Enantioselective Rh-catalyzed arylation of N-tosylarylimines with arylboronic acids

Article abstract of DOI:10.1021/ol060755w

The asymmetric arylation of N-tosylarylimines with arylboronic acids was realized by using rhodium/(S)-ShiP as catalyst. The reaction proceeded in aqueous toluene to give diarylmethylamines in good yields with up to 96% ee.

Full text of DOI:10.1021/ol060755w

ORGANIC
LETTERS
2
006
Vol. 8, No. 12
567-2569
Enantioselective Rh-Catalyzed Arylation
of N-Tosylarylimines with Arylboronic
Acids
2
Hai-Feng Duan, Yi-Xia Jia, Li-Xin Wang, and Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai UniVersity,
Tianjin 300071, China
qlzhou@nankai.edu.cn
Received March 28, 2006
ABSTRACT
The asymmetric arylation of N-tosylarylimines with arylboronic acids was realized by using rhodium/(S)-ShiP as catalyst. The reaction proceeded
in aqueous toluene to give diarylmethylamines in good yields with up to 96% ee.
The addition of organometallic reagents to imines represents
an attractive area in current organic synthesis. The catalytic
enantioselective version of this reaction provides a particu-
imines mediated by rhodium complexes were developed by
Hayashi and Tomioka by using monophosphines, bisphos-
phines, amidophosphanes, and chiral dienes as chiral ligands,
giving N-tosyldiarylmethylamides in excellent ee values.
Nevertheless, the requirement for the use of toxic, moisture-
sensitive, or noncommercially available organometallic re-
agents and sometimes the need for sterically tuned substrates
for high enantioselectivity may limit their application. Thus,
the development of an efficient and general method for the
synthesis of optically active diarylmethylamines is still highly
desirable.
1
larly useful access to chiral amines, which are synthetically
important chiral building blocks for pharmaceutically active
2
compounds. In recent years, considerable efforts have been
made and great progress has been achieved in the catalytic
enantioselective arylation of imines. Br a¨ se and co-workers
reported the addition of diphenylzinc to N-formylimines em-
3
ploying chiral ketimine catalysts. Transformations of aryl-
4
5
6
stannanes, aryltitaniums, and arylboroxines to N-sulfonyl-
Absent from these organometallic reagents, however, are
the arylboronic acids, which are attractive compounds due
to their low cost, low toxicity, stability toward air and mois-
ture, and tolerance to a variety of functional groups. The
arylboronic acids can be transformed to various electrophiles
(
1) (a) Bloch, R. Chem. ReV. 1998, 98, 1407. (b) Kobayashi, S.; Ishitani,
H. Chem. ReV. 1999, 99, 1069. (c) Taniyama, D.; Hasegawa, M.; Tomioka,
K. Tetrahedron Lett. 2000, 41, 5533. (d) Pflum, D. A.; Krishnamurthy, D.;
Han, Z.; Wald, S. A.; Senanayake, C. H. Tetrahedron Lett. 2002, 43, 923.
e) Han, Z.; Krishnamurthy, D.; Grover, P.; Fang, Q. K.; Pflum, D. A.;
Senanayake, C. H. Tetrahedron Lett. 2003, 44, 4195. (f) Cabello, N.;
Kizirian, J.-C.; Alexakis, A. Tetrahedron Lett. 2004, 45, 4639.
(
7
in the presence of Rh(I) complex as catalyst. However, their
(2) (a) Spencer, C. M.; Foulds, D.; Peters, D. H. Drugs 1993, 46, 1055.
(
b) Calderon, S. N.; Rothman, R. B.; Porreca, F.; Flippen-Anderson, J. L.;
(4) (a) Hayashi, T.; Ishigedani, M. J. Am. Chem. Soc. 2000, 122, 976.
(b) Hayashi, T.; Ishigedani, M. Tetrahedron 2001, 57, 2589.
(5) Hayashi, T.; Kawai, M.; Tokunaga, N. Angew. Chem., Int. Ed. 2004,
43, 6125.
(6) (a) Kuriyama, M.; Soeta, T.; Hao, X. Y.; Chen, O.; Tomioka, K. J.
Am. Chem. Soc. 2004, 126, 8128. (b) Tokunaga, N.; Otomaru, Y.; Okamoto,
K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126,
13584.
McNutt, R. W.; Xu, H.; Smith, L. E.; Bilsky, E. J.; Davis, P.; Rice K. C.
J. Med. Chem. 1994, 37, 2125. (c) Bishop, M. J.; McNutt, R. W. Bioorg.
Med. Chem. Lett. 1995, 5, 1311. (d) Sakurai, S.; Ogawa, N.; Suzuki, T.;
Kato, K.; Ohashi, T.; Yasuda, S.; Kato, H.; Ito, Y. Chem. Pharm. Bull.
1
996, 44, 765.
3) Hermanns, N.; Dahmen, S.; Bolm, C.; Br a¨ se, S. Angew. Chem., Int.
Ed. 2002, 41, 3692.
(
1
0.1021/ol060755w CCC: $33.50
© 2006 American Chemical Society
Published on Web 05/13/2006

