Catalytic enantioselective arylation of N-tosylarylimines with arylboronic acids using C2-symmetric cationic N-heterocyclic carbene Pd 2+ diaquo complexes

Article abstract of DOI:10.1021/ol802861s

The asymmetric arylation of N-tosylimines with arylboronic acids was realized by using chiral cationic C₂-symmetric N-heterocyclic carbene (NHC) Pd²⁺ diaquo complex 5b as the catalyst in combination with 1.0 equiv of K₃PO<

Full text of DOI:10.1021/ol802861s

ORGANIC
LETTERS
2009
Vol. 11, No. 4
875-878
Catalytic Enantioselective Arylation of
N-Tosylarylimines with Arylboronic Acids
Using C2-Symmetric Cationic N-Heterocyclic
Carbene Pd2+ Diaquo Complexes
Guang-Ning Ma,† Tao Zhang,† and Min Shi*,†,‡
School of Chemistry & Molecular Engineering, East China UniVersity of Science and
Technology, 130 Mei Long Road, Shanghai 200237, China, and State Key Laboratory
of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
mshi@mail.sioc.ac.cn
Received December 11, 2008
ABSTRACT
The asymmetric arylation of N-tosylimines with arylboronic acids was realized by using chiral cationic C2-symmetric N-heterocyclic carbene
(NHC) Pd2+ diaquo complex 5b as the catalyst in combination with 1.0 equiv of K3PO4·3H2O in THF at 4 °C in the presence of powdered 4 Å
MS to afford the corresponding adducts in excellent yields (up to 99%) and good to high enantioselectivities (up to 94% ee).
In the past decade, the use of N-heterocyclic carbenes
(NHCs) as ligands for metal-mediated reactions has attracted
considerable attention.1 NHCs as the chiral ligands showed
several advantages over their phosphine counterparts. Usu-
ally, NHC ligands are stronger σ donors and weaker π
acceptors than phosphine ligands; these ligands are also air/
moisture stable, which makes handling much more con-
venient. These advantages have attracted several research
groups to search for new catalytic systems using NHCs as
ancillary ligands for many catalytic reactions, such as
NHC-Ru catalyzed olefin metathesis,2a,b transition-metal-
mediated cross-coupling reactions,2c-e and transfer hydro-
genation of ketones.2f,g Thus far, there have been few reports
* To whom correspondence should be addressed. Fax: 86-21-64166128.
† East China University of Science and Technology.
‡ Shanghai Institute of Organic Chemistry.
(1) For selected reviews on NHC ligands, see: (a) Nolan, S. P., Ed.
N-Heterocyclic Carbenes in Synthesis; Wiley-VCH: Weinheim, Germany,
2006. (b) Glorius, F. N-Heterocyclic Carbenes in Transition Metal Catalysis;
Springer: Berlin, 2007. (c) Herrmann, W. A. Angew. Chem., Int. Ed. 2002,
41, 1290. (d) Kirmse, W. Angew. Chem., Int. Ed. 2004, 43, 1767. (e) Perry,
M. C.; Burgess, K. Tetrahedron: Asymmetry 2003, 14, 951. (f) Cesar, V.;
Bellemin-Laponnaz, S.; Gade, L. H. Chem. Soc. ReV. 2004, 33, 619. (g)
Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed.
2007, 46, 2768.
(2) (a) Scholl, M.; Dong, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953. (b) Choi, T. -L.; Grubbs, R. H. Angew. Chem., Int. Ed. 2003, 42,
1743. (c) Navarro, O.; Kelly, R. A., III; Nolan, S. P. J. Am. Chem. Soc.
2003, 125, 16194. (d) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.;
Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101. (e) Navarro,
O.; Marion, N.; Mei, J.; Nolan, S. P. Chem.sEur. J. 2006, 12, 5142. (f)
Albrecht, M.; Crabtree, R. H.; Mata, J.; Peris, E. Chem. Commun. 2002,
32. (g) Albrecht, M.; Miecznikowski, J. R.; Samuel, A.; Faller, J. W.;
Crabtree, R. H. Organometallics 2002, 21, 3596.
