A Novel Class of Ferrocenyl-Aryl-Based Diphosphine Ligands for Rh- And Ru-Catalysed Enantioselective Hydrogenation

Article abstract of DOI:10.1002/adsc.200390003

A series of diphosphines of the novel Walphos ligand family all based on a phenylferrocenylethyl backbone were synthesised in a four-step sequence. In the rhodium- or ruthenium-catalysed asymmetric hydrogenation of olefins and ketones enantioselectivities of up to 95% and 97%, respectively, were obtained. A 2-isopropylcinnamic acid derivative of industrial interest was hydrogenated in 95% ee and with turnover numbers of > 5000.

Full text of DOI:10.1002/adsc.200390003

COMMUNICATIONS
A Novel Class of Ferrocenyl-Aryl-Based Diphosphine Ligands
for Rh- and Ru-Catalysed Enantioselective Hydrogenation
Thomas Sturm,a Walter Weissensteiner,a,* Felix Spindlerb,*
a
Institute of Organic Chemistry, University of Vienna, W‰hringer Strasse 38, 1090 Vienna, Austria
Solvias AG, Catalysis Research, Klybeckstrasse 191, 4002 Basel, Switzerland
b
Fax: ( ‡ 41)-61-686-6311, e-mail: felix.spindler@solvias.com
Received: July 27, 2002; Accepted: October 30, 2002
In our search for novel classes of diphosphines, we
Abstract: A series of diphosphines of the novel
Walphos ligand family all based on a phenylferroce-
nylethyl backbone were synthesised in a four-step
sequence. In the rhodium- or ruthenium-catalysed
asymmetric hydrogenation of olefins and ketones
enantioselectivities of up to 95% and 97%, respec-
tively, were obtained. A 2-isopropylcinnamic acid
derivative of industrial interest was hydrogenated in
95% ee and with turnover numbers of > 5000.
focused on the design of ligands that fulfil all relevant
prerequisites particularly with regard to industrial
applications: shortness and modularity of ligand syn-
thesis that should allow an efficient fine tuning of
catalysts× properties. In addition, such ligands should be
readily accessible from enantiopure key intermediates.
In this context, we have examined the potential of a new
family with a novel phenylferrocenylethyl backbone
that we named Walphos (1; Figure 1). The synthesis
concept for this ligand family is straightforward: (i) the
enantiomerically pure ligand framework an ortho-
bromophenylferrocenylethylamine (3) is constructed
from Ugi×s amine[4] and (ii) the final functional groups
are implemented stepwise.[5] (Scheme 1) In this prelimi-
nary contribution, we report the synthesis of six
representatives of the Walphos family with varying
phosphino substituents R1 and R2, together with first
Keywords: alkene reduction; asymmetric catalysis;
asymmetric hydrogenation; ketone reduction; P-
ligands; rhodium; ruthenium
Over a period of more than three decades homogenous applications in the enantioselective hydrogenation.
enantioselective hydrogenation has been investigated Starting from amine 2, six derivatives with electron-
extensively by numerous researchers in academia and rich and electron-withdrawing phosphino substituents
industry, and is now being considered as a mature R1 and R2 were prepared in a four-step sequence. In a
methodology for the production of enantiopure, bio- Negishi coupling reaction[6] of (Rc)-N,N-dimethyl-1-
active ingredients and fine chemicals on an industrial ferrocenylethylamine, (Rc)-2, with 2-bromoiodoben-
scale.[1] The most efficient catalysts for the asymmetric zene the enantiomerically pure key intermediate
hydrogenation of olefins, ketones or imines[2] are (Rc,Rp)-3 was built up. A subsequent lithiation of this
rhodium, ruthenium and iridium complexes of chiral bromide followed by trapping with the appropriate
diphosphine ligands. However, even though innumer- electrophile either chlorodiphenylphosphine or chloro-
able chiral diphosphines have been designed and inves- bis(3,5-dimethyl-4-methoxyphenyl)phosphine result-
tigated in the past, only a few out ofmore than thousands ed in the formation of the corresponding aminophos-
have been found suitable for industrial processes. phines. In order to prevent a ring closure reaction in the
Representative examples are biaryl-, phospholane- next step, the aminophosphines had to be protected by
and ferrocenyl-based ligands like binap, duphos or oxidation with H2O2 to afford the corresponding phos-
josiphos type ferrocenes.[3]
phine oxides (Rc,Rp)-4a and (Rc,Rp)-4f, respectively.
