Bis-(2,5-diphenylphospholanes) with sp2 carbon linkers: Synthesis and application in asymmetric hydrogenation

Article abstract of DOI:10.1021/jo7014938

(Chemical Equation Presented) Four chiral diphosphine ligands consisting of bis(2,5-diphenylphospholan-1-yl) groups connected by the sp² carbon linkers 2,3-quinoxaline ((S,S)-Ph-Quinox), 2,3-pyrazine ((S,S)-Ph-Pyrazine), maleic anhydride ((S,S)-Ph-MalPhos), and 1,1′-ferrocene ((S,S)-Ph-5-Fc) were synthesized, and their cationic [rhodium-(I)(COD)] complexes were prepared. These complexes were tested in asymmetric hydrogenation of functionalized olefins. [((S,S)-Ph-Quinox)Rh(COD)]BF₄ showed high activity and selectivity against itaconate and dehydroamino acid substrates. The corresponding (S,S)-Ph-Pyrazine and (S,S)-Ph-MalPhOS complexes exhibited lower activities and selectivities. [((S,S)-Ph-S-Fc)Rh(COD)]BF₄ showed high activity with low selectivity for these substrates, but high activity and selectivity against 2-C-substituted cinnamate salts, whereas rhodium complexes of (S,S)-Ph-Quinox and (R,R)-Ph-BPE showed low activity and selectivity against 2-C-substituted cinnamate salts.

Full text of DOI:10.1021/jo7014938

VOLUME 73, NUMBER 3
FEBRUARY 1, 2008
© Copyright 2008 by the American Chemical Society
Bis-(2,5-diphenylphospholanes) with sp2 Carbon Linkers: Synthesis
and Application in Asymmetric Hydrogenation
Martin E. Fox,*,† Mark Jackson,† Ian C. Lennon,† Jerzy Klosin,‡ and Khalil A. Abboud§
Dowpharma, Chirotech Technology Ltd, a subsidiary of The Dow Chemical Company, Unit 162
Cambridge Science Park, Milton Road, Cambridge, CB4 0GH, U.K., Corporate R&D,
The Dow Chemical Company, Midland, Michigan 48674, and Department of Chemistry,
UniVersity of Florida, GainesVille, Florida 32611
Mfox@dow.com
ReceiVed July 18, 2007
Four chiral diphosphine ligands consisting of bis(2,5-diphenylphospholan-1-yl) groups connected by the
sp2 carbon linkers 2,3-quinoxaline ((S,S)-Ph-Quinox), 2,3-pyrazine ((S,S)-Ph-Pyrazine), maleic anhydride
((S,S)-Ph-MalPhos), and 1,1′-ferrocene ((S,S)-Ph-5-Fc) were synthesized, and their cationic [rhodium-
(I)(COD)] complexes were prepared. These complexes were tested in asymmetric hydrogenation of
functionalized olefins. [((S,S)-Ph-Quinox)Rh(COD)]BF4 showed high activity and selectivity against
itaconate and dehydroamino acid substrates. The corresponding (S,S)-Ph-Pyrazine and (S,S)-Ph-MalPhos
complexes exhibited lower activities and selectivities. [((S,S)-Ph-5-Fc)Rh(COD)]BF4 showed high activity
with low selectivity for these substrates, but high activity and selectivity against 2-C-substituted cinnamate
salts, whereas rhodium complexes of (S,S)-Ph-Quinox and (R,R)-Ph-BPE showed low activity and
selectivity against 2-C-substituted cinnamate salts.
Introduction
hydrogenation,6 and rhodium-catalyzed asymmetric hydro-
formylation.7,8 In view of the excellent properties of the (R,R)-
Ph-BPE (1)5 and (R,R)-Ph-BPM (2)6 ligands (Figure 1) in these
reactions, we set out to extend the range of available bis(2,5-
diphospholane) ligands and hence prepare asymmetric hydro-
genation catalysts with novel capabilities by synthesis of a
corresponding series of ligands with sp2 carbon linkers. We
intended to use the monophospholane methodology successfully
applied to the synthesis of (R,R)-Ph-BPE (1)5 and (R,R)-Ph-
BPM (2)6 ligands, in which the resolved acid 39 was used as a
monophospholane precursor and coupled to the linker after
suitable manipulation of the phosphorus functionality. The 2,3-
Asymmetric hydrogenation of olefins, ketones, and imines
using modular phospholane-based catalysts is a powerful method
to produce enantiomerically enriched products.1-4 A subset of
this class is diphosphines based on bis(2,5-diphenylphospholane)
groups connected by sp3 carbon linkers (Figure 1), which
provide valuable ligands for rhodium-catalyzed asymmetric
olefin hydrogenation,2,5,6 ruthenium-catalyzed asymmetric imine
† Dowpharma, Chirotech Technology Ltd.
‡ Corporate R&D, Dow Chemical Company.
§ University of Florida.
(1) Tang, W.; Zhang, X. Chem. ReV. 2003, 103, 3029-3069.
(2) Lennon, I. C.; Pilkington, C. J. Synthesis 2003, 1639-1642.
(3) Burk, M. J. Acc. Chem. Res. 2000, 33, 363-372.
(4) Clark, T. C.; Landis, R. C. Tetrahedron: Asymmetry 2004, 15, 2123-
2137.
(5) Pilkington, C. J.; Zanotti-Gerosa, A. Org. Lett. 2003, 5, 1273-1275.
(6) Jackson, M.; Lennon, I. C. Tetrahedron Lett. 2007, 48, 1831-1834.
(7) Axtell, A. T.; Cobley, C. J.; Klosin, J.; Whiteker, G. T.; Zanotti-
Gerosa, A.; Abboud, K. A. Angew. Chem., Int. Ed. 2005, 44, 5834-5838.
(8) Axtell, A. T.; Klosin, J.; Abboud, K. A. Organometallics 2006, 25,
5003-5009.
(9) Galland, A.; Dobrota, C.; Toffano, M.; Fiaud, J.-C. Tetrahedron:
Asymmetry 2006, 17, 2354-2357.
10.1021/jo7014938 CCC: $40.75 © 2008 American Chemical Society
Published on Web 10/19/2007
J. Org. Chem. 2008, 73, 775-784
775

Fox et al.
FIGURE 1. Bis(2,5-diphenylphospholane) ligands and monophospholane precursors.
SCHEME 1. Synthesis of Quinoxaline and Pyrazine Linked Ligands
quinoxalinyl group had previously been reported by Imamoto
et al.10,11 as a two-carbon linker for P-chiral diphosphine ligands
exhibiting high activity and selectivity in rhodium-catalyzed
asymmetric hydrogenation. Furthermore, synthesis of diphos-
phine ligands based on this linker was achieved by substitution
using a nucleophilic phosphorus species. Hence, we anticipated
that the bis(2,5-diphenylphospholane) ligand 5 based on this
linker could also be valuable in asymmetric hydrogenation and
that its synthesis should be achievable using the monophospo-
lane borane adduct 4 previously employed as a P-nucleophile
in the synthesis of the (R,R)-Ph-BPE (1)5 and (R,R)-Ph-BPM
(2)6 ligands. We were also interested in making the analogous
ligands with two carbon sp2 linkers 2,3-pyrazinyl (6) and maleic
anhydride12 ((S,S)-Ph-MalPhos (7)) for comparison, which we
expected to be accessible by similar nucleophilic substitution
chemistry. Diphosphine ligands with a 1,1′-ferrocenyl linker
have also shown high and unique selectivities in rhodium-
catalyzed asymmetric hydrogenation of certain olefin sub-
strates.13-15 Thus, we sought to achieve the synthesis of the
bis(2,5-diphospholane) ligand based on this linker, (S,S)-Ph-5-
Fc (8). However, formation of P-ferrocenyl carbon bonds is most
readily achieved by reaction of a metalated ferrocene with a
phosphorus electrophile. Therefore, extension of the monophos-
pholane strategy to this ligand would require the use of an
electrophilic (2,5-diphenylphospholane) synthon.
Results and Discussion
Synthesis of 2,3-Quinoxaline and 2,3-Pyrazine Linked
Ligands. The quinoxaline linked ligand 5 ((S,S)-Ph-Quinox)
was prepared in a procedure analogous to that described by
Imamoto et al.:10 by reaction of the lithiated phospholane borane
adduct (S,S)-4 with 2,3-dichloroquinoxaline (Scheme 1). We
observed the free phosphine rather than the borane adduct to
be the product of the coupling reaction, with loss of borane
occurring spontaneously during the reaction or workup, to give
the free ligand 5. This was similar to the findings of Imamoto
et al. with his ligand system; however, we found that the addition
of TMEDA as employed by Imamoto et al. was unnecessary.
If TMEDA is added, the borane is lost from the remaining
monophospholane borane adduct 4, and the resulting free
phosphine and oxidation products are difficult to separate from
the product 5. The pyrazine linked ligand 6 was prepared using
the enantiomeric phospholane borane adduct (R,R)-4. A large
amount of monophospholane 9 was also observed in this case.
These procedures have not been optimized, but sufficient
quantities of the target ligands 5 and 6 were obtained for our
studies.
(10) Imamoto, T.; Sugita, K.; Kazuhiro, Y. J. Am. Chem. Soc. 2005,
127, 11934-11935.
(11) Imamoto, T.; Nishimura, M.; Koide, A.; Yoshida, K. J. Org. Chem.
2007, 72, 7413-7416.
