienes as
New Chiral Diene Ligands for
Asymmetric Rhodium-Catalyzed
Arylation of N-Tosylarylimines
Cheng Shao, Hong-Jie Yu, Nuo-Yi Wu, Chen-Guo Feng,* and Guo-Qiang Lin*
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road,
Shanghai 200032, China
fengcg@sioc.ac.cn; lingq@sioc.ac.cn
Received July 1, 2010
ABSTRACT
Monosubstituted C1-symmetric dicyclopentadienes as a new class of diene ligands have been developed for asymmetric arylation of
N-tosylarylimines in excellent yields (98-99%) with high enantioselectivities (90-96%). The preparation of these diene ligands relied on an
efficient lipase-catalyzed resolution as the key step.
Specifically designed ligands play a key role in transition-
metal-catalyzed asymmetric reactions.1 Thanks to the seminal
work of Hayashi and Carreira,2 the rapid development of
chiral dienes as steering ligands has paved a new avenue
for ligand design. The chiral dienes have proven to be
excellent ligands for transition-metal-catalyzed asymmetric
reactions in terms of both catalytic activities and enantiose-
lectivities.3 However, the structural diversity of chiral diene
ligands, which is very important to satisfy the demand of
different asymmetric reactions, is still limited. The majority
of chiral diene ligands used presently have a six-membered
cyclohexadiene as the basic binding framework (Scheme 1,
1-3),4-6 and a few others have eight-membered cyclooc-
tadiene (4 and 5).7,8 The ligand framework is one of the
crucial factors to determine the binding affinity and the
binding angle toward a metal center, which in turn influences
the catalytic activity and enantioselectivity of the catalyst.3b
Compared with the tunability of steric and electronic issues
(3) For reviews on chiral diene ligands, see: (a) Glorius, F. Angew.
Chem., Int. Ed. 2004, 43, 3364. (b) Defieber, C.; Gru¨tzmacher, H.; Carreira,
E. M. Angew. Chem., Int. Ed. 2008, 47, 4482. (c) Johnson, J. B.; Rovis, T.
Angew. Chem., Int. Ed. 2008, 47, 840. (d) Shintani, R.; Hayashi, T.
Aldrichim. Acta 2009, 42, 31.
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis II; Wiley:
New York, 1994. (b) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Compre-
hensiVe Asymmetric Catalysis; Springer: Berlin, 1999; Vols. 1-3. (c) Ojima,
I. Catalytic Asmmetric Synthesis; Wiley-VCH: New York, 2000.
(2) (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am.
Chem. Soc. 2003, 125, 11508. (b) Fisher, C.; Defieber, C.; Suzuki, T.;
Carreira, E. M. J. Am. Chem. Soc. 2004, 126, 1628.
(4) For recent examples on dienes 1 and 2, see: (a) Nishimura, T.; Tokuji,
S.; Sawano, T.; Hayashi, T. Org. Lett. 2009, 11, 3222. (b) Gendrineau, T.;
Chuzel, O.; Eijsberg, H.; Genet, J.-P.; Darses, S. Angew. Chem., Int. Ed.
2008, 47, 7669. (c) Mahoney, S. J.; Dumas, A. M.; Fillion, E. Org. Lett.
2009, 11, 5346
.
10.1021/ol101531r  2010 American Chemical Society
Published on Web 08/12/2010

Scheme 1
.
Design of New Diene Ligands
Scheme 2. Preparation of New DCP-Based Dienes
of the diene ligands, the modification of the ligand framework
is more difficult.9 In 2007, we successfully introduced a
series of diene ligands 5 with a nonbridged bicyclic
skeleton.8a-d In our continuing interest in finding structurally
novel diene ligands, several chiral dienes (6 and 7) with a
dicyclopentadiene (DCP) backbone were designed. Though
racemic DCP is one of the most common chelating diene
ligands for transition-metal complexes with rigid structure,10
no chiral diene ligand based on the DCP backbone has been
reported yet. Herein, we report a class of C1-symmetric
monosubstituted chiral DCPs as the first type of chiral diene
ligand with a nine-membered cyclononadiene as the basic
binding framework.