10.1021/ol802861s CCC: $40.75
Published on Web 01/13/2009
2009 American Chemical Society

regarding the use of chiral NHC-metal complexes in
asymmetric catalysis.1c,3 In this paper, we report the first
example of using chiral C2-symmetric cationic NHC-Pd2+
diaquo complexes,4 derived from 1,1′-binaphthalenyl-2,2′-
diamine (BINAM) and H8-BINAM, for the enantioselective
arylation of N-tosylimines with arylboronic acids under mild
conditions.5-7
The cationic NHC-Pd(II) catalysts 5a-c were prepared in
quantitative yields by mixing NHC-PdX2 complexes 4a-c
with 1.1 equiv of AgOTf in CH2Cl2 and CH3CN. Similarly,
NHC-Pd(II) complexes 5d and 5e were synthesized from
(S)-1 and (R)-H8-1 by the same procedures, respectively. The
detailed reaction procedures as well as the spectroscopic data
can be found in the Supporting Information. The crystalline
catalyst, 5a, was obtained and determined by X-ray structural
analysis, and its ORTEP drawing is shown in Figure 2, and
its CIF data are presented in the Supporting Information.8
Figure 1.
Chiral cationic NHC-Pd2+ diaquo complexes 5a-e.
As shown in Figure 1, a series of the chiral cationic
NHC-Pd2+ diaquo complexes 5a-e were designed and
synthesized in a three-step pathway starting from optically
active 2,2′-di(1H-benzo[d]imidazol-1-yl)-1,1′-binaphthyl 1.
The corresponding imidazolium salts 3a-c were afforded
in good yields from the reaction of optically active (R)-1
with alkyl halides 2a-c (RX, X ) Br, I) in dioxane under
reflux, which were then converted to the NHC-PdX2
complexes 4a-c (X ) Br, I) by treatment with Pd(OAc)2.
Figure 2. ORTEP drawing of NHC-Pd(II) complex 5a. Thermal
ellipsoids at the 30% probability level. Counterions (OTf-) and
hydrogen atoms are omitted for clarity. Selected bond distances
(Å) and angles (deg): Pd-C1 ) 1.940(5), Pd-C29 ) 1.970(5),
Pd-O1 ) 2.094 (4), Pd-O2 ) 2.102 (4), N2-C9 ) 1.428 (6),
N4-C28 ) 1.449(6), O1-Pd-O2 ) 90.73(18), C1-Pd-C29 )
92.3(2),C1-Pd-O1)88.5(2),C29-Pd-O2)88.7(2),O1-Pd-C29
) 175.9(2), C1-Pd-O2 ) 179.2(2), N1-C1-N2 ) 106.5(4),
N3-C29-N4 ) 107.8(4).
(3) (a) Bonnet, L. C.; Douthwaite, R. E.; Kariuki, B. M. Organometallics
2003, 22, 4187. (b) Gade, L. H.; Cesar, V.; Bellemin-Laponnaz, S. Angew
Chem., Int. Ed. 2004, 43, 1014. (c) Van Veldhuizen, J. J.; Garber, S. B.;
Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954. (d)
Van Veldhuizen, J. J.; Gillingham, D. G.; Garber, S. B.; Kataoka, O.;
Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 12502. (e) Larsen, A. O.;
Leu, W.; Oberhuber, C. N.; Campbell, J. E.; Hoveyda, A. H. J. Am. Chem.
Soc. 2004, 126, 11130.
An initial experiment was carried out by reacting N-
tosylimine 6a with phenylboronic acid 7a in the presence
of NHC-Pd2+ diaqua catalyst 5a (3 mol %) together with 4
Å molecular sieves. The reaction was conducted in anhydrous
THF at 20 °C to afford 8aa in 43% yield and 58% ee with
the S-configuration for the major enantiomer. Adding 1.0
equiv of KOH or K3PO4·3H2O to the catalytic system led to
product, 8aa, in 82% yield/84% ee and 81% yield/80% ee,
respectively (Table S1 in the Supporting Information).9
(4) For the papers of our group on the chiral NHC-Pd(II) complexes,
see: (a) Chen, T.; Jiang, J. J.; Xu, Q.; Shi, M. Org. Lett. 2007, 9, 865. (b)
Zhang, T.; Shi, M. Chem.sEur. J. 2008, 14, 3759.
(5) For the synthesis and application of chiral cationic Pd2+ diaquo
complexes with BINAP phosphine ligand, see: (a) Sedeoka, M.; Tokunoh,
R.; Miyazaki, F.; Hagiwara, E.; Shibasaki, M. Synlett 1997, 463. (b)
Sedeoka, M.; Shibasaki, M. Pure Appl. Chem. 1998, 70, 411. (c) Fujii, A.;
Hagiwara, E.; Sedeoka, M. J. Am. Chem. Soc. 1999, 121, 5450
.
(6) Selected papers of Rh(I)-catalyzed asymmetric addition of N-
tosylarylimines with arylboronic acids: (a) Tokunaga, N.; Otomaru, Y.;
Okamoto, K.; Ueyama, K.; Shinatani, R.; Hayashi, T. J. Am. Chem. Soc.