Synthesis of Maleic Anhydride Linked Ligand (S,S)-Ph-
MalPhos (7). In the preparation of maleic anhydride linked bis-
(2,5-dialkylphospholane) ligands,12 Bo¨rner et al. employed the
reaction between dichloromaleic anhydride and a 1-trimethyl-
silylphospholane nucleophile. However, we found that for the
2,5-diphenylphospholane analogue, the use of the free phosphine
(12) Holz, J.; Monsees, A.; Jiao, H.; You, J.; Komarov, I. V.; Fischer,
C.; Drauz, K.; Bo¨rner, A. J. Org. Chem. 2003, 68, 1701-1707.
(13) Burk, M. J.; Gross, M. F. Tetrahedron Lett. 1994, 35, 9363-9366.
(14) Berens, U.; Burk, M. J.; Gerlach, A.; Hems, W. Angew. Chem.,
Int. Ed. 2000, 39, 1981-1984.
(15) Rieke-Zapp, J.; Billen, G. WO, 2006005436; Chem. Abstr. 2006,
144, 129241.
776 J. Org. Chem., Vol. 73, No. 3, 2008

Bis-(2,5-diphenylphospholanes) with sp2 Carbon Linkers
SCHEME 2. Synthesis of Maleic Anhydride Linked Ligand (S,S)-Ph-MalPhos (7)
SCHEME 3. Synthesis of 1-1′-Ferrocenyl Linked Ligand (S,S)-Ph-5-Fc (8)
109 was more convenient (Scheme 2). The phosphine was
generated by reduction of the acid 3 with phenylsilane.7
Subsequently, this was reacted in situ with dichloromaleic
anhydride using triethylamine as a base to give the maleic
anhydride linked ligand 7 ((S,S)-Ph-MalPhos). The yield we
obtained in this process was moderate, but comparable to that
reported for the parent MalPhos ligand using a more complicated
procedure.12
Synthesis of 1,1′-Ferrocene Linked Ligand (R,R)-Ph-5-Fc
(8). The most straightforward means of preparation of 1,1′-
disubstituted ferrocenyl derivatives is by dilithiation of ferrocene
followed by reaction of the dilithioferrocene with an electro-
phile.13 Therefore, for the monophospholane methodology to
be employed for the synthesis of the bis(2,5-diphenylphosphol-
anyl) ligand with this linker, the preparation of a suitable 2,5-
diphenylphospholane electrophile was required (Scheme 3). This
required reduction from the phosphorus(V) oxidation state of
the phospholanic acid 3 to the phosphorus(III) oxidation state.
This was achieved in two steps: first by conversion of the
phospholanic acid 3 to the phospholanoyl chloride 11,9 and then
by reduction to the secondary phosphine oxide 129 with DIBAL.
Owing to the insoluble nature of the phospholanyl chloride 11
in other suitable solvents, this was carried out in dichlo-
romethane. It remained to activate the secondary phosphine
oxide 12 to an electrophile suitable for reaction with 1,1′-
dilithioferrocene. This was accomplished by conversion of 12
to the 1-chlorophospholane 1316 using phosphorus trichloride.
This reactive intermediate was characterized by H, 13C{1H},
and 31P{1H} NMR. The 31P NMR spectrum is remarkable in
showing two resonances in a 3:1 ratio with a separation of 31
ppb (Figure 2). This phenomenon is ascribed to the occurrence
of an isotopic chemical shift due to the presence of 35Cl or 37Cl
attached to phosphorus and is thus analogous to the 35Cl/37Cl
isotopic shifts previously described for carbon (observed by
13C)17 and fluorine (observed by 19F).18 To our knowledge, this
is the first time this effect has been observed in 31P NMR.
Reaction of the chloride 13 with 1,1′-dilithioferrocene13 gave
1,1′-bis(2,5-diphenylphospholan-1-yl)ferrocene ((S,S)-Ph-5-Fc)
8. In addition to NMR, HRMS, and elemental analysis, this
ligand was further characterized by single-crystal X-ray dif-
fraction (Figure 3).
1
Synthesis of Rh(I)(COD)BF4 Complexes of Ligands 5-8.
The cationic rhodium(I)(COD) complexes of ligands 5-8 [L
Rh(COD)]BF4 were prepared in good yields by reaction of the
ligand with [Rh(COD)2]BF4.19 The molecular structure of the
Rh complex of (S,S)-Ph-5-Fc (8) was determined by X-ray
crystallography (Figure 4). This shows a Rh-P bond length of
2.3326(5)/2.3611(5) Å and a bite angle of 96.34(2)°, similar to
those of [Et-Ferrotane Rh(NBD)]BF4.20
(17) (a) Braddock, D. C.; Bhuva, R.; Millan, D. S.; Pe´rez-Fuertes, Y.;
Roberts, C. A.; Sheppard, R. N.; Solanki, S.; Stokes, E. S. E.; White, A. J.
P. Org. Lett. 2007, 9, 445-448. (b) Sergeyev, N. M.; Sandor, P.; Sergeyeva,
N. D.; Raynes, W. T. J. Magn. Reson., Ser. A 1995, 115, 174-182.
(18) Bernard, G. M.; Schurko, R. W. Magn. Reson. Chem. 1995, 33,
879-882.
(19) Green, M.; Kuc, T. A.; Taylor, S. H. J. Chem. Soc. D 1970, 22,
1553-1554.
(20) You, J.; Drexler, H.-J.; Zheng, S.; Fischer, C.; Heller, D. Angew.
Chem., Int. Ed. 2003, 42, 913-916.
(16) An alternative process to chlorophosphane 13 has been recently
reported. Galland, A.; Paris, J. M.; Schlama, T.; Guillot, R.; Fiaud, J.-C.;
Toffano, M. Eur. J. Org. Chem. 2007, 863-873.
J. Org. Chem, Vol. 73, No. 3, 2008 777

Fox et al.
TABLE 1. Asymmetric Hydrogenation of Substrates 14-18 with
a
[(Ligand)Rh(COD)]BF4
time to
entry
ligand
substrate
completion
ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
(S,S)-Ph-Quinox (5)
(S,S)-Ph-Quinox (5)
(S,S)-Ph-Quinox (5)
(S,S)-Ph-Quinox (5)
(S,S)-Ph-Quinox (5)
(R,R)-Ph-Pyrazine (6)
(R,R)-Ph-Pyrazine (6)
(R,R)-Ph-Pyrazine (6)
(R,R)-Ph-Pyrazine (6)
(S,S)-Ph-MalPhos (7)
(S,S)-Ph-MalPhos (7)
(S,S)-Ph-MalPhos (7)
(S,S)-Ph-MalPhos (7)
(S,S)-Ph-5-Fc (8)
14
15
16
17
18
14
15
17
18
14
15
17
18
14
15
16
17
18
15 min
10 min
10 min
20 minb
25 minb
18 h
99.8 (S)
99.9 (R)
98.7 (R)
>99.5 (R)
99.5 (R)
78 (R)
94 (S)
96 (S)
76 (S)
96.6 (S)
99.7 (R)
98.8 (R)
racemic
8 (R)
6 (S)
49 (R)
6 (S)
56 (R)
18 h
18 hb
18 hb
16 h
2 h
6 hb
4 hb
35 min
20 min
10 min
20 min
80 minb
(S,S)-Ph-5-Fc (8)
(S,S)-Ph-5-Fc (8)
(S,S)-Ph-5-Fc (8)
(S,S)-Ph-5-Fc (8)
FIGURE 2. 31P{1H} NMR spectrum of (2S,5S)-1-chloro-2,5-diphe-
nylphospholane (13) showing isotope-induced shift for the resonance
arising from the chlorine-bearing phosphorus.
a Reaction conditions: 2 mmol substrate, S/C 1000:1, MeOH, 25 °C,
10 bar H2. b 30 °C.
Me-MalPhos that a higher ee was obtained in THF (86%).12
However, at S/C 1000 in THF, (S,S)-Ph-MalPhos-Rh showed
only 5% conversion. The Ph-Malphos-derived catalyst provided
an excellent ee for methyl R-acetamidocinnamate 17, but
unexpectedly gave racemic product in hydrogenation of R-ac-
etamidocinnamic acid 18 (entries 12 and 13).
[((S,S)-Ph-5-Fc)Rh(COD)]BF4 showed a pattern of activity
and selectivity different from that of the other catalysts. This
catalyst was active, but not highly selective, with the enantio-
meric excess values for hydrogenation of dimethyl itaconate
14, methyl R-acetamidoacrylate 15, and methyl R-acetamido-
cinnamate 17 being near-racemic (Table 1, entries 14, 15, and
17). Moreover, the selectivities obtained for dimethyl itaconate
14 (8% ee) and methyl R-acetamidoacrylate 15 (6% ee) are
much lower than those reported for Me-5-Fc-Rh (64 and 72%,
respectively).13 Under the conditions of Table 1, with these
substrates, we obtained 28% ee (S) and 66% ee (R), respectively,
with [((R,R)-Me-5-Fc)Rh(COD)]BF4. We also carried out the
hydrogenation of methyl R-acetamidocinnamate 17 with [((R,R)-
Me-5-Fc)Rh(COD)]BF4 under the conditions of Table 1 for
comparison, obtaining complete conversion and 66% ee (R).
(S,S)-Ph-5-Fc-Rh showed a selectivity for the acids 16 and
18 that was higher than that of the corresponding esters 15 and
17, which is counter to the trend seen with the other catalysts.
