Application of phosphine-oxazoline ligands in Ir-catalyzed asymmetric hydrogenation of acyclic aromatic N-arylimines

Article abstract of DOI:10.1021/ol048399+

(Chemical Equation Presented) A new class of chiral phosphine-oxazoline ligands have been developed. Chiral Ir complexes prepared from these ligands induced high enantioselectivities (66-90% ee) when applied to the asymmetric hydrogenation of acyclic aromatic N-arylimines.

Full text of DOI:10.1021/ol048399+

ORGANIC
LETTERS
2004
Vol. 6, No. 21
3825-3827
Application of Phosphine−Oxazoline
Ligands in Ir-Catalyzed Asymmetric
Hydrogenation of Acyclic Aromatic
N-Arylimines
Anna Trifonova, Jarle S. Diesen, Christopher J. Chapman, and
Pher G. Andersson*
Department of Chemistry, Organic Chemistry, Uppsala UniVersity, Box 599,
SE-75124 Uppsala, Sweden
phera@kemi.uu.se
Received August 12, 2004
ABSTRACT
A new class of chiral phosphine−oxazoline ligands have been developed. Chiral Ir complexes prepared from these ligands induced high
enantioselectivities (66 90% ee) when applied to the asymmetric hydrogenation of acyclic aromatic N-arylimines.
−
Chiral amines are useful synthetic intermediates in the
preparation of many biologically active compounds, and
development of an efficient method for their preparation is
of great synthetic importance. One procedure which has
received much attention in recent years is the enantioslective
reduction of C-N double bonds.1 The first investigations
on Ru2a and Rh2b homogeneous catalysis were published in
1975; however, the enatioselectivities were low (15-22%).
In recent years, a variety of chiral metal catalysts, including
Rh,3 Ru,4,5 Ti,6 Zr,6c and Ir7 complexes, have been success-
fully applied to the asymmetric hydrogenation of imines.
However, these procedures often require high catalyst
loadings, elevated pressures, and long reaction times to obtain
the desired amines in high yield. Although several useful
methods have been described for hydrogenation of cyclic
imines,5b,6c,7h,8 the enantioselective hydrogenation of acyclic
imines is more difficult to achieve.1 The main reason for
this problem is ease of interconversion between E and Z
isomers of an acyclic imine in solution.6a,b
In 1979, Crabtree9 reported (pyridine)(phosphane)iridium
complexes displaying high catalytic activity as a homoge-
neous hydrogenation catalyst. Since that report, a number
of research groups10 have evaluated chiral analogues of the
Crabtree catalyst in asymmetric hydrogenations,11 including
the hydrogenation of imines7d,f with varying success.
(1) (a) Blaser, H.-U.; Spindler, F. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
1999; Vol. 1, Chapter 6.2, pp 247-265. (b) Ohkuma, T.; Noyori, R. In
ComprehensiVe Asymmetric Catalysis, Suppl.1; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Berlin, 2004; pp 43-53.
(2) (a) Botteghi, C.; Bianchi, M.; Benedetti, E.; Matteoli, U. Chimia 1975,
29, 256. (b) Kagan, H. B.; Langlois, N.; Dang, T. P. J. Organomet. Chem.
1975, 90, 353.
(4) (a) Oppolzer, W.; Wills, M.; Starkemann, C.; Bernardinelli, G.
Tetrahedron Lett. 1990, 31, 4117. (b) Cobley, C. J.; Henschke, J. P. AdV.
Synth. Catal. 2003, 345, 195.
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B.; Marko, L. J. Mol. Catal. 1984, 22, 283. (b) Becalski, A. G.; Cullen, W.
R.; Fryzuk, M. D.; James, B. R.; Kang, G.-J.; Rettig, S. J. Inorg. Chem.
1991, 30, 5002. (c) Burk, M. J.; Feaster, J. E. J. Am. Chem. Soc. 1992,
114, 6266. (d) Buriak, J. M.; Osborn, J. A. Organometallics 1996, 15, 3161.
(e) Lensink, C.; Rijnberg, E.; de Vries, J. G. J. Mol. Catal. A: Chem. 1997,
116, 199.
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Brintzinger, H. H. J. Am. Chem. Soc. 1999, 121, 1524.
10.1021/ol048399+ CCC: $27.50
© 2004 American Chemical Society
Published on Web 09/18/2004

