Synthesis of heterofunctionalized multidentate diphosphines

Article abstract of DOI:10.1016/S0040-4020(99)01075-3

The synthesis of new chiral multidentate amino- and amidophosphine ligands bearing up to six potential coordination sites were synthesized starting from L-valine. Based on these compounds chiral Ru(II) complexes were prepared, characterized and tested in the asymmetric transfer hydrogenation of aryl-alkyl ketones. In all cases investigated the catalyst bearing additional hydroxy groups gave lower conversions than the complex without hydroxy groups. Highest enantioselectivity was achieved with isobutyrophenone as substrate (69%ee). (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01075-3

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 775–780
Synthesis of Heterofunctionalized Multidentate Diphosphines
a
a
a,b
a,
*
¨
Michael Quirmbach, Jens Holz, Vitali I. Tararov and Armin Borner
a
¨
¨
Institut fur Organische Katalyseforschung an der Universitat Rostock e.V., Buchbinderstr. 5/6, D-18055 Rostock, Germany
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, 117813 Moscow,
Russian Federation
Received 22 October 1999; revised 1 December 1999; accepted 13 December 1999
Abstract—The synthesis of new chiral multidentate amino- and amidophosphine ligands bearing up to six potential coordination sites were
synthesized starting from l-valine. Based on these compounds chiral Ru(II) complexes were prepared, characterized and tested in the
asymmetric transfer hydrogenation of aryl–alkyl ketones. In all cases investigated the catalyst bearing additional hydroxy groups gave lower
conversions than the complex without hydroxy groups. Highest enantioselectivity was achieved with isobutyrophenone as substrate (69%ee).
᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
group to act as a hemilabile ligand and to establish secondary
interactions with the substrate by hydrogen bonds.
The catalytic asymmetric hydrogenation of prochiral
ketones to chiral alcohols using transition metal complexes
has gained increasing interest during recent years.1 In par-
ticular, catalytic asymmetric transfer hydrogenation using
2-propanol has been shown to be an elegant and economic
method due to the cheap hydrogen source employed and the
avoidance of high pressure equipment. The mechanism for
the transfer of hydrogen differs to that of hydrogenations
utilizing molecular hydrogen. Therefore this approach can
be used alternatively and may provide for higher enantio-
selectivity and productivity. During the last decade much
effort has been directed towards the development of efficient
catalytic systems but only recently success has been
reported. Thus, ligands and corresponding metal complexes
disclosed by Lemaire,2 Noyori,3 Helmchen,4 Knochel,5 and
Zhang6 have been shown to be efficacious. Noteworthy, are
observations by Noyori7 and Lemaire8 that a NH moiety in
the ligand is crucial for the achievement of high activity and
selectivity. It was explained that the NH group promotes a
cyclic transition state by formation of a hydrogen bond with
the carbonyl group of the substrate.
In an extension of this work, currently we are investigating
the effect caused by hydroxy groups in phosphine metal
complexes upon other asymmetric reactions. Herein we
describe our first results obtained in the synthesis of new
polyfunctionalized phosphines and their application in the
transfer hydrogenation with Ru(II) complexes.
Due to the multifunctionality of the target compounds the
synthesis of chiral functionalized phosphines requires a
careful retrosynthetic planning.11 Furthermore, in order to
obtain a simple and economic pathway we focused our
effort on the development of a modular approach allowing
the simultaneous synthesis of a range of different ligands.
We anticipated that b-aminoalkylphosphines could serve as
appropriate templates. By the reaction of the amino group
with, e.g. functionalized carboxylic acid chlorides or alde-
hydes additional functional groups can be easily incorpo-
rated affording multidentate ligands.
Results and Discussion
For a couple of years we have been interested in the construc-
tion of chiral bifunctional HO-bearing phosphine ligands and
their application in rhodium catalysed asymmetric hydro-
genations.9 We and others showed that in several instances
the enantioselectivity of the parent catalyst could be signifi-
cantly improved due to the additional functional group.10
This effect is caused likely by the dual property of the HO
The synthesis of aminophosphine 4 (‘ValPHOS’) represen-
ting our building block for subsequent transformations was
carried out as detailed in Scheme 1. This synthetic pathway
is similar to the previously described approach by Hirol and
Achiwa.12 Thus, l-valinol available by the reduction of
l-valine with LiAlH4 was converted quantitatively into
N-Boc-valinol by protection of the amino group with
di-tert-butyl dicarbonate. Subsequent esterification with
p-toluenesulfonyl chloride in pyridine gave tosylate 2. In
contrast to the synthesis described in the literature12 we
deprotected the amino group prior to the introduction of
Keywords: phosphines; hydrogenation; asymmetric synthesis; ruthenium
compounds.
