The First Application of a Planar-Chiral Phosphorus Heterocycle in Asymmetric Catalysis: Enantioselective Hydrogenation of Dehydroamino Acids

Full text of DOI:10.1021/jo980624b

4168
J . Org. Chem. 1998, 63, 4168-4169
Th e F ir st Ap p lica tion of a P la n a r -Ch ir a l
P h osp h or u s Heter ocycle in Asym m etr ic
Ca ta lysis: En a n tioselective Hyd r ogen a tion of
Deh yd r oa m in o Acid s
Shuang Qiao and Gregory C. Fu*
Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
Received April 8, 1998
We recently initiated a program directed at the develop-
ment of planar-chiral heterocycles as enantioselective nu-
cleophilic catalysts1 and as chiral ligands for transition
metals.2 These studies provided the first reports of applica-
tions of planar-chiral heterocycles in asymmetric catalysis.
While our earliest work focused on π-bound nitrogen het-
erocycles, more recently we have expanded the scope of our
investigation to include phosphorus heterocycles.3 In this
paper, we describe the synthesis and resolution of a new,
planar-chiral bisphosphine (1), and we establish its utility
in enantioselective catalysis, specifically, in the Rh(I)-
catalyzed asymmetric hydrogenation of dehydroamino acids
(eq 1).
F igu r e 1. Synthesis of enantiopure planar-chiral bisphosphine
1.
Ta ble 1. Ca ta lytic Asym m etr ic Hyd r ogen a tion in th e
P r esen ce of Bisp h osp h in e 1
entry
R
% ee
yield
1
2
3
4
5
6
7
8
H
Ph
87
87
87
85
79
88
96
90
99
95
96
95
100
96
4-OMeC6H4
4-ClC6H4
4-NO2C6H4
Me
Et
i-Pr
92
96
Achiral phosphaferrocene 2, first prepared by Mathey,4,5
serves as the starting point for our synthesis of planar-chiral
bisphosphine 1 (Figure 1).6 Vilsmeier-Haack formylation
of 2 through treatment with N-methylformanilide and POCl3
provides racemic phosphaferrocene 3 in 70% yield.7 Reduc-
tion with LiAlH4 then furnishes alcohol 4 (98%),7 which can
be resolved by chiral HPLC (Chiralcel OD). We have
determined the absolute configuration of enantiopure (+)-4
through X-ray crystallography. Subjection of 4 to a one-pot
chlorination and displacement sequence then affords bis-
phosphine 1 (50% for two steps). It is important to note that
Ganter has recently described the resolution of the Cp
analogue of 3,8 as well as the synthesis and coordination
chemistry of the racemic Cp analogue of 1.9
The asymmetric hydrogenation of dehydroamino acids is
frequently used as a proving ground for new chiral bisphos-
phines,10,11 in part because of the significance of the product
R-amino acids. We have established that, in the presence
(8) Through chromatographic separation of diastereomeric aminal
derivatives: Ganter, C.; Brassat, L.; Ganter, B. Tetrahedron: Asymmetry
1997, 8, 2607-2611.
(9) Ganter, C.; Brassat, L.; Ganter, B. Chem. Ber./ Recueil 1997, 130,
1771-1776. Ganter prepared the racemic Cp analogue of 1 by a route that
is somewhat different from that outlined in Figure 1. See also: Ganter, C.;
Brassat, L.; Glinsbo¨ckel, C.; Ganter, B. Organometallics 1997, 16, 2862-
2867. Deschamps, B.; Ricard, L.; Mathey, F. J . Organomet. Chem. 1997,
548, 17-22.
(10) For recent examples, see: (a) Imamoto, T.; Watanabe, J .; Wada, Y.;
Masuda, H.; Yamada, H.; Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J .
Am. Chem. Soc. 1998, 120, 1635-1636. (b) Chan, A. S. C.; Hu, W.; Pai,
C.-C.; Lau, C.-P.; J iang, Y.; Mi, A.; Yan, M.; Sun, J .; Lou, R.; Deng, J . J .
Am. Chem. Soc. 1997, 119, 9570-9571. (c) Pye, P. J .; Rossen, K.; Reamer,
R. A.; Tsou, N. N.; Volante, R. P.; Reider, P. J . J . Am. Chem. Soc. 1997,
119, 6207-6208.
(11) For reviews, see: (a) Noyori, R. Asymmetric Catalysis in Organic
Synthesis; Wiley: New York, 1994; Chapter 2. (b) Knowles, W. S. Acc. Chem.
Res. 1983, 16, 106-12. (c) Pfaltz, A.; Brown, J . M. In Stereoselective
Synthesis; Helmchen, G., Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.;
Thieme: New York, 1996; Part D, Section 2.5.1.2. Most of the effective
bisphosphines that have been reported to date have C2 symmetry.
(1) (a) Ruble, J . C.; Fu, G. C. J . Org. Chem. 1996, 61, 7230-7231. (b)
Ruble, J . C.; Latham, H. A.; Fu, G. C. J . Am. Chem. Soc. 1997, 119, 1492-
1493. (c) Ruble, J . C.; Tweddell, J .; Fu, G. C. J . Org. Chem. 1998, 63, 2794-
2795. (d) Liang, J .; Ruble, J . C.; Fu, G. C. J . Org. Chem. 1998, 63, 3154-
3155. (e) Garrett, C. E.; Fu, G. C. Submitted for publication.
(2) Dosa, P. I.; Ruble, J . C.; Fu, G. C. J . Org. Chem. 1997, 62, 444-445.
(3) (a) Nucleophilic catalysis (achiral): Garrett, C. E.; Fu, G. C. J . Org.
Chem. 1997, 62, 4534-4535. (b) Synthesis of an enantiopure diphospha-
ferrocene: Qiao, S.; Hoic, D. A.; Fu, G. C. Organometallics 1998, 17, 773-
774.
(4) Synthesized in two steps from commercially available compounds:
Roman, E.; Leiva, A. M.; Casasempere, M. A.; Charrier, C.; Mathey, F.;
Garland, M. T.; le Marouille, J .-Y. J . Organomet. Chem. 1986, 309, 323-
332. See also ref 3a.
(5) For a review of phospholide and phosphaferrocene chemistry, see:
Mathey, F. Coord. Chem. Rev. 1994, 137, 1-52.
(6) All yields in Figure 1 are the average of g2 runs.
(7) For precedent with the Cp analogue of phosphaferrocene 2, see: de
Lauzon, G.; Deschamps, B.; Fischer, J .; Mathey, F.; Mitschler, A. J . Am.
Chem. Soc. 1980, 102, 994-1000.
S0022-3263(98)00624-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/30/1998