Previously, 2-azanorbornan-3-ylmethanol and its deriva-
tives have been used by our research group as efficient
transition-metal ligands in different catalytic asymmetric
reactions.12 Recently, we have published the preparation of
a new class of 2-azanorbornane-oxazoline ligands, which
proved to be potent in the iridium-catalyzed transfer hydro-
genation of acetophenone.13
Functionalization of 2-azanorbornane-oxazoline with
phosphine leads to the novel class of phosphine-oxazoline
ligands 3. Herein, we report the synthesis of these new chiral
phosphine-oxazolines and their efficient application as
ligands in the iridium-catalyzed hydrogenation of acyclic
N-arylimines.
2b with diisopropylethylamine in CH2Cl2 followed by
addition of diphenylphosphine chloride. The use of triethyl-
amine as a base resulted in the low yield of phosphine-
oxazoline (20-30%). Iridium complexes 4a and 4b were
prepared by heating to reflux the appropriate phosphine-
oxazoline and [Ir(cod)Cl]2 in CH2Cl2 followed by anion
exchange with NaBArF in CH2Cl2/H2O solution.15 The crude
complexes were purified by column chromatography on silica
gel to afford the desired complexes 4a and 4b as crystalline
solids. Stored at low temperatures, no decomposition is
1
detected by H and 31P NMR after several months.
Iridium complex 4a was tested in asymmetric hydrogena-
tion of various aromatic N-arylimines; the results of this study
are presented in the Table 1. Hydrogenation of the model
substrate N-(1-phenylethylidene)aniline (5)7d revealed that
optimal results were obtained when the reaction was
performed in dichloromethane under a pressure of 20 bar
(H2), with a catalyst loading of 0.5 mol %. Under these
conditions, the corresponding (R)-N-phenyl-N-(1-phenyl-
ethyl)amine was obtained with 90% ee and 98% conversion
in 2 h. Although it was possible to carry on the reaction at
reduced pressures (5 bar) and lower catalyst loadings (0.05
mol %) without loss of enantioselectivity, the reaction rate
is decreased. The same standard conditions were applied to
the hydrogenation of imines 6-13.
The syntheses of complexes 4a and 4b are shown in
Scheme 1. The (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-3-
Scheme 1. Synthesis of Ir Complexes 4a and 4b
For substrates 6 and 7 (entries 2 and 3), having o-methyl
substituents on the aromatic rings, a decrease in the reaction
rate together with a slight decrease of enantioselectivity (80-
83% ee) was observed. The imines 8-12 bearing electron-
withdrawing and electron-donating groups at the para-
positions in aromatic rings (entries 2-8) were reduced in
similar enantiomeric excess to imine 5 (86-89% ee). Full
conversion was achieved for all compounds 8-12 after
1.5-3 h. A correlation between the electronic nature of the
para-substituent of the substrate and ee of the product was
not observed. N-(1-Phenylethylidene)benzylamine (13)7d
(entry 9) which exists as a mixture of E/Z isomers in a 13:1
ratio in CDCl3, was reduced to (R)-N-benzyl-N-(1-phenyl-
ethyl)amine with 66% ee; however, a catalyst loading of 1
mol % was required to obtain 63% conversion in 12 h.
Iridium complex 4b prepared from bulky ligand 3b did
not show catalytic activity in the reduction of imines (Table
2, entries 1 and 2) under the standard conditions. However,
it was efficient in the hydrogenation of olefins 14 and 15.
(R)-1,2-Diphenylpropane15a was obtained in 96% ee and 81%
carboxylic acid (1) is easily available from a stereoselective
aza-Diels-Alder reaction.14 2-Azanorbornane-oxazolines 2a
and 2b were prepared according to methods developed within
our research group.13 The phosphines 3a and 3b were
obtained in high yield by treatment of compounds 2a and
(7) (a) Morimoto, T.; Nakajima, N.; Achiwa, K. Synlett 1995, 748. (b)
Sabllong, R.; Osborn, J. A. Tetrahedron: Asymmetry 1996, 7, 3059. (c)
Sablong, R.; Osborn, J. A. Tetrahedron Lett. 1996, 37, 4937. (d) Schnider,
P.; Koch, G.; Pre´toˆt, R.; Wang, G.; Bohnen, F. M.; Kru¨ger, C.; Pfaltz, A.
Chem. Eur. J. 1997, 3, 887. (e) Bianchini, C.; Barbaro, P.; Scapacci, G.;
Farnetti, E.; Graziani, M. Organometallics 1998, 17, 3308. (f) Kainz, S.;
Brinkmann, A.; Leitner, W.; Pfaltz, A. J. Am. Chem. Soc. 1999, 121, 6421.
(g) Xiao, D.; Zhang, X. Angew. Chem., Int. Ed. 2001, 40, 3425. (h) Blaser,
H.-U.; Buser, H.-P.; Ha¨usel, R.; Jalett, H.-P.; Spindler, F. J. Organomet.
Chem. 2001, 621, 34. (i) Menges, F.; Pfaltz, A. AdV. Synth. Catal. 2002,
344, 40. (j) Chi, Y.; Zhou, Y.-G.; Zhang, X. J. Org. Chem. 2003, 68, 4120.
(k) Jiang, X.-b.; Minnaard, A. J.; Hessen, B.; Feringa, B. L.; Duchateau,
A. L. L.; Andrien, J. G. O.; Boogers, J. A. F.; de Vries, J. G. Org. Lett.
2003, 5, 1503. (l) Cozzi, P. G.; Menges, F.; Kaiser, S. Synlett 2003, 833.
(m) Dorta, R.; Broggini, D.; Stoop, R.; Ru¨egger, H.; Spindler, F.; Togni,
A. Chem. Eur. J. 2004, 10, 267. (n) Blanc, C.; Agbossou-Niedercorn, F.;
Nowogrocki, G. Tetrahedron: Asymmetry 2004, 15, 2159.
(10) (a) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
566. (b) Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769. (c)
Dawson, G. J.; Frost, C. G.; Williams, J. M. J.; Coote, S. J. Tetrahedron
Lett. 1993, 34, 3149.
(11) Review: (a) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33,
336. (b) Pfaltz, A.; Blankenstein, J.; Hilgraf, R.; Ho¨rmann, E.; McIntyre,
S.; Menges, F.; Scho¨nleber, M.; Smidt, S.; Wu¨stenberg, B.; Zimmermann,
N. AdV. Synth. Catal. 2003, 345, 33.
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(13) Trifonova, A., Ka¨llstro¨m, K. E.; Andersson, P. G. Tetrahedron 2004,
60, 3393.
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Org. Lett., Vol. 6, No. 21, 2004

