Ytterbium(III) triflate/TMSCI: Efficient catalyst for imino ene reaction

Article abstract of DOI:10.1021/ol991260s

(equation presented) Ytterbium trifluoromethanesulfonate [Yb(OTf)₃] catalyzed the imino ene reaction of N-tosyl aldimine with α-methylstyrene to give a homoallylamine in moderate yield. Furthermore, addition of a catalytic amount of chlorotrime

Full text of DOI:10.1021/ol991260s

ORGANIC
LETTERS
2000
Vol. 2, No. 2
159-161
Ytterbium(III) Triflate/TMSCl: Efficient
Catalyst for Imino Ene Reaction
Masamichi Yamanaka, Atsushi Nishida, and Masako Nakagawa*
Faculty of Pharmaceutical Science, Chiba UniVersity, Yayoi-cho 1-33, Inage-ku,
Chiba 263-8522, Japan
nakagawa@p.chiba-u.ac.jp
Received November 19, 1999
ABSTRACT
Ytterbium trifluoromethanesulfonate [Yb(OTf)3] catalyzed the imino ene reaction of N-tosyl aldimine with r-methylstyrene to give a homoallylamine
in moderate yield. Furthermore, addition of a catalytic amount of chlorotrimethylsilane (TMSCl) dramatically enhanced the imino ene reaction.
The development of new methods for the synthesis of chiral
or achiral amines is an important issue for the synthesis of
nitrogen-containing natural products and biologically active
compounds. As part of our ongoing project along these lines,
we previously reported the diastereo- and enantioselective
Pictet-Spengler reaction,1 and the diastereoselective addition
of alkyllithium to chiral imines.2
Although there have been many reports on catalytic C-C
bond-forming reactions using imines with electron-rich
alkenes3 and organometallic reagents,4 reactions between
imines and simple alkenes, i.e., imino ene reactions,5,6 have
not yet been studied as intensively as carbonyl ene reactions.7
Recent advances in the chemistry of lanthanoid metal
catalysts8,9 prompted us to study the catalytic activity of rare
earth metal salts in imino ene reactions. We present here a
preliminary report on ytterbium trifluoromethanesulfonate
[(Yb(OTf)3] catalyzed imino ene reactions in the presence
of TMS-Cl or TMS-OTf.
Initially, we chose the reaction of N-toluenesulfonyl
benzaldimine 1a with R-methylstyrene. When imine 1a was
treated with 2 equiv of R-methylstyrene in CH2Cl2-THF
(4:1) in the presence of Yb(OTf) (25 mol %) at room
3
temperature for 48 h, the imino ene product 2a was obtained
in 58% yield (entry 1, Table 1). Addition of 1.2 equiv of
TMS-Cl to the reaction mixture facilitated the reaction
dramatically.10 The reaction was completed within only 15
min and gave 2a in 90% yield (entry 2).
Although TMS-Cl itself did not act as a catalyst (entry
3), if TMS-OTf was formed in situ from TMS-Cl and
Yb(OTf)3, it might catalyze this reaction. To clarify this issue,
the reaction using 1.2 equiv of TMS-OTf without Yb(OTf)3
(1) (a) Kawate, T.; Yamada, H.; Soe, T.; Nakagawa, M. Tetrahedron:
Asymmetry 1996, 7, 1249-1252. (b) Kawate, T.; Yamada, H.; Matsumizu,
M.; Nishida, A.; Nakagawa, M. Synlett 1997, 761-762. (c) Yamada, H.;
Kawate, T.; Matsumizu, M.; Nishida, A.; Yamaguchi, K.; Nakagawa, M.
J. Org. Chem. 1998, 63, 6348-6354. (d) Kawate, T.; Yamanaka, M.;
Nakagawa, M. Heterocycles 1999, 50, 1033-1039.
(2) (a) Kawate, T.; Yamada, H.; Yamaguchi, K.; Nishida, A.; Nakagawa,
M. Chem. Pharm. Bull. 1996, 44, 1776-1778. (b) Yamada, H.; Kawate,
T.; Nishida, A.; Nakagawa, M. J. Org. Chem. 1999, 64, 8821-8828.
(3) (a) Kobayashi, S.; Ishitani, H.; Ueno, M. J. Am. Chem. Soc. 1998,
120, 431-432. (b) Fujii, A.; Hagiwara, E.; Sodeoka, M. J. Am. Chem. Soc.
1999, 121, 5450-5458. (c) Ferraris, D.; Young, B.; Dudding, T.; Lectka,
T. J. Am. Chem. Soc. 1998, 120, 4548-4549.
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Evans, D. A.; Burgey, C. S.; Paras, N. A.; Vojkovsky, T.; Tregay, S. W. J.
Am. Chem. Soc. 1998, 120, 5824-5825.
(4) (a) Bloch, R. Chem. ReV. 1998, 98, 1407-1438. (b) Nakamura, H.;
Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242-4243.
(5) (a) Achmatowicz, O., Jr.; Pietraszkiewicz, M. Chem. Commun. 1976,
484. (b) Borzilleri, R. M.; Weinreb, S. M. Synthesis 1995, 347-360. (c)
Laschat, S.; M. Grehl, Angew. Chem., Int. Ed. Engl. 1994, 33, 458-461.
(d) Mikami, K.; Kaneko, M.; Yajima, T. Tetrahedron Lett. 1993, 34, 4841-
4842.
(6) The catalytic enantioselective imino ene reactions of R-imino esters
have recently been reported: (a) Druy, W. J., III: Ferraris, D.; Cox, C.;
Young, B.; Lectka, T. J. Am. Chem. Soc. 1998, 120, 11006-11007. (b)
Yao, S.; Fang, X.; Jørgensen, K. A. Chem. Commun. 1998, 2547-2548.
(8) (a) Kobayashi, S. Synlett 1994, 689-701. (b) Inanaga, J.; Sugimoto,
Y.; Hanamoto, T. New. J. Chem. 1995, 19, 707-712. (c) Shibasaki, M.;
Sasai, H.; Arai, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1236-1256. (d)
Nishida, A.; Yamanaka, M.; Nakagawa, M. Tetrahedron Lett. 1999, 40,
1555-1558.
(9) (a) Kobayashi, S.; Nagayama, S. J. Am.. Chem. Soc. 1997, 119,
10049-10053. (b) Gro¨ger, H.; Saida, Y.; Sasai, H.; Yamaguchi, K.; Martens,
J.; Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 3089-3103.
(10) Rate acceleration by R3SiCl in addition of diethyl zinc: Jimeno,
C.; Vidal-Ferran, A.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron
Lett. 1999, 40, 777-780.
10.1021/ol991260s CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/22/1999