2004, 126, 13584. (b) Jagt, R. B. C.; Toullec, P. Y.; Geerdink, D.; de Vries,
J. G.; Feringa, B. L.; Minnaard, A. J. Angew. Chem., Int. Ed. 2006, 45,
2789. (c) Duan, H.; Jia, Y.; Wang, L.; Zhou, Q. Org. Lett. 2006, 8, 2567.
(d) Wang, Z. Q.; Feng, C. G.; Xu, M. H.; Lin, G. Q. J. Am. Chem. Soc.
2007, 129, 5336. (e) Chiara, M.; Chiara, M.; Cesare, G.; Umberto, P. Synlett
2007, 2213. For Rh(I)-catalyzed asymmetric addition of N-Boc-arylimines
(Boc ) tert-butyloxycarbonyl) with arylboronic acids, see: (f) Nakagawa,
H.; Rech, J. C.; Sindelar, R. W.; Ellman, J. A. Org. Lett. 2007, 9, 5155.
For Rh(I)-catalyzed asymmetric addition of N-Dpp-arylimines (Dpp )
diphenylphosphinoyl) with arylboronic acids, see: (g) Weix, D. J.; Shi, Y.;
Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 1092. For selected papers of
Pd(II)-catalyzed asymmetric addition of N-tosylarylimines with arylboronic
acids, see: (h) He, P.; Lu, Y.; Hu, Q. S. Tetrahedron Lett. 2007, 48, 5283.
(i) Zhang, Q.; Chen, J.; Wu, M.; Cheng, J.; Qin, C.; Su, W.; Ding, J. Synlett
We next evaluated the cationic NHC-Pd2+ catalysts 5b-e
for the arylation of N-tosylimine 6a with 7a by using 1.0
equiv of KOH or K3PO4·3H2O as the base in various solvents
under the standard conditions. The results of these experi-
ments are summarized in Table 1 (Table S2 in the Supporting
Information). Using 5b as the catalyst produced 8aa in >99%
(8) The crystal data of 5a have been deposited with the CCDC (no.
299484): empirical formula, C38H32F6N4O9PdS2; formula weight, 973.20;
crystal color, habit, colorless, prismatic; crystal dimensions, 0.339 × 0.167
× 0.119 mm; crystal system, orthorhombic; lattice type, primitive; lattice
parameters, a ) 8.9946(5) Å, b ) 19.7790(10) Å, c ) 22.9386(12) Å, R
) 90°, ꢀ ) 90°, γ ) 90°, V ) 4080.6(4) Å3; space group, P2(1); Z ) 4;
Dcalc ) 1.584 g/cm3; F000 ) 1968; diffractometer, Rigaku AFC7R; residuals,
R; wR, 0.0507, 0.0966.
2008, 935
.
(7) (a) Dai, H.; Lu, X. Org. Lett. 2007, 9, 3077. (b) Dai, H.; Yang, M.;
Lu, X. AdV. Synth. Catal. 2008, 350, 249
.
(9) Sakuma, S.; Miyaura, N. J. Org. Chem. 2001, 66, 8944.
876
Org. Lett., Vol. 11, No. 4, 2009

yield and 80% ee, which is more effective than 5c and 5e
under the standard conditions (Table 1, entries 1, 2, and 4).
Moreover, using 5d as the catalyst afforded 8aa in >99%
yield and 82% ee with the R-configuration for the major
enantiomer (Table 1, entry 3). The examination of the
solvents using 5a as the catalyst revealed that THF is the
solvent of choice. In acetonitrile, the reaction became
sluggish, and in DMF, no reaction occurred (Table 1, entries
5 and 19, 4 > 11). Upon examination of the reaction
temperature, we found that carrying out the reaction at 4 °C
provided 8aa in 86% ee and 75% yield using 5a as the
catalyst after 36 h (Table 1, entries 12-15). Pleasingly, it
was found that the use of NHC-Pd2+ diaqua catalyst 5b as
the catalyst and K3PO4·3H2O as the base led to the adduct
8aa in >99% yield and 90% ee in THF at 4 °C (Table 1,
entry 17). In the presence of NHC-Pd2+ catalyst 5d, adduct
8aa was obtained in >99% yield and 88% ee with the
R-configuration under identical conditions (Table 1, entry
18).
they have electron-donating or electron-withdrawing sub-
stituents on their benzene rings. Furthermore, the position
of substituents of imine substrates is not restrictive for
obtaining high enantioselectivities (Table 2, entries 1-16).