Despite the low selectivities exhibited by Ph-5-Fc-Rh, the high
activity of this catalyst encouraged us to examine the hydro-
genation of other substrates. The higher enantiomeric excesses
obtained with the enamide acid substrates than those of the
enamide ester substrates suggested that the preferred secondary
binding site of this catalyst was the carboxylate rather than the
acetamide group. Therefore, we tested this catalyst against the
tert-butylamine salts of substituted cinnamic acids, substrates
24-26 (Scheme 5). We were pleased to find that the catalyst
exhibited both high activity and enantioselectivity against these
substrates (Table 2, entries 1-3), especially the 2-aryl substrate
25 (entry 2). In contrast, Ph-phospholane ligands with other
linkers, (R,R)-Ph-BPE-Rh (entries 4-6) and (S,S)-Ph-Quinox-
Rh (entries 7 and 8), exhibited low activity and selectivity
against these three substrates. 5-Fc ligands with alkyl instead
of aryl groups exhibited high activity but much lower selectivity
(entries 9-17).
FIGURE 3. Molecular structure of (S,S)-Ph-5-Fc (8) at 40% probability
level. Hydrogen atoms were omitted for clarity.
Rhodium-Catalyzed Asymmetric Hydrogenation with
Ligands 5-8. The asymmetric hydrogenation of standard
enamide and itaconate substrates 14-18 (Scheme 4) with
rhodium complexes [L Rh(COD)]BF4 was examined. The results
are given in Table 1.
The quinoxaline catalyst [((S,S)-Ph-Quinox)Rh(COD)]BF4
showed high selectivities (>98.7% ee) and rates for all five
substrates and is clearly an excellent general asymmetric olefin
hydrogenation catalyst (Table 1, entries 1-5). The pyrazine-
based catalyst 6-Rh was both less selective and much less active
than 5-Rh (entries 6-9). (S,S)-Ph-MalPhos-Rh was also much
less active than 5-Rh, but did show good selectivity with methyl
acetamidomalonate 15 and methyl acetamidocinnamate 17
(entries 11 and 12). The enantiomeric excess obtained for the
hydrogenation of dimethyl itaconate 14 (entry 10) was much
higher than that reported for Me-MalPhos (60.2% ee at S/C
100 in MeOH and 1 bar H2).12 It has also been reported with
778 J. Org. Chem., Vol. 73, No. 3, 2008

Bis-(2,5-diphenylphospholanes) with sp2 Carbon Linkers
FIGURE 4. Molecular structure of [((S,S)-Ph-5-Fc)Rh(COD)]BF4 at 40% probability level. Hydrogen atoms were omitted for clarity.
SCHEME 4. Asymmetric Hydrogenation of Itaconate and Enamides
SCHEME 5. Asymmetric Hydrogenation of r-C-Substituted Cinnamic Acid Salts
The asymmetric hydrogenation of (E)-2-methylcinnamic acid
and (E)-2-phenylcinnamic acid using homogeneous rhodium
catalysts has been reported, but we find that the amine salts,
such as tert-butylamine, provide more active and reproducible
reactions. Previous reports on the asymmetric hydrogenation
of (E)-2-methylcinnamic acid provide variable enantiomeric
excess values (17-92%), but all at high catalyst loadings (0.5-
2 mol %).21-23 The (S,S)-Ph-5-Fc (8) based catalyst gave 85%
ee at a catalyst loading of 0.1 mol % for the asymmetric
hydrogenation of (E)-2-methylcinnamic acid tert-butylammo-
nium salt 24. The asymmetric hydrogenation of (E)-2-phenyl-
cinnamic acid has previously been reported to give good
enantiomeric excess (95-96% ee), but again at high catalyst
loading.22-24 Here, (S,S)-Ph-5-Fc (8) gives outstanding results
with the tert-butylamine salt 25 (96.5% ee, 0.075 mol %).
Furthermore, the hydrogenation reaction was complete in 40
min, suggesting that even better catalyst utility can be achieved.
Both free acid substrates have been hydrogenated using Ru-
H8-BINAP complexes, but lower enantiomeric excess values
were obtained (74-89% ee).25
Asymmetric hydrogenation of the R-isopropylcinnamic acid
substrate 26 provides an intermediate for the renin inhibitor
aliskiren (Figure 5).26 The enantiomeric excess achieved with
the (S,S)-Ph-5-Fc (8) catalyst using the tert-butylamine salt
(84.6%) is quite high, and the activity is high, with complete
(24) Jones, M. D.; Raja, R.; Thomas, J. M.; Johnson, B. F. G.; Lewis,
D. W.; Rouzaud, J.; Harris, K. D. M. Angew. Chem., Int. Ed. 2003, 42,
4326-4331.
(21) Wang, Y.; Weissensteiner, W.; Mereiter, K.; Spindler, F. HelV. Chim.
Acta 2006, 89, 1772-1782.
(22) Co, T. T.; Shim, S. C.; Cho, C. S.; Kim, T.-J.; Kang, S. O.; Han,
W.-S.; Ko, J.; Kim, C.-K. Organometallics 2005, 24, 4824-4831.
(23) Hoen, R.; Boogers, J. A. F.; Bernsmann, H.; Minnaard, A. J.;
Meetsma, A.; Tiemersma-Wegman, T. D.; de Vries, A. H. M.; de Vries, J.
G.; Feringa, B. L. Angew. Chem., Int. Ed. 2005, 44, 4209-4212.
(25) Uemura, T.; Zhang, X.; Matsumura, K.; Sayo, N.; Kumobayashi,
H.; Ohta, T.; Nozaki, K.; Takaya, H. J. Org. Chem. 1996, 61, 5510-
5516.
(26) Goeschke, R.; Stutz, S.; Heizelmann, W.; Maibaum, J. HelV. Chim.
Acta 2003, 86, 2848-2870.
J. Org. Chem, Vol. 73, No. 3, 2008 779

Fox et al.
FIGURE 5. Structures of aliskiren and other ligands effective in asymmetric hydrogenation of 26.
a
TABLE 2. Asymmetric Hydrogenation of Substrates 24-26 with [(Ligand)Rh(COD)]BF4
mmol
reaction
ee (%)
entry
ligand
substrate
substrate
S/C
time
conv %
(config)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
(S,S)-Ph-5-Fc (8)
(S,S)-Ph-5-Fc (8)
(S,S)-Ph-5-Fc (8)
(R,R)-Ph-BPE (1)
(R,R)-Ph-BPE (1)
(R,R)-Ph-BPE (1)
(S,S)-Ph-Quinox (5)
(S,S)-Ph-Quinox (5)
(R,R)-Me-5-Fc
(R,R)-Me-5-Fc
(S,S)-Me-5-Fc
(R,R)-Et-5-Fc
(R,R)-Et-5-Fc
(S,S)-Et-5-Fc
(R,R)-iPr-5-Fc
(R,R)-iPr-5-Fc
(S,S)-iPr-5-Fc
(S,S)-Me-DuPhos
24
25
26
24
25
26
24
25
24
25
26
24
25
26
24
25
26
26
1
1.5
1
1000
1500
1000
1000
1000
250
1000
1000
1000
1000
250
1000
1000
250
1000
1000
250
1 h
40 min
1 h
100
100
100
65
50
100
10
85 (R)
96.5 (S)
84.6 (S)
25 (S)
20 (R)
25
2
18 h
18 h
16 h
18 h
18 h
18 h
18 h
16 h
18 h
18 h
16 h
18 h
18 h
16 h
16 h
1.5
0.4
2
1.5
2
1.5
0.4
2
1.5
0.4
2
0
5
11 (R)
52 (R)
46 (S)
61
45 (R)
65 (S)
57
69 (S)
65 (R)
69
100
100
100
100
100
100
100
65
1.5
0.4
0.4
100
34
250
0
a Reaction conditions: MeOH, 10 bar H2, 25 °C.
conversion being achieved in 1 h at 25 °C and a catalyst loading
of 0.1 mol %, but higher enantiomeric excesses have been
reported with Rh-Walphos,27 Rh-phosphoramidite,28 and Rh-
TriFer29 catalysts using the free acid.
[rhodium(I)(COD)] complexes were tested in asymmetric olefin
hydrogenation. The syntheses of the 2,3-quinoxaline, 2,3-
pyrazine, and maleic anhydride linked ligands were achieved
using the established nucleophilic 2,5-diphenylphospholane
synthon5,6,9 by displacement of chloride leaving groups from
the linker. Synthesis of the 1,1′-ferrocenyl linked ligand required
synthesis of an electrophilic 2,5-diphenylphospholane unit
suitable for coupling with 1,1′-dilithioferrocene. Cationic rhod-
ium complexes of these ligands exhibited contrasting activity
and selectivity in asymmetric hydrogenation. Thus, [((S,S)-Ph-
Quinox)Rh(COD)]BF4 showed high activity and selectivity in
asymmetric hydrogenation of standard itaconate and enamide
substrates and is an excellent general asymmetric olefin
hydrogenation catalyst comparable to (R,R)-Ph-BPE-Rh. The
corresponding pyrazine and maleic anhydride catalysts were less
active and selective. [((S,S)-Ph-5-Fc)Rh(COD)]BF4 showed high
activity but low selectivity against standard enamide and
itaconate substrates, but high activity and selectivity against 2-C-
Conclusions
Four chiral diphosphine ligands comprising 2,5-diphenylphos-
pholane groups connected by the sp2 carbon linkerss2,3-
quinoxaline, (S,S)-Ph-Quinox (5); 2,3-pyrazine, (S,S)-Ph-
Pyrazine (6); maleic anhydride, (S,S)-Ph-MalPhos (7); and 1,1′-
ferrocene, (S,S)-Ph-5-Fc (8)swere synthesized, and their cationic
(27) Sturm, T.; Weissensteiner, W.; Spindler, F. AdV. Synth. Catal. 2003,
345, 160-164.