* Corresponding author. Tel.: ϩ49-381-4669-310/350; fax: ϩ49-381-
4669-324/10; e-mail: armin.boerner@ifok.uni-rostock.de
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01075-3

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M. Quirmbach et al. / Tetrahedron 56 (2000) 775–780
Scheme 1. Synthesis of the aminophosphine ValPHOS: 9a) 2.5 equiv. LiAlH4, THF, 6 h, reflux, 60%; (b) 1.0 equiv. Boc2O, Et3N, dioxane/H2O 1:1, 12 h, RT,
95%; (c) 1.0 equiv. TsCl, pyridine, 0ЊC, 12 h, 80%; (d) 30% HBr/HOAc, 0.5 h, 95%; (e) 2.1 equiv. LiPPh2, THF, RT, 3 h, 43%.
the phosphino group. Removal of the Boc-group was carried
out by treatment of 2 with HBr/HOAc yielding ammonium
salt 3. This procedure revealed to be more advantageous
because the formation of byproducts frequently observed
in the reaction of 2 with LiPPh2 was prevented. The subse-
quent phosphinylation of 3 took place under consumption of
2 equiv. of LiPPh2 to give ValPHOS 4 in 43% yield. In turn
we investigated exemplarily the potential of chiral amino
phosphine 4 to serve as building block for the construction
of chiral multidentate phosphine ligands. Thus, the reaction
of 2 equiv. of 4 with oxalic chloride yielded diamide 5
(Scheme 2). The reduction of the amido groups with
LiAlH4 furnished the diamine 6 in an overall yield of 47%
based on ValPHOS.
dichloride prepared according to Choi et al.13 in three
steps starting from dimethyl 2,3-O-isopropylidene-l-
tartrate, to yield 7. Surprisingly, the cleavage of the isopro-
pylidene acetal under acidic conditions required rather
severe conditions and long reaction time. The desired
hydroxy amidophosphine 8 was finally obtained in 60%
yield. The second approach that started from 2,3-O-diace-
tyl-l-tartaric acid-dichloride14 was more advantageous,
because the cleavage of the acetyl groups in 7 under basic
conditions occurred smoothly and fast, and afforded 8 in
79% overall yield based on 4.
As a starting material for the synthesis of the Ru(II) catalysts
15
trans-RuCl2(DMSO)4
was chosen. The reaction of
2 equiv. of 4 with RuCl2(DMSO)4 in toluene furnished
after 18 h a C1-symmetrical Ru complex. It is important to
note that the phosphine groups were situated trans at the
ruthenium centre. The 31P–31P-coupling constants of
295.5 Hz derived from the 31P{1H} NMR spectrum gave
unambiguous proof for this coordination mode (d 22.2 and
More challengingly, it revealed the preparation of the
hydroxy amidophosphine 8. Two synthetic routes were
encountered (Scheme 3). Both have in common the use of
HO-protected tartaric acid dichlorides. In our first approach
4 was treated with 2,3-O-isoproylidene-l-tartaric acid
Scheme 2. Synthesis of 6: (a) 0.5 equiv. (COCl)2, 1.6 equiv. Et3N, Et2O, Ϫ78ЊC to RT, 5 h, 63%; (b) 6 equiv. LiAlH4, THF, reflux, 24 h, 75%.
Scheme 3. Synthesis of hydroxy amidophosphine 8: (a) 1.6 equiv. Et3N, Et2O, Ϫ78ЊC to RT, 5 h, 90%; (b) 8 equiv. TFA, MeOH/H2O 10:1, 4 d, 60ЊC, 60%;
(c) 1.6 equiv. Et3N, Et2O, Ϫ78ЊC to RT, 5 h, 83%; (d) cat. NaOMe, MeOH, RT, 3 h, 95%.

M. Quirmbach et al. / Tetrahedron 56 (2000) 775–780
777
Scheme 4. New Ru(II) complexes prepared.
d 32.8). Due to this feature we ascribe structure 10 to the
formed complex (Scheme 4). Under the same reaction
conditions trans-RuCl2(DMSO)4 was treated with the tetra-
dentate ligand 6, to give complex 11 featuring C2-symme-
try. The 31P{1H} NMR spectrum of the complex was
characterized by a single resonance at d 51.0. When 8
reacted with trans-RuCl2(DMSO)4 the C2-symmetric
complex 12 was formed. The geometry was derived from
the 31P{1H} NMR spectrum where a singlet at d 47.6 was
observed. It is noteworthy, that exclusively amido and
phosphine groups were bound to the ruthenium. Proof for
this coordination mode came from the 13C{1H} NMR spec-
trum where the resonance of the CyO group in the ligand 8
shifted by complexation downfield from d 171.0 to 181.7.
The coordination of the HO groups was excluded due to the
nearly unchanged shift of the resonance of the carbon
attached to the HO group. Unfortunately, attempts to
synthesize a ruthenium complex based on the amido-
phosphine 7 failed. This is probably due to the rigid back-
bone of 7 preventing the simultaneous complexation of all
four ligating atoms.
Experimental
General procedures
All solvents were dried and distilled under argon. Reactions
involving phosphines and organometallic compounds were
performed under an Ar atmosphere by using standard
Schlenk techniques. Tetrahydrofuran (THF), diethyl ether
(Et2O) and toluene were distilled from sodium/benzophen-
one ketyl. Dichloromethane (CH2Cl2) was distilled from
CaH2. Commercial reagents were used without further
purification. Thin-layer chromatography was performed on
pre-coated TLC plates (silica gel 60 F254, Merck). Flash
chromatography was carried out with silica gel 60 (particle
size 0.040–0.063 mm, Merck). Melting points are
corrected. The optical rotation was measured on a ‘gyro-
mat-HP’ instrument (Fa. Dr. Kernchen). NMR spectra were
recorded on a Bruker ARX 400 instrument at 303 K. Spectra
were obtained at the following frequencies: 400.13 (1H),
100.63 (13C), 161.98 (31P). Chemical shifts of H and 13C
1
NMR spectra are given relative to the residual solvent peak
(d). Chemical shifts of 31P NMR spectra are reported in ppm
referred to H3PO4 as external standard. The mass spectra
were recorded on an AMD 402 instrument (Fa. Intectra).
