1050
M. Suginome et al.
LETTER
(4) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.;
Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61, 3849.
(5) Gutierrez, C. D.; Bavetsias, V.; McDonald, E. Tetrahedron
Lett. 2005, 46, 3595.
(6) (a) Suginome, M.; Yamamoto, A.; Ito, Y. Chem. Commun.
2002, 1392. (b) Suginome, M.; Uehlin, L.; Yamamoto, A.;
Murakami, M. Org. Lett. 2004, 6, 1167. (c) Suginome, M.;
Uehlin, L.; Murakami, M. J. Am. Chem. Soc. 2004, 126,
13196.
(7) Although the addition of 2-piperidinone is not crucial to
attain the reductive amination product, it moderately
accelerates the reaction and improves the yield to some
extent.
In summary, we have demonstrated reductive amination
of aldehydes using iminium ion generator 1 with NaBH4.
In certain reactions, we have found that the use of this new
reagent system is advantageous over some conventional
reaction systems, in which rather elaborated hydride
sources such as NaBH(OAc)3 and NaBH3CN are used. In
addition, the aminoborane’s capability for mild and selec-
tive iminium ion generation may offer new possibilities
for amine synthesis.
Acknowledgment
(8) (a) Sodium borohydride has rarely been utilized in reductive
aminations, unless imines are preformed in situ before the
reduction step, see ref. 1b. For reduction of preformed
imines by NaBH4, see: Schellenberg, K. A. J. Org. Chem.
1963, 28, 3259. (b) Very recently, a combination of NaBH4
and a solid acid, such as boric acid and p-TsOH, was
reported as an efficient reagent for reductive amination: Cho,
B. T.; Kang, S. K. Tetrahedron 2005, 61, 5725.
(9) Typical Procedure for Reductive Amination Using 1b.
To a solution of 2-piperidinone (0.048 mmol) in 1,2-
dichloroethane (0.5 mL) were added 1b (57 mg, 0.24 mmol),
amines (0.24–0.48 mmol), aldehyde (0.24 mmol) and
NaBH4 (11 mg, 0.29 mmol) at r.t. After stirring for 0.5–3 h,
MeOH (0.5 mL) was added and the mixture was subjected
directly to column chromatography on silica gel pretreated
with 5% Et3N in hexane.
This work was supported by a Grant-in-Aid for Scientific Research
(No. 17655040) from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
References and Notes
(1) (a) Hutchins, R. O. In Comprehensive Organic Synthesis,
Vol. 8; Trost, B. M., Ed.; Pergamon: Oxford, 1991, 25.
(b) Baxter, E. W.; Reitz, A. B. Org. React. 2002, 59, 1.
(2) For recent examples, see: (a) Tararov, V. I.; Kadyrov, R.;
Riermeier, T. H.; Börner, A. Chem. Commun. 2000, 1867.
(b) Apodaca, R.; Xiao, W. Org. Lett. 2001, 3, 1745.
(c) Basu, B.; Jha, S.; Bhuiyan, M. M. H.; Das, P. Synlett
2003, 555. (d) Gross, T.; Seayad, A. M.; Ahmad, M.; Beller,
M. Org. Lett. 2002, 4, 2055. (e) Miura, K.; Ootsuka, K.;
Suda, S.; Nishikori, H.; Hosomi, A. Synlett 2001, 1617.
(f) Shibata, I.; Suwa, T.; Sugiyama, E.; Baba, A. Synlett
1998, 1081.
(10) 3,3-Diphenylcyclobutylamine derivatives have been
reported as potential antidepressant agents. See: Rämsby, B.
C.; Renyi, A. L.; Ross, S. B.; Ögren, S.-O.; Stjernström, N.
E. J. Med. Chem. 1978, 21, 78.
(3) Borch, R. F.; Bernstein, M. D.; Durst, H. P. J. Am. Chem.
Soc. 1971, 93, 2897.
Synlett 2006, No. 7, 1047–1050 © Thieme Stuttgart · New York