BINAP/1,4-diamine-ruthenium(II) complexes for efficient asymmetric hydrogenation of 1-tetralones and analogues

Article abstract of DOI:10.1021/ol049157c

A combined system of a RuCl₂(binap)(1,4-diamine) complex and t-C₄H₉OK in i-C₃H₇OH catalyzes enantioselective hydrogenation of various 1-tetralone derivatives and some methylated 2-cyclohexenones. Hydrogenation of 2-methyl-1-tetralone under dynamic kinetic resolution gives the cis alcohol with high ee.

Full text of DOI:10.1021/ol049157c

ORGANIC
LETTERS
2
004
Vol. 6, No. 16
681-2683
BINAP/1,4-Diamine−Ruthenium(II)
Complexes for Efficient Asymmetric
Hydrogenation of 1-Tetralones and
Analogues
2
†
†
‡
‡
Takeshi Ohkuma, Tomonori Hattori, Hirohito Ooka, Tsutomu Inoue, and
Ryoji Noyori*
,†
Department of Chemistry and Research Center for Materials Science,
Nagoya UniVersity, Chikusa, Nagoya 464-8602, Japan, and Odawara Research Center,
Nippon Soda Co., Ltd., 345 Takada, Odawara 250-0280, Japan
noyori@chem3.chem.nagoya-u.ac.jp
Received May 9, 2004
ABSTRACT
A combined system of a RuCl
-tetralone derivatives and some methylated 2-cyclohexenones. Hydrogenation of 2-methyl-1-tetralone under dynamic kinetic resolution gives
the cis alcohol with high ee.
2 4 9 3 7
(binap)(1,4-diamine) complex and t-C H OK in i-C H OH catalyzes enantioselective hydrogenation of various
1
Chiral diphosphine/1,2-diamine-RuX
2
complexes (X )
in i-C
3 7
H OH effect rapid, enantioselective hydrogenation of
anionic ligand) combined with1 or without an alkaline base
-5
6
simple, unfunctionalized aryl, heteroaryl, alkenyl,
and certain aliphatic ketones.
Our recent mechanistic study revealed that acetophenone,
the simplest aromatic ketone, is reduced with an 18e trans-
2
RuH (binap)(1,2-diamine) intermediate via a six-membered
pericyclic transition state. Because the ketone enantiofaces
are differentiated on the chiral molecular surface of the
2
saturated RuH complex, suitable combination of the catalyst
and substrate is necessary for high efficiency. The enanti-
oselectivity and reaction rate are affected by subtle changes
in electronic and steric parameters of the Ru complexes and
ketones. No universal chiral catalysts exist because of the
structural diversity of ketonic substrates. Thus, hydrogenation
of 1-tetralones 1 has remained very slow and poorly
3,6
4
3b-d,g,4-6
3
d
†
Nagoya University.
Nippon Soda Co., Ltd.
‡
(
(
1) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40-73.
2) BINAP ) 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl. TolBINAP
)
3
2,2′-bis(di-4-tolylphosphino)-1,1′-binaphthyl. XylBINAP ) 2,2′-bis(di-
7
,5-xylylphosphino)-1,1′-binaphthyl. DAIPEN ) 1,1-di(4-anisyl)-2-isopro-
pyl-1,2-ethylenediamine. DPEN ) 1,2-diphenylethylenediamine.
3) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J.
(
Am. Chem. Soc. 1995, 117, 2675-2676. (b) Ohkuma, T.; Doucet, H.; Pham,
T.; Mikami, K.; Korenaga, T.; Terada, M.; Noyori, R. J. Am. Chem. Soc.
1
998, 120, 1086-1087. (c) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa,
T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R.
Angew. Chem., Int. Ed. 1998, 37, 1703-1707. (d) Ohkuma, T.; Koizumi,
M.; Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.;
Yokozawa, T.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1998, 120, 13529-
1
3530. (e) Ohkuma, T.; Koizumi, M.; Ikehira, H.; Yokozawa, T.; Noyori,
R. Org. Lett. 2000, 2, 659-662. (f) Ohkuma, T.; Ishii, D.; Takeno, H.;
Noyori, R. J. Am. Chem. Soc. 2000, 122, 6510-6511. (g) Ohkuma, T.;
Takeno, H.; Honda, Y.; Noyori, R. AdV. Synth. Catal. 2001, 343, 369-
3
2
1
75.