The synthesis of new diene ligands was illustrated in
Scheme 2. Both enantiomerically pure (>99%) (S)-9 and (R)-
10 were prepared via an efficient lipase-catalyzed resolution
of racemic alcohol 8, which was made from the readily
available DCP in three steps.11 Hydrolysis of (R)-10 followed
by oxidation afforded the enone 11 in high yield. Selective
reduction12 of 11 and subsequent treatment with the N-
phenyltriflimide13 gave the triflate 12. The following cross-
coupling with arylboronic acids or Grignard reagents afforded
a serial ligand 13 and 14 with different substitutes on the
double bond. The derivatization of (R)-9 generated 15a and
15b in moderate yields. The absolute stereochemical assign-
ment of compounds 9-15 was based upon the single-crystal
X-ray diffraction analysis of p-bromobenzoate 15b.14
Compared with the common diene ligands, C1-symmetric
monosubstituted chiral dienes have only one bulky substi-
tutent on the diene binding framework, which makes the
ligand synthesis easier. Though these ligands have exhibited
good performance in rhodium-catalyzed asymmetric conju-
gate additions,15 further application in other rhodium-
catalyzed reactions has not been reported yet. In order to
test the ability of our new ligands as well as explore the
new application of the C1-symmetric monosubstituted chiral
dienes, a rhodium-catalyzed arylation of N-tosylarylimines
with arylboronic acids was carried out.16,17
(5) For leading references on diene 3, see: (a) Nishimura, T.; Yasuhara,
Y.; Nagaosa, M.; Hayashi, T. Tetrahedron: Asymmetry 2008, 19, 1778. (b)
Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem. Commun.
2009, 5713. (c) Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto,
H.; Hayashi, T. Angew. Chem., Int. Ed. 2010, 49, 1638. (d) Nishimura, T.;
Wang, J.; Nagaosa, M.; Okamoto, K.; Shintani, R.; Kwong, F. Y.; Yu,
W. Y.; Chan, A. S. C.; Hayashi, T. J. Am. Chem. Soc. 2010, 132, 464.
(6) For other diene ligands based on cyclohexadiene framework: (a)
Okamoto, K.; Hayashi, T.; Rawal, V. H. Org. Lett. 2008, 10, 4387. (b)
Shintani, R.; Tsutsumi, Y.; Nagaosa, M.; Nishimura, T.; Hayashi, T. J. Am.
Chem. Soc. 2009, 131, 13588. (c) Brown, M. K.; Corey, E. J. Org. Lett.
2010, 12, 172. (d) Luo, Y.; Carnell, A. J. Angew. Chem., Int. Ed. 2010, 49,
2750.
Under the standard conditions,8a the reaction of phenyl-
boronic acid with N-tosylimine 16 in the presence of dienes
9-11 or 15a proceeded sluggishly, and low enantioselec-
tivities (4-64% ee) were obtained (entries 1-4 in Table 1).
To our delight, when a phenyl-substituted chiral diene 13a
was screened, the excellent enantioselectivity appeared (93%
(7) For leading references on diene 4: (a) Otomaru, Y.; Tokunaga, N.;
Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307. (b) Otomaru, Y.; Kina,
A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673. (c)
Shintani, R.; Ichikawa, Y.; Takatsu, K.; Chen, F. X.; Hayashi, T. J. Org.
Chem. 2009, 74, 869. (d) Punniyamurthy, T.; Mayr, M.; Dorofeev, A. S.;
Bataille, C. J. R.; Gosiewska, S.; Nguyen, B.; Cowley, A. R.; Brown, J. M.
Chem. Commun. 2008, 5092.
(11) (a) Tanaka, K.; Ogasawara, K. Synthesis 1995, 1237. (b) Hiroya,
K.; Zhang, H. L.; Ogasawara, K. Synlett 1999, 529. (c) A modified reaction
condition was applied for the scalable lipase-catalyzed resolution; see the
Supporting Information for details.