Figure 1. Examples of diphosphine ligands used in industrial enantioselective hydrogenation processes.
160
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Adv. Synth. Catal. 2003, 345, No. 1+2

A Novel Class of Ferrocenyl-Aryl-Based Diphosphine Ligands
COMMUNICATIONS
COOCH3
COOH
COOCH3
NHAc
COOCH3
Ph
Ph
CH3
F3C
6
7
8
O
Et
O
OCH3
OiPr
OCH3
Ph
O
O
O
O
O
O
9
10
11
12
Figure 2. Olefins and ketones used as substrates in catalytic
hydrogenations.
genation reaction, conversion was quantitative or nearly
quantitative (Tables 1 and 2). The diphosphines 1c 1e
proved to be particularly valuable ligands in rhodium-
catalysed hydrogenations of olefins (Table 1) while 1e
and 1f gave excellent results in ruthenium-catalysed
hydrogenations of ketones (Table 2).
The hydrogenation of a-acetamidocinnamic acid (6)
and dimethyl itaconate (8) afforded N-acetylphenylala-
nine methyl ester and dimethyl 2-methylsuccinate with
95% and 91% enantiomeric purity, respectively, while 2-
methylcinnamic acid (7) gave 2-methyl-3-phenylpro-
pionic acid of 82% ee. (Table 1, entries 3, 12 and 14). For
both substrates, 6 and 8, catalysts prepared with ligands
1c 1e with two diarylphosphino substituents (R1 ˆ
R2 ˆ aryl) yielded hydrogenation products of higher
enantioselectivity than 1a and 1b with one diaryl- and
one dialkylphosphino unit (R1 ˆ Ph, R2 ˆ alkyl). How-
Scheme 1. Synthesis of ligands 1a 1f.
Treatment of (Rc,Rp)-4a with either a dialkyl- or ever, it is interesting to note that for 6 as the substrate
diarylphosphine (R2 PH) in acetic acid[7] led to deriva- ligand 1c with an electron-donating phosphino group
2
ˆ
tives 5a 5e [R2
Cy: 5a; t-Bu: 5b; 3,5-(CH3)2-4- [R2 ˆ 3,5-(CH3)2-4-CH3OC6H2] gave the best result,
CH3OC6H2: 5c; Ph: 5d; 3,5-(CF3)2C6H3: 5e] while while in the case of olefin 7 ligand 1e with an electron-
reaction of (Rc,Rp)-4f with [3,5-(CF3)2C6H3]2PH gave withdrawing phosphino group [R2 ˆ 3,5-(CF3)2C6H3]
5f. It is interesting to note that 5a 5c were obtained in performed best. As shown with the catalyst
diastereomerically pure form with (Rc,Rp) configura- [(NBD)2Rh]BF4/1d in the hydrogenation of 6, both
tions, indicating clean retention of configuration in the pressure and temperature significantly influence the
nucleophilic substitution step. However, in the case of enantioselectivity. Increasing the pressure from 1 to
5d 5f the respective (Sc,Rp)-diastereomer was formed 10 bar results in lowering of the enantiomeric purity of
as a by-product [ratio of (Rc,Rp)/(Sc,Rp) diastereomers; the N-acetylphenylalanine methyl ester from 87% to
5d: 10/1; 5e: 6/1; 5f: 6/1]. In this particular case the 82% (Table 1, entries 4 and 5). At lower temperatures,
observed diastereoselectivity of the nucleophilic sub- i.e., at 5 8C, a higher enantiomeric excess was obtained
stitution step seems to depend strongly on the nucleo- than at 25 8C: 90% compared to 87% (Table 1, entries 4
philicity of the phosphine, since only the electron-rich and 6).
phosphines gave products with full retention of config-
uration (5a 5c). Reduction of 5a 5f (in the case of 5d
In the hydrogenation of ketones, the test substrates
were a 1,3-diketone (acetylacetone, 9, Figure 2), b-keto
5f the mixtures of diastereomer were used) with poly- esters (10, 11) and an a-keto ester (12). Typically,
methylhydrosiloxane (PMHS)/titanium isopropoxide[8] turnover numbers of 1,000 were obtained smoothly, and
or trichlorosilane/triethylamine[9] gave the desired Wal- the average turnover frequency (tof) of approximately
phos ligands 1a 1f. Separation of major diastereomers 200 hÀ1 (entry 2) as measured for example in the Ru/1f-
was achieved by flash chromatography.