(6) Ohkuma, T.; Koizumi, M.; Mu n˜ iz, K.; Hilt, G.; Kabuto, C.; Noyori,
R. J. Am. Chem. Soc. 2002, 124, 6508-6509.
(7) Sandoval, C. A.; Ohkuma, T.; Mu n˜ iz, K.; Noyori, R. J. Am. Chem.
Soc. 2003, 125, 13490-13503. See also: Abdur-Rashid, K.; Clapham, S.
E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H. J. Am. Chem.
Soc. 2002, 124, 15104-15118.
(4) Ohkuma, T.; Koizumi, M.; Yoshida, M.; Noyori, R. Org. Lett. 2000,
, 1749-1751.
(5) (a) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
995, 117, 10417-10418. (b) Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori,
R. Synlett 1997, 467-468.
1
0.1021/ol049157c CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/03/2004

Table 1. Asymmetric Hydrogenation of 1-Tetralone (1a)a
conditions (R)-2a
time yield
Scheme 1
Ru catalyst
no.
H2
ee
S/Cb
solventc [atm]
[h]
[%]d
[%]d
(S,R)-3a
(S,R)-3b
(S,R)-3c
(S,R)-3c
(S,R)-3c
11 000
1 000e
3 000
3 000
11 000f
A
A
A
B
B
9
8
9
9
50
3
1.2
8
8
17
99.9
98
72
99.6
99.8
90
89
99
99
98
a
Unless otherwise stated, reactions were conducted using 3.0 mmol of
a (1.0 M) in solvent containing an (S,R) Ru catalyst and t-C4H9OK (8-
1
b
c
20 mM) at 25 °C. Substrate/catalyst molar ratio. Solvent: A ) i-C3H7OH;
B ) 3:1 i-C3H7OH-t-C4H9OH. Determined by chiral GC analysis. e [t-
d
f
C4H9OK] ) 100 mM. Reaction using 11.5 mmol of 1a.
enantioselective. We here report that replacement of con-
ventional 1,2-diamine ligands by certain chiral 1,4-diamines
8
can solve this difficult problem. A chiral RuCl
2
(binap)(1,4-
4 9
diamine)/t-C H OK combined system promotes hydrogena-
tion of ketones 1 with a substrate to catalyst molar ratio (S/
C) as high as 55 000 to afford chiral 1-tetralols 2 in up to
9
9% ee and high yield.9
(
2R,3R,4R,5R)-3,4-O-Isopropylidenehexane-2,5-diamine
(R)-IPHAN], a chiral 1,4-diamine, was synthesized from
natural (2R,3R,4R,5R)-mannitol. Treatment of the known
2S,3S,4S,5S)-3,4-O-isopropylidenehexane-2,5-diol bismethane-
[
(
10
sulfonate with NaN
by hydrogenation on 5% Pd/C in methanol (25 °C, 1 atm
) gave (R)-IPHAN in 59% yield (see Supporting Informa-
3
in DMF (4 equiv, 50 °C) followed
H
2
tion). (2S,3S)-2,3-O-Isopropylidenebutane-1,4-diamine [(S)-
IPBAN] is obtainable from diethyl (R,R)-tartrate according
11
to the literature. trans-RuCl
2
[(S)-tolbinap][(R)-iphan] [(S,R)-
3
a] was prepared in 50% isolated yield by reaction of
12
3 7
genated with (S,R)-3c in a 3:1 mixture of i-C H OH and
oligomeric RuCl
IPHAN in DMF (25 °C, 15 h). The P{ H} NMR spectrum
showing a singlet at 44.3 ppm indicated a trans-RuCl
2
[(S)-tolbinap](dmf)
n
and 1.1 equiv of (R)-
31
1
t-C H OH under 50 atm of H (S/C ) 11 000, [1a] ) 1.0
4
9
2
4 9
M, [t-C H OK] ) 20 mM, 25 °C, 17 h), (R)-2a was obtained
2
3c
in 98% ee and 99.8% yield. The reaction proceeded even at
geometry. Other diphosphine/1,4-diamine-Ru complexes
9
3
atm. The less congested Ru complexes (S,R)-3a and (S,R)-
b hydrogenated 1a faster but less stereoselectively, giving
(S,R)-3b-d were synthesized by similar procedures.