Table 1. Asymmetric Hydrogenation of Acyclic N-Arylimines
Catalyzed by Ir Complex 4a
Table 2. Asymmetric Hydrogenation Catalyzed by Ir Complex
4b
1
a Determined by H NMR. b Determined by chiral HPLC or chiral GC
MS, absolute configuration assigned by comparison of retention times with
literature values15 (see the Supporting Information for details).
In conclusion, we have developed a new class of chiral
phosphine-oxazoline ligands. These ligands were used for
preparation of chiral iridium complexes for asymmetric
hydrogenation. Complex 4a was applied to enantioselective
acyclic aromatic N-arylimines to induce high enantioselec-
tivities (66-90% ee). Complex 4b was efficient in hydro-
genation of olefins. Our current effort is concentrated on
improving enantioselectivity and broadening the scope of
these hydrogenation reactions.
Acknowledgment. This work was supported by grants
from the Swedish Research Council (VR). We are also
grateful to Mr. Magnus Enqvist, Mr. Christian Hedberg, Mr.
Klas Ka¨llstro¨m, and Ms. Jessica Lemke for preparation of
the substrates.
a Determined by 1H NMR. b Determined by chiral HPLC, absolute
configuration assigned by comparison of retention times with literature
values7d or the sign of optical rotation is reported. c 1 mol % of catalyst
was used (see the Supporting Information for details).
Supporting Information Available: Experimental pro-
cedures, characterization data, and NMR spectra for unknown
compounds, references to known compounds, and chiral
separation data. This material is available free of charge via
the Internet at http://pubs.acs.org.
conversion (entry 3), and 6-methoxy-1-(S)-methyl-1,2,3,4-
tetrahydronaphthalene15b was produced in 77% ee with full
conversion (entry 4) in 12 h.
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