(28) Boogers, J. A. F.; Felfer, U.; Kotthaus, M.; Lefort, L.; Steinbauer,
G.; de Vries, A. H. M.; de Vries, J. G. Org. Process Res. DeV. 2007, 11,
585-591.
(29) Chen, W.; McCormack, P. J.; Mohammed, K.; Mbafor, W.; Roberts,
S. M.; Whittall, J. Angew. Chem., Int. Ed., 2007, 46, 4141-4144.
780 J. Org. Chem., Vol. 73, No. 3, 2008

Bis-(2,5-diphenylphospholanes) with sp2 Carbon Linkers
the pyrazine was added). After 5 h, TMEDA (0.45 mL, 3.0 mmol,
1.5 equiv) was added, and the mixture was stirred overnight. The
reaction was quenched with 1 M aqueous HCl (5 mL) and extracted
with ethyl acetate (10 mL). The organic solution was washed with
half-saturated brine (10 mL), dried (MgSO4), filtered, and concen-
trated under reduced pressure. The residue was chromatographed
on silica and eluted with ethyl acetate/heptane (1:8) to give the
title compound 6 as a yellow solid (105 mg, 0.19 mmol, 21%). 1H
NMR (400 MHz, CDCl3): δ 8.36 (s, 2H), 7.35-7.21 (m, 10H),
6.48 (t, J ) 7 Hz, 2H), 6.40 (d, J ) 8 Hz, 4H), 6.24 (t, J ) 8 Hz,
4H), 4.27-4.20 (m, 2H), 3.80-3.69 (m, 2H), 2.54-2.43 (m, 2H),
2.07-1.99 (m, 4H), 1.80-1.66 (m, 2H). 13C NMR (100 MHz,
CDCl3,): δ 163.9 (br d), 144.6 (t, J ) 10 Hz), 142.4, 139.9, 129.4
(t, J ) 5 Hz), 128.5, 127.5 (m), 126.1, 125.9, 50.0 (t, J ) 10 Hz),
43.8, 38.9, 33.5. 31P NMR (162 MHz, CDCl3): δ 7.2. HRMS (ESI,
M + H)+: (m/z) calcd for C36H34N2P2: 557.2275. Found: 557.228.
Further elution with ethyl acetate/heptane (1:5) gave the mono-
substituted phospholane product, 2-chloro-3-(2,5-diphenylphos-
substituted cinnamate salts, whereas rhodium complexes of
(S,S)-Ph-Quinox and (R,R)-Ph-BPE showed low activity and
selectivity against 2-C-substituted cinnamate salts. Thus, these
ligands, especially (S,S)-Ph-Quinox and (S,S)-Ph-5-Fc, represent
valuable additions to the available ligands for asymmetric
hydrogenation. Yet again, this emphasizes the need for catalyst
diversity when screening substrates for asymmetric hydrogena-
tion.2
Experimental Section
Preparation of (S,S)-2,3-Bis(2,5-diphenylphospholan-1-yl)-
quinoxaline (5). (S,S)-2,5-trans-Diphenylphospholane borane ad-
duct ((S,S)-4)5 (381 mg, 1.50 mmol) was dissolved in dry THF (3
mL) under nitrogen. The solution was cooled to -20 °C. A solution
of n-BuLi (2.5 M in hexanes, 0.6 mL, 1.50 mmol) was added
dropwise, and the mixture was stirred for 30 min (a yellow solution
formed). 2,3-Dichloroquinoxaline (136 mg, 0.68 mmol) was added
in one portion, and the residues were washed in with dry THF (1
mL) (the quinoxaline was only sparingly soluble in THF). The
mixture was allowed to warm to room temperature (red/orange
solution was observed). The reaction mixture was stirred overnight
and then quenched with 1 M aqueous HCl (5 mL) (effervescence
was observed) and extracted with ethyl acetate (10 mL). The organic
solution was washed with water (5 mL) and brine (5 mL), dried
(MgSO4), filtered, and concentrated under reduced pressure. The
residue was chromatographed on silica and eluted with dichlo-
romethane/heptane (2:3) to give (S,S)-Ph-Quinox (5) as a yellow
solid (200 mg, 0.33 mmol, 48%). 1H NMR (400 MHz, CDCl3): δ
8.11-8.06 (m, 2H), 7.77-7.73 (m, 2H), 7.36-7.21 (m, 10H), 6.37
(t, J ) 8 Hz, 2H), 6.29 (d, J ) 8 Hz, 4H), 6.07 (t, J ) 8 Hz, 4H),
4.53-4.46 (m, 2H), 3.83-3.73 (m, 2H), 2.58-2.45 (m, 2H), 2.09-
1.99 (m, 4H), 1.87-1.75 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 163.2 (br d), 144.2 (t, J ) 10 Hz), 141.2, 139.8, 129.4,
129.2, 129.1 (t, J ) 5 Hz), 128.1, 127.4, 126.9, 125.7, 125.4, 49.6
(t, J ) 10 Hz), 43.3, 37.9, 33.7. 31P{1H} NMR (CDCl3, 162
MHz): δ 9.1. Anal. Calcd for C40H36N2P2: C, 79.19; H, 5.98; N,
4.62. Found: C, 79.20; H, 5.85; N, 4.73.
Preparation of 2,3-Bis[(S,S)-2,5-diphenylphospholan-1-yl]-
quinoxaline-(1,5-cyclooctadiene) Rhodium(I) Tetrafluoroborate.
2,3-Bis-[(S,S)-2,5-diphenylphospholan-1-yl]-quinoxaline (5) (104
mg, 0.171 mmol) and [Rh(COD)2]BF4 (70 mg, 0.171 mg) were
charged to a 25-mL Schlenk flask. The flask was evacuated and
filled with nitrogen (×5). Degassed dichloromethane (2 mL) was
added (a deep red solution formed), and the mixture was stirred
for 3 h. The solvent was evaporated, and the residue was triturated
with degassed ether (3 mL). The solid was filtered under nitrogen,
washed with degassed ether (2 × 2 mL), and dried to give the title
compound as an orange solid (119 mg, 0.13 mmol, 77%). 1H NMR
(400 MHz, CDCl3): δ 8.38 (dd, J ) 6, 4 Hz, 2H), 8.15 (dd, J )
7, 4 Hz, 2H), 7.30-7.23 (m, 6H), 7.02-6.93 (m, 6H), 6.83-6.75
(m, 8H), 5.75-5.69 (m, 2H), 4.77-4.67 (m, 2H), 4.33-4.26 (m,
2H), 3.98-3.90 (m, 2H), 3.09-2.97 (m, 2H), 2.88-2.75 (m, 2H),
2.61-2.47 (m, 4H), 2.27-2.18 (m, 2H), 1.93-1.81 (m, 2H), 1.76-
1.65 (m, 2H), 1.35-1.25 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 156.4 (t, J ) 49 Hz), 142.6, 138.6, 135.3, 134.1, 130.4,
129.3, 128.8, 128.3, 127.8 (d, J ) 11 Hz), 105.1 (m), 98.9 (m),
53.0 (t, J ) 8 Hz), 49.8 (t, J ) 10 Hz), 33.8, 31.9, 31.8, 28.2.
31P{1H} NMR (162 MHz, CDCl3): δ 58.6 (d, J ) 151 Hz).
Preparation of (R,R)-2,3-Bis(2,5-diphenylphospholan-1-yl)-
pyrazine (6). (R,R)-2,5-trans-Diphenylphospholane borane adduct
((R,R)-4) (518 mg, 2.04 mmol) was dissolved in dry THF (3 mL)
under nitrogen. The solution was cooled to -20 °C. A solution of
n-BuLi (2.5 M in hexanes, 0.82 mL, 2.04 mmol) was added
dropwise, and the mixture was stirred for 30 min (a yellow solution
formed). A solution of 2,3-dichloropyrazine (137 mg, 0.92 mmol)
in THF (2 mL) was added, and the solution was allowed to warm
to room temperature (red/brown color was observed instantly when
1
pholan-1-yl)-pyrazine (9) (100 mg, 0.28 mmol, 31%). H NMR
(400 MHz, CDCl3): δ 8.60 (d, J ) 2 Hz, 1H), 8.12 (d, J ) 2 Hz,
1H), 7.40-7.37 (m, 2 H), 7.31 (t, J ) 7 Hz, 2H), 7.22-7.17 (m,
1H), 7.06-7.03 (m, 3H), 6.82-6.78 (m, 2H), 4.87-4.80 (m, 1H),
3.96 (ddd, J ) 22, 12, 6 Hz, 1H), 2.76-2.64 (m, 1H), 2.39-2.20
(m, 2H), 2.11-2.00 (m, 1H). 31P{1H} NMR (162 MHz, CDCl3):
δ 14.2.
Preparation of 2,3-Bis[(R,R)-2,5-diphenylphospholan-1-yl]-
pyrazine-(1,5-cyclooctadiene) Rhodium(I) Tetrafluoroborate.