8
application in the asymmetric addition to imines is rare. The
only example of catalytic asymmetric addition of arylboronic
acids to N-diphenylphosphinoylbenzaldimine was reported
by Ellman for a limited set of substrates.8a,9 Recently, we
reported that the rhodium complexes with spiro monophos-
phite ligands were efficient catalysts for the asymmetric
addition of arylboronic acids to aromatic aldehydes, produc-
ing diarylmethanols in high ee values.10 Herein, we wish to
present the highly enantioselective addition of arylboronic
acids to N-tosylarylimines catalyzed by Rh complexes with
a spiro monophosphite ligand (S)-ShiP. This investigation
expands the scope of application of arylboronic acids as aryl
sources and provides a practical entry to the synthesis of
optically active diarylmethylamines.
Figure 1. Tested chiral ligand.
We began our experiment under the identical conditions
used in our previous study of rhodium-catalyzed addition of
phenylboronic acid to aldehydes.10 The reaction of phenyl-
boronic acid and N-tosyl-4-chlorobenzaldehyde imine 7a
was performed in aqueous toluene at 35 °C using [RhCl-
a spirobiindane scaffold gave the desired product 9aa in
5
8-69% yields with 62-84% ee (Table 1, entries 7-9),
though these were lower than those obtained with ligand
. However, the binaphthol-based ligands 5 (MeO-MOP)
1
2 2 2
(CH CH )] (3 mol % of Rh) as a precatalyst and (S)-ShiP
and 6 (BINAP) were found to be less efficient in this reac-
tion in terms of either reactivity or enantioselectivity (en-
tries 10 and 11). These results indicated that the spiro mono-
dentate ligands having a large dihedral angle backbone,
especially (S)-ShiP, were crucial for efficient control of enan-
tioselectivity in the Rh-catalyzed addition of arylboronic
acids to imines. The use of KF as an additive is important
for achieving high yield. For example, the reaction in the
absence of KF gave only 25% of the addition product, while
the reactions with 2 or 4 equiv of KF provided the addi-
tion product in 77% and 85% yield, respectively (entries 6
and 13).
as a chiral ligand. The addition product 9aa was gratifyingly
obtained in 70% yield with 89% ee after 20 h (Table 1, entry
Table 1. Optimization of the Reaction Conditions
a
b
entry
[Rh]
ligand yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
[RhCl(C2H4)2]2
[Rh(COD)(MeCN)2]BF4
Rh(COD)2BF4
[Rh(COD)2Cl]2
Rh(acac)(CO)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
1
1
1
1
1
1
2
3
4
5
6
1
1
75
72
43
56
70
77
69
58
63
30
9
89
19
49
48
81
93
83
62
84
13
10
88
Having established an optimal protocol, the arylation of a
variety of aromatic imines was examined (Scheme 1) with
3
2 4 2
mol % of Rh(acac)(C H ) /(S)-ShiP catalyst at 35 °C in
aqueous toluene. The results are summarized in Table 2.
Interestingly, the imines bearing both electron-donating and
-withdrawing groups are tolerated in the arylation reaction
with arylboronic acids. Furthermore, the positions of sub-
stituents of imine substrates is not restrictive for obtaining
high enantioselectivites, as the phenylations of para-, meta-,
and ortho-subsitituted arylimines were all successful to give
the desired products in 92-96% ee (Table 2, entries 1-10).
1
1
1
1
0
1
2
3
25
85
c
d
93 (99)
1
-Naphthaldehyde imine 7k and 2-furaldehyde imine 7l can
a
b
Isolated yield after chromatography. Determined by chiral HPLC using
also react with phenylboronic acid to produce the corre-
sponding addition products in 76% yield with 96% ee and
c
d
a Chiralcel OD column. With 4 equiv of KF. After a simple recrystal-
lization.
(7) For rhodium-catalyzed addition of arylboronic acids to aldehydes,
imines and R,â-unsaturated compounds, see reviews: (a) Fagnou, K.;
Lautens, M. Chem. ReV. 2003, 103, 169. (b) Hayashi, T.; Yamasaki, K.
Chem. ReV. 2003, 103, 2829.
1
). Hydrolysis of imine was the main side reaction, which
became substantial when the reaction was carried out in
solvents other than toluene.11 Other Rh(I) compounds as
precursors were also investigated with ligand 1 (entries 2-6).
The use of cationic [Rh(COD)(MeCN)
conditions gave a comparable yield (72%) but a lower
enantioselectivity (19%). The Rh(acac)(C emerged as
the best choice of catalyst precursors, affording the addition
product in good yield (77%) and high ee (93%).
Encouraged by this result, we tested different chiral ligands
shown in Figure 1. The monodentate ligands 2-4 containing
(
8) For the diastereoselective addition of arylboronic acids to chiral
sulfinimines, see: (a) Weix, D. J.; Shi, Y.-L.; Ellman, J. A. J. Am. Chem.
Soc. 2005, 127, 1092. (b) Bolshan, Y.; Batey, R. A. Org. Lett. 2005, 7,
1
481.
2 4
]BF under the same
(9) When this manuscript was submmited, a related publication by
Feringa and Minnaard on the addition of arylboronic acids to N-sulfamonyl
aldimines using phosphoramidite ligands appeared on the Internet: 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.
(10) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org.
Lett. 2006, 8, 1479.
2 4 2
H )
(11) The reactions in aqueous ClCH2CH2Cl, MeOCH2CH2OMe, THF,
dioxane, and i-PrOH all gave the isolated yield of 9aa below 40%.
2568
Org. Lett., Vol. 8, No. 12, 2006