(12) Borsato, G.; De Lucchi, O.; Fabris, F.; Lucchini, V.; Frascella, P.;
Zambon, A. Tetrahedron Lett. 2003, 44, 3517.
(8) For references on diene 5: (a) Wang, Z.-Q.; Feng, C.-G.; Xu, M.-
H.; Lin, G.-Q. J. Am. Chem. Soc. 2007, 129, 5336. (b) Feng, C.-G.; Wang,
Z.-Q.; Shao, C.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2008, 10, 4101. (c) Feng,
C.-G.; Wang, Z.-Q.; Tian, P.; Xu, M.-H.; Lin, G.-Q. Chem. Asian J. 2008,
3, 1511. (d) Wang, Z.-Q.; Feng, C.-G.; Zhang, S.-S.; Xu, M.-H.; Lin, G.-
Q. Angew. Chem., Int. Ed. 2010, 49, 5780. (e) Helbig, S.; Sauer, S.; Cramer,
N.; Laschat, S.; Baro, A.; Frey, W. AdV. Synth. Catal. 2007, 349, 2331.
(9) Chiral chain dienes as ligands: (a) Hu, X.; Zhuang, M.; Cao, Z.;
Du, H. Org. Lett. 2009, 11, 4744. (b) Hu, X.; Cao, Z.; Liu, Z.; Wang, Y.;
Du, H. AdV. Synth. Catal. 2010, 352, 651.
(13) (a) Hendrickson, J. B.; Bergeron, R. Tetrahedron Lett. 1973, 14,
4607. (b) McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1983, 24, 979.
(14) See the Supporting Information for details.
(15) (a) References 4b,c and 6c. (b) Gendrineau, T.; Genet, J. P.; Darses,
S. Org. Lett. 2009, 11, 3486. (c) Gendrineau, T.; Genet, J. P.; Darses, S.
Org. Lett. 2010, 12, 308.
(16) For the asymmetric arylation of aromatic imines using chiral dienes
as ligands, see: (a) References 7a and 8a. (b) Tokunaga, N.; Otomaru, Y.;
Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc.
2004, 126, 13584. (c) Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem.
(10) Omae, I. Coord. Chem. ReV. 1983, 51, 1.
Commun. 2009, 4815.
Org. Lett., Vol. 12, No. 17, 2010
3821

Table 1. Ligand Screening in the Rhodium-Catalyzed
Phenylation of N-Tosylarylimine 16a
Table 2. Optimization of the Reaction Conditionsa
entry
solvent
additive
yieldb (%)
eec (%)
entry
ligand
time (h)
yieldb (%)
eec (%)
1
2
3
4
5
6
7
toluene
dioxane
THF
Et3N
Et3N
Et3N
Et3N
92
92
92
85
89
trace
99
93
93
92
88
90
1
2
3
4
(R)-9
(R)-10
11
15a
13a
13a
13b
13c
13d
14
24
24
24
24
6
6
6
6
6
6
32
72
77
92
92
91
93
94
86
6
17
64
4
93
93
90
88
91
32
DCE
acetone
toluene
toluene
Et3N
d
aq K3PO4
5
d
6d
7
aq KHF2
95
a The reaction was carried out with 16 (0.2 mmol), phenylboronic acid
(0.4 mmol), Et3N (0.4 mmol), [RhCl(C2H4)2]2 (0.003 mmol), and 13a
(0.0066 mmol) in solvent (1.2 mL) at 55 °C, unless otherwise noted.
b Isolated yield. c Determined by chiral HPLC analysis. d 1.5 M aqueous
solution, 0.45 mmol.
8
9
10
8
a The reaction was carried out with 16 (0.2 mmol), phenylboronic acid
(0.4 mmol), Et3N (0.4 mmol), [RhCl(C2H4)2]2 (0.005 mmol), and chiral
dienes (0.011 mmol) in toluene (1.2 mL) at 55 °C. b Isolated yield.
c Determined by chiral HPLC analysis. d Catalyst loading was reduced to
3 mol %.