2,3-Bis[(R,R)-2,5-diphenylphospholan-1-yl]-pyrazine (6) (50 mg,
0.09 mmol) and [Rh(COD)2]BF4 (36 mg, 0.09 mmol) were charged
to a Schlenk flask. The flask was evacuated and filled with nitrogen
(×5). Degassed dichloromethane (1 mL) was added (a deep red
solution formed), and the mixture was stirred for 3 h. The solvent
was evaporated, and the residue was washed with degassed diethyl
ether (4 × 2 mL) and dried to give the title compound as an orange
solid (76 mg, 0.088 mmol, 98%). 1H NMR (400 MHz, CDCl3): δ
9.10 (br d, 2H), 7.26-7.12 (m, 12H), 6.83 (d, J ) 8 Hz, 4H), 6.76-
6.73 (m, 4H), 5.67-5.60 (m, 2H), 4.56-4.46 (m, 2H), 4.26-4.19
(m, 2H), 3.85-3.78 (m, 2H), 2.97-2.84 (m, 2H), 2.79-2.65 (m,
2H), 2.56-2.41 (m, 4H), 2.24-2.14 (m, 2H), 1.89-1.78 (m, 2H),
1.73-1.62 (m, 2H), 1.30-1.20 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 158.3 (t, J ) 49 Hz), 147.5, 138.5, 135.2, 129.3, 129.1,
128.7, 128.1, 128.0, 127.7, 104.9 (m), 98.5 (m), 52.6 (t, J ) 8
Hz), 49.2 (t, J ) 11 Hz), 33.7, 31.8, 31.7, 28.1. 31P{1H} NMR
(162 MHz, CDCl3): δ 60.2 (d, J ) 151 Hz).
Preparation of 3,4-Bis[(S,S)-2,5-diphenylphospholan-1-yl]-
furan-2,5-dione [(S,S)-Ph-MalPhos] (7). (S,S)-1-Hydroxy-1-oxo-
2,5-trans-diphenylphospholane (3) (600 mg, 2.20 mmol) was
suspended in toluene (6 mL). The mixture was degassed by
evacuation and filled with nitrogen (×5) and then heated in an oil
bath at 110 °C (external temperature). Phenylsilane (0.54 mL, 4.41
mmol) was added in one portion, and the mixture was heated for
2 h (during this time vigorous effervescence was observed and a
clear solution formed). The solution was cooled to room temper-
ature, and the solvent was evaporated under reduced pressure. The
crude phosphine was further dried under high vacuum (2.9 mbar,
60 °C). The residue was cooled to room temperature and dissolved
in THF (3 mL) under nitrogen. Triethylamine (0.31 mL, 2.20 mmol)
was added, followed by a solution of 2,3-dichloromaleic anhydride
(167 mg, 1.00 mmol) in THF (2 mL). The mixture was heated in
an oil bath at 60 °C (external temperature) and stirred for 18 h
(dark purple solution formed). The solution was cooled to room
temperature, and the solvent was evaporated under reduced pressure.
The residue was chromatographed on silica and eluted with
dichloromethane/heptane (2:3) to give (S,S)-Ph-MalPhos (7) as a
deep red oil that solidified on standing (180 mg, 0.31 mmol, 31%).
1H NMR (400 MHz, CDCl3): δ 7.51-7.34 (m, 10H), 6.90 (d, J )
8 Hz, 4H), 6.80 (t, J ) 7 Hz, 2H), 6.56 (t, J ) 8 Hz, 4H), 4.60-
4.53 (m, 2H), 4.05-3.93 (m, 2H), 2.73-2.61 (m, 2H), 2.58-2.45
(m, 2H), 2.44-2.35 (m, 2H), 1.97-1.85 (m, 2H). 13C{1H} NMR
J. Org. Chem, Vol. 73, No. 3, 2008 781

Fox et al.
(100 MHz , CDCl3): δ 161.7, 156.2 (m), 141.1 (t, J ) 11 Hz),
136.6, 127.1, 127.0, 126.9, 126.8, 125.0, 124.9, 124.7, 48.2 (d, J
) 7 Hz), 41.1 (d, J ) 5 Hz), 38.0, 31.6. 31P{1H} NMR (162 MHz,
CDCl3): δ 3.5. HRMS (ESI, [M + Na]+): (m/z) calcd for
C36H32O3P2: 597.172. Found: 597.169.
MHz, CDCl3): δ +55.2. HRMS (ESI, [M + Na]+): (m/z) calcd
for C16H17PO: 279.091. Found: 279.087.
Preparation of (2S,5S)-1-Chloro-2,5-diphenylphospholane
(13).16 (2S,5S)-Diphenylphospholane-1-oxide (12) (1.83 g, 1.95
mmol) was suspended in 40 mL of toluene, and the solution was
cooled to -40 °C. To this suspension was added 3.92 g (28.6 mmol)
of PCl3 dissolved in 4 mL of toluene within 1 min. The solution
was warmed to room temperature and stirred overnight, resulting
in formation of a white sticky solid and colorless solution. The
solution was transferred into another vessel, and the solvent was
removed under reduced pressure, leaving an oily residue. Toluene
was added (30 mL), and the solvent was removed again under
reduced pressure, leaving 1.918 g of product 13 as a colorless oil.
Yield 97.8%. 1H NMR (300 MHz, 23 °C C6D6): δ 6.97-715 (m,
Preparation of 3,4-Bis[(S,S)-2,5-diphenylphospholan-1-yl]-
furan-2,5-dione-(1,5-cyclooctadiene) Rhodium(I) Tetrafluorobo-
rate. (S,S)-Ph-MalPhos (7) (102 mg, 0.178 mmol) and [Rh(COD)2]-
BF4 (72 mg, 0.178 mg) were charged to a 25-mL Schlenk flask.
The flask was evacuated and filled with nitrogen (×5). Degassed
dichloromethane (2 mL) was added (a dark brown solution formed),
and the mixture was stirred overnight. The solvent was evaporated,
and the residue was triturated with degassed diethyl ether (3 mL).
The solid was filtered under nitrogen, washed with degassed ether
(2 × 2 mL), and dried to give the title compound as a brown solid
(133 mg, 0.15 mmol, 86%). 1H NMR (400 MHz, CDCl3): δ 7.41-
7.36 (m, 4H), 7.30-7.26 (m, 6H), 7.22-7.18 (m, 6H), 7.11-7.07
(m, 4H), 5.68-5.62 (m, 2H), 4.51-4.36 (m, 4H), 4.00 (dd, J )
13, 6 Hz, 2H), 3.08-2.94 (m, 2H), 2.66-2.43 (m, 6H), 2.05-1.96
(m, 2H), 1.82-1.71 (m, 2H), 1.31-1.13 (m, 4H). 31P{1H} NMR
(162 MHz, CDCl3): δ 62.8 (d, J ) 154 Hz).
Preparation of (S,S)-2,5-Diphenyl-1-oxo-1-chlorophospholane
(11).9 (S,S)-1-Hydroxy-1-oxo-2,5-trans-diphenylphospholane (3)
(5.0 g, 18.4 mmol) was placed in a flask. This was purged with
nitrogen, and then anhydrous dichloromethane (50 mL) was added.
The suspension was cooled to 0-5 °C, and then oxalyl chloride
(3.2 mL, 36.7 mmol) was added over 20 min, the suspension was
stirred at 0-5 °C for 1 h, and then allowed to warm to room
temperature and stirred for 22 h. Anhydrous toluene (20 mL) was
added, and the solvent was evaporated. The residue was evaporated
with toluene (2 × 20 mL) to give the title compound 11 as a white
solid (5.38 g, quant). Mp 133-136 °C. 1H NMR (400 MHz,
CDCl3): δ 7.42-7.30 (m, 10H), 3.85-3.78 (m, 1H), 3.75-3.64
(m, 1H), 2.78-2.61 (m, 1H), 2.59-2.42 (m, 1H), 2.37-2.19 (m,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ 135.1 (d, JC-P ) 5.9
Hz), 134.2 (d, JC-P ) 6.4 Hz), 129.3 (d, JC-P ) 2.2 Hz), 129.2,
129.2 (d, JC-P ) 3.5 Hz), 128.3 (d, JC-P ) 4.6 Hz), 128.1 (d, JC-P
) 4.2 Hz), 128.0 (d, JC-P ) 3.9 Hz), 52.5 (d, JC-P ) 53.7 Hz),
51.7 (d, JC-P ) 68.1 Hz), 30.9 (d, JC-P ) 14.1 Hz), 25.7 (d, JC-P
) 14.8 Hz). 31P{1H} NMR (162 MHz, CDCl3): δ 80.9. Anal. Calcd
for C16H16ClPO: C, 66.10; H, 5.55; Cl, 12.19. Found: C, 66.21;
H, 5.53; Cl, 11.93.
3
2
10H), 3.75 (td, JH-H ) 8.7 Hz, JH-P ) 2.1 Hz, 1H), 3.11 (ddd,
2JH-P ) 33.6 Hz, JH-H ) 12.6 Hz, JH-H ) 6.0 Hz, 1H), 2.24-
2.49 (m, 2H), 1.97-2.08 (m, 1H), 1.50-1.65 (m, 1H). 13C{1H}
NMR (75 MHz, 23 °C C6D6): δ 141.92 (d, 2JC-P ) 19.8 Hz, quat),
137.09 (quat), 129.05, 128.54, 128.51 (d, 3JC-P ) 3.8 Hz) , 128.01
3
3
3
2
(d, JC-P ) 8.4 Hz), 126.82, 126.79, 58.16 (d, JC-P ) 32.8 Hz),
2
3
53.64 (d, JC-P ) 32.8 Hz), 34.68 (d, JC-P ) 2.3 Hz), 31.91 (d,
3JC-P ) 2.3 Hz). 31P{1H} NMR (121 MHz, 23 °C, C6D6): δ
137.687/137.656 in 3:1 ratio (35Cl/37Cl isotopic shift).
Preparation of Ferrocene Dilithium TMEDA Complex. Fer-
rocene (5 g, 26.9 mmol) was suspended in 60 mL of hexane.
TMEDA (4.5 mL) was added followed by addition (within 1 min)
of 42 mL (1.6 M) of n-BuLi in hexane. The reaction was not
exothermic. The reaction was stirred overnight. Precipitated product
(orange powder) was filtered off, washed with hexane (2 × 30 mL),
and dried under reduced pressure to give 6.84 g of product. Yield
81%.