catalysed hydrogenation of 9 is sufficiently high for
All ligands 1a 1f of (Rc,Rp) configuration were evaluation of synthetic applications. In ruthenium-
screened in catalytic hydrogenation of olefins and mediated hydrogenations, the ligands 1e and 1f with
ketones (for substrates see Figure 2). All catalysts either one electron-donating diarylphosphino or one
were formed in situ with use of an appropriate Rh or diphenylphosphino group attached to the phenyl part of
Ru source (see footnotes to Tables). In each hydro- the scaffold and one electron-withdrawing phosphino
Adv. Synth. Catal. 2003, 345, 160 164
161

Thomas Sturm et al.
COMMUNICATIONS
Table 1. Rhodium-catalysed hydrogenation of olefins.
Entry
Substrate
Ligand
p(H2) [bar]
T [8C]
Time [h]
Conv. [%]
ee [%]
Config.
1[d]
2
6[a, b]
6
6
6
6
6
1a
1b
1c
1d
1d
1d
1e
1a
1b
1c
1d
1e
1d
1e
1
1
1
1
10
1
1
5
5
5
25
25
25
25
25
5
25
25
25
25
25
25
0
18
66
20.5
17.5
18
19
20.5
21
18
22
> 97
> 99
> 99
> 98
> 99
> 99
> 99
> 99
> 99
> 98
> 98
> 99
> 99
> 99
25
8
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
3
95
87
82
90
60
51
31
68
66
82
90
91
4[d]
5
6
7
8
9
10
11
12
13
14
6
7[a, c]
7
7
7
7
5
5
1
1
20.5
20
16
8[a, e]
8
25
21
[a]
Catalyst precursor: [(NBD)2Rh]BF4; S/C ˆ 200; solvent: methanol (10 mL); Ligand/Rh ˆ 1.1.
ee determination by GC on Chirasil-L-Val, (He carrier, 135 8C, isothermic).
[b]
[c]
[d]
[e]
ee determination as methyl ester by HPLC on Chiralcel OB, (Daicel; eluent: hexane/2-propanol ˆ 97/3, flow: 0.1 mL/min).
S/C ˆ 187.
ee determination by GC on Lipodex-E, (He carrier, 100 8C, isothermic).
Table 2. Ruthenium-catalysed hydrogenation of ketones.
Entry
Substrate
Ligand
p(H2) [bar]
T [8C]
Time [h]
Conv. [%]
ee [%]
Config.
1[a, b]
2[a, b]
9
9
1e
1f
1a
1e
1f
1f
1f
1f
1f
1e
1f
1f
100
20
100
100
20
80
80
80
80
80
60
80
60
80
77
80
80
17
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 90
97
96
50
91
94
94
90
91
95
77
60
22
(2R,4R)[h]
(2R,4R)[h]
(S)
(S)
(S)
(S)
(S)
(S)
(S)
16[g]
19
3[a, c]
10
10
10
10
10
10
10
11
11
12
4[a, c]
16.5
16,5
16.5
17.5
17
16
16
16
16
5[a, c]
6[a, c]
20
7[a, c]
100
100
5
20
20
8[a, c]
9[a, c]
10[a, c,d]
11[a, c,d]
12[a, f]
(S)
(S)
(R)
20
[a]
Catalyst precursor: [RuI2(p-cymene)]2; S/C ˆ 1000; Ligand/Ru ˆ 1.1; solvent: methanol (10 mL); additives: 1 N HCl
(120 mL).
ee determination as bis(trifluoroacetate) by GC on Lipodex-E, (He carrier, 80 8C, isothermic).
ee determination as trifluoroacetate by GC on Lipodex-E, (He carrier, 80 8C, isothermic).
Solvent: 2-propanol (10 mL).
ee determination by GC on Chirasil-L-Val, (45 8C, isothermic).
ee determination by HPLC on Chiralcel OJ (Daicel; eluent: hexane/2-propanol ˆ 9/1, flow: 0.1 mL/min).