Having established the optimal reaction conditions, ary-
lation with other arylboronic acids and N-tosylarylimines was
examined (Table 3). Compared with the previous results
ee for entry 5). Replacing the phenyl group with other more
sterically bulky aryl groups resulted in a slight decrease of
enantioselectivities (entries 7-9). A significant loss of
enantioselectivity was observed when ligand 14, which had
a benzyl group on the double bond (entry 10), was used.
When the catalyst loading was reduced to 3 mol %, the yield
and enantioselectivity were maintained (entry 6).
Table 3. Asymmetric Rhodium-Catalyzed Arylation of
N-Tosylarylimines with Arylboronic Acidsa
With the best ligand 13a obtained by screening, we further
optimized the reaction conditions including solvents and
additives. It was found that when dioxane or THF was used,
high yields and enantioselectivities were maintained com-
pared with the use of toluene (Table 2, entries 2 and 3 vs
1). A slight decrease in both activities and enantioselectivities
occurred when DCE or acetone was used as the solvent
(entries 4 and 5). Replacing Et3N with aqueous K3PO4
resulted in a quick decomposition of N-tosylimine 16, and
only a trace of product 17a was observed (entry 6).
Gratifyingly, when aqueous KHF2 was used as the additive,
higher yield (99%) and improved enantioselectivity (95%
ee) were achieved (entry 7).18,19
entry
Ar1
Ar2
17
yieldb (%) eec,d (%)
1
2
3
4
5
6
7
8
4-MeOC6H4 Ph
17a
17b
17c
17d
17e
17f
17g
17h
17i
99
99
99
98
98
99
99
99
99
99
99
99
98
98
99
98
95 (S)
94 (S)
94 (S)
95 (S)
96 (S)
93 (S)
95 (S)
95 (S)
94 (S)
94 (R)
93 (R)
92 (R)
90 (R)
93 (R)
93 (R)
94 (R)
4-MeC6H4
4-ClC6H4
4-BrC6H4
2-MeC6H4
2-MeOC6H4 Ph
1-naphthyl Ph
4-MeOC6H4 4-MeC6H4
4-MeOC6H4 4-CF3C6H4
4-MeOC6H4 4-ClC6H4
4-MeOC6H4 3-MeC6H4
4-MeOC6H4 3-MeOC6H4 17l
4-MeOC6H4 1-naphthyl 17m
Ph
Ph
Ph
Ph
9
10
11
12
13
14
15
16
17j
17k
(17) For selected examples of the Rh(I)-catalyzed asymmetric arylation
of aromatic imines using other catalysts, see: (a) Hayashi, T.; Ishigedani,
M. J. Am. Chem. Soc. 2000, 122, 976. (b) Hayashi, T.; Kawai, M.;
Tokunaga, N. Angew. Chem., Int. Ed. 2004, 43, 6125. (c) Kuriyama, M.;
Soeta, T.; Hao, X. Y.; Chen, O.; Tomioka, K. J. Am. Chem. Soc. 2004,
126, 8128. (d) Weix, D. J.; Shi, Y. L.; Ellman, J. A. J. Am. Chem. Soc.
2005, 127, 1092. (e) Jagt, R. B. C.; Toullec, P. Y.; Geerdink, D.; de Vries,
J. G.; Feringa, B. L.; Minnaard, A. D. J. Angew. Chem., Int. Ed. 2006, 45,
2789. (f) Duan, H. F.; Jia, Y. X.; Wang, L. X.; Zhou, Q. L. Org. Lett.
2006, 8, 2567. (g) Nakagawa, H.; Rech, J. C.; Sindelar, R. W.; Ellman,
J. A. Org. Lett. 2007, 9, 5155. (h) Kurihara, K.; Yamamoto, Y.; Miyaura,
N. AdV. Synth. Catal. 2009, 351, 260. (i) Hao, X.; Kuriyama, M.; Chen,
Q.; Yamamoto, Y.; Yamada, K.; Tomioka, K. Org. Lett. 2010, 12, 4470.