Preparation of 1,1′-Bis[(2S,5S)-diphenylphospholane-1-yl]-
ferrocene [(S,S)-Ph-5-Fc] (8). To a 40-mL chilled (-40 °C)
solution of (2S,5S)-1-chloro-2,5-diphenylphospholane (0.900 g, 3.28
mmol) in toluene was added 0.5145 g (1.64 mmol) of ferrocene
dilithium TMEDA complex as a solid. The reaction mixture was
stirred at room temperature for 24 h. Methylene chloride (10 mL)
was added to the mixture to dissolve some of the product that
crystallized. The 31P{1H} NMR of this reaction mixture showed
formation of the desired product in about 90% together with about
10% of monophosphine, (2S,5S)-diphenylphospholan-1-yl]fer-
rocene. The solvent was removed under reduced pressure to give
a yellow-orange solid. Toluene was added (12 mL), and the
suspension was stirred for 1 h. Yellow solid was collected on the
frit, washed with 10 mL of hexane, and dried under reduced pressure
to give 0.76 g of clean product 8. Yield 70%. X-ray quality crystals
Preparation of (S,S)-2,5-Diphenyl-1-oxophospholane (12).9
(S,S)-2,5-Diphenyl-1-oxo-1-chlorophospholane (11) (4.80 g, 16.5
mmol) was placed in a dry flask. This was purged with nitrogen,
and then dichloromethane (38 mL) was added. The solution was
cooled to -70 °C, and then diisobutylaluminum hydride (1.0 M in
dichloromethane, 17.3 mL) was added over 40 min. The solution
was stirred at -70 °C for 1 h, and then quenched with methanol
(3.84 mL) over 15 min. The solution was allowed to warm to room
temperature, and then quenched with 1 M citric acid (50 mL). The
layers were separated, and then the aqueous layer was extracted
with dichloromethane (2 × 20 mL). The combined organic layers
were washed with brine (50 mL), and then the brine was extracted
with dichloromethane (2 × 10 mL). The combined organic layers
were dried (Na2SO4) and filtered, and the solvent was evaporated
to give a white solid (4.34 g). The solid was dissolved in
dichloromethane (15 mL) and precipitated by addition of heptane
(60 mL). After being dried, the title compound 12 was obtained as
1
were obtained from toluene at room temperature. H NMR (300
3
MHz, 23 °C, C6D6): δ 7.47 (dm, JH-H ) 8.4 Hz, 4H, ortho1-H),
3
3
7.24 (tm, JH-H ) 7.8 Hz, 4H, meta1-H), 7.10 (tm, JH-H ) 7.7
Hz, 2H, para1-H), 6.92-6.99 (m, 4H), 6.84-6.92 (m, 6H), 4.08
(m, 2H, Cp), 4.06 (m, 2H, Cp), 3.75 (m, 2H, Cp), 3.72 (m, 2H,
CH), 3.47 (m, 2H, Cp), 3.30 (m, 2H, CH), 2.47 (m, 2H, CH2),
1.95-2.18 (m, 4H, CH2), 1.64 (m, 2H, CH2). 13C{1H} NMR (75
2
MHz, 23 °C, C6D6): δ 146.24 (d, JC-P ) 18.9 Hz, quat), 139.16
3
(quat), 128.95 (meta-C), 128.46 (d, JC-P ) 10.4 Hz, ortho-C),
3
128.09 (d, JC-P ) 3.6 Hz, ortho-C), 127.96, 126.27 (para-C),
125.69 (para-C), 77.33 (d, JC-P ) 31.1 Hz, Cp), 76.02 (d, 1JC-P
)
27.5 Hz, Cp, quat), 72.67 (d, JC-P ) 7.9 Hz, Cp), 71.63 (s, Cp),
2
69.86 (d, JC-P ) 4.2 Hz, Cp), 50.07 (d, JC-P ) 15.9 Hz, CH),
48.85 (d, 2JC-P ) 14.6 Hz, CH), 39.20 (s, CH2), 33.73 (d, 3JC-P
)
a white solid (3.07 g, 74%). Mp 141-143 °C. [R]25 -61.4° (c
3.6 Hz, CH2). 31P{1H} NMR (121 MHz, 23 °C, C6D6): δ 12.19.
HSQC (23 °C, C6D6): δ 128.95/7.24, 128.46/7.47, 128.09/(6.92-
6.99), 127.96/(6.84-6.92), 126.27/7.10, 125.69/(6.92-6.99), 77.33/
3.47, 72.67/3.75, 71.63/4.08, 69.86/4.06, 50.07/3.30, 48.85/3.72,
39.20/(2.47, 1.64), 33.73/(1.95-2.18). HRMS (ESI, [M + H]+):
(m/z) calcd for C42H41FeP2: 663.203. Found: 663.200. Anal. Calcd
for C42H40FeP2: C, 76.14; H, 6.09. Found: C, 76.02; H, 5.88.
Preparation of 1,1′-Bis[(2S,5S)-diphenylphospholane-1-yl]-
ferrocene(1,5-cyclooctadiene) Rhodium(I) Tetrafluoroborate.
D
1.02, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.41-7.27 (m, 10H),
7.18 (dq, 1JH-P ) 470.0, JH-H ) 2.8 Hz, 1H), 3.63-3.52 (m, 1H),
3.32-3.25 (m, 1H), 2.70-2.49 (m, 2H), 2.44-2.32 (m, 1H), 2.07-
1.95 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 136.8 (d, JC-P
) 2.8 Hz), 135.6 (d, JC-P ) 5.7 Hz), 129.6, 129.5, 129.2, 127.9
(d, JC-P ) 5.6 Hz), 127.7 (d, JC-P ) 2.1 Hz), 127.6 (d, JC-P ) 2.1
Hz), 48.9 (d, JC-P ) 60.0 Hz), 45.9 (d, JC-P ) 59.4 Hz), 33.4 (d,
JC-P ) 7.2 Hz), 33.4 (d, JC-P ) 10.9 Hz). 31P{1H} NMR (162
782 J. Org. Chem., Vol. 73, No. 3, 2008

Bis-(2,5-diphenylphospholanes) with sp2 Carbon Linkers
1,1′-Bis-[(2S,5S)-2,5-diphenylphospholane-1-yl]ferrocene (8) (0.354
g, 0.53 mmol) and Rh(COD)2BF4 (0.2171 g, 0.53) were dissolved
in 10 mL of CH2Cl2, giving rise to a red-orange solution. After
being stirred for 30 min, the 31P{1H} NMR showed clean formation
of the desired complex. The solvent volume was reduced to about
1 mL, and 0.5 mL of ether was added, causing formation of orange-
red crystals. After 30 min more ether was added (1 mL), and
solution was left standing for 2 h. The solvent was decanted, and
the remaining crystals were washed with ether (2 mL) and then
dried under reduced pressure to give 0.446 g of product as red-
orange crystals. X-ray quality crystals were obtained from meth-
ylene chloride/ether mixture at room temperature. Crystals contained
dure for dimethyl itaconate 14 was followed: analysis for 2-acety-
laminopropionic acid 21 and 2-acetylamino-3-phenylpropionic acid
23 as for methyl 2-acetylaminopropionate 20 and methyl 2-acety-
lamino-3-phenylpropionate 22, but samples were derivatized to the
methyl ester using TMS diazomethane before analysis.
Preparation of (E)-2-Methylcinnamic Acid tert-Butylammo-
nium Salt (24). (E)-2-Methylcinnamic acid (10.0 g, 61.7 mmol)
and THF (100 mL) were placed in a flask. tert-Butylamine (6.54
mL, 61.7 mmol) was added over 30 min. The white suspension
was stirred for 30 min and then filtered, and the solid was washed
with THF (3 × 20 mL) and then dried to give (E)-2-methylcinnamic
acid tert-butylammonium salt 24 as a fine, white solid (14.1 g,
1
1
one molecule of methylene chloride. Yield 79.8%. H NMR (300
97%). H NMR (400 MHz, DMSO): δ 8.3 (br s, 3H), 7.40-7.34
MHz, 23 °C, CD2Cl2): δ 7.81 (m, 4H, ortho1-H), 7.40 (m, 6H,
meta1/para1), 7.13 (m, 6H, meta2/para2), 6.68 (d, 3JH-H ) 7.5 Hz,
4H, ortho2-H), 5.59 (br t, 3JH-H ) 6.9 Hz, 2H, COD), 4.50 (br, 2H
COD), 4.42 (m, 6H, Cp), 4.14 (qm, JH-P ) 9.6 Hz, 2H, PCH),
3.60 (m, 2H, Cp), 3.36 (dd, JH-P ) 11.7 Hz, 3JH-H ) 6.3 Hz, 2H,
PCH), 2.61-2.80 (m, 2H, PCHCH2), 2.24-2.46 (m, 4H, PCHCH2),
1.70-2.50 (m, 10H, PCHCH2/COD). 13C{1H} NMR (75 MHz, 23
°C, CD2Cl2): δ 140.21 (t, JC-P ) 2.4 Hz, quat), 136.29 (quat),
129.17 (meta1), 128.89 (t, JC-P ) 1.8 Hz, ortho2), 128.76 (t, JC-P
) 3.7 Hz, ortho1), 128.38 (meta2), 128.13 (para1), 127.28 (para2),
98.41 (dt, JC-Rh ) 9.3 Hz, JC-P ) 2.4 Hz, COD), 89.57 (q, J )
7.2 Hz, COD), 76.54 (dt, J ) 18.3 Hz, J ) 7.9 Hz, Cp), 75.38 (t,
JC-P ) 4.3 Hz, Cp), 73.11 (Cp), 72.65 (t, JC-P ) 1.8 Hz, Cp),
70.92 (d, 1JC-P ) 42.7 Hz, Cp, quat), 49.72 (dt, J ) 20.7 Hz, J )
8.5 Hz, PCH), 46.47 (dt, J ) 14.6 Hz, J ) 10.3 Hz, PCH), 35.35
(PCHCH2), 33.23 (PCHCH2), 33.13 (COD), 28.12 (COD). HSQC
(23 °C, CD2Cl2): δ 129.17/7.40, 128.89/6.68, 128.76/7.81, 128.38/
7.13, 128.13/7.40, 127.28/7.13, 98.41/5.59, 89.57/4.50, 76.54/3.60,
75.38/4.42, 73.11/4.42, 72.65/4.42, 49.72/4.14, 46.47/3.30, 35.35/
(2.70, 2.31), 33.23/(2.38, 2.18), 33.13/1.99, 28.12/1.85. 31P{1H}
NMR (CD2Cl2, 23 °C, 121 MHz): δ 36.79 (d, 1JP-Rh ) 146.5 Hz).