The new ruthenium complexes 10–12 were tested in the
asymmetric transfer hydrogenation of several aryl–alkyl
ketones employing 2-propanol as a hydrogen source. All
Ru(II) complexes catalysed the reaction. With the exception
of 10, affording racemic product, other Ru(II) complexes
gave the corresponding alcohols in moderate enantioselec-
tivities. Highest ee was achieved with isobutyrophenone as
substrate (69%ee). It is interesting to note that the complex
12 bearing two hydroxy groups performed in all trials
rather sluggish and required prolonged reaction time to
achieve some conversion. Unfortunately, an increase of
the enantioselectivity due to the additional hydroxy groups
was not observed.
(S)-1-( p-Toluenesulfonylmethyl)-2-methyl-propylammon-
ium bromide (3). The Boc-protected amine 2 (87 mmol,
31.0 g) was slowly added to a 2 M solution of HBr in HOAc
(72 mL) at room temperature. After completion of the gas
evolution stirring was continued for a further hour followed
by the addition of Et2O (400 mL). The precipitated product
was filtered off, washed with Et2O (3×200 mL) and dried in
vacuo yielding 3 as a colourless solid. Yield 28.0 g (95%); mp
125ЊC; [a]2D5ˆ10.5 (c 1.0, CHCl3); 1H NMR (CDCl3) dˆ8.30
(br, 3H, NHϩ3 ), 7.89 (d, 3Jˆ8.4 Hz, 2H, Ph), 7.34 (d,
3
2
3Jˆ8.4 Hz, 2H, Ph), 4.45 (dd, Jˆ3.7 Hz, Jˆ11.3 Hz, Hb–
3
2
The decelerating effect of HO groups described above was
already noted several times in the Rh(I) catalysed hydro-
genation with hydroxy phosphines as ligands in methanol as
solvent.9,16 NMR spectroscopic studies gave proof that this
effect is due to the intermediate coordination of the hemi-
labile hydroxy group on the rhodium and the formation of a
coordinatively saturated metal centre.17 Apparently, also
during the Ru(II) catalysed transfer hydrogenation in
2-propanol such interactions come into play and affect the
rate of the reaction. Further investigations are in progress to
verify the utility of the new ligands also in other catalytic
reactions.
CH2), 4.35 (dd, Jˆ5.9 Hz, Jˆ11.3 Hz, Ha–CH2), 3.43 (m,
1H, CHN), 2.43 (s, 3H, CH3–Ph), 2.20 (m, 1H, CH(CH3)2),
1.10 (d, 3Jˆ6.9 Hz, 3H, CH3), 0.96 (d, 3Jˆ6.9 Hz, 3H, CH3);
13C NMR (CDCl3) dˆ145.4, 131.7, 130.1, 128.3 (Ph), 69.9
(CH2), 56.6 (CHN), 27.9 (CH(CH3)2), 21.7 (CH3–Ph), 19.1
(CH3), 18.4 (CH3); IR (KBr) n~ ˆ 3192; 3161, 3137 (m,
NHϩ3 ), 2995, 2974, 2918, 2886, 2846 (s, C–H), 1594 (m),
1575 (w), 1492 (s), 1361, 1190, 1176 (s, SO2–OR), 1002, 950
(s), 853, 817 (s, C–Harom), 773 (m), 669 (s), 622 (m); MS (EI,
70 eV) [m/z] (rel. int.%): 259 [MϩϪBrϪ] (3), 122 (90), 72
(100), 43 [C3H7ϩ] (90); calcd: C12H20BrNO3S (338.26) C
42.61, H 5.96, N 4.14; found: C 42.77, H 6.08, N 4.19.