First, the reactivity and stereoselectivity of the chiral Ru
(
(
R)-2a in ca. 90% ee and quantitative yield. (S)-TolBINAP/
S)-IPBAN-based Ru complex, a diastereomer of (S,R)-3b,
complexes 3 were tested by using parent 1-tetralone (1a) as
substrate (Table 1). The (S)-XylBINAP/(R)-IPHAN-Ru
complex [(S,R)-3c] was found to exhibit the highest enan-
tioselectivity in reaction of 1a. Thus when 1a was hydro-
exhibited a comparable activity in the hydrogenation of 1a
to form (R)-2a in 85% ee, where the absolute configuration
of the 1,4-diamine was relatively unimportant. However, the
combination of (S)-TolBINAP and simple 1,4-butanediamine
led to a low reactivity (11% yield, R in 52% ee, S/C ) 1000,
9 atm, 25 °C, 2 h), suggesting that the acetonide ring on the
diamine backbone contributes to the stability of the catalytic
species. 1-Tetralone (1a) is not a simple analogue of
acetophenone. Although acetophenone was best hydroge-
(8) Asymmetric hydrogenation of 1a, giving 2a in 95% ee and 88% yield,
was achieved with a BINAP-Ir complex with an achiral amino phosphine
under harsh conditions and with a rather high catalyst loading (50-57 atm,
9
0 °C, 75 h, S/C ) 190-230). Zhang, H.; Taketomi, T.; Yoshizumi, T.;
Kumobayashi, H.; Akutagawa, S.; Mashima, K.; Takaya, H. J. Am. Chem.
Soc. 1993, 115, 3318-3319.
(9) Transfer hydrogenation of 1a catalyzed by a chiral Ru complex in a
formic acid-(C2H5)3N mixture gave 2a in 99% ee and quantitatively but
only with S/C ) 200. Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.;
Noyori, R. J. Am. Chem. Soc. 1996, 118, 2521-2522.
nated with RuCl
OK ) 1000:1:20, 9 atm H
-phenylethanol in 99% ee and 100% yield, reaction of
2
[(S)-xylbinap][(S)-daipen]
2
(ketone/Ru/t-
(10) (a) Yan, Y.-Y.; RajanBabu, T. V. J. Org. Chem. 2000, 65, 900-
C
1
H
4 9
2
, 25 °C, 14 h), giving (R)-
9
06. (b) Li, W.; Zhang, X. J. Org. Chem. 2000, 65, 5871-5874.
11) (a) Kim, D.-K.; Kim, G.; Gam, J.; Cho, Y.-B.; Kim, H.-T.; Tai,
J.-H.; Kim, K. H.; Hong, W.-S.; Park, J.-G. J. Med. Chem. 1994, 37, 1471-
485. (b) Shainyan, B. A.; Ustinov, M. V.; Bel’skii, V. K.; Nindakova, L.
O. Russ. J. Org. Chem. 2002, 38, 112-117.
12) Kitamura, M.; Tokunaga, M.; Ohkuma, T.; Noyori, R. Org. Synth.
993, 71, 1-13.