1e was subjected to similar reaction conditions, aza Diels-
Alder cycloadduct 3 was obtained, and no imino ene product
was observed (entry 12).11
Table 1. Imino Ene Reaction of N-Substituted Aldimine with
R-Methylstyrene
There have been several efforts to explain the reactivity
of lanthanoid metal triflates systematically.12 Yamaguchi and
Imamoto recently developed a scale of oxophilicity of
lanthanoid metal complexes using tandem mass spectros-
copy.12b To obtain greater insight into the reaction mechanism
of these catalysts, we surveyed the catalytic activities of other
combinations of lanthanoid metal triflates [M(OTf)3] and
TMS-Cl in this imino ene reaction of 1a and R-methyl-
styrene. The catalytic activity profile of M(OTf)3/TMS-Cl
is shown in Figure 1 with the oxophilicity scale. The activity
a Isolated yield. b Aza Diels-Alder reaction took place to give adduct 3
in 63% yield.
was carried out (entry 4). The imino ene reaction proceeded,
and 2a was obtained in only 43% yield, even though an
excess amount of TMS-OTf was present. We also suspected
that triflic acid (TfOH) produced in situ might catalyze the
reaction. However, the similar reaction of 1a with TfOH (120
mol %) for 15 min gave only 39% yield of 2a (compare
with entries 2 and 4). Therefore, while TMS-OTf or TfOH
catalyzes this reaction to some extent, the presence of both
Yb(OTf)3 and TMS-X (X ) Cl, OTf) is essential. We
briefly studied the effect of the amount of the catalyst. The
reaction using 5 mol % of Yb(OTf)3 and TMS-Cl (entry 5)
afforded almost the same result as entry 2. Even 1 mol % of
catalyst was effective to afford 2a in 86% yield, although
the reaction rate was slightly decreased (entry 6). TMS-
OTf was also effective when it was used with Yb(OTf)3
(entry 7).
The N-substituent on the imino group also influenced this
reaction. In contrast to the reaction of N-tosyl imine 1a,
Yb(OTf)3 (25 mol %) itself did not catalyze the ene reaction
between N-methoxycarbonyl imine 1b and R-methylstyrene
(entry 8). However, a combination of Yb(OTf)3 (10 mol %)
and TMS-Cl (10 mol %) induced the reaction to give 2b in
moderate yield (entry 9). In this case, the effect of TMS-
OTf is notable. The yield of 2b increased up to 74% when
TMS-OTf was added instead of TMS-Cl (entry 10).
Phosphinoyl imine 1c also gave 2c under these conditions,
whereas the similar reaction of N-benzyl imine 1d did not
proceed at all. These results indicate that the N-substituent
must possess an electron-withdrawing character for the imino
ene reaction to occur. Interestingly, when N-phenyl imine
Figure 1. Catalytic activity of M(OTf)3/TMS-Cl in the imino ene
reaction. Notes: (a) All reactions were carried out at room
temperature for 1 h. (b) The reported oxophilicity data, evaluated
based on the dissociation of [MCl2(tepo)3]+ as observed by tandem
mass spectrometry. See ref 12b.
profile was almost consistent with the oxophilicity scale.
These observations suggest that the oxophilicity, i.e., the
Lewis acidity of the lanthanoid metal may play an important
role in these reactions.
Under the conditions described above, three-component
coupling11a,b,13 among aromatic or aliphatic aldehyde, tosyl-
(11) (a) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995, 1195-
1202. (b) Ishitani, H.; Kobayashi, S. Tetrahedron Lett. 1996, 37, 7357-
7360. (c) Batey, R. A.; Simoncic, P. D.; Lin, D.; Smyj, R. P.; Lough, A. J.
Chem. Commun. 1999, 651-652.
(12) (a) Imamoto, T.; Nishiura, M.; Yamanoi, Y.; Tsuruta, H.; Yamagu-
chi, K. Chem. Lett. 1996, 875-876. (b) Tsuruta, H.; Yamaguchi, K.;
Imamoto, T. J. Chem. Soc., Chem. Commun. 1999, 1703-1704.
(13) (a) Kobayashi, S.; Busujima, T.; Nagayama, S. Chem. Commun.
1998, 19-20. (b) Kobayashi, S.; Busujima, T.; Nagayama, S. Chem.
Commun. 1998, 981-982. (c) Kobayashi, S.; Sugita, K.; Oyamada, H.
Synlett 1999, 138-139. (d) Kobayashi, S.; Busujima, T.; Nagayama, S.
Synlett 1999, 545-546.
160
Org. Lett., Vol. 2, No. 2, 2000

