"Achiral" benzophenone ligand for highly enantioselective Ru catalysts in ketone hydrogenation

Article abstract of DOI:10.1021/ol052936o

The chirality of an "achiral" benzophenone-based complex can be controlled. The benzophenone-based complex thus controlled affords high enantioselectivity in the catalytic asymmetric ketone hydrogenation (up to 99% ee, >99% yield).

Full text of DOI:10.1021/ol052936o

ORGANIC
LETTERS
2006
Vol. 8, No. 8
1517-1519
“Achiral” Benzophenone Ligand for
Highly Enantioselective Ru Catalysts in
Ketone Hydrogenation
Koichi Mikami,* Kazuki Wakabayashi, and Kohsuke Aikawa
Department of Applied Chemistry, Tokyo Institute of Technology,
Tokyo 152-8552, Japan
kmikami@o.cc.titech.ac.jp
Received December 2, 2005 (Revised Manuscript Received February 2, 2006)
ABSTRACT
The chirality of an “achiral” benzophenone-based complex can be controlled. The benzophenone-based complex thus controlled affords high
enantioselectivity in the catalytic asymmetric ketone hydrogenation (up to 99% ee, >99% yield).
The development of asymmetric catalysts for organic reac-
tions is one of the most challenging subjects in modern sci-
ence and technology.1 Generally, asymmetric catalysis em-
ploys metal complexes bearing chiral and atropisomeric2
(originating from atropos in Greek3) ligands, normally in
enantiopure forms.
ligand.5 In a fluid phase, however, enantiomeric resolution
or control to single conformational chirality is rather difficult
due to thermal fluctuations and/or molecular diffusion.6
We report here enantiocontrol of achiral benzophenone
ligands7,8 in the solution phase and the use of the metal
complexes for highly enantioselective catalysis9 of ketone
hydrogenation10 (up to 99% ee, 99% yield) (Scheme 1).
Inherently, achiral or racemic ligands provide only racemic
products. However, asymmetric catalysis might be developed
via enantiomeric fluctuation or discrimination of conforma-
tional chirality of achiral ligands.4 Indeed, the racemic
BIPHOS ligand was recently reported to spontaneously
crystallize and the conglomerate was then used as a chiral
Scheme 1
(1) (a) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. ComprehensiVe
Asymmetric Catalysis; Springer: Berlin, Germany, 1999; Vols. 1-3. (b)
Transition Metals for Organic Synthesis; Beller, M., Bolm, C., Eds.;
VCH: Weinheim, Germany, 1998. (c) Noyori, R. Asymmetric Catalysis in
Organic Synthesis; Wiley: New York, 1994. (d) Brunner, H.; Zettlmeier,
W. Handbook of EnantioselectiVe Catalysis; VCH: Weinheim, Germany,
1993. (e) Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York,
1993 and 2000; Vols. I and II.
(2) Kuhn, W. Stereochemie; Freudenberg, K., Ed.; Franz Deuticke:
Leipzig, Germany, 1933; pp 803-824.
(3) The word atropos consists of “a” meaning “not” and “tropos”
meaning “turn” in Greek. Therefore, the chirally rigid or flexible nature of
a ligand can be called atropos or tropos, respectively. Mikami, K.; Aikawa,
K.; Yusa, Y.; Jodry, J. J.; Yamanaka, M. Synlett 2002, 1561-1578.
10.1021/ol052936o CCC: $33.50
© 2006 American Chemical Society
Published on Web 03/21/2006