3d
(
the structurally rigid, cyclic ketone 1a with the same complex
and the same reaction conditions afforded (R)-2a in only 30%
ee and 15% yield. On the other hand, (S,R)-3c, the best
catalyst for 1a (Table 1), smoothly hydrogenated acetophe-
1
(
1
2682
Org. Lett., Vol. 6, No. 16, 2004

such as potent hypnotic and antimycotic agents and empomil
1
4
Table 2. Asymmetric Hydrogenation of Cyclic Ketonesa
conditions alcohol
base time yield ee
inhibitors. Hydrogenation of 4,5,6,7-tetrahydrobenzofuran-
-one (4) with (S,R)-3a gave (R)-5 in 96% ee quantitatively
4
4
without saturation of the furan ring (Table 2). Attempted
hydrogenation of highly base-sensitive 1-chromanone and
-indanone resulted in complex mixtures.
ketone Ru catalyst
S/Cb
[%]c [%]c
15
no.
no.
[mM] [h]
no.
1
a d
Hydrogenation of racemic 2-methyl-1-tetralone [(()-6]
1
(S,R)-3c
(S,R)-3a
(S,R)-3a
(S,R)-3a
(S,R)-3c
(S,R)-3c
(S,R)-3d
(S,R)-3a
(S,R)-3a
(S,R)-3d
(S,R)-3a
(R,S)-3b
3 000
10 000
55 000
1 000
3 300
3 000
10
20
20
50
20
20
30
20
20
16
20
20
8
2
(R)-2a
(R)-2b 100
99.6 99
1
1
1
1
1
1
1
4
6
8
8
b
be
c
d d
ed
f
98
98
92
99f
98f
with (S,R)-3d under the basic, protic conditions ([6] ) 1.0
M in i-C OH, [t-C OK] ) 15 mM, ketone/Ru/base )
0 000:1:100, 25 °C, 9 atm) proceeded via dynamic kinetic
14 (R)-2b 100
13 (R)-2c 98
8
8
2
18 (R)-2g
14 (R)-5
16 (R,R)-7
H
3 7
4 9
H
1
(R)-2d 100
(R)-2e 100
(R)-2f
16,17
resolution
to afford (1R,2R)-7 in 87% ee and 97% yield
(
cis:trans ) 98.6:1.4).
Certain alkylated 2-cyclohexenones behave similarly to
-tetralones. For example, 2,4,4-trimethyl-2-cyclohexenone
3 300
99.9 95f
99.9 93
g
12 000
12 000
10 000
10 000
1 000
1
98
97g
96
87
(8a) was hydrogenated with (S,R)-3a (S/C ) 10 000, 9 atm,
25 °C, 7 h) to give the chiral allylic alcohol (R)-9a in 96%
a
b
7
8
(R)-9a
(S)-9b 100h
99.5 96
80
18
ee, leaving the olefinic bond intact. Reaction of the simpler
a
3-methyl-2-cyclohexenone (8b) with (R,S)-3b gave (S)-9b
in 80% ee and 98% yield, accompanied by 2% of a fully
saturated alcohol.
Unless otherwise stated, reactions were conducted using 3.0 mmol of
1
9
ketone (0.5-1.0 M) in i-C3H7OH containing a chiral Ru catalyst and
t-C4H9OK at 25 °C under 9 atm of H2. Substrate/catalyst molar ratio.
Determined by chiral GC analysis. In a 3:1 i-C3H7OH-t-C4H9OH
mixture. Reaction using 11.3 g (63.9 mmol) of 1b. Determined after
conversion to the acetate. cis:trans ) 98.6:1.4. Contaminated by 2% of
-methylcyclohexanol.
b
c
d
e
f
The chiral BINAP/1,4-diamine-Ru catalysts enable the
enantioselective hydrogenation of a series of 1-tetralones and
analogues with a low catalyst loading (S/C ) 1000-55 000).
The reason for the high efficiency of the 1,4-diamine ligands
remains unclear. It might be ascribed to the increased
flexibility of the resulting seven-membered Ru chelate ring,
in comparison to the five-membered ring formed with 1,2-
diamines, or the structural change in reactive Ru hydride
species. It should be emphasized that the newly devised
catalysts are not substitutes for the previously found BINAP/
1,2-diamine-Ru catalysts. Because these have different
characteristics, both are used complementarily, depending
on the ketone structures.
g
h
3
none to give the R alcohol in 77% ee. Most notably, the
reaction of acetophenone and 1a using (S,R)-3b under the
same conditions (Table 1) displayed an opposite sense of
asymmetric induction, giving (S)-1-phenylethanol in 81% ee
and (R)-2a and 89% ee, respectively.
