Table 2 Ruthenium-catalysed asymmetric hydrosilylation of ketoximes
(3)a
1987, 60, 395; (c) Y. Sakito, Y. Yoneyoshi and G. Suzukamo,
Tetrahedron Lett., 1988, 29, 223.
3 (a) M. T. Reetz and C. Dreisbach, Chimia, 1994, 48, 570 and references
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Reaction Conv. of Yield of ee of 4
5 (a) S. Kobayashi and H. Ishihara, Chem. Rev., 1999, 99, 1069; (b) T.
Ohkuma, M. Kitamura and R. Noyori, in Catalytic Asymmetric
Synthesis, ed. I. Ojima, Wiley-VCH, New York, 2000, ch. 1.
6 (a) K. Tani, J.-I. Onouchi, T. Yamagata and Y. Kataoka, Chem. Lett.,
1995, 955; (b) S. Kainz, A. Brinkmann, W. Leitner and A. Pfaltz, J. Am.
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H. Morris, Organometallics, 2001, 20, 1047; (d) N. Uematsu, A. Fujii,
S. Hashimoto, T. Ikariya and R. Noyori, J. Am. Chem. Soc., 1996, 118,
4916; (e) X. Verdaguer, U. E. W. Lange, M. T. Reding and S. L.
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Nishibayashi, K. Segawa, Y. Arikawa, K. Ohe, M. Hidai and S. Uemura,
J. Organomet. Chem., 1997, 545–546, 381 and references cited
therein.
Run Ketoxime Catalyst Solvent time/h 3 (%)
4 (%)b (%)c
1
2
3
4
5
6
7
8
9
3a
3a
3b
3b
3c
3d
3d
3e
3f
2a
2a
2a
2b
2a
2a
2b
2b
2b
2b
2a
THF
DME
DME
DME
THF
THF
THF
THF
THF
DME
THF
20
25
40
40
90
20
40
25
25
40
90
> 95
> 95
> 95
> 95
> 95
> 95
> 95
> 95
70
50
62
26
10
45
5
21
22
26
15
6
79 (R)
83 (R)
18 (R)
35 (R)
60 (R)
58 (R)
89 (R)
61 (R)
74 (R)
69 (R)
12 (R)
10 3g
11 3h
> 95
> 95
a All reactions were carried out in the presence of catalyst (0.010 mmol) and
AgOTf (0.010 mmol) using ketoxime 3 (0.50 mmol) and Ph2SiH2 (2.0
mmol) in solvent (5 ml) at rt.b GLC yield.c Determined by GLC analysis of
the corresponding trifluoroacetamide.
9 (a) Y. Nishibayashi, I. Takei, S. Uemura and M. Hidai, Organome-
tallics, 1998, 17, 3420; (b) I. Takei, Y. Nishibayashi, Y. Arikawa, S.
Uemura and M. Hidai, Organometallics, 1999, 18, 2271.
oxime (3d),14 the best enantioselectivity of 89% ee was
achieved (Table 2, run 7). Introduction of a p-halogeno or p-
methyl substituent to the aromatic ring of acetophenone oxime
slightly decreased the enantioselectivity (Table 2, runs 8–10).
When 2b was used in place of 2a as catalyst, a slightly better
enantioselectivity was obtained in several cases (Table 2, runs
7–10). Dialkyl ketoxime (3h) was also converted into the
corresponding dialkyl amine, but unfortunately in low yield
with low enantioselectivity (Table 2, run 11).
10 In the present study, the prochiral ketoximes were used as formed from
the corresponding ketones and hydroxylamine liberated from hydrox-
ylammonium chloride.7 A single isomer of each ketoxime was
tentatively assigned as (E)-form from the following arguments: G. L.
Karabatsos and N. Hsi, Tetrahedron, 1967, 23, 1079; K. Maruoka, T.
Miyazaki, M. Ando, Y. Matsumura, S. Sakane, K. Hattori and H.
Yamamoto, J. Am. Chem. Soc., 1983, 105, 2831; D. L. Boger and W. L.
Corbett, J. Org. Chem., 1992, 57, 4777; K. D. Sugi, T. Nagata, T.
Yamada and T. Mukaiyama, Chem. Lett., 1997, 493.
In summary, we have developed the highly enantioselective
ruthenium(II)-catalysed hydrosilylation of ketoximes to give the
corresponding primary amines with high enantioselectivities
(up to 89% ee) after hydrolysis. This may provide a versatile
method for the straightforward synthesis of chiral primary
amines because of the ready accessibility of ketoximes by
reaction of ketones with hydroxylamine. Further work is
currently in progress aiming at the elucidation of the reaction
mechanism and broadening the scope of this asymmetric
hydrosilylation.
11 When the reaction of 3a (2.50 mmol) with diphenylsilane (10.0 mmol)
was carried out under the same reaction conditions, 4a was isolated in
67% yield (70% GLC yield) with 80% ee.
12 G. Helmchen and A. Pfaltz, Acc. Chem. Res., 2000, 33, 336 and
references cited therein.
13 A typical procedure for ruthenium-catalysed asymmetric hydro-
silylation of ketoximes is as follows. In a 20 ml flask were placed
catalyst 2a (10.3 mg, 0.010 mmol; 2.0 mol%) and AgOTf (2.6 mg, 0.010
mmol; 2.0 mol%) under N2. Anhydrous DME (5 ml) was added, and
then the mixture was magnetically stirred at rt for 1 h. After the addition
of 1-tetralone oxime (3a) (80 mg, 0.50 mmol), diphenylsilane (2.0
mmol) was slowly added at rt and the mixture was stirred at rt for an
appropriate time. The mixture was then quenched with MeOH (1.0 ml),
stirred at rt for 30 min, and subsequently hydrolysed by the addition of
1 N HCl aq. The mixture was extracted with water (50 ml), and 3 N
NaOH aq. (20 ml) was added to the aqueous solution to obtain a free
amine. This solution was extracted with diethyl ether (50 ml 3 3) and
the extract was dried over anhydrous MgSO4. For GLC analysis of the
yield of 4a, n-tetradecane was added as an internal standard. The optical
purity was determined by GLC analysis of the corresponding tri-
fluoroacetamide on a cyclodextrin phase (Chiraldex GT-A, 30 m). The
absolute configuration of 4a was determined by an optical rotation..
14 Acetophenone oxime (3d) was assigned as the (E)-isomer by 1H NMR;
F. G. Bordwell and G.-Z. Ji, J. Org. Chem., 1992, 57, 3019.
This work was supported by Grant-in-Aid for Scientific
Research (Nos. 09102004 and 12750747) from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
Notes and references
1 For recent reviews, (a) E. Juaristi, J. Escalante, J. L. Le-Romo and A.
Reyes, Tetrahedron: Asymmetry, 1998, 9, 715; (b) E. Juaristi, J. L. Le-
Romo, A. Reyes and J. Escalante, Tetrahedron: Asymmetry, 1999, 10,
2441.
2 (a) S. Itsuno, M. Nakano, K. Miyazaki, H. Masuda, K. Ito, A. Hirao and
S. Nakahama, J. Chem. Soc., Perkin Trans. 1, 1985, 2039; (b) S. Itsuno,
Y. Sakurai, K. Ito, A. Hirao and S. Nakahara, Bull. Chem. Soc. Jpn.,
Chem. Commun., 2001, 2360–2361
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