Figure 1. X-ray structure of [RuCl(OTf)(dpbp){(S,S)-dpen}]2AgOTf (3).
The asymmetric catalysts are generally metal complexes
bearing chiral and atropisomeric ligands such as BINAP,
which usually allow the C2-symmetric metal complexes for
enantiocontrol.11
Achiral and tropos 2,2′-bis(diphenylphosphino)benzophe-
none (DPBP) might possess conformational chirality such
as BINAP. Upon addition of DPBP to [RuCl2(C6H6)]2, RuCl2-
(dpbp)(dmf)n complex 1 was obtained.
top view of Figure 1 shows that the benzophenone skeleton
of the DPBP ligand adopts a chiral propeller conformation.
The advantage of the “achiral” and tropos benzophenone
ligand over the enantiopure atropos BINAP counterpart for
asymmetric catalysis can be seen in hydrogenation of 1′-
acetonaphthone (Table 1). A virtually complete (99% ee,
The chiral control of RuCl2(dpbp)(dmf)n complex 1 by
(1S,2S)-(-)-1,2-diphenylethylenediamine ((S,S)-DPEN) led
to the formation of enantiomerically pure RuCl2(dpbp)[(S,S)-
dpen] complex 2 as shown in the solution NMR (Scheme
2). The single crystal of RuCl2(dpbp)[(S,S)-dpen] (2) was
Table 1. Asymmetric Hydrogenation of 1′-Acetonaphthone
Scheme 2
alcohol product
entry
diphosphine
conv (%)
ee (%)
1
2
3a
DPBP
DPBOL
(S)-BINAP
>99
67
>99
99
66
97
a Also see ref 10a.
>99% yield) enantioselectivity was attained by the ben-
zophenone catalyst 2. The enantioselectivity thus obtained
is higher than 97% ee obtained by our own hand13 with the
enantiopure BINAP counterpart (Table 1, entry 1 vs entry
3). There was a possibility that hydrogenated DPBP, namely
not obtained. Fortunately, however, the single crystal of the
monotriflate derivative, [RuCl(OTf)(dpbp){(S,S)-dpen}]2AgOTf
(3), was obtained (Figure 1).
The X-ray analysis of [RuCl(OTf)(dpbp){(S,S)-dpen}]2-
AgOTf (3)12 showed the enantiopure structure of this
benzophenone-derived diphosphine-metal complex 3. The
(7) Enantiocontrol of BIPHEP: (a) Mikami, K.; Korenaga, T.; Terada,
M.; Ohkuma, T.; Pham, T.; Noyori, R. Angew. Chem., Int. Ed. 1999, 38,
495-497. (b) Mikami, K.; Aikawa, K.; Yusa, Y.; Hatano, M. Org. Lett.
2002, 4, 91-94. (c) Tudor, M. D.; Becker, J. J.; White, P. S.; Gagne´, M.
R. Organometallics 2000, 19, 4376-4384. (d) Becker, J. J.; White, P. S.;
Gagne´, M. R. J. Am. Chem. Soc. 2001, 123, 9478-9479. (e) Mikami, K.;
Aikawa, K.; Yusa, Y. Org. Lett. 2002, 4, 95-97. (f) Mikami, K.; Kataoka,
S.; Yusa, Y.; Aikawa, K. Org. Lett. 2004, 6, 3699-3701.
(8) Enantiocontrol of NUPHOS: (a) Doherty, S.; Newman, C. R.; Rath,
R. K.; Luo, H.-K.; Nieuwenhuyzen, M.; Knight J. G. Org. Lett. 2003, 5,
3863-3866. (b) Doherty, S.; Newman, C. R.; Rath, R. K.; van den Berg,
J.-A.; Hardacre, C.; Nieuwenhuyzen, M.; Knight J. G. Organometallics
2004, 23, 1055-1064.
(4) (a) Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem. ReV. 2003, 103,
3297-3344. (b) Faller J. W.; Lavoie, A. R.; Parr, J. Chem. ReV. 2003, 103,
3345-3368. (c) Mikami, K.; Yamanaka, M. Chem. ReV. 2003, 103, 3369-
3400.
(5) Tissot, O.; Gouygou, M.; Dallemer, F.; Daran, J. C.; Balavoine, G.
A. G. Angew. Chem., Int. Ed. 2001, 40, 1076-1078.
(6) (a) Toda, F.; Tanaka, K.; Kuroda, R. Chem. Commun. 1997, 1227-
1228. (b) Takanishi, Y.; Takezoe, H.; Suzuki, Y.; Kobayashi, I.; Yajima,
T.; Terada, M.; Mikami, K. Angew. Chem., Int. Ed. 1999, 38, 2354-2356.
1518
Org. Lett., Vol. 8, No. 8, 2006

