C O M M U N I C A T I O N S
Table 1. Ligand Screening and Reaction Condition Optimization
Scheme 3
entrya
ligand
solvent
time (h)
yield (%)b
eec
1
2
3
4
5
6
4a
4b
4c
4a
4a
4a
acetone
acetone
acetone
THF
toluene
dioxane
2
2
48
4
4
8
75
79
15
70
85
75
98
83
83
98
98
98
In summary, we have developed a new type of C2-symmetric
chiral diene ligand bearing a simple bicyclic [3.3.0] backbone. 4a
is proved to be a remarkably efficient ligand for asymmetric
arylation of N-tosylarylimines using arylboronic acids instead of
arylboroxines.10 With the current catalytic system, a broad range
of highly enantiomerically enriched diarylmethylamines as well as
3-aryl substituted phthalimidines could be easily prepared.
a The reaction was carried out with 2 equiv of boronic acid 9 in the
presence of 2 equiv of Et3N, 3 mol % of [RhCl(C2H4)2]2 and 3.3 mol % of
chiral diene 4 at 55 °C. b Isolated yield. c Determined by chiral HPLC
analysis using Chiralcel OD-H column.
Table 2. Catalytic Asymmetric Arylation of N-Tosylarylimines with
Arylboronic Acids
Acknowledgment. Financial support from the National
Natural Science Foundation of China, the Chinese Academy of
Sciences, the Major State Basic Research Development Program
(2006CB806106), and the Shanghai Rising-Star Program
(05QMX1467) is acknowledged.
entrya
Ar1
Ar2
10
yield (%)b
eec,d
1
2
C6H5
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
C6H5
10a
10b
10c
10d
10e
10f
85
90
85
92
85
93
65
93
81
72
97
78
56
88
74
93
81
99
97
91
98 (R)
99 (S)
98 (S)
99 (R)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
98 (S)
99 (R)
98 (S)
99 (R)
99 (S)
Supporting Information Available: Experimental procedures and
4-FC6H4
1
characterization data; copies of H and 13C NMR spectra and HPLC
3
4-ClC6H4
4-MeC6H4
2-MeOC6H4
2-MeC6H4
2-ClC6H4
1-naphthyl
4-ClC6H4
4-BrC6H4
4-MeOC6H4
2-MeC6H4
2-ClC6H4
1-naphthyl
2-furanyl
4
spectra. This material is available free of charge via the Internet at
5
6
7
10g
10h
10i
References
8
9
(1) For a mini review: Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 3364.
(2) (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem.
Soc. 2003, 125, 11508. (b) Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi,
T. Org. Lett. 2004, 6, 3425. (c) Tokunaga, N.; Otomaru, Y.; Okamoto,
K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126,
13584. (d) Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org.
Lett. 2005, 7, 307. (e) Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama,
K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54. (f) Otomaru, Y.;
Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503.
(g) Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron:
Asymmetry 2005, 16, 1673. (h) Shintani, R.; Tsurusaki, A.; Okamoto, K.;
Hayashi, T. Angew. Chem., Int. Ed. 2005, 44, 3909. (i) Shintani, R.;
Okamoto, K.; Hayashi, T. Org. Lett. 2005, 7, 4757. (j) Kina, A.; Ueyama,
K.; Hayashi, T. Org. Lett. 2005, 7, 5889. (k) Chen, F.-X.; Kina, A.;
Hayashi, T. Org. Lett. 2006, 8, 341.
(3) (a) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem.
Soc. 2004, 126, 1628. (b) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira,
E. M. Org. Lett. 2004, 6, 3873. (c) Paquin, J.-F.; Stephenson, C. R. J.;
Defieber, C.; Carreira, E. M. Org. Lett. 2005, 7, 3821. (d) Paquin, J.-F.;
Defieber, C.; Stephenson, C. R. J.; Carreira, E. M. J. Am. Chem. Soc.
2005, 127, 10850.