19F NMR (282 MHz, 23 °C, CD2Cl2): δ -153.43, HRMS (ESI,
M+): (m/z) calcd for C50H52FeP2Rh: 873.1949. Found: 873.194.
Anal. Calcd for C51H54FeCl2P2RhBF4: C, 58.60; H, 5.21. Found:
C, 58.76; H, 5.17.
Hydrogenation Procedure for Dimethyl Itaconate (14) Using
[((S,S)-Ph-MalPhos)Rh(COD)]BF4. An Argonaut Endeavor cata-
lyst screening system was used. The glass liner of a vessel was
charged with dimethyl itaconate 14 (316 mg, 2.0 mmol) and 3,4-
bis-[(S,S)-2,5-diphenylphospholane-1-yl]-furan-2,5-dione-(1,5-cy-
clooctadiene) rhodium(I) tetrafluoroborate (1.7 mg, 0.002 mmol,
S/C 1000). The vessel was charged to 10 bar nitrogen and vented
(×5). Degassed methanol (4 mL) was added. The vessel was
charged to 10 bar nitrogen and vented (×2). Stirring was com-
menced at 1000 rpm, and the contents were heated to 25 °C. The
vessel was charged to 10 bar hydrogen. Hydrogen uptake was
complete after 16 h. The mixture was vented and evaporated to
give (S)-2-methylsuccinic acid dimethyl ester 19, conversion 100%,
96.6% ee (Chiraldex GTA, 30 m × 0.25 mm, injector/detector
180 °C, helium 14 psi, 90 °C for 6 min then ramp at 1 °C/min to
105 °C, retention times S 10.11 min, R 10.48 min).
(m, 5H), 7.28-7.23 (m, 1H), 2.00 (d, J ) 1.2 Hz, 3H), 1.25 (s,
9H). 13C{1H} NMR (100 MHz, DMSO): δ 171.8, 138.0, 136.3,
132.1, 129.4, 128.6, 127.2, 49.9, 28.7, 15.6.
Hydrogenation Procedure for (E)-2-Methylcinnamic Acid
tert-Butylammonium Salt (24) Using [((S,S)-Ph-5-Fc)Rh(COD)]-
BF4. The reaction was carried out in an Argonaut Endeavor
hydrogenation vessel. The glass liner was charged with (E)-2-
methylcinnamic acid tert-butylammonium salt 24 (235 mg, 1.0
mmol). The vessel was charged to 10 bar nitrogen and vented (×5).
Degassed methanol (3 mL) followed by a solution of 1,1′-bis-
[(2S,5S)-diphenylphospholane-1-yl]ferrocene(1,5-cyclooctadiene) rhod-
ium(I) tetrafluoroborate in degassed methanol (1 mL of a solution
of 20 mg, 0.02 mmol in methanol, 20 mL) were added. The vessel
was charged to 10 bar nitrogen and vented (×2). Stirring was
commenced at 1000 rpm, and the vessel was heated to 25 °C. The
vessel was charged to 10 bar H2, and hydrogen uptake was
monitored. After completion, the vessel was vented, and the solvent
was evaporated to give (R)-2-methyl-3-phenylpropionic acid tert-
butylammonium salt 27 as a pale orange solid. 1H NMR (400 MHz,
DMSO): δ 7.6 (br s, 3H), 7.24 (t, J ) 7.0 Hz, 2H), 7.18-7.13 (m,
3H), 2.94 (dd, J ) 13.0, 6.2 Hz, 1H), 2.43 (dd, J ) 13.0, 7.4 Hz,
1H), 2.39-2.34 (m, 1H), 1.17 (s, 9H), 0.93 (d, J ) 7.6 Hz, 3H).
96.5% ee (SFC, 2 × Chiralpak AD-H columns 10% methanol, 3000
psi CO2, 35 °C, flow rate 3 mL/min, retention times R 7.1 min, S
7.71 min, substrate 11.8 min). The salt was shaken with 2 M
hydrochloric acid (5 mL) and dichloromethane (5 mL). The organic
layer was separated, and the aqueous layer was extracted with
dichloromethane (5 mL). The combined organic layers were dried
(Na2SO4) and filtered, and the solvent was evaporated. The product
was distilled (kugelrohr, 0.5 mbar, oven temperature 150 °C) to
give (R)-2-methyl-3-phenylpropionic acid 27 as a colorless liquid
(100 mg, 63%). [R]25D -22.7° (c 1.02, CHCl3). Lit.30 [R]25D -23.1°
1
(c 1, CHCl3). H NMR (400 MHz, CDCl3): δ 10.0 (br s, 1H),
7.31-7.28 (m, 2H), 7.25-7.17 (m, 3H), 3.08 (dd, J ) 13.2, 6.4
Hz, 1H), 2.81 (m, 1H), 2.67 (dd, J ) 12.8, 8.0 Hz, 1H), 1.18 (d, J
) 6.4 Hz, 1H). 85% ee (derivatized using TMS diazomethane,
Chirasil Dex CB column, 25 m × 0.25 mm, injector/detector
200 °C, helium 20 psi, 100 °C for 21 min then ramp at 15 °C/min
to 200 °C, hold for 5 min, retention times R 30.40 min, S 31.06
min, (E)-methyl-2-methylcinnamate, 34.79 min). 1H NMR analysis
of the (S)-methyl mandelate ester30 confirmed assignment of the
(R)-configuration.
Hydrogenation Procedure for Methyl r-Acetamidoacrylate
(15). The hydrogenation procedure for dimethyl itaconate 14 was
followed: method of analysis for methyl 2-acetylaminopropionate
20 (Chirasil Dex CB, 25 m × 0.25 mm, injector/detector 200 °C,
helium 20 psi, 130 °C for 10 min then ramp at 15 °C/ min to
200 °C, retention times S 2.91 min, R 2.98 min).
Hydrogenation Procedure for Methyl r-Acetamidocinnamate
(17). The hydrogenation procedure for dimethyl itaconate 14 was
followed: method of analysis for methyl 2-acetylamino-3-phenyl-
propionate 22 (Chirasil Dex CB, 25 m × 0.25 mm, injector/detector
200 °C, helium 20 psi, 150 °C for 21 min then ramp at 15 °C/min
to 200 °C, hold for 5 min, retention times R 17.65 min, S 17.92
min).
Preparation of (E)-2-Phenylcinnamic Acid tert-Butylammo-
nium Salt (25). (E)-2-Phenylcinnamic acid (10.0 g, 44.6 mmol)
and THF (100 mL) were placed in a flask. tert-Butylamine (4.69
mL, 44.6 mmol) was added over 30 min. The white suspension
was stirred for 1 h and then filtered, and the solid was washed
with THF (4 × 20 mL) and then dried to give (E)-2-phenylcinnamic
acid tert-butylammonium salt 25 as a fine, white solid (11.2 g,
1
84.4%). H NMR (400 MHz, DMSO): δ 8.0 (br s, 3H), 7.37 (s,
1H), 7.23-7.14 (m, 3H), 7.07-7.02 (m, 5H), 6.89-6.87 (m, 2H),
1.16 (s, 9H). 13C{1H} NMR (100 MHz, DMSO): δ 170.3, 140.3,
132.7, 129.8, 129.7, 128.3, 128.1, 127.5, 126.5, 50.1, 28.5.
Hydrogenation Procedures for r-Acetamidoacrylic Acid (16)
and r-Acetamidocinnamic Acid (18). The hydrogenation proce-
(30) Tyrrell, E.; Tsang, M. W. H.; Skinner, G. A.; Fawcett, J. Tetrahedron
1996, 52, 9841-9852.
J. Org. Chem, Vol. 73, No. 3, 2008 783

Fox et al.
Hydrogenation Procedure for (E)-2-Phenylcinnamic Acid tert-
Butylammonium Salt (25) Using [((S,S)-Ph-5-Fc)Rh(COD)]BF4.