778
M. Quirmbach et al. / Tetrahedron 56 (2000) 775–780
(S)-1-(Diphenylphosphinomethyl)-2-methyl-propylamine
(4), ValPHOS. A solution of lithium diphenylphosphide,
prepared from p-chlorodiphenylphosphine (40.4 mmol,
8.91 g) and lithium metal (132 mmol, 0.91 g), was slowly
added to a suspension of 3 (13.0 mmol, 4.40 g) in THF
(50 mL) at 0ЊC. The reaction mixture was then warmed to
room temperature, stirred for 5 h followed by removal of the
solvent under reduced pressure. The obtained red residue
was dissolved in water (20 mL) and CH2Cl2 (40 mL). The
organic layer was separated, dried (Na2SO4) and the solvent
evaporated. The obtained crude product was purified by
flash chromatography (n-hexane/EtOAc/Et3N 1:2:0.02,
Rfˆ0.2) yielding a colourless oil. Yield 1.5 g (43%);
[a]D25ˆ84.4 (cˆ1.0, CHCl3); 31P NMR (CDCl3) dˆϪ21.0
was extracted several times with CH2Cl2 and the combined
organic layers were dried (Na2SO4). After evaporation of
the solvent the residue was purified by flash chroma-
tography giving a viscous oil (n-hexane/EtOAc 1:1,
Rfˆ0.35). Yield 3.5 g (75%); [a]2D5ˆ56.4 (cˆ1.4, CHCl3);
1
31P NMR (CDCl3) dˆϪ21.1 (s, PPh2); H NMR (CDCl3)
dˆ7.49–7.24 (m, 20H, Ph), 2.46 (m, 4H, CH2N), 2.29 (m,
2H, CHN), 2.11 (ddd, 2JPHˆ1.8 Hz, 3Jˆ4.9 Hz,
2
2Jˆ13.9 Hz, 2H, Hb–CH2), 1.95 (ddd, JPHˆ1.6 Hz,
2
3Jˆ8.5 Hz, Jˆ13.9 Hz, 2H, Ha–CH2), 1.85 (m, 2H, CH),
3
3
0.87 (d, Jˆ6.7 Hz, 6H, CH3), 0.82 (d, Jˆ6.7 Hz, 6H,
CH3); 13C NMR (CDCl3) dˆ139.6–128.2 (Ph), 60.3 (d,
2JPCˆ14.3 Hz, CHN), 47.8 (CH2N), 31.2 (CH(CH3)2), 30.6
(d, 1JPCˆ13.4 Hz, CH2), 18.1 (CH3), 17.7 (CH3); IR (neat):
n~ ˆ 3371 (w, NH2), 3070, 3053 (s, C–Harom), 2955 (vs),
2930 (sh, C–H), 1585 (m), 1480 (s), 1465 (sh), 1433 (vs,
P–C), 1384, 1366 (m, CH(CH3)2), 1182 (w), 1097 (m), 1068
(m), 1027, 999 (w), 739, 696 (vs, C–Harom); MS (CI, isobu-
tane) [m/z] (rel. int.%): 625 [MϩC(CH3)3] (3), 569 [MϩH]
(100), 297 (20); calcd: C36H46N2P2 (568.72) C 76.03, H
7.99, N 4.93; found: C 75.57, H 8.15, N 4.50.
1
(s, PPh2); H NMR (CDCl3) dˆ7.50–7.29 (m, 10 H, Ph),
2.63 (m, 1H), 2.32 (m, 1H), 1.95 (m, 1H), 1.71 (m, 1H), 1.35
3
(brs, 2H, NH2), 0.89 (d, Jˆ6.7 Hz, 3H, CH3), 0.87 (d,
3Jˆ6.7 Hz, 3H, CH3); 13C NMR (CDCl3) dˆ139.8–128.7
(Ph), 54.0 (d, 2JPCˆ13.4 Hz, CHN), 34.5 (d, 1JPCˆ12.4 Hz,
3
CH2), 34.2 (d, JPCˆ7.6 Hz, CH(CH3)2), 18.9 (CH3), 17.1
(CH3); IR (neat): n~ ˆ 3372; 3305 (w, NH2), 3070, 3053 (s,
C–H), 2957 (vs), 2930 (sh, C–H), 1585 (m), 1480 (s), 1465
(sh), 1434 (vs, P–C), 1385, 1366 (m, CH(CH3)2), 1185,
1095 (w), 1027 (w), 863 (br), 740, 697 (vs, C–Harom); MS
(EI, 70 eV) [m/z] (rel. int.%): 271 [Mϩ] (11), 254
[MϩϪNH3] (18), 200 (100), 183 (57), 72 (46); calcd:
C17H22NP (271.34) C 75.25, H 8.17, N 5.16; found: C
74.87, H 7.96, N 5.05.
(R,R)-2,2-Dimethyl-1,3-dioxolane-4,5-diacid-bis{[(10S)-10-
(diphenylphosphinomethyl)-20-methyl-propyl]-amide} (7).
Following the procedure described above for the prepara-
tion of 5 a solution of 2,3-O-isopropylidene-l-tartaric acid
dichloride (0.80 mmol, 0.18 g) in Et2O was allowed to react
with 4 (1.60 mmol, 0.44 g) in the presence of triethylamine
(2.15 mmol, 0.3 mL). After flash chromatography (n-hex-
ane/EtOAc 1:2, Rfˆ0.7) a colourless solid was obtained.
Yield 0.5 g (90%); mp 68ЊC; [a]2D5ˆ37.4 (cˆ0.2, CHCl3);
(S,S)-N,N0-Bis(1-diphenylphosphinomethyl-2-methyl-pro-
pyl)oxaldiamide (5). A solution of oxalyl chloride (4.49
mmol, 0.57 g) in Et2O (20 mL) was added dropwise via
syringe to a stirred solution of 4 (9.20 mmol, 2.49 g) and
triethylamine (14.4 mmol, 2.0 mL) in Et2O (50 mL) at
Ϫ78ЊC. When the addition was completed the reaction
mixture was allowed to warm to room temperature with
continuous stirring at ambient temperature for an additional
5 h. After evaporation of the solvent the residue was
dissolved in CH2Cl2 (20 mL), washed with water
(2×20 mL) and then the organic layer was dried (Na2SO4).
