W. Chen et al. / Tetrahedron: Asymmetry 17 (2006) 1161–1164
1163
CHO
OH 1) Ac2O
pyridine
NH2
PPh2
MeMgBr
PPh2
PPh2
Fe
Fe
Fe
2
) NH H O
3. 2
THF, MeOH
(SFc)-5
(
SC
,SFc)-6
(SC
,
SFc)-1f
90%
8
3%
Scheme 2.
1
,2
Table 1. Asymmetric hydrogenation of 1-acetonaphthone catalysed by
various Ru-complexes
(NH -Q-NH ). Thus, precatalyst 2, generated in situ by
2 2
a
stirring a mixture of ligand 1 and [Ru(benzene)Cl ] in
2
2
i-PrOH for 15 min at room temperature, gave the same
results as using the prepared precatalyst 2 (entry 7 and
entry 8 vs entry 1 and entry 3). The easy formation of pre-
catalyst 2 indicates a possibility of finding a better catalyst
in a combinatorial manner, using two different aminophos-
phine ligands. The concept of using two different chiral
monodentate phosphine ligands for asymmetric catalysis,
H (20 bar)
2
HO
O
RuCl -L (0.1 mol%)
2
2
t
-BuOK (1 mol%)
i-PrOH, rt
b
Entry Ligand
Precatalyst Time (h) Conv. (%) ee (%)
1
2
3
4
5
6
7
8
(R
(R
(R
(R
C
C
C
C
,SFc)-1a 2a
,SFc)-1b 2b
,SFc)-1c 2c
,SFc)-1d 2d
,RFc)-1e 2e
,SFc)-1f 2f
3
3
3
4
3
3
3
3
100
88
100
3.7
100
56
66.7 (R)
44.3 (R)
78.7 (R)
20.5 (R)
66.5 (S)
16.4 (S)
66.5 (R)
78.9 (R)
20
which was first proposed by us, has been confirmed suc-
21
cessfully by other groups.
(S
(S
C
C
3. Conclusion
c
c
(R
(R
C
,SFc)-1a
,SFc)-1c
100
100
C
In conclusion, ferrocene-based aminophosphine ligands
have been shown to be effective in the Ru(II)-catalysed
asymmetric hydrogenation of ketones. The enantioselectiv-
ity is mainly determined by the C-centred chirality of the
ligands but the planar chirality is also important, and
a
b
c
Reaction conditions: 5 mmol of substrate, 0.005 mmol of 2, 0.05 mmol of
t-BuOK, 3 mL of i-PrOH, room temperature and H pressure of 20 bar.
Determined by GC using Chrompack Chirasil-Dex CB (25 m ·
.25 mm).
Catalyst 2 was prepared in situ by reaction of ligand 1 with [Ru(benz-
ene)Cl in i-PrOH at room temperature for 15 min.
2
0
(
R ,S )- or (S ,R )- is the matched combination of chi-
C Fc C Fc
2 2
]
ralities. Studies are currently under way in order to obtain
highly enantioselective ligands by modification of Ar on
phosphorus and R on carbon.
group in 1a with phenyl group, (R ,S )-1b, lowered both
C
Fc
the reactivity and enantioselectivity (entry 2). In contrast,
and mimicking Noyori’s precatalysts of the type trans-
1
–5
RuXY(PAr -Q-PAr )(NH -Q-NH ),
the introduction
2
2
2
2
References
of 3,5-dimethyl groups to P-phenyl rings, (R ,S )-1c, sig-
C
Fc
nificantly increased the enantioselectivity to 78.7% ee (entry
). Substitution of one hydrogen atom of the amino group
in 1a with a benzyl group, (R ,S )-1d, dramatically low-
1. For reviews see: (a) Noyori, R.; Koizumi, M.; Ishii, D.;
Ohkuma, T. Pure Appl. Chem. 2001, 73, 227–232; (b) Noyori,
R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40–73; (c)
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M. Adv. Synth. Catal. 2003, 345, 103–151.
3
C
Fc
ered both reactivity and enantioselectivity (entry 4).
Carbon-centred chirality plays the decisive role in the
Ru(II)-catalysed asymmetric hydrogenation of ketones a
ligand 1. Thus, in the presence of precatalyst 2f, generated
2
. (a) Ralph, C. K.; Akotsi, O. M.; Bergens, S. H. Organomet-
allics 2004, 23, 1484–1486; (b) Hartmann, R.; Chen, P. Adv.
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C
Fc
thone gave (S)-1-naphthylethanol in only 16.4% ee and
6% conversion under the standard reaction conditions
entry 6 vs entry 1 and entry 5). While the atom-centred
2
963–2968; (d) Henschke, J. P.; Zanotti-Gerosa, A.; Moran,
5
(
P.; Harrison, P.; Mullen, B.; Casy, G.; Lennon, I. C.
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2
003, 193, 21–25; (f) Xie, J.-H.; Wang, L.-X.; Fu, Y.; Zhu,
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C
Fc
C
Fc
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with matched C-centred and planar chiralities. The match-
ing of planar and central chiralities is essential for obtain-
ing high asymmetric induction and also demonstrates the
importance of planar chirality.
3
4
5
Finally, precatalyst 2 is very easy to form and, in this
respect, is quite different from the formation of Noyori’s
precatalysts of the type trans-RuCl (PAr -Q-PAr )-
2
2
2