Scheme 1. Asymmetric Arylation of Imines 7 with
Arylboronic Acids 8
Scheme 2. Deprotection of N-Tosyldiarylmethylamides
Thus, 9da or 9ka were treated with SmI in refluxing THF-
2
HMPA for 6 h to give free amines 10 or 11 in good yield
without loss of their enantiomeric purities.
A stereorecognition model for understanding the pathway
of the transformation of phenyl to imine was proposed based
+
12
2
on the crystal structure of catalyst [Rh(1) (COD)] . From
Scheme 3, we can see that the (S)-ShiP ligands created an
Scheme 3. Stereorecognition Model for the
Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids
to Imine
84% yield with 85% ee, respectively (entries 11 and 12). A
highly asymmetric induction was also observed in the
addition of a variety of arylboronic acids to benzaldehyde
imine 7m (entries 13-17). The corresponding N-tosyldiaryl-
methylamides with reverse configuration were achieved with
excellent enantiomeric excesses (91-95%), even as the
electron-deficient 4-fluorophenylboronic acid was used as
nucleophile.
The chiral diarylmethylamines can be obtained by depro-
tection of the N-tosyl group on the arylation products using
samarium(II) iodide under standard conditions (Scheme 2).
efficient chiral environment around the rhodium atom.
N-Tosyl-4-chlorobenzaldehyde imine favorably coordinated
to the Rh atom on the Re face, and the phenyl group trans-
formed to the imine from its Re face, providing the addition
product with R configuration. In contrast, the coordination
of imine to Rh on the Si face was very unfavorable due to
the repulsions of the 4-chlorophenyl and tosyl groups of the
imine substrate with the backbone of the ligand.
Table 2. Asymmetric Arylation of Imines 7 with Arylboronic
Acids 8a
In conclusion, we have developed an efficient catalyst,
rhodium complex of monodentate spiro phosphite (S)-ShiP
for asymmetric arylation of N-tosylarylimines using aryl-
boronic acids. This highly enantioselective method provided
a facile access to a variety of optically active diarylmethyl-
amine derivatives. Further application of this rhodium/
phosphite catalyst in other C-C bond-forming reactions is
in progress in our group.
Ar1
Ar2
yield (%)
b
ee (%)
c
entry
1
2
3
4
5
6
7
8
9
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7m
7m
7m
7m
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8b
8c
8d
8e
8f
85 (9aa)
80 (9ba)
82 (9ca)
77 (9da)
65 (9ea)
72 (9fa)
79 (9ga)
76 (9ha)
73 (9ia)
67 (9ja)
76 (9ka)
84 (9la)
56 (9mb)
75 (9mc)
70 (9md)
68 (9me)
65 (9mf)
93 (R)
93 (R)
93 (R)
94 (R)
93 (R)
96 (R)
95 (R)
93 (R)
95 (R)
92 (R)
96 (R)
85 (R)
94 (S)
92 (S)
95 (S)
91 (S)
93 (S)
Acknowledgment. We thank the National Natural Sci-
ence Foundation of China, the Major Basic Research De-
velopment Program (Grant No. G2000077506), and the
Ministry of Education of China for financial support.
10
11
12
13
14
15
16
17
Supporting Information Available: Experimental pro-
cedures, characterization, and analysis of ee values of
arylation products. This material is available free of charge
via the Internet at http://pubs.acs.org.
a
Reaction conditions: 7/8/KF/[Rh]/(S)-ShiP ) 1:2:4:0.03:0.06 (mmol);
toluene/H2O (1:1, 2 mL) at 35 °C for 20 h. Isolated yield. Determined
b
c
OL060755W
by chiral HPLC (Supporting Information).
(12) See the Supporting Information for details.
Org. Lett., Vol. 8, No. 12, 2006
2569