Time for complete hydrogen uptake: 5 h;
[b]
[c]
[d]
[e]
[f]
[g]
[h]
rac.:meso > 99:1.
substituent at the stereogenic C atom, performed best.
Overall, these results obtained with the Walphos
For substrates 9 and 10, products with enantioselectiv- ligands 1e and 1f in the hydrogenation of b-keto esters
ities of 97% and 95% were obtained (Table 2, entries 1, and the 1,3-diketone are relatively remarkable. Only a
9). In the case of 10, both the temperature and the few Ru catalysts with ligands other than atropisomeric
pressure dependence was found to be rather small diphosphines have been reported to hydrogenated such
(entries 5 9). Only when the hydrogen pressure was functionalised ketones efficiently with high enantiose-
raised to 100 bar did the enantioselectivity drop slightly lection, i.e., bis(phospholanes),[10] taniaphos,[11] or josi-
(90%, entry 7). In contrast, the hydrogenation of a-keto phos.[7] Hence, the application of Walphos ligands could
ester 12 by means of Ru/1f afforded methyl mandelate be a valuable alternative to the atropisomeric diaryl-
only with 22% enantiomeric purity.
diphosphines.
162
Adv. Synth. Catal. 2003, 345, 160 164

A Novel Class of Ferrocenyl-Aryl-Based Diphosphine Ligands
COMMUNICATIONS
In order to evaluate the synthetic potential of the Experimental Section
Walphos family and encouraged by the very promising
screening results, particularly with ligands 1c, 1e, and 1f,
the enantioselective hydrogenation of the substituted
General
The synthesis of all ligands 1a 1f starts from commercially
available enantiopure (R)-2 and follows the reaction sequence
given in Scheme 1. Typical reaction procedures are given for
ligand 1d. All other ligands were prepared analogously.[14]
acyclic acid 13 was investigated. Synthon A is an
intermediate for the synthesis of the renin inhibitor
SPP100, which is currently being developed.[12] The key
step for the preparation of the enantiopure Synthon A is
the enantioselective hydrogenation of 13. The applica-
tion of 1 mol % of an Rh catalyst generated in situ from
[(NBD)2Rh]BF4 and ligand 1e afforded at 50 bar hydro-
gen and ambient temperature the saturated acid 14 with
95% ee. All of the other diphosphines available on
technical scale afforded 14 with significantly lower
enantiomeric purity. Among the various other catalysts
tested at 20 60 bar hydrogen and 40 50 8C, the
cationic Rh catalyst with (S,S)-Me-duphos provided 14
only with 15% ee. Rh/(R)-MeO-biphep hydrogenated
13 with 35% ee (S), Rh/(R)-(S)-PPF-t-Bu2[7] with 49% ee
(S), Rh/1d with 79% (S), and Achiwa×s (2S,4S)-bcpm
yielded 14 with fairly high 80% ee (S).
We rationalised that this remarkably high enantiose-
lectivity of the Rh/1e catalyst compared with the
hydrogenation of model substrate 7 is probably due to
a large extent to the bulkier substituent at the C-2
position of the cinnamic acid derivative 13. However, we
anticipate the electronic effects of the two alkoxy
substituents of the aryl moiety of 13 to trigger the
enantioselectivity, too.
(Rc,Rp)-1-[1-(Diphenylphosphino)ethyl]-2-(2-
diphenylphosphinylphenyl)-ferrocene (5d)
To a degassed solution of 1.2 g (2.25 mmol) 4a in 15 mL acetic
acid were added 0.72 mL (4 mmol) of diphenylphosphine and
the reaction mixture was stirred at 100 8C for 18 hours. After a
saturated aqueous solution of NaHCO3 had been added the
organic layer was separated and the aqueous layer was
extracted twice with 30 mL of CH2Cl2. The combined organic
layers were dried over MgSO4 and after removal of the solvent
the residue was purified by chromatography on alumina. Petrol
ether eluted non-polar impurities and subsequently CH2Cl2
eluted the product as a mixture of diastereomers. Yield: 1.330 g
(1.97 mmol, 89.8%). According to 31P NMR the ratio of the
(Rc,Rp) and (Sc,Rp) diastereomers was found to be 10:1. 1H and
13C NMR data are given for the major isomer only. 1H NMR:
ˆ
ˆ
ˆ
d ˆ 1.40 (dd, J1 J2 7.0 Hz, 3H), 3.67 (m, 1H, Cp), 3.73 (q, J
ˆ
7.0 Hz, 1H), 3.80 (t, J 2.5 Hz, 1H, Cp), 4.03 (s, 5H, Cp), 5.15
(m, 1H, Cp), 7.13 7.31 (m, 13H, Ph), 7.37 7.48 (m, 4H, Ph),
7.49 7.59 (m, 4H, Ph), 7.65 7.70 (m, 2H, Ph), 8.28 8.31 (m,
1H, Ph). 13C NMR: d ˆ 17.53 (CH3), 28.06 (d, J 19.9 Hz, CH),
ˆ
ˆ
ˆ
65.38 (Cp), 67.82 (d, J 4.6 Hz, Cp), 70.13 (5 Cp), 70.47 (d, J
At bench-scale under technical reaction conditions,
39 mol of 13 could be hydrogenated with an S/C ˆ 5700
yielding intermediate 14 with 95% ee.