2,2′-bis(diphenylphosphino)benzhydrol (DPBOL), might be
involved in the present hydrogenation of 1′-acetonaphthone.
However, the hydrogenation with DPBOL was confirmed to be
much lower in enantioselectivity than that obtained with DPBP.
The hydrogenation by achiral DPBP is also effective even
in the case of ortho-, meta-, or para-substituted acetophe-
nones. DPBP catalyst 2 gave ortho-, meta-, or para-
substituted phenethyl alcohols with higher enantioselective
(up to 98% ee) than that obtained with BINAP-Ru or tol-
BINAP-Ru catalysts (Table 2).
benzophenone complexes can be controlled even in the
solution phase. The enantiopure benzophenone complex thus
obtained affords even higher enantioselectivity than those
attained by the enantiopure BINAP counterpart in the
asymmetric catalysis of ketone hydrogenation.
Acknowledgment. We are grateful to Dr. K. Yoza of
Nippon Bruker AXS K.K. for X-ray analysis.
Supporting Information Available: Experimental pro-
cedures for the preparations of 2 and 3 and for the
hydrogenation of ketones, and crystal data for 3 (PDF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
Table 2. Asymmetric Hydrogenation with DPBP-Ru
Complexes
OL052936O
(9) (a) Reetz, M. T.; Mehler, G. Tetrahedron Lett. 2003, 44, 4593-
4596. (b) Reetz, M. T.; Li, X. Angew. Chem., Int. Ed. 2005, 44, 2959-
2962. (c) Monti, C.; Gennart, C.; Piarulli, U. Chem. Commun. 2005, 5281-
5283.
(10) (a) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem.
Soc. 1995, 117, 2675-2676. (b) Ohkuma, T.; Ooka, H.; Yamakawa, M.;
Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 10417-10418. (c)
Ohkuma, T.; Ooka, H.; Yamakawa, M.; Ikariya, T.; Noyori, R. J. Org.
Chem. 1996, 61, 4872-4873. (d) 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. (e) 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,
13529-13530. (f) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001,
40, 40-73. (g) Xie, J.-H.; Wang, L.-X.; Fu, Y.; Zhu, S.-F.; Fan, B.-M.;
Duan, H.-F.; Zhou, Q.-L. J. Am. Chem. Soc. 2003, 125, 13529-13530.
(11) (a) BINAP: Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345-
350. (b) DET (Diethyl tartrate): Katsuki, T.; Sharpless, K. B. J. Am. Chem.
Soc. 1980, 102, 5974-5976. (c) DIOP: Sinou, D.; Kagan, H. B. J.
Organomet. Chem. 1976, 114, 325-337.
(12) Crystal data for [RuCl(OTf)(dpbp){(S,S)-dpen}]2AgOTf (3): for-
mula C107H90.50AgCl9.50F7.50N4O9.50P4Ru2S2.50, orthorhombic, space group
P2(1)2(1)2, a ) 20.9715(16) Å, b ) 39.437(3) Å, c ) 13.8177(10) Å, R
) â ) γ ) 90°, V ) 11428.0(15) Å3, Z ) 4, and D ) 1.498 Mg/m3. The
final cycle of full-matrix least-squares on F2 was based on 26 825 observed
reflections and 1448 variable parameters and converged to R ) 0.0754 and
Rw ) 0.2099. Goodness of fit ) 1.145, shift/error ) 0.04(3). Crystal-
lographic data (excluding structure factors) for the structure reported in
this paper have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC-257768. Copies of the data
can be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB21EZ, UK (Fax (+44)1223-336-033; E-mail deposit@
ccdc.cam.ac.uk).
a Also see:ref 10a. b Also see ref 10e.
(13) The enantioselectivity thus obtained is exactly the same as re-
ported: see ref 10a.
In summary, we have uncovered that the chirality of
Org. Lett., Vol. 8, No. 8, 2006
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