The solvent was removed under reduced pressure and the
obtained crude product was purified by flash chromato-
graphy (n-hexane/EtOAc 4:1, Rfˆ0.4) yielding a colourless
solid. Yield 1.7 g (63%); mp 63–65ЊC; [a]2D5ˆϪ3.8 (cˆ1.1,
1
31P NMR (CDCl3) dˆϪ23.1 (s, PPh2); H NMR (CDCl3)
dˆ7.50–7.27 (m, 20H, Ph), 7.12 (d, 3Jˆ9.35 Hz, 2H, NH),
4.30 (s, 2H, CHO), 3.95 (m, 2H, CHN), 2.32 (ddd,
3
2
2JPHˆ1.9 Hz, Jˆ4.9 Hz, Jˆ14.0 Hz, 2H, Hb–CH2), 2.20
2
3
2
(ddd, JPHˆ1.5 Hz, Jˆ9.1 Hz, Jˆ14.0 Hz, 2H, Ha–CH2),
3
1.98 (m, 2H, CH), 1.50 (s, 6H, CH3), 0.92 (d, Jˆ6.9 Hz,
6H, CH3), 0.90 (d, 3Jˆ6.9 Hz, 6H, CH3); 13C NMR (CDCl3)
dˆ168.9 (NCyO), 138.4–128.5 (Ph), 112.0 (C(CH3)2), 77.6
(CHO), 51.8 (d, 2JPCˆ14.3 Hz, CHN), 32.3 (d, 3JPCˆ7.6 Hz,
1
CH(CH3)2), 32.2 (d, JPCˆ11.5 Hz, CH2), 26.5 (CH3), 26.4
(CH3), 19.1 (CH3), 17.5 (CH3); IR (nujol): n~ ˆ 3277 (br,
CONH), 1656 (s, amid I), 1559 (amid II), 1435 (s, P–C),
1377 (m), 742, 697 (m, C–Harom); MS (EI, 70 eV) [m/z] (rel.
int.%): 695 [MϩϩH] (1), 496 (3), 424 (100), 366 (11), 201
(59); calcd: C41H48N2O4P2 (694.79) C 70.88, H 6.96, N 4.03;
found: C 70.30, H 7.12, N 3.90.
1
CHCl3); 31P NMR (CDCl3) dˆϪ22.6 (s, PPh2); H NMR
(CDCl3) dˆ7.40–7.21 (m, 20 H, Ph), 3.77 (m, 2H, CHN),
2.21 (m, 4H), 1.94 (m, 2H), 0.81 (d, 3Jˆ6.3 Hz, 6 H, CH3),
0.81 (d, 3Jˆ6.3 Hz, 6 H, CH3); 13C NMR (CDCl3) dˆ158.2
2
(CyO), 137.3–127.5 (Ph), 52.8 (d, JPCˆ15.3 Hz, CHN),
(2R,3R)-N,N0-Bis[(10S)-10-(diphenylphosphinomethyl)-20-
methyl-propyl]-2,3-dihydroxy-succinediamide (8). From
7. Trifluoracetic acid (TFA) (5.2 mmol, 0.4 mL) was
added dropwise to a stirred solution of 7 (0.71 mmol,
0.50 g) in MeOH/water (10:1).The resulting reaction
mixture was heated to 60ЊC and kept for 4 d at this tempera-
ture. After evaporation of the solvent the residue was
dissolved in CH2Cl2 (40 mL), washed with saturated
NaHCO3 (2×20 mL), NaCl solution (40 mL), water
(40 mL) and the organic layer was dried (Na2SO4).The
solvent was removed under reduced pressure and the
crude product was purified by flash chromatography (n-hex-
ane/EtOAc 1:2, Rfˆ0.5). Yield 0.27 g (60%).
3
1
31.9 (d, JPCˆ8.6 Hz, CH(CH3)2), 31.8 (d, JPCˆ14.3 Hz,
CH2), 19.2 (CH3), 16.9 (CH3); IR (nujol): n~ ˆ 3268 (br,
CONH), 1652 (s, amide), 1433 (s, P–C), 1377 (m), 737,
695 (m, C–Harom); MS (EI, 70 eV) [m/z] (rel. int.%): 596
[Mϩ] (19), 325 (100), 202 (69); calcd: C36H42N2O2P2
(596.27) C 72.47, H 7.09, N 4.69; found: C 71.98, H 7.18,
N 4.63.
(S,S)-N,N0-Bis(1-diphenylphosphinomethyl-2-methyl-pro-
pyl)ethylen-1,2-diamine (6). LiAlH4 (52.7 mmol, 2.00 g)
were added in small portions to a stirred solution of 5
(8.25 mmol, 5.0 g) in THF (75 mL) at room temperature.