ˆ
2.3 Hz, Cp), 86.56 (q-Cp), 93.14 (d, J 21.6 Hz, q-Cp), 125.91
(d, J 13.0 Hz, Ph), 127.64 (d, J 6.1 Hz, Ph), 127.67 (Ph),
128.15 128.51 (3 Ph), 130.62 (d, J 3.1 Hz, Ph), 130.81 (d, J
2.4 Hz, Ph), 131.09 (d, J 3.1 Hz, Ph), 131.27 (d, J 3.8 Hz, Ph),
131.37 (d, J 3.8 Hz, Ph), 132.02 (d, J 8.4 Hz, Ph), 132.21 (d, J
16.8 Hz, Ph), 132.70 (q-Ph), 133.75 (q-Ph), 134.54 (d, J
9.9 Hz, Ph), 134.79 (d, J 19.9 Hz, Ph), 134.78 (q-Ph), 135.17
ˆ
ˆ
ˆ
ˆ
In conclusion, we have prepared six derivatives of a
novel diphosphine family named Walphos with a
phenylferrocenylethyl scaffold and tested their poten-
tial in enantioselective hydrogenation reactions. The
concise and modular synthesis allows the efficient
incorporation of two different phosphino groups in
two subsequent steps. The results obtained in the initial
screening showed the versatility of the Walphos ligand
family. More results documenting our current inves-
tigations on scope and limitations of this ligand family
will be published in due course.
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
(d, J 12.2 Hz, Ph), 136.17 (d, J 22.0 Hz, q-Ph), 138.44 (d, J
19.2 Hz, q-Ph), 143.31 (d, J 7.2 Hz, q-Ph). 31P NMR: major
isomer: d ˆ 4.25, 31.38; minor isomer: d ˆ 3.41, 29.91. MS: m/e
ˆ
‡
(rel %) ˆ 674.0 (6.7, M ), 609.9 (11.8), 608.8 (24.6), 489.9 (11.5),
488.8 (31.0), 423.9 (40.0), 422.9 (100.0), 182.9 (24.4), 165.0
(13.6), 120.9 (11.6). HRMS: calcd. for C42H36FeOP2: 674.1853;
found: 674.1612.
(Rc,Rp)- and (Sc,Rp)-1-[(1-Diphenylphosphino)ethyl]-
2-(2-diphenylphosphinophenyl)-ferrocene [(Rc,Rp)-1d
and (Sc,Rp)-1d]
To a solution of 1.2 g (1.78 mmol) phosphine oxide 5d in 20 mL
of THF were added 7 mL of polymethylhydrosiloxane and
3.8 mL of Ti(O-i-Pr)4. The solution was degassed and sub-
sequently refluxed for 18 hours. After addition of 15 mL
hexane the reaction mixture was refluxed for additional two
hours. The reaction mixture was poured into 25 mL of water
and the organic layer was separated. The aqueous layer was
extracted with hexane (3 Â 20 mL) and the combined organic
layers were washed with water (2 Â 20 mL). After drying over
MgSO4 and evaporation of the solvent the residue was
Scheme 2. Synthesis of Synthon A, a key intermediate in the
preparation of the renin inhibitor SPP100.
Adv. Synth. Catal. 2003, 345, 160 164
163

Thomas Sturm et al.
