E. H. M. Kirton et al. / Tetrahedron Letters 45 (2004) 853–855
855
More hindered than
conformation B
A
B
Me
Me
_
B
_
B
O
O
+
+
N
N
+
+
N
H B
2
H B
2
H
N
Me
H
Me
HN
NH
Me
Me
R
S
D
C
Me
_
Me
_
B
O
O
+
N
B
+
O
N
O
+
+
B
H
B
H
N
N
O
Me
O
Me
More hindered than
conformation C
Figure 2. Model to account for asymmetry in oxazaborolidine-mediated imine reduction.12
6. The low yield of amino-ester 3 is accompanied by
formation of the corresponding amino-alcohol (49%
yield), albeit of the R-configuration (45% ee) (the change
in stereochemistry is not accounted for). On moving from
borane–THF to the less reactive catecholborane, forma-
tion of the amino-alcohol was no longer evident.
7. General procedure for oxazaborolidine-catalysed imine
reduction: reduction was achieved by a modification of the
procedure described by Cho and Chun.3b In THF
Acknowledgements
This study was supported by EPSRC and GSK (CASE
award to E.H.M.K.). We gratefully acknowledge
invaluable support form the EPSRC Mass Spectrometry
Service, Swansea.
References and notes
(1.5 mL), phenyl(1-phenylethylidene)amine
6
(25 mg,
130 lmol), (S)-methyl-CBS-oxazaborolidine 1, (13 lmol,
10 mol %) were stirred under nitrogen for 10 min. Reduc-
ing agent (150 lmol) was added and the reaction was
stirred at room temperature. Reactions were assessed by
HPLC after 1 h (250 · 4.6 mm Chiralcel OD-H column; 5%
ethanol in heptane; 0.5 mL/min; detection at 215/254 nm).
8. Morimoto, T.; Nakajima, N.; Achiwa, K. Tetrahedron:
Asymmetry 1995, 6, 23–26.
1. Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc.
1987, 109, 5551–5553; Reviewed in: Srebnik, M.; Deloux,
L. Chem. Rev. 1993, 93, 763–784; Corey, E. J.; Helal, C. J.
Angew. Chem., Int. Ed. 1998, 37, 1986–2012.
2. For selected recent examples of ketone reductions with
immobilised oxazaborolidines see: Price, M. D.; Sui, J. K.;
Kurth, M. J.; Schore, N. E. J. Org. Chem. 2002, 67, 8086–
8089; Schunicht, C.; Biffis, A.; Wulff, G. Tetrahedron
2000, 56, 1693–1699, and references cited therein.
3. (a) Cho, B. T.; Ryu, M. H.; Chun, Y. S.; Dauelsburg, C.;
Wallbaum, S.; Martens, J. Bull. Korean Chem. Soc. 1994,
15, 53–57; (b) Cho, B. T.; Chun, Y. S. J. Chem. Soc.,
Perkin Trans. 1 1990, 3200–3201.
9. Corey, E. J.; Azimioara, M.; Sarshar, S. Tetrahedron Lett.
1992, 33, 3429–3430.
10. Corey, E. J.; Link, J. O.; Bakshi, R. K. Tetrahedron Lett.
1992, 33, 7107–7110; Jones, D. K.; Liotta, D. C.; Shinkai,
I.; Mathre, D. J. J. Org. Chem. 1993, 58, 799–801.
11. These models are based on the premise that only the trans
form of the imine is subject to oxazaborolidine-catalysed
reduction.
4. Cho, B. T.; Chun, Y. S. Tetrahedron: Asymmetry 1992, 3,
337–340.
12. The effect of imine structure, including N-substitution, on
the stereoselectivity of oxazaborolidine-catalysed imine
reduction has been noted (see Ref. 3).
5. Sakai, T.; Yan, F.; Uneyama, K. Synlett 1995, 753–754;
Sakai, T.; Yan, F.; Kashino, S.; Uneyama, K. Tetrahedron
1996, 52, 233–244.