The reaction was carried out as for 24 using (E)-2-phenylcinnamic
acid tert-butylammonium salt 25 (448 mg, 1.51 mmol) and [(2S,5S)-
diphenylphospholane-1-yl]ferrocene(1,5-cyclooctadiene) rhodium-
(I) tetrafluoroborate (4 mL of a solution of 8.3 mg, 0.0086 mmol
in degassed methanol, 32 mL) to give (S)-2,3-diphenylpropionic
min, R 5.0 min, substrate 10.9 min).34 The salt was shaken with 2
M hydrochloric acid (5 mL) and dichloromethane (5 mL). The
organic layer was separated, and the aqueous layer was extracted
with dichloromethane (2 mL). The combined organic layers were
dried (Na2SO4) and filtered, and the solvent was evaporated to give
(S)-2-isopropyl-3-{2-[3-methoxy(propyloxy)]-4-methoxyphenyl}-
propionic acid as an orange oil (302 mg, 98%). [R]25 -33.0° (c
D
1
acid tert-butylamine salt 28 as a pale orange solid. H NMR (400
1.01, CH2Cl2). Lit.26 (enantiomer) [R]25 +42.5° (c 1.0, CH2Cl2).
D
MHz, DMSO): δ 7.5 (br s, 3H), 7.11 (d, J ) 7.2 Hz, 2H), 7.03-
6.88 (m, 8H), 3.36 (t, J ) 7.4 Hz, 1H), 3.10 (d, J ) 13.6, 8.8 Hz,
1H), 2.61 (dd, J ) 13.4, 7.0 Hz, 1H), 0.95 (s, 9H). 96.5% ee (SFC,
2 × Chiralpak AD-H columns 10% methanol, 3000 psi CO2,
35 °C, flow rate 3 mL/min, retention times R 7.1 min, S 7.7 min,
substrate 11.8 min). The salt was shaken with 2 M hydrochloric
acid (5 mL) and dichloromethane (5 mL). The organic layer was
separated, and the aqueous layer was extracted with dichlo-
romethane (5 mL). The combined organic layers were dried (Na2-
SO4) and filtered, and the solvent was evaporated to give (S)-2,3-
1H NMR (400 MHz, CDCl3,): δ 6.76 (d, J ) 8.2 Hz, 1H), 6.74 (s,
1H), 6.73 (dd, J ) 7.6, 1.6 Hz, 1H), 3.82 (s, 3H), 3.57 (t, J ) 6.2
Hz, 2H), 3.36 (s, 3H), 2.83-2.76 (m, 1H), 2.47-2.41 (m, 1H),
2.08 (q, J ) 6.4 Hz, 2H), 1.98-1.90 (m, 1H), 1.04 (d, J ) 7.2 Hz,
3H), 1.01 (d, J ) 7.2 Hz, 3H).
General Hydrogenation Procedure Using Multiple Vessels
Used for Comparative Examples in Table 2. A Baskerville 10-
well multiple pressure vessel was used. The glass liner of a vessel
was charged with substrate and catalyst. The vessel was charged
to 10 bar nitrogen and vented (×5). Degassed methanol (4 mL)
was added, and stirring was commenced. The vessel was charged
to 10 bar nitrogen and vented (×3). The vessel was charged to 10
bar H2 and stirred for 18 h. The vessel was vented, charged with
nitrogen, and vented, and then the solvent was evaporated to give
the crude hydrogenation product.
diphenylpropionic acid as an orange solid (300 mg, quant). [R]25
D
+98.6° (c 2.03, CHCl3); [R]25 +100.6° (c 0.54, acetone). [R]25
D
D
+103.5° (c 1.00, methanol). Lit.31 +140.8° (c 2.04, CHCl3). Lit.31
+133.8° (c 0.535, acetone). Lit.32 (enantiomer) -93.2° (c 1,
1
MeOH). H NMR (400 MHz, DMSO): δ 7.5 (br s, 3H), 7.11 (d,
J ) 7.2 Hz, 2H), 7.03-6.88 (m, 8H), 3.36 (t, J ) 7.4 Hz, 1H),
3.10 (d, J ) 13.6, 8.8 Hz, 1H), 2.61 (dd, J ) 13.4, 7.0 Hz, 1H),
0.95 (s, 9H). 1H NMR analysis of the (S)-methyl mandelate ester30
confirmed assignment of the (R)-configuration.
X-ray Analysis of (S,S)-Ph-5-Fc (8) and [((S,S)-Ph-5-Fc)Rh-
(COD)]BF4. Data for both structures were collected at 173 K on a
Siemens SMART PLATFORM equipped with a CCD area detector
and a graphite monochromator utilizing Mo KR radiation (λ )
0.71073 Å). Cell parameters were refined using up to 8192
reflections. A hemisphere of data (1381 frames) was collected using
the ω-scan method (0.3° frame width) for each structure. The first
50 frames were remeasured at the end of data collection to monitor
instrument and crystal stability (maximum correction on I was
<1 %). Absorption corrections by integration were applied on the
basis of measured indexed crystal faces.
The structures were solved by the Direct Methods in SHELXTL5
and refined using full-matrix least-squares. The non-hydrogen atoms
were treated anisotropically, whereas the methyl hydrogen atoms
were calculated in ideal positions and were riding on their respective
carbon atoms. For (S,S)-Ph-5-Fc, a total of 469 parameters were
refined in the final cycle of refinement to yield R1 and wR2 of
3.25 and 6.88%, respectively. In addition to the complex, a toluene
molecule in general position was found and refined. Space group
C2 was chiral, and the Flack x parameter was refined to a value of
-0.002(11) to confirm the correct enantiomer. For [((S,S)-Ph-5-
Fc)Rh(COD)]BF4, a total of 571 parameters were refined in the
final cycle of refinement to yield R1 and wR2 of 2.28 and 5.83%,
respectively. The Flack x parameter was refined to a value of
-0.001(9) to confirm the correct enantiomer. Refinement was done
using F2.
Preparation of (E)-2-Isopropyl-3-{2-[3-methoxy(propyloxy)]-
4-methoxyphenyl}acrylic Acid tert-Butylamine Salt (26). (E)-
2-Isopropyl-3-{2-[3-methoxy(propyloxy)]-4-methoxyphenyl}-
acrylic acid33 was dissolved in MTBE (70 mL). tert-Butylamine
(2.4 mL, 22.4 mmol) was added, and the mixture was stirred for 3
h. The dense precipitate was diluted with MTBE (20 mL) and
filtered. The filter cake was washed with MTBE (30 mL) and
dried to give (E)-2-isopropyl-3-{2-[3-methoxy(propyloxy)]-4-
methoxyphenyl}acrylic acid tert-butylamine salt 26 as a white solid
(7.43 g, 89%). 1H NMR (400 MHz, CDCl3): δ 7.28 (s, 3H), 6.85
(m, 3H), 4.11 (t, J ) 6.5 Hz, 2H), 3.87 (s, 3H), 3.57 (t, J ) 6 Hz,
2H), 3.34 (s, 3H), 3.10 (m, 1H), 1.39 (s, 9H), 1.29 (d, J ) 6.5 Hz,
6H).
Hydrogenation Procedure for (E)-2-Isopropyl-3-{2-[3-meth-
oxy(propyloxy)]-4-methoxyphenyl}acrylic Acid tert-Butylamine
Salt (26) Using [((S,S)-Ph-5-Fc)Rh(COD)]BF4. The reaction was
carried out as for 24 using (E)-2-isopropyl-3-{2-[3-methoxy-
(propyloxy)]-4-methoxyphenyl}acrylic acid tert-butylamine salt 26
(382 mg, 1.00 mmol), degassed methanol (3 mL), and [(2S,5S)-
diphenylphospholane-1-yl]ferrocene(1,5-cyclooctadiene) rhodium-
(I) tetrafluoroborate (1 mL of a solution of 20 mg, 0.02 mmol in
methanol, 20 mL) to give (S)-2-isopropyl-3-{2-[3-methoxy(propy-
loxy)]-4-methoxyphenyl}propionic acid tert-butylamine salt 29 as
Acknowledgment. We thank Colin Dewar and Brendan
Mullen for assistance with chiral analysis. We thank the Friends’
School in Lisbum, Northern Ireland, for use of the old
photograph of the Chemistry Laboratory. We also thank Francis
Timmers for the cover art design.
1
a pale orange solid. H NMR (400 MHz, DMSO): δ ppm 6.7 (br
s, 3H), 6.63-6.61 (m, 2H), 6.51 (dd, J ) 8.2, 1.8 Hz, 1H), 3.78 (t,
J ) 3.78 Hz, 2H), 3.54 (s, 3H), 3.30 (t, J ) 6.4 Hz, 2H), 3.09 (s,
3H), 2.54 (dd, J ) 13.4, 10.2 Hz, 1H), 2.41 (dd, J ) 13.8, 4.6 Hz,
1H), 2.05-2.00 (m, 1H), 1.76 (q, J ) 6.2 Hz, 2H), 1.65-1.56 (m,
1H), 0.96 (s, 9H), 0.77 (d, J ) 7.0 Hz, 3H), 0.76 (d, J ) 7.2 Hz,
3H). 84.6% ee (SFC, 2 × Chiralpak AD-H columns 10% methanol,
3000 psi CO2, 35 °C, flow rate 3 mL/min, retention times S 4.6
Supporting Information Available: NMR spectra of ligands
5-8 and their [Rh(I)(COD)]BF4 complexes and X-ray data for
ligand (S,S)-Ph-5-Fc and [((S,S)-Ph-5-Fc)Rh(COD)]BF4. This mate-
rial is available free of charge via the Internet at http://pubs.acs.org.
(31) Watson, M. B.; Youngson, G. W. J. Chem. Soc. C 1968, 258-262.
(32) Camps, P.; Gimenez, S. Tetrahedron: Asymmetry 1996, 7, 1227-
JO7014938
1234.
(33) Herold, P.; Stutz, S. WO, 2002002500; Chem. Abstr. 2002, 136,
85662.
(34) The peaks were assigned by comparison with a sample made using
(R)-Walphos-Rh.27
784 J. Org. Chem., Vol. 73, No. 3, 2008