amine, and R-methylstyrene in the presence of Yb(OTf)3 and
TMS-Cl or TMS-OTf was realized (Table 2). Thus, using
aldehyde, whose imines are difficult to isolate, afforded imino
ene products 4 and 5 in good yields without any difficulty.
In summary, we have shown that the combination of
Yb(OTf)3 and either TMS-Cl or TMS-OTf is an effective
catalyst system for the imino ene reaction using imines with
an electron-withdrawing substituent at the nitrogen. We also
showed that the catalytic activities of M(OTf)3/TMS-Cl in
the imino ene reaction were highly dependent on the
oxophilicity of the lanthanoid metal. The three-component
coupling reaction of aldehydes, tosylamine, and R-methyl-
styrene was also successful under these conditions. In this
reaction, the use of aliphatic aldehydes, such as acetaldehyde,
is noteworthy. Further studies to elucidate the detailed
mechanism of the activity of these catalysts and its applica-
tion to asymmetric processes are underway.
Table 2. Three-Component Coupling
Acknowledgment. Financial support from the Ministry
of Education, Science, Sports and Culture in the form of a
Grant-in-Aid for Scientific Research is gratefully acknowl-
edged. We also thank Ms. R. Hara at the Chemical Analysis
Center of Chiba University for measuring mass spectral data.
a Isolated yield based on TsNH2. b Two equivalents of acetaldehyde was
employed.
Supporting Information Available: General experimen-
tal procedure and characterization data for products 2-5.
This material is available free of charge via the Internet at
http://pubs.acs.org.
50 mol % of Yb(OTf)3/TMS-X, the reaction proceeded
smoothly to give 2a in good to excellent yield. In this
reaction, the combination with TMS-OTf gave better results.
Aliphatic aldehydes, such as acetaldehyde and isobutyr-
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