Communications
J . Org. Chem., Vol. 63, No. 13, 1998 4169
of planar-chiral phosphaferrocene 1, the [Rh(cod)2]PF6-
catalyzed hydrogenation of methyl R-acetamidocinnamate
proceeds with modest ee in CH2Cl2, but with very good ee
in THF or EtOH (eq 2).12
Unfortunately, we have not yet been able to obtain a
crystal structure of a rhodium complex of ligand 1. However,
a
31P NMR study of the reaction of [Rh(cod)2]PF6 with 1
equiv of ligand 1 (31P {1H} NMR of 1: δ -61.4 (d, J ) 27
Hz) for phosphole, -11.6 (d, J ) 27 Hz) for tertiary
phosphine) establishes that both phosphines bind to rhodium
(31P {1H} NMR of reaction mixture: δ 22.6 (dd, J ) 28, 172
Hz) for phosphole, 61.8 (dd, J ) 28, 141 Hz) for tertiary
phosphine).
In summary, we have developed a straightforward syn-
thesis and resolution of a new, planar-chiral bisphosphine
(1), and we have described its use in the rhodium-catalyzed
enantioselective hydrogenation of dehydroamino acids. To
the best of our knowledge, this is the first example of the
application of a planar-chiral phosphorus heterocycle in
asymmetric catalysis. In future work, we intend to explore
the utility of this and related chiral ligands in other
transition metal-catalyzed processes.
As illustrated in Table 1, a wide array of dehydroamino
acids are reduced with good to excellent enantioselectivity
under the following conditions: 5% [Rh(cod)2]PF6, 6% 1, 1
atm of H2, EtOH, room temperature.13 An investigation of
a range of cinnamate derivatives reveals an electronic effect
on selectivity for this class of compoundssmore electron-
rich systems furnish higher ee (Table 1, entries 2-5).
â-Alkyl-substituted esters are also reduced stereoselectively
(Table 1, entries 6-8), with methyl R-acetamidobut-2-enoate
providing the highest enantiomeric excess (96% ee; Table
1, entry 7).
Ack n ow led gm en t. We thank Michael Man-Chu Lo for
solving the crystal structure of (+)-4 and J ack Liang for
helpful discussions. Support has been provided by the
Alfred P. Sloan Foundation, the American Cancer Society,
the Camille and Henry Dreyfus Foundation, Eli Lilly,
Firmenich, Glaxo Wellcome, the National Science Founda-
tion (Young Investigator Award, with funding from Merck,
Pharmacia & Upjohn, Bristol-Myers Squibb, DuPont,
Bayer, Rohm & Haas, and Novartis), Pfizer, Procter &
Gamble, and the Research Corporation.
(12) The use of counterions other than PF6 (e.g., SbF6, OTf, and BF4)
results in lower enantioselectivities.
(13) General procedure for asymmetric hydrogenation: A 100 mL Schlenk
tube was charged with substrate (0.22 mmol), (-)-1 (6.7 mg, 0.013 mmol),
Rh(cod)2PF6 (5.1 mg, 0.011 mmol), and anhydrous EtOH (6.0 mL). After
three vacuum/H2-refill cycles, the valve to the Schlenk tube was closed. The
reaction mixture was then stirred for 12 h at rt, at which time TLC indicated
that all of the starting material had been consumed. The reaction mixture
was concentrated and then passed through a short column (50:50 EtOAc/
hexane). The ee was determined by chiral GC.
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures, compound characterization data, and X-ray structural data
(16 pages).
J O980624B