C O M M U N I C A T I O N S
Table 1. Catalytic Asymmetric Hydrogenation of Aromatic
Ketones Using R-BINAN-R′-Py and Ru Precursorsa
In summary, we have succeeded in highly enantioselective
hydrogenation of aromatic ketones by combination of a Ru-π-
allyl complex and an sp2N/sp3N-based chiral ligand R-BINAN-R′-
Py. The new system catalyzes the reaction essentially in the ab-
sence of base. Although the efficiency does not exceed that of the
original BINAP-Ru-diamine complexes, the present results should
significantly expand the range of possibilities in designing catalysts
not only for hydrogenation but also for many other reactions.6,7
entry
substrate
ligand
Ru precursor
% yieldb
% ee (abs)b
1
2
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
(R)-1a
(S)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1b
(R)-1c
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
(R)-1a
A
A
A
A
A
A
A
A
A
A
A
B
C
D
A
A
A
A
A
A
A
A
A
A
A
A
A
A
>99
>99
>99
>99
0
93 (R)
93 (S)
93 (R)
94 (R)
-
3c
4d
5e
6f
>99
90
94 (R)
87 (R)
15 (R)
-
7g,h
8i,h
9j,h
10k,h
11l,h
12
13
14
15h
16
17
18
19
20
21
22
23
24
25
26
27
28n
Acknowledgment. This work was aided by the Grant-in-Aid
for Scientific Research (No. 14078212) from the Ministry of
Education, Science, Sports and Culture, Japan. We are grateful to
Professor R. Noyori for valuable discussions, and to Messrs. T.
Noda, K. Oyama, and Y. Maeda for their technical support.
5.5
0
0
0
-
-
51
0
0
-
-
Supporting Information Available: General procedure for the
hydrogenation of acetophenone, determination of the enantiomeric
excess and the absolute configuration of products, and synthetic
procedures, and characterization of all ligands. This material is available
4.3m
29
55 (R)
21 (R)
98 (R)
96 (R)
80 (R)
95 (R)
98 (R)
94 (R)
98 (R)
97 (R)
86 (R)
94 (R)
99 (R)
93 (R)
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
References
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2m
a Reaction conditions: scale, 5.0 mmol; [2] ) 2 M; [1] ) [Ru] )
[KOC(CH3)3] ) 2 mM; H2, 50 atm; solvent, i-C3H7OH; temp, 25 °C; time,
12-18 h. A: Ru(π-CH2C(CH3)CH2)2(cod). B: [RuCl2(cod)]n. C: [RuCl2-
(C6H6)]2. D: Ru(cod)(cot). The Ru precursors are not aged with 1.
1
b Determined by H NMR, GC, or HPLC analysis.10 c Aged at 70 °C for
2 h. d No base, 48 h. e H2, 0 atm. f [1a] ) [Ru]) 0.2 mM, 66 h. g C2H5OH.
h 24 h. i CH3OH. j CH2Cl2. k THF. l Toluene. m 1-Cyclohexylethanol was
obtained in 95.7% yield with 14% ee (R). Intractable black solid was formed.
n [2m] ) 400 mM, no base.
(entries 26 and 27). 1-Indanone (2m) is not hydrogenated under
the standard conditions, but instead without KOC(CH3)3, giving
1-indanol in 93% ee (entry 28). The presence of base may result
in the enolization of the ketone that has relatively acidic R-proton,14
thus retarding the reaction.
(8) R-BINAN-R′-Py ) 3,3′-R,R-N2,N2′-bis(6-R′-pyridin-2-ylmethyl)-1,1′-
binaphthyl-2,2′-diamine. R represents the substitutions at C(3) and C(3′)
of binaphthyl, and R′ does that at C(6) of pyridine ring.
The mechanism is not clear at the present stage. Among many
possibilities, we suppose that a dihydride mechanism is operating
as proposed in the BINAP-Ru-diamine-base ternary system.15
The RuH2 formation would be facilitated by use of the Ru-π-
allyl precursor possessing the easily hydrogenolyzed Ru-C bond.
If so, the linear tetradentate chiral ligand (R)-1 can theoretically
form five geometrical isomers,16 which are in equilibrium and have
their own reactivity and enantioselectivity. Drawn below are the
most plausible RuH2 isomers, C2-Λ-cis-R complex, the C1 sym-
metric ∆-cis-â, and the C2 symmetric trans. The overall enantio-
selectivity is expressed as an average of their contributions.17 The
R,R′ substituent effects as well as the aging effect12,13 may be
ascribed to the change in the relative ratios of these species. The
detailed mechanistic study is now underway.
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Ikariya, T.; Murata, K.; Noyori, R. Org. Biomol. Chem. 2006, 4, 393-
406. The origin of the concept: (c) Noyori, R.; Kitamura, M. Angew.
Chem., Int. Ed. Engl. 1991, 30, 49-69. For the redox-involved donor-
acceptor bifunctional catalyst, see: (d) Saburi, H.; Tanaka, S.; Kitamura,
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(10) For the details, see Supporting Information.
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of the BINAP-Ru complexes: (b) Geneˆt, J. P.; Pinel, C.;
Ratovelomanana-Vidal, V.; Mallart, S.; Pfister, X.; Can˜o De Andrade,
M. C.; Laffitte, J. A. Tetrahedron: Asymmetry 1994, 5, 665-674.
(12) In some cases, for example, with (R)-Ph-BINAN-Me-Py, the aging
conditions exert a significant effect on the reaction profile. The close
investigation is now being pursued.
(13) The reactivity is highly affected by the inner glass vessel of stainless steel
autoclaves. For a report on a similar effect, see: Ashby, M. T.; Halpern,
J. J. Am. Chem. Soc. 1991, 113, 589-594.
(14) Dubois, J.-E.; El-Alaoui, M.; Toullec, J. J. Am. Chem. Soc. 1981, 103,
5393-5401.
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G.; Miskolzie, M.; Bergens, S. H. J. Am. Chem. Soc. 2005, 127, 4152-
4153.
(16) (a) Knof, U.; von Zelewsky, A. Angew. Chem., Int. Ed. 1999, 38, 302-
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