New chiral ruthenium(II)-phosphinite complexes containing a ferrocenyl group in enantioselective transfer hydrogenations of aromatic ketones

Article abstract of DOI:10.1016/j.tetasy.2013.09.004

A new and versatile class of unsymmetrical ferrocenyl-phosphinite ligands possessing a stereogenic center has been prepared from commercially available, inexpensive aminoacids such as, d-, l-phenylglycine and d-, l-phenylalanine, through a concise synthetic procedure. These ligands are not very sensitive to air and moisture, and display good enantioselectivities in the ruthenium-catalyzed asymmetric transfer hydrogenation of acetophenone derivatives, in which up to 91% ee was obtained. A comparison of the catalytic properties of amino alcohols and other analogues based on a ferrocenyl backbone is also discussed briefly. The structures of these ligands and their corresponding complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy, and elemental analysis.

Full text of DOI:10.1016/j.tetasy.2013.09.004

Tetrahedron: Asymmetry 24 (2013) 1257–1264
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
New chiral ruthenium(II)–phosphinite complexes containing
a ferrocenyl group in enantioselective transfer hydrogenations
of aromatic ketones
Bünyamin Ak, Duygu Elma, Nermin Meriç, Cezmi Kayan, U g˘ ur I ßs ık, Murat Aydemir, Feyyaz Durap,
⇑
Akın Baysal
Dicle University, Department of Chemistry, TR-21280 Diyarbakır, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
A new and versatile class of unsymmetrical ferrocenyl-phosphinite ligands possessing a stereogenic cen-
Received 29 April 2013
Revised 29 August 2013
Accepted 5 September 2013
Available online 7 October 2013
ter has been prepared from commercially available, inexpensive aminoacids such as,
D-, L-phenylglycine
and -, -phenylalanine, through a concise synthetic procedure. These ligands are not very sensitive to air
D
L
and moisture, and display good enantioselectivities in the ruthenium-catalyzed asymmetric transfer
hydrogenation of acetophenone derivatives, in which up to 91% ee was obtained. A comparison of the cat-
alytic properties of amino alcohols and other analogues based on a ferrocenyl backbone is also discussed
briefly. The structures of these ligands and their corresponding complexes have been elucidated by a
combination of multinuclear NMR spectroscopy, IR spectroscopy, and elemental analysis.
Ó 2013 Elsevier Ltd. All rights reserved.
1
. Introduction
Ru(II) complexes. Although some ferrocenyl amino alcohols, dia-
mines, and phosphines have been employed successfully as ligands
The asymmetric reduction of ketones is a pivotal reaction for
in the Ru(II)-promoted transfer hydrogenation of ketones,10
a
the preparation of chiral alcohols,1 which form an extremely
important class of intermediates for fine chemicals and pharma-
ceuticals. Catalytic asymmetric synthesis using chiral metal com-
plexes as catalyst precursors offers an ideal method for reducing
ketones to chiral alcohols.3 Over the past ten years, an efficient
method has been developed for the catalytic transfer hydrogena-
tion of ketones using chiral Rh(III), Ir(III), Ru(II), or lanthanoid com-
screening of catalytic activities of ferrocenyl-phosphinites in this
reaction has not yet been reported. To the best of our knowledge,
there is no report on the utility of these complexes including chiral
phosphinites based on the ferrocenyl moiety in ruthenium cata-
lyzed transfer hydrogenation reactions. On the basis of previous
2
1
2,13
work,
we here report the results obtained in the asymmetric
transfer hydrogenation of ketones using chiral phosphinite ligands
based on the ferrocenyl moiety, possessing central chirality, as li-
gands. The synthesis and full characterization of neutral ruthe-
nium(II)–phosphinites complexes are also reported.
3
plexes as catalyst precursors and iso-PrOH/KOH or HCOOH/Et N as
4
a hydride source. In particular, ruthenium(II)-catalyzed asymmet-
ric transfer hydrogenation (ATH) has recently received much atten-
tion due to its operational simplicity and the use of non-hazardous
hydrogen donors.
Ferrocene ligands have attracted much attention due to their
chemical features, namely diastereoselective metallation on the
5
2
2
. Results and discussion
.1. Synthesis and characterization of the amino alcohols,