COMMUNICATIONS
chromatographed on alumina (petrol ether/chloroform ˆ 8/2)
to afford 971 mg (1.48 mmol, 83%) of 1d as a mixture of two
diastereomers, which were separated in a second chromatog-
raphy on silica (eluent: petrol ether/methylene chloride ˆ 7/3).
reaction (total reaction times 16 66 h), the conversion was
determined by gas chromatography and the product was
recovered quantitatively after filtration of the reaction solution
through a plug of silica to remove the catalyst. The enantiomeric
purity of the product was determined either by gas chromatog-
raphy or by HPLC (see footnotes in Tables 1 and 2).
1
ˆ
ˆ
(Rc,Rp)-1c: mp 73 77 8C; H NMR: d ˆ 1.28 (dd, J1 J2
ˆ
7.2 Hz, 3H), 3.40 (q, J 7.2 Hz, 1H), 3.62 (m, 1H, Cp), 3.84 (m,
1H, Cp), 3.93 (m, 1H, Cp), 4.05 (s, 5H, Cp), 6.90 6.94 (m, 1H,
Ph), 7.06 7.23 (m, 14H, Ph), 7.25 7.36 (m, 8H, Ph), 8.03 8.06
(m, 1H, Ph). 13C NMR: d ˆ 16.48 (CH3), 28.71 (d, J 19.9 Hz,
ˆ
Acknowledgements
ˆ
CH), 65.07 (Cp), 66.92 (d, J 5.4 Hz, Cp), 69.43 (5 Cp), 70.96
ˆ
ˆ
(d, J 10.7 Hz, Cp), 89.80 (q-Cp), 92.26 (d, J 18.2 Hz, q-Cp),
This work was kindly supported by Novartis Services AG (T.S.,
W.W.). We acknowledge the skilful technical assistance of
Andrea Holderer, Robert H‰usel and Bernd Geiser.
ˆ
126.94 (Ph), 127.07 (Ph), 127.58 (d, J 7.6 Hz, Ph), 127.72 (Ph),
128.01 128.09 (3 Ph), 128.31 (Ph), 128.39 (d, J 6.9 Hz, Ph),
ˆ
ˆ
ˆ
128.75 (Ph), 131.70 (dd, J1 1.5 Hz, J2 15.3 Hz, Ph), 132.81 (d,
ˆ
ˆ
ˆ
J
5.4 Hz, Ph), 133.47 (dd, J1 3.1 Hz, J2 18.4 Hz, Ph), 134.01
ˆ
ˆ
ˆ
(d, J 19.9 Hz, Ph), 134.74 (d, J 2.3 Hz, Ph), 135.50 (d, J
References
ˆ
ˆ
22.2 Hz, q-Ph), 135.64 (dd, J1 3.1 Hz, J2 20.7 Hz, Ph), 138.47
ˆ
ˆ
ˆ
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ˆ
ˆ
138.83 (q-Ph), 139.59 (d, J 15.1 Hz, q-Ph), 143.26 (d, J
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ˆ
‡
ˆ
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Weinheim, 1998, p. 1.
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Landert, A. Tijani, J. Am. Chem. Soc. 1994, 116, 4062.
[8] T. Coumbe, N. J. Lawrence, F. Muhammad, Tetrahedron
Lett. 1965, 625.
[9] M. Sawamura, H. Hamashima, M. Sugawara, R. Kuwa-
no, Y. Ito, Organometallics 1995, 14, 4549.
[10] M. Burk, G. Harper, C. Kalberg, J. Am. Chem. Soc. 1995,
117, 4423.
[11] T. Ireland, K. Tappe, G. Grossheimann, P. Knochel,
Chem. Eur. J. 2002, 8, 843.
16.4 Hz); MS: m/e (rel %) ˆ 657.8 (49.5, M ), 472.7 (100),
406.7 (22.1), 350.8 (12.2), 182.9 (9.5), 97.0 (21.6); HRMS: calcd.
for C42H36FeP2): 658.1642; found: 658.1640; anal. calcd. for
C42H36FeP2: C 76.60, H 5.51, P 9.41%; found: C 76.39, H 5.76, P
9.17%. [a]20 (nm): ‡ 9.48 (589), 08 (578), À 65.28 (546) (c 0.5,
CHCl3); CD: De (nm) ˆ 28.88 (236), 28.71 (242), À 2.70 (304),
4.07 (349), À 1.45 (467) (c 1 Â 10À3, CH2Cl2).
