Moreover, naphthols are relatively weak nucleophiles and
thus strong Lewis acid activation of electrophiles is generally
required.8 Herein we wish to report a catalytic enantioselective
aza-Friedel-Crafts reaction, catalyzed by a bifunctional
organocatalyst (Scheme 1).
Scheme 1. Bifunctional Catalyst Catalyzed an Asymmetric
Aza-Friedel-Crafts Reaction
Table 1. Exploration of Catalytic Asymmetric Friedel-Crafts
Reaction of 1-Naphthol (1a) with N-Ts Phenyl Imine (2a)a
entry
cat.
t (h)
% yieldb
% eec
1
I
11
32
48
22
32
18
72
24
62
120
92
69
62
76
72
84
80
NRg
49
64
-42
-37
80
2
II
3
III
IV
IV
IV
IV
V
4
88
5d
6e
83
93
7e,f
8
94
-
-32
92
as valuable tools for the formation of chiral amines.7 How-
ever, significant efforts have been directed toward developing
asymmetric organocatalytic Friedel-Crafts reactions using
active indoles and pyrroles.6,7 The asymmetric Friedel-Crafts
reaction of naphthols with aldimines represents an attractive
approach to the optically active aminoarylnaphthols. While
catalytic asymmetric Friedel-Crafts reactions of naphthols
with highly active electrophiles have been disclosed,8,9 the
asymmetric Friedel-Crafts reactions with aldimines remain
elusive. The reduced electrophilicity of imines in conjunction
with regioselectivity renders this transformation difficult.
9
VI
IV
10e,f,h
a Unless otherwise specified, the reaction was carried out using 1a
(0.5 mmol) and 2 (0.1 mmol) in the presence of 10 mol % of catalyst in
CH2Cl2 (0.5 mL) at rt. b Isolated yield. c Determined by chiral HPLC
analysis (chiralpark AS-H). d Using 1a (0.2 mmol) and 2a (0.1 mmol).
e Using toluene (0.5 mL) as solvent. f The reaction was run at 0 °C. g No
reaction. h 5 mol % IV used.
It is noteworthy that to date organocatalytic enantiose-
lective aza-Friedel-Crafts reactions have been mainly
carried out by using chiral phosphoric acids due to their
strong activation with imines.7 In contrast, the examples of
employment of weakH-bondbifunctional organocatalysts
in aza-Friedel-Crafts reactions have not been reported.10
We envisioned that chiral bifunctional Brønsted acid/base
catalysts could serve as an ideal promoter for the asym-
metric process (Scheme 1).11 The capacity of activation of
(5) During our investigation, a study using Trost’s bis-ProPhenol
dinuclear zinc complex as a chiral inducer (not a catalytic version) in an
asymmetric Friedel-Crafts reaction of 2-naphthol with tosylimines has
been reported: Niu, L.-F.; Xin, Y.-C.; Wang, R.-L.; Jiang, F.; Xu, P.-F.;
Hui, X.-P. Synlett 2010, 765.
(6) For recent reviews on catalytic asymmetric Friedel-Crafts reac-
tions, see: (a) Poulsen, T.; Jørgensen, K. A. Chem. Rev. 2008, 108, 2903.
(b) You, S.-L.; Cai, Q.; Zeng, M. Chem. Soc. Rev. 2009, 38, 2190. (c)
Bandini, M.; Eichholzer, A. Angew. Chem., Int. Ed. 2009, 48, 9608. (d)
Bandini, M.; Umani-Ronchi, A. Catalytic Asymmetric Friedel-Crafts
Alkylations; Wiley-VCH: Weinheim, 2009. (e) Rueping, M.; Nachtsheim,
B. J. Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6. (f)
Terrasson, V.; de Figueiredo, R. M.; Campagne, J. M. Eur. J. Org. Chem.
2010, 2635. (g) Zen, M.; You, S.-L. Synlett 2010, 1289.
(7) For a review, see: (a) Akiyama, T.; Itoh, J.; Fuchibe, K. Chem.
Rev. 2007, 107, 5744. For organocatalytic asymmetric aza-Friedel-
Crafts reaction of imines, see:(b) Uraguchi, D.; Sorimachi, K.; Terada,
M. J. Am. Chem. Soc. 2004, 126, 11804. (c) Wang, Y.-Q.; Song, J.; Hong,
R.; Li, H.; Deng, L. J. Am. Chem. Soc. 2006, 128, 8156. (d) Yu, P.; He, J.;
Guo, C. Chem. Commun. 2008, 2355. (e) Kang, Q.; Zhao, Z.-A.; You,
S.-L. J. Am. Chem. Soc. 2007, 129, 1484. (f) Terada, M.; Yokoyama, S.;
Sorimachi, K.; Uraguchi, D. Adv. Synth. Catal. 2007, 349, 1863. (g)
Rowland, G. B.; Rowland, E. B.; Liang, Y.; Perman, J. A.; Antilla, J. C.
Org. Lett. 2007, 9, 4065. (h) Terada, M.; Sorimachi, K. J. Am. Chem.
Soc. 2007, 129, 292. (i) Jia, Y.-X.; Zhong, J.; Zhu, S.-F.; Zhang, C.-M.;
Zhou, Q.-L. Angew. Chem., Int. Ed. 2007, 46, 5565. (j) Zhang, G.-W.;
Wang, L.; Nie, J.; Ma, J.-A. Adv. Synth. Catal. 2008, 350, 1457. (k)
Kang, Q.; Zheng, X.-J.; You, S.-L. Chem.;Eur. J. 2008, 14, 3539.
(l) Enders, D.; Matthias, S.; Tobias, B. Adv. Synth. Catal. 2010, 352, 1413.
(8) Using highly active trifluoromethyl ketones, see: (a) Erker, G.;
van der Zeijden, A. A. H. Angew. Chem., Int. Ed. Engl. 1990, 29, 512. (b)
Johannsen, M. Chem. Commun. 1999, 2233. (c) Ishii, A.; Soloshonok,
V. A.; Mikami, K. J. Org. Chem. 2000, 65, 1597.
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nitroolefins, and enals with naphthols have been reported; see: (a)
Brandes, S.; Bella, M.; Kjærsgaard, A.; Jørgensen, K. A. Angew. Chem.,
Int. Ed. 2006, 45, 1147. (b) Liu, T.-Y.; Cui, H.-L.; Chai, Q.; Long, J.; Li,
B.-J.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. Chem. Commun. 2007, 2228. (c)
Hong, L.; Wang, L.; Sun, W.; Wong, K.; Wang, R. J. Org. Chem. 2009,
74, 6881.
(10) Recently Jacobsen and co-workers developed an elegant coop-
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S. J.; Woll, M. G.; Tao, Y.; Jacobsen, E. N. Science 2010, 327, 986.
(11) For recent reviews of H-bond mediated catalysis, see: (a)
Schreiner, P. R. Chem. Soc. Rev. 2003, 32, 289. (b) Tian, S.-K.; Chen,
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