For N-tosyl heterocyclic imines 6q and 6r, the adducts 8qa
and 8ra were obtained in 99% yield/80% ee and 87% yield/
83% ee, respectively (Table 2, entries 17 and 18).
Table 2. Catalytic Asymmetric Arylation of N-Tosylimines 6
with Phenylboronic Acid 7aaa
yield of
8 (%)b
ee of
8 (%)c,d
entry
Ar1
Ar2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
4-ClC6H4 (6a)
3-ClC6H4 (6b)
2-ClC6H4 (6c)
4-BrC6H4 (6d)
3-BrC6H4 (6e)
2-BrC6H3 (6f)
C6H5 (7a) 99 (8aa)
90 (S)
82 (S)
90 (S)
60 (S)
94 (S)
84 (S)
94 (S)
90 (S)
86 (S)
90 (S)
88 (S)
92 (S)
84 (S)
81 (S)
85 (S)
90 (S)
80 (S)
83 (S)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
C6H5 (7a)
97 (8ba)
99 (8ca)
64 (8da)
85 (8ea)
93 (8ea)
99 (8ga)
96 (8ha)
96 (8ia)
99 (8ja)
99 (8ka)
99 (8la)
99 (8ma)
99 (8na)
85 (8oa)
95 (8pa)
99 (8qa)
87 (8ra)
Having established an optimal reaction condition, the
arylation of a variety of N-tosylimines 6b-r having diverse
substituents on the benzene rings was evaluated for the
reaction with 7a. The results are summarized in Table 2.
The diarylmethyltosylamide products 8 were generated in
high yields (up to 99%) and good ee’s (up to 94%) whether
4-FC6H4 (6g)
2,4-Cl2C6H3 (6h)
2,3-Cl2C6H3 (6i)
4-CH3C6H4 (6j)
4-CH3OC6H4 (6k)
2-CH3OC6H4 (6l)
4-NO2C6H4 (6m)
3-NO2C6H4 (6n)
2-NO2C6H4 (6o)
Table 1. Catalyst Screening and Reaction Condition
Optimizationa
1-naphthalene (6p) C6H5 (7a)
2-furanyl (6q)
thiophen-2-yl (6r)
C6H5 (7a)
C6H5 (7a)
a See the Supporting Information for details. b Isolated yields. c Determined
by chiral HPLC analysis. d The absolute configurations were determined
by comparing the optical rotation with those of known data.
yield of ee of
T
time 8aab 8aac
entry catalyst
base
KOH
solvent (°C) (h)
(%)
(%)
1
2
5b
5c
5d
5e
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
5b
5d
5b
5b
THF
THF
THF
THF
toluene
dioxane 20
CH2Cl2
CHCl3
MeOH
20
20
20
20
20
12 >99
36 20
12 >99
80 (S)
77 (S)
82 (R)
66 (S)
11 (S)
40 (S)
20 (R)
35 (R)
31 (S)
n.d.
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KF
Encouraged by the above results, we then studied the
substrates of a variety of arylboronic acids 7b-h that were
subjected to the reactions with N-tosylimines 6 under the
standard conditions. The results are summarized in Table 3.
The corresponding diarylmethylamide products 8 were
produced in good to excellent yields (80-99%) and ee’s
(85-93%), whether they have electron-donating or electron-
withdrawing substituents on their benzene rings (Table 3,
entries 1-7). Very recently, Ellman reported an efficient
asymmetric addition of arylboronic acids to aliphatic N-
tosylimines with Rh(I)/(R,R)-1-benzyl-3,4-bis(diphenylphos-
phino)pyrrolidine [(R,R)-Deguphos] catalytic system and
showed great success.10 To our delight, by using cationic
Pd2+ diaquo complex 5b as the catalyst, N-tosyl aliphatic
imine substrates 6s and 6u led to products 8ue and 8uh in
80% yield/94% ee and in 65% yield/94% ee, respectively
(Table 3, entries 11 and 12). Even for the linear N-tosyl
3
4
5
6
7
8
9
36
36
36
36
36
36
47
83
82
75
94
60
20
20
20
10
11
12
13
14
15
16
17
18
19
20
CH3CN 20
48 <10
DMF
THF
THF
THF
THF
THF
20
4
-10
50
36
36
n.r. n.d.
75
86 (S)
n.d.
36 <10
36
68
40
73 (S)
62 (S)
83 (S)
90 (S)
88 (R)
83 (S)
90 (S)
reflux 36
4
4
4
0
0
12 >99
12 >99
12 >99
24 <99
K3PO4·3H2O THF
K3PO4·3H2O THF
KOH
THF
K3PO4·3H2O THF
24
93
a Reaction conditions: phenylboronic acid (7a, 0.5 mmol), N-tosyl-p-
chlorobenzaldehyde imine (6a, 0.25 mmol), NHC-Pd2+ (3 mol %, 0.0075
mmol), and 4 Å MS (200 mg). b Isolated yields. c The ee value was
determined by HPLC using a Chiralcel OD-H column.