10
11
12
13
14
15
16
17
18
19
20
C6H5
10j
C6H5
10a′
10k
10l
C6H5
C6H5
C6H5
10m
10n
10o
10p
10d′
10c′
10q
C6H5
2-thiopheneyl
C6H5
4-MeOC6H4
4-MeOC6H4
1-naphthyl
C6H5
4-MeC6H4
4-MeC6H4
4-ClC6H4
2-naphthyl
a The reaction was carried out with 0.5 mmol of N-tosylarylimine, 2
equiv of arylboronic acid in the presence of 2 equiv of Et3N, 3 mol % of
[RhCl(C2H4)2]2 and 3.3 mol % of chiral diene 4a at 55 °C; see Supporting
Information for details. b Isolated yield. c Determined by chiral HPLC
analysis. d The absolute configurations of 10i, 10a′, 10l, 10m, 10p and 10c′
were determined by comparing the optical rotation [R]D with known data.
Assuming an analogous reaction mechanism, the configurations of other
diarylmethylamine products are assigned as indicated in the table.
(4) (a) Grundl, M. A.; Kennedy-Smith, J. J.; Trauner, D. Organometallics
2005, 24, 2831. (b) La¨ng, F.; Breher, F.; Stein, D.; Gru¨tzmacher, H.
Organometallics 2005, 24, 2997.
Scheme 2
(5) The enantiomerically pure (S, S)-5 and its enantiomer (R, R)-5 (>99%
ee) were obtained through the lipase-catalyzed kinetic resolution of rac-5
following the literature procedure, see: (a) Lemke, K.; Ballschuh, S.;
Kunath, A.; Theil, F. Tetrahedron: Asymmetry 1997, 8, 2051. (b) Zhong,
Y.-W.; Lei, X.-S.; Lin, G.-Q. Tetrahedron: Asymmetry 2002, 13, 2251.
(6) (a) Kuriyama, M.; Soeta, T.; Hao, X.; Chen, Q.; Tomioka, K. J. Am. Chem.
Soc. 2004, 126, 8128. (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.-F.; Jia, Y.-X.; Wang, L.-X.; Zhou, Q.-L. Org.
Lett. 2006, 8, 2567.
(7) For other recent examples of asymmetric synthesis of diarylmethylamines,
see: (a) Hayashi, T.; Kawai, M.; Tokunaga, N. Angew. Chem., Int. Ed.
2004, 43, 6125. (b) Weix, D. J.; Shi, Y.; Ellman, J. A. J. Am. Chem. Soc.
2005, 127, 1092. (c) Bolshan, Y.; Batey, R. A. Org. Lett. 2005, 7, 1481.
(8) Only a limited number of examples were given by the asymmetric reaction
of N-tosylarylimines with arylboroxines (see ref 2c and 6a).
(9) For recent chiral auxiliary-mediated asymmetric synthesis, see: (a)
Comins, D. L.; Schilling, S.; Zhang, Y. Org. Lett. 2005, 7, 95. (b) Comins,
D. L.; Hiebel, A.-C. Tetrahedron Lett. 2005, 46, 5639. (c) Deniau, E.;
Enders, D.; Couture, A.; Grandclaudon, P. Tetrahedron: Asymmetry 2005,
16, 875. For a review, see: Stajer, G.; Csende, F. Curr. Org. Chem. 2005,
9, 1277.
(10) In the cases of asymmetric arylation of N-tosylarylimines using Hayashi’s
chiral diene ligand and Tomioka’s chiral amidomonophosphane ligand,
arylboroxines were used (see ref 2c and 6a).
ester functionality was also found to be suitable substrate. Under
the similar reaction conditions, 11 was subjected to the arylation
with different arylboronic acid catalyzed by Rh-4a complex. The
corresponding diarylmethyltosylamides formation followed by the
in situ lactamization gave the chiral 3-substituted N-tosylphthali-
midine products 12a-c in good yields and with excellent enanti-
oselectivities (99% ee) (Scheme 2). Chiral phthalimidines (isoin-
dolinones) are valuable pharmacological compounds. They are
usually difficult to access by catalytic asymmetric strategy.9
We are also currently studying on the application of this new
diene ligand 4a to other asymmetric reactions such as 1,4-addition
to R,â-unsaturated ketones and arylation of N-nosylimines, and two
very preliminary results are shown in Scheme 3.
JA0710914
9
J. AM. CHEM. SOC. VOL. 129, NO. 17, 2007 5337