The resulting reaction mixture was refluxed for 24 h
followed by slow addition of water (20 mL). The residue
From 9. To a stirred solution of 9 (2.43 mmol, 1.80 g) in

M. Quirmbach et al. / Tetrahedron 56 (2000) 775–780
779
methanol a solution of sodium methoxide (1.3 M, 0.3 mL)
was added at room temperature. After stirring for 3 h the
reaction mixture was hydrolysed with water (0.2 mL) and
the solvent removed under reduced pressure. The crude
product was purified by flash chromatography (n-hexane/
EtOAC 1:2, Rfˆ0.5) yielding a colourless solid. Yield
1.45 g (95%).
evaporation of the solvent gave the crude complex. It was
washed with diethyl ether (5×10 mL) and dried in vacuo.
[Ru(4)2Cl2] Complex 10. According to the general proce-
dure for preparation of Ru(II) complexes, ValPHOS (4)
(0.49 mmol, 0.13 g) was treated with trans-RuCl2(DMSO)4
(0.25 mmol, 0.13 g) in toluene (3 mL). The complex was
washed with diethyl ether and dried under reduced pressure
affording yellow plates. Yield 0.16 g (91%); mp 105–
The succinediamide 8 obtained from 7 and 9, respectively,
featured the same physical properties: mp 60–62ЊC;
[a]D25ˆ78.0 (cˆ1.0, CHCl3); 31P NMR (CDCl3) dˆϪ22.5
2
108ЊC; 31P NMR (CD2Cl2) dˆ22.2 (d, JPPˆ295.5 Hz),
2
1
32.8 (d, JPPˆ295.5 Hz); H NMR (CD2Cl2) dˆ8.35–7.16
1
(s, PPh2); H NMR (CDCl3) dˆ7.46–7.30 (m, 20H, Ph),
(m, 20H, Ph), 3.43 (m, 2H, CHN), 3.08 (m, 4H, CH2P), 2.75
6.96 (d, 3Jˆ10.1 Hz, 2H, NH), 4.28 (brs, 4H, OH,
(m, 1H, CH), 2.00 (m, 1H, CH), 1.11 (d, Jˆ6.6 Hz, 3H,
3
3
3
CHOH),), 3.93 (m, 2H, NCH), 2.34 (m, 2H, CH2), 2.15
CH3), 0.85 (d, Jˆ6.6 Hz, 3H, CH3), 0.60 (d, Jˆ6.6 Hz,
3H, CH3), 0.53 (d, 3Jˆ6.6 Hz, 3H, CH3); 13C NMR
(CD2Cl2) dˆ133.0–127.9 (Ph), 66.5 (br, CHN), 63.5 (br,
CHN), 34.9 (d, 1JPCˆ26.7 Hz, CH2), 33.5 (d, 3JPCˆ15.3 Hz,
3
(m, 2H, CH2), 1.93 (m, 2H, CH), 0.87 (d, Jˆ6.7 Hz, 12
H, CH3); 13C NMR (CDCl3) dˆ171.0 (CyO), 137.8–128.5
2
(Ph), 71.6 (CHO), 51.6 (d, JPCˆ14.3 Hz, CHN), 32.7 (d,
3JPCˆ7.6 Hz, CH(CH3)2), 32.6 (d, 1JPCˆ14.3 Hz, CH2), 19.2
(CH3), 17.6 (CH3); IR (nujol): n~ ˆ 3382; 3288 (br, CONH),
1647 (s, amid I), 1523 (m, amid II), 1434 (s, P–C), 1377
(m); 739, 695 (m, C–Harom); MS (EI, 70 eV) [m/z] (rel.
int.%): 657 [MϩϩH] (3), 386 (43), 312 (13), 271 (29),
202 (100); calcd: C38H46N2O4P2 (656.74) C 69.50, H 7.06,
N 4.22; found: C 69.23, H 7.12, N 4.23.
CH(CH3)), 33.3 (d, JPCˆ15.3 Hz, CH(CH3)), 28.6 (d,
3
1JPCˆ27.7 Hz, CH2), 21.2, (CH3), 21.8 (CH3), 18.9 (CH3),
18.8 (CH3); IR (nujol): n~ ˆ 3317 (w, NH2), 1572 (w), 1435
(s, P–C), 1074, 1019 (br), 742, 697 (s, C–Harom); MS (EI,
70 eV) [m/z] (rel. int.%): 713 [MϩϩH] (100), 679 [MϩϪCl]
(9), 642 (70), 557 (30), 244 (50); calcd: C34H44Cl2N2P2Ru
(714.14) C 57.13, H 6.21, N 3.92; found: C 56.89, H 6.10, N
3.83.
(2R,3R)-Acetic acid-2-acetoxy-1,2-bis[(10S)-10-(diphenyl-
phosphinomethyl)-20-methyl-propyl-carbamoyl]ethyl-
ester (9). Following the procedure described above for the
preparation of 5 a solution of 2,3-O-diacetyl-l-tartaric acid
dichloride (2.73 mmol, 0.74 g) in Et2O was allowed to react
with 4 (5.34 mmol, 1.45 g) in the presence of triethylamine
(10.8 mmol, 1.5 mL). After flash chromatography (CH2Cl2/
EtOAc 10:1, Rfˆ0.4) a colourless solid was obtained. Yield
1.68 g (83%); mp 116–118ЊC; [a]2D5ˆ44.7 (cˆ1.0, CHCl3);
[Ru(6)(Cl)2] Complex 11. According to the general proce-
dure for the preparation of Ru(II)-complexes, aminophos-
phine 6 (0.49 mmol, 0.28 g) was treated with trans-
RuCl2(DMSO)4 (0.49 mmol, 0.25 g) in toluene (6 mL).