(10) For Rh(I)-catalyzed addition of arylboronic acids with N-tosyl and
N-Dpp aliphatic imines, see: Trincado, M.; Ellman, J. A. Angew. Chem.,
Int. Ed. 2008, 47, 5623.
Org. Lett., Vol. 11, No. 4, 2009
877

Table 3. Catalytic Asymmetric Arylation of N-Tosylimines 6
with Arylboronic Acids 7a
Scheme 1. Proposed Mechanism for the Catalytic Asymmetric
Arylation of N-Tosylimines with Phenylboronic Acid
yield of
8b (%)
ee of
8c,d (%)
entry
R
Ar
1
2
3
4
5
4-ClC6H4 (6a)
4-ClC6H4 (6a)
C6H5 (6t)
C6H5 (6t)
2-ClC6H4 (6c)
2-ClC6H4 (6c)
4-CH3OC6H4 (7b) 90 (8ab) 84 (S)
3-CH3C6H4 (7c)
4-FC6H4 (7d)
4-PhC6H4 (7e)
4-CF3C6H4 (7f)
3-ClC6H4 (7g)
92 (8ac)
90 (8td)
80 (8te)
99 (8cf)
99 (8cg)
84 (S)
81 (R)
93 (S)
86 (S)
91 (S)
6
7
8
9
1-naphthyl (6p) 2-naphthyl (7h)
1-naphthyl (6p) 4-PhC6H4 (7e)
CH3CH2CH2 (6s) C6H5 (7a)
92 (8ph) 91 (S)
95 (8pe) 90 (S)
64 (8sa)
66 (S)
10
11
12
cyclohexyl (6u)
cyclohexyl (6u)
cyclohexyl (6u)
C6H5 (7a)
4-PhC6H4 (7e)
2-naphthyl (7h)
99 (8ua) 85 (S)
80 (8ue) 94 (S)
65 (8uh) 94 (S)
a See the Supporting Information for details. b Isolated yields. c Determined
by chiral HPLC analysis. d The absolute configurations were determined
by comparing the optical rotation [R]D with those known data.
aliphatic imine substrate 6s, the corresponding adduct 8sa
was obtained in 64% yield and 66% ee (Table 3, entry 9).
A possible mechanism for this reaction is shown in
Scheme 1. For the first step, the cationic NHC-Pd2+ diaquo
complex 5 is converted into the Pd hydroxo complex A in
the presence of base. Transmetalation of arylboronic acid 7
with palladium species A gives the corresponding palladium
boronate complex B, which undergoes ꢀ-aryl elimination to
result in the palladium-aryl complex C. The coordination
of species C with the N-tosylimine 6 led to intermediate D.
The addition of the aryl group to the imine from the Si-face
furnishes the formation of adduct 8 upon hydrolysis in a
highly stereoselective manner and regenerates the active
species A to continue the catalytic cycle.11,12
arylation of N-tosyl imines with arylboronic acids. This mild
system provides easy access to chiral diarylmethylamides 8
in excellent yields and good to high enantioselectivities. The
reactions showed a broad substrate scope which enables the
use of a variety of N-tosylimines and arylboronic acids.
Further optimizing this new catalytic system and probing
the detailed mechanism is in progress in our group.
Acknowledgment. We thank the Shanghai Municipal
Committee of Science and Technology (06XD14005,
08dj1400100-2), National Basic Research Program of China
(973)-2009CB825300, and the National Natural Science
Foundation of China for financial support (20472096,
20872162, 20672127, and 20732008).
In conclusion, we have successfully established new,
efficient, chiral C2-symmetric cationic NHC-Pd2+ diaquo
complex catalysts and a catalytic system for enantioselective
Supporting Information Available: Experimental pro-
cedures, spectral and analytic data for 4a-e, 5a-e, and 8,
and X-ray crystal data of 5a as well as chiral HPLC traces
of 8. This material is available free of charge via the Internet
at http://pubs.acs.org.
(11) For directly observed transmetalation from boron to rhodium, see:
Zhao, P.; Incarvito, D. C.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129,
1876
.
(12) The formation of the key species B and C has been confirmed
by 19F NMR and ESI-Mass spectroscopic data (see the Supporting
Information).
OL802861S
878
Org. Lett., Vol. 11, No. 4, 2009