3
108
T. Itoh et al. / Tetrahedron Letters 43 (2002) 3105–3108
2
9
amines. A most remarkable point of the reaction is
that the reduction is completely selective toward imines.
Studies aimed at broadening the scope of the present
reaction and understanding its mechanism are now in
progress.
20. Kobayashi, S. Eur. J. Org. Chem. 1999, 15 and references
cited therein.
21. Westheimer et al. reported that 5 A sieves is a good
,
dehydrating agent for the formation of imines from a
ketone and an amine in benzene, see: Westheimer, F. H.;
Taguchi, K. J. Org. Chem. 1971, 36, 1570. Although we
investigated other dehydrating agents such as 4 A
Ti(OR) , and so on, 5 A sieves afforded the best results.
,
sieves,
References
,
4
2
2
2. Under the same conditions in entry 5 except the solvent,
some solvents were investigated, but the yields were
found to be low; 14% in THF, 52% in CH Cl , and 8% in
1
2
. The reductive amination reaction is termed as direct
when a mixture of the aldehyde or ketone and the amine
is treated with a reducing agent in a single step.
. Hutchins, R. O.; Hutchins, M. K. In Comprehensive
Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Perga-
mon: Oxford, 1991; Vol. 8; p. 25.
2
2
CH CN.
3
3. Typical procedure: In a THF solution (1 ml) of benzalde-
hyde (0.2 mmol), p-anisidine (0.2 mmol), and 1 (0.2
mmol) under Ar, Sc(OTf) (0.004 mmol) were added and
3
3
4
5
. Gustafsson, M.; Olsson, R.; Anderson, C.-M. Tetra-
hedron Lett. 2001, 42, 133 and references cited therein.
. Lane, C. F. Synthesis 1975, 135 and references cited
therein.
. Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.;
Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61,
the mixture was allowed to react for 4 h at room temper-
ature. Then AcOEt (15 ml) was added and the mixture
was washed with 5% Na CO (4 ml) and H O (4 ml). The
2
3
2
organic layer was dried over MgSO and evaporated in
4
vacuo to give a residue, which was chromatographed on
silica gel (CH Cl /AcOEt=10) to afford the product. The
2
2
3
949 and references cited therein.
. Bomann, M. D.; Guch, I. C.; DiMare, M. J. Org. Chem.
995, 60, 5995.
aromatized 4 was readily separated since polarity of 4
was much higher than that of the product. In the case of
ketones, a benzene solution (1 ml) of a ketone (0.2
6
1
7. Bhattacharyya, S. Synth. Commun. 1997, 27, 4265.
mmol), p-anisidine (0.2 mmol) and 5 A
(
(
,
molecular sieves
400 mg) was treated with 1 (0.2 mmol) and Sc(OTf)3
0.02 mmol) under Ar for 24 h at room temperature. The
8. Ranu, B. C.; Majee, A.; Sarkar, A. J. Org. Chem. 1998,
6
3, 370.
9. Bhattacharyya, S.; Neidigh, K. A.; Avery, M. A.;
work-up procedure was similar to that of aldehydes
mentioned above.
Williamson, J. S. Synlett 1999, 1781.
1
1
1
0. Saxena, I.; Borah, R.; Sarma, J. C. J. Chem. Soc., Perkin
2
2
4. When trifluoromethanesulfonic acid was used under the
same conditions, the yield of 9 was 30%.
5. (a) Kobayashi, S. Chem. Soc. Rev. 1999, 28, 1 and
references cited therein; (b) Saito, S.; Hatanaka, K.;
Yamamoto, H. Synlett 2001, 1859.
Trans. 1 2000, 503.
1. Suwa, T.; Sugiyama, E.; Shibata, I.; Baba, A. Synlett
2
000, 556.
2. (a) Shibata, I.; Moriuchi-Kawakami, T.; Tanizawa, D.;
Suwa, T.; Sugiyama, E.; Matsuda, H.; Baba, A. J. Org.
Chem. 1998, 63, 383; (b) Shibata, I.; Suwa, T.; Sugiyama,
E.; Baba, A. Synlett 1998, 1081; (c) Suwa, T.; Shibata, I.;
Nishino, K.; Baba, A. Org. Lett. 1999, 1, 1579; (d) Suwa,
T.; Sugiyama, E.; Shibata, I.; Baba, A. Synthesis 2000,
2
6. Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1997,
119, 10049.
2
7. In the reaction, p-anisidine was slowly added to the
reaction mixture over 4 h in order to prevent the forma-
tion of a diimine derivative.
7
89.
2
8. (a) Kronenthal, D. R.; Han, C. Y.; Taylor, M. K. J. Org.
Chem. 1982, 47, 2765; (b) Ishitani, H.; Ueno, M.;
Kobayashi, S. J. Am. Chem. Soc. 1997, 119, 7153; (c)
Bravo, P.; Guidetti, M.; Viani, F.; Zanda, M.;
Markovsky, A. L.; Sorochinsky, A. E.; Soloshonok, I. V.;
Soloshonok, V. A. Tetrahedron 1998, 54, 12789; (d) Ishi-
tani, H.; Komiyama, S.; Hasegawa, Y.; Kobayashi, S. J.
Am. Chem. Soc. 2000, 122, 762; (e) List, B. J. Am. Chem.
Soc. 2000, 122, 9336; (f) Saito, S.; Hatanaka, K.;
Yamamoto, H. Org. Lett. 2000, 2, 1891; (g) Porter, J. R.;
Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L. J. Am.
Chem. Soc. 2001, 123, 984; (h) Porter, J. R.; Traverse, J.
F.; Hoveyda, A. H.; Snapper, M. L. J. Am. Chem. Soc.
1
1
3. Chen, B.-C.; Sundeen, J. E.; Guo, P.; Bednarz, M. S.;
Zhao, R. Tetrahedron Lett. 2001, 42, 1245.
4. Chandrasekhar, S.; Reddy, C. R.; Ahmed, M. Synlett
2
000, 1655.
1
1
5. Apodaca, R.; Xiao, W. Org. Lett. 2001, 3, 1745.
6. (a) Itoh, T.; Nagata, K.; Okada, M.; Ohsawa, A. Tetra-
hedron Lett. 1995, 36, 2269; (b) Nagata, K.; Itoh, T.;
Okada, M.; Ohsawa, A. Tetrahedron 1996, 52, 6569; (c)
Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.;
Ohsawa, A. J. Org. Chem. 1997, 62, 3582.
7. Eisner, U.; Kuthan, J. Chem. Rev. 1972, 72, 1.
8. For a reference of the reduction by organic dihydro
derivatives, see: Kellog, R. M. In Comprehensive Organic
Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 8; p. 79.
1
1
2
001, 123, 104409.
9. A preliminary result showed that oxidation of an amine
obtained from the reaction in Table 3, entry 9) with
(NH Ce(NO in CH CN/H O afforded the corre-
sponding primary amine in 60% yield.
2
(
1
9. Other solvents such as CH Cl and CH CN gave com-
2
2
3
parable, but slightly less yields than those of THF in this
case.
)
4
2
3
)
6
3
2