The complex yielded was washed with diethyl ether and
dried under reduced pressure to give a light brown powder.
Yield 0.27 g (75%); mp 183–185ЊC; 31P NMR (CDCl3)
1
dˆ51.0 (s, PPh2); H NMR (CD2Cl2) dˆ7.55–6.97 (m,
1
31P NMR (CDCl3) dˆϪ23.9 (s, PPh2); H NMR (CDCl3)
20H, Ph), 4.55 (m, 1H), 3.97 (m, 1H), 3.23 (m, 6H), 2.93
(m, 4H), 1.22 (d, 3Jˆ6.9 Hz, 6H, CH3), 0.98 (d, 3Jˆ6.9 Hz,
3H, CH3); 13C NMR (CD2Cl2) dˆ134.8–127.0 (Ph), 63.6
3
dˆ7.45–7.30 (m, 20H, Ph), 6.08 (d, Jˆ9.4 Hz, 2H, NH),
5.70 (s, 2H, CHO), 3.85 (m, 2H, CHN), 2.27 (ddd,
2
1
2JPHˆ2.2 Hz, Jˆ4.9 Hz, Jˆ13.8 Hz, 2H, Hb–CH2), 1.91
(CHN), 49.0 (CH2), 35.3 (d, Jˆ14.3 Hz, CH2), 35.3 (d,
3
(m, 2H,CH), 2.15 (m, 8H, CH3CO, Ha–CH2), 0.79 (d,
1Jˆ14.3 Hz, CH2), 26.9 (d, Jˆ7.6 Hz, CH(CH3)2), 26.9
3
3Jˆ6.6 Hz, 6H, CH3), 0.79 (d, Jˆ6.6 Hz, 6H, CH3); 13C
(d, 3Jˆ7.6 Hz, CH(CH3)2), 21.1 (CH3), 13.3 (CH3); IR
(nujol): n~ ˆ 3433 (br, NH), 3208 (w, C–Harom), 1434 (s,
P–C), 1098, 1058, 1027 (m), 739, 695 (s, C–Harom); MS
(EI, 70 eV) [m/z] (rel. int.%): 740 [Mϩ] (100), 666 (61),
625 (29), 332 (22), 183 (52); calcd: C36H46Cl2N2P2Ru
(740.68) C 58.38, H 6.26, N 3.78; found: C 57.83, H 6.12,
N 3.65.
NMR (CDCl3) dˆ169.4 (NCyO), 165.6 (CyO), 138.3–
2
128.5 (Ph), 72.3 (CHO), 51.9 (d, JPCˆ14.3 Hz, CHN),
3
1
32.1 (d, JPCˆ7.6 Hz, CH(CH3)2), 31.9 (d, JPCˆ14.3 Hz,
CH2), 21.1 (CH3CO), 21.0 (CH3CO), 18.8 (CH3), 17.2
(CH3); IR (nujol): n~ ˆ 3310; 3247 (br, CONH), 1749 (s,
CyO), 1660 (s, amid), 1435 (s, P–C), 1377 (m), 739, 696
(m, C–Harom); MS (EI, 70 eV) [m/z] (rel. int.%): 739
[MϩϪH] (3), 696 [MϩϪHϪCH3CO] (2), 636 (11), 620
(11), 468 (90), 270 (90), 201 (100); calcd: C42H50N2O6P2
(740.82) C 68.09, H 6.80, N 3.78; found: C 67.70, H 6.61, N
3.72.
[Ru(8)Cl2] Complex 12. According to the general proce-
dure for the preparation of Ru(II) complexes, amidophos-
phine 8 (1.05 mmol, 0.69 g) was treated with trans-
RuCl2(DMSO)4 (1.05 mmol, 0.69 g) in toluene (10 mL).
The complex yielded was washed with diethyl ether and
dried under reduced pressure to give a dark red powder.
Yield 0.70 g (80%); mp Ͼ250ЊC; 31P NMR (CD2Cl2)
dˆ47.6 (s, PPh2); 1H NMR (CD2Cl2) dˆ7.71 (d,
3Jˆ4.9 Hz, 2H, NH), 6.90–7.40 (m, 20H, Ph), 5.70 (d,
3Jˆ6.4 Hz, 2H, CHO), 4.80 (d, 3Jˆ6.4 Hz, 2H, OH,
exchangeable with D2O), 3.84 (m, 2H, NCH), 3.17 (m,
2H, CH2), 2.15 (m, 2H, CH2), 1.79 (m, 2H, CH), 0.83 (d,
General procedure for the synthesis of Ru(II)-complexes
using RuCl2(DMSO)
A Schlenk tube was charged with 1.00 mmol of a tetraden-
tate aminophosphine (2.00 mmol if a bidentate ligand was
used) and dissolved in toluene. After complete dissolution
of the phosphine RuCl2(DMSO)4 (1.00 mmol) was added at
once. The suspension was heated to 75ЊC and kept for 18 h
at this temperature. After this period the solution became
nearly homogeneous. Filtration of the mixture followed by
3
3Jˆ6.6 Hz, 6H, CH3), 0.81 (d, Jˆ6.9 Hz, 6H, CH3); 13C
NMR (CD2Cl2) dˆ181.7 (NCyO), 139.9–125.3 (Ph), 72.7
1
(CHO), 52.4 (CHN), 34.3 (d, Jˆ13.4 Hz, CH2), 34.3 (d,
1Jˆ13.4 Hz, CH2), 33.6 (br, CH(CH3)2), 19.0 (CH3), 15.9

780
M. Quirmbach et al. / Tetrahedron 56 (2000) 775–780
3. (a) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori,
R. J. Am. Chem. Soc. 1995, 117, 7562–7563. (b) Takehara, J.;
Hashiguchi, S.; Fujii, A.; Inoue, S.; Ikariya, T.; Noyori, R.