1
ˆ
(Sc,Rp)-1c: mp 157 170 8C; H NMR: d ˆ 0.79 (dd, J1
ˆ
ˆ
ˆ
7.0 Hz, J2 9.0 Hz, 3H), 3.28 (dq, J1 4.0 Hz, J2 7.0 Hz, 1H),
ˆ
3.76 3.78 (m, 1H, Cp), 3.93 (s, 5H, Cp), 4.03 (t, J 2.5 Hz, 1H,
Cp), 4.11 (m, 1H, Cp), 6.91 6.94 (m, 1H, Ph), 6.96 7.00 (m,
2H, Ph), 7.08 7.13 (m, 3H, Ph), 7.17 7.34 (m, 12H, Ph), 7.36
7.41 (m, 1H, Ph), 7.45 7.50 (m, 2H, Ph), 7.53 7.57 (m, 2H,
Ph), 7.95 7.98 (m, 1H, Ph). 13C NMR: d ˆ 21.41 (dd, J1
ˆ
ˆ
ˆ
3.8 Hz, J2 6.9 Hz, CH3), 29.07 (d, J 14.5 Hz, CH), 65.73 (Cp),
ˆ
ˆ
ˆ
67.28 (d, J 9.2 Hz, Cp), 69.82 (5 Cp), 70.64 (dd, J1 2.3 Hz, J2
9.9 Hz, Cp), 89.87 (dd, J1 6.8 Hz, J2 11.4 Hz, q-Cp), 93.83 (d,
18.3 Hz, q-Cp), 127.11 (Ph), 128.05 (d, J 1.5 Hz, Ph),
128.09 (d, J 7.6 Hz, Ph), 128.14 (d, J 1.5 Hz, Ph), 128.21 (Ph),
128.33 128.43 (4 Ph), 128.83 (Ph), 133.25 (d, J 17.6 Hz, Ph),
133.49 (d, J 19.9 Hz, Ph), 133.80 (d, J 19.9 Hz, Ph), 133.81 (d,
5.4 Hz, Ph), 134.12 (d, J 1.4 Hz, Ph), 135.03 (d, J 21.4 Hz,
Ph), 137.66 (d, J 15.4 Hz, q-Ph), 137.81 (d, J 9.9 Hz, q-Ph),
ˆ
ˆ
ˆ
ˆ
J
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
ˆ
J
ˆ
ˆ
ˆ
ˆ
138.54 (d, J 12.8 Hz, q-Ph), 138.76 (d, J 13.5 Hz, q-Ph),
138.90 (d, J 14.7 Hz, q-Ph), 143.01 (d, J 30.5 Hz, q-Ph);
ˆ
ˆ
31
ˆ
ˆ
P NMR: d ˆÀ 14.40 (d, J 5.9 Hz), À 1.82 (d, J 5.9 Hz); MS:
‡
m/e (rel %) ˆ 658.4 (19.3, M ), 474.1 (40.3), 473.0 (100), 407.1
(25.3), 337.1 (11.1), 183.0 (11.7); HRMS: calcd. for C42H36FeP2:
658.1642; found: 658.1648; [a]20 (nm): ‡ 88.68 (589), ‡ 81.18
(578), ‡ 25.78 (546) (c 0.49, CHCl3).
Standard Procedure for Hydrogenation Reactions
The substrate (2.53 mmol) and the catalyst (formed in situ, for
details see Tables 1 and 2) were dissolved separately in 5 mL of
the solvent under argon (total volume: 10 mL). The catalyst
solution was stirred for 15 min. Both the catalyst and the
substrate solution were transferred via a steel capillary into a
180 mL thermostatted glass reactor or a 50 mL stainless steel
autoclave. The inert gas was then replaced by hydrogen (three
cycles) and the pressure was set. After completion of the
[12] P. Herold, S. Stutz, T. Sturm, W. Weissensteiner, F.
Spindler, WO 02/02500 (assigned to Speedel Pharma
AG), 2002.
[13] H. Takahashi, M. Hattori, M. Chiba, T. Morimoto, K.
Achiwa, Tetrahedron Lett. 1986, 27, 4477.
[14] W. Weissensteiner, T. Sturm, F. Spindler, WO 02/02578
(assigned to Solvias AG), 2002.
164
Adv. Synth. Catal. 2003, 345, 160 164