(18) For reviews on organotrifluoroborates, see: (a) Molander, G. A.;
Figueroa, R. Aldrichim. Acta 2005, 38, 49. (b) Stefani, H. A.; Cella, R.;
Vieira, A. S. Tetrahedron 2007, 63, 3623. (c) Molander, G. A.; Ellis, N.
Acc. Chem. Res. 2007, 40, 275. (d) Darses, S.; Genet, J.-P. Chem. ReV.
Ph
Ph
Ph
4-MeOC6H4 17a′
4-MeC6H4
4-ClC6H4
17b′
17c′
a The reaction was carried out with N-tosylarylimine (0.2 mmol),
arylboronic acid (0.4 mmol), 1.5 M aq KHF2 (0.45 mmol), [RhCl(C2H4)2]2
(0.003 mmol), and 13a (0.0066 mmol) in toluene (1.2 mL) at 55 °C.
b Isolated yield. c Determined by chiral HPLC analysis. d The absolute
configurations were determined by comparing with the known optical
rotations [R]D in the literature. The configurations of 17i, 17k, and 17l were
tentatively assigned by consideration of the stereochemical pathway.
obtained with other diene ligands, the diarylmethyltosylamide
products 17 were generated in higher yields (98-99%) but
2008, 108, 288
.
3822
Org. Lett., Vol. 12, No. 17, 2010

with slightly lower enantioselectivities (90-96% ee). The
phenylation of substituted benzaldimines with both electron-
withdrawing and electron-donating groups at the para posi-
tion gave the desired products in 94-95% ee (entries 1-4).
The additions of more sterically hindered imines derived
from 2-MeC6H4CHO, 2-MeOC6H4CHO, and 1-naphthalde-
hyde proceeded equally well with high enantioselectivities
(entries 5-7). High enantioselectivities (90-95%) were also
observed in the addition of a variety of arylboronic acids
bearing different substituents to 16 (entries 8-13). Similar
results were obtained when the corresponding aryl acceptor
and donor were switched, constituting a flexible apporach
for chiral diarylmethylamine synthesis (entries 1 vs 14, 2 vs
15, and 3 vs 16).
Scheme 3
.
Stereochemical Defining Pathway with Rh-13a
Complex
The stereochemical defining pathway in our arylation of
imines with 13a as the ligand is assumed to be consistent
with the similar model proposed by Hayashi16b and Darses4b
(Scheme 3). After the initial transmetalation step, the aryl
group will occupy the position far away from the phenyl
groups on the diene ligand to minimize a potential steric
repulsion. In the following step, the sterically bulky phenyl
groups on the double bond efficiently recognize the enan-
tioface of the imine when it coordinates to the rhodium
center. Accordingly, the aryl group in the metal center attacks
the activated aldimine from the Si face to give the corre-
sponding adduct.
In summary, a new class of monosubstituted C1-symmetric
diene ligands with a DCP backbone has been developed.
With an efficient lipase-catalyzed resolution as the key step,
the ligand synthesis is convenient and high yielding. These
new ligands were successfully applied in the rhodium-
catalyzed asymmetric arylation of N-tosylarylimines. The
reaction proceeded smoothly and resulted in the correspond-
ing diarylmethyltosylamides with excellent yields (98-99%)
and high enantioselectivities (90-96%). Further application
of the new ligands in asymmetric synthesis is currently
underway.
Acknowledgment. Financial support from the Major State
Basic Research Development Program (2010CB833302), the
Chinese Academy of Sciences (KJCX2-YW-H-07), and the
Shanghai Municipal Committee of Science and Technology
(09JC1417300) is acknowledged.
Supporting Information Available: Experimental pro-
cedures and characterization data, copies of 1H and 13C NMR
spectra, HPLC profiles, and X-ray data of 15b. This material
is available free of charge via the Internet at http://pubs.acs.org.
(19) For the example of KHF2 used as an additive in arylboronic acid
participated reactions, see: Su, Y.; Jiao, N. Org. Lett. 2009, 11, 2980.
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