J. Chem. Soc., Chem. Commun. 1996, 233–234. (c) Haack, K.-J.;
Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R. Angew. Chem.
1997, 109, 297–300; Angew. Chem., Int. Ed. Engl. 1997, 36, 285–
288. (d) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30,
97–102.
(CH3); IR (nujol): n~3379; 3237, 3047 (br, CONH, OH),
1614 (s, amid I), 1550 (s, amid II), 1436 (s, P-C), 1376
(m), 1110 (m), 1094 (m), 801 (m), 696 (s, C–Harom); MS
(EI, 70 eV) [m/z] (rel. int.%): 712 [MϩϪC4H4O4] (11), 614
(9), 368 (20), 255 (37), 199 (100); calcd:
C38H46N2O4P2RuCl2 (828.72) C 55.08, H 5.59, N 3.38;
found: C 54.98, H 5.55, N 3.30.
General procedure for transfer hydrogenation
4. Langer, T.; Helmchen, G. Tetrahedron Lett. 1996, 37,
1381–1384.
A Schlenk tube was charged with isopropanol (5 mL), the
chiral Ru(II) complex (0.01 mmol) and sodium hydroxide
(5 mg). The solution was stirred for 20 min at room
temperature followed by the addition of the appropriate
ketone. Then the temperature was adjusted at 50ЊC and
the solution kept for 1 to 144 h. After cooling to room
temperature the mixture was passed through a plug of silica
gel to remove the catalyst. Product analyses were performed
by gas chromatography and by HPLC.
5. Schwink, L.; Ireland, T.; Pu¨ntener, K.; Knochel, P. Tetra-
hedron: Asymmetry 1998, 9, 1143–1163.
6. (a) Jiang, Q.; Van Plew, D.; Murtuza, S.; Zhang, X. Tetrahedron
Lett. 1996, 37, 797–800. (b) Jiang, Y.; Jiang, Q.; Zhu, G.; Zhang,
X. Tetrahedron Lett. 1997, 38, 6565–6568. (c) Jiang, Y.; Jiang, Q.;
Zhang, X. J. Am. Chem. Soc. 1998, 120, 3817–3818.
7. Gao, J.-X.; Ikariya, T.; Noyori, R. Organometallics 1996, 15,
1087–1089.
8. Gamez, P.; Fache, F.; Lemaire, M. Tetrahedron: Asymmetry
1995, 6, 705–718.
(S)-Isobutylphenyl carbinol. According to the general
procedure for the transfer hydrogenation isobutyrophenone
was reduced at 55ЊC for 3 h to give (S)-isobutylphenyl
carbinol in 27% yield and 69%ee.
¨
9. (a) Borner, A.; Kless, A.; Kempe, R.; Heller, D.; Holz, J.;
Baumann, W. Chem. Ber. 1995, 128, 767–773. (b) Borns, S.;
Kadyrov, R.; Heller, D.; Baumann, W.; Spannenberg, A.;
Kempe, R.; Holz, J.; Borner, A. Eur. J. Inorg. Chem. 1998,
¨
1291–1295.
10. (a) Carmichael, D.; Doucet, H.; Brown, J. M. Chem. Commun.
1999, 261–262. (b) Li, W.; Zhang, Z.; Xiao, D.; Zhang, X. Tetra-
hedron Lett. 1999, 40, 6701–6704.
Acknowledgements
We are grateful for the financial support provided by the
Deutsche Forschungsgemeinschaft (DFG) for a grant given
to M.Q., the European Commision (Inco-Copernicus,
ERBIC 15 CT 960722), and the Fonds der Chemischen
Industrie. We thank Mrs G. Voß for skilled technical
assistance and Mrs K. Kortus for GC analysis of the hydro-
genation products.
¨
11. For a review see: Holz, J.; Quirmbach, M.; Borner, A.
Synthesis 1997, 983–1006.
12. (a) Hirol, K.; Haraguchi, M.; Masuda, Y.; Abe, J. Chem. Lett.
1992, 2409–2412. (b) Saitoh, A.; Morimoto, T.; Achiwa, K. Tetra-
hedron: Asymmetry 1997, 8, 3567–3570.
13. Choi, H. -J.; Kwak, M. -O.; Song, H. Synth. Commun. 1997,
27, 1273–1280.
14. Schmidt, M.; Amstutz, R.; Crass, G.; Seebach, D. Chem. Ber.
1980, 113, 1691–1707.
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