A series of 1-tetralone derivatives 1 was hydrogenated with
high enantioselectivity as shown in Table 2. Here, one must
carefully choose the precatalyst 3 depending on the substitu-
tion pattern. In most cases, i-C
solvent, while a 3:1 mixture of i-C
higher yield for the reaction catalyzed by 3c with an S/C
ratio of >3000. Hydrogenation of 5-methoxy-1-tetralone (1b)
3
H
7
OH served as the best
OH and t-C OH gave
3
H
7
4 9
H
Acknowledgment. We thank Drs. Kunihiko Murata and
Takeaki Katayama at Kanto Chemical Co., Inc. for measure-
ment of the decomposition points and IR spectra of the Ru
complexes and Dr. Shigeyuki Tamogami at T. Hasegawa
Co., Ltd. for determination of the ee values of some chiral
alcohols. This work was financially supported by grants-in-
aid from the Japan Society for the Promotion of Science
with (S,R)-3a and t-C
H
4 9
OK proceeded smoothly with an
OH, 9 atm, 14 h) to give (R)-2b in
8% ee. With the same catalyst, the 6-methoxy ketone 1c
S/C of 55 000 (i-C H
3
7
1
3
9
was hydrogenated slowly, as a result of the electron-donating
para substituent, to give (R)-2c in 92% ee. The 7-methoxy-
and 7-fluoro-1-tetralone, 1d and 1e, were hydrogenated with
(JSPS) (nos. 14GS0214 and 15350079).
(
S,R)-3c in excellent enantioselectivity (>99:1). Electronic
Supporting Information Available: Preparative methods
and properties of a chiral 1,4-diamine, IPHAN, and Ru
complexes 3. Procedures of hydrogenation of the cyclic
D
ketones, GC behavior of alcoholic products, and [R] values
and absolute configuration determination procedure for chiral
alcohols. This material is available free of charge via the
Internet at http://pubs.acs.org.
properties of the C(7) substituents did not affect the rate and
enantioselectivity. The 5,7- and 4,4-dimethyl ketones, 1f and
1
3
mend the Ru complex 3c for hydrogenation of unsubstituted
and 7-substituted 1-tetralones and the complex 3a for reaction
of the 4-, 5-, and 6-substituted derivatives. The complex 3d
is the best for reaction of 1f. None of these tetralones were
efficiently hydrogenated with the conventional BINAP/1,2-
diamine complexes. The resulting chiral 1-tetralols 2 are
useful intermediates for the synthesis of bioactive compounds
g, were quantitatively hydrogenated with (S,R)-3d and (S,R)-
a, respectively, in good enantioselectivity. Thus, we recom-
OL049157C
1
(
15) RuH(η -BH4)(diphosphine)(1,4-diamine) complexes could not be
1
used because of their instability. For the RuH(η -BH4)(diphosphine)(1,2-
diamine) complex, see refs 6 and 7.
(16) Noyori, R.; Tokunaga, M.; Kitamura, M. Bull. Chem. Soc. Jpn. 1995,
6
8, 36-56.
(
13) A single recrystallization from a 1:3 mixture of methanol and hexane
at -30 °C gave pure (R)-2b in 81%.
14) (a) Tombo, G. M. R.; Bellus, D. Angew. Chem., Int. Ed. Engl. 1991,
(17) Ohkuma, T.; Ooka, H.; Yamakawa, M.; Ikariya, T.; Noyori, R. J.
Org. Chem. 1996, 61, 4872-4873.
(
(18) Use of (S)-TolBINAP/(R,R)-DPEN-Ru catalyst gave the R alcohol
5
b
3
0, 1193-1215. (b) Keith, R. A.; Warawa, E. J.; Simpson, T. R. PCT Int.
Appl. WO 9932461, 1999.
in 94% ee.
(19) An (R)-BINAP/(R,R)-DPEN-Ru complex gave only 47% ee.5b
Org. Lett., Vol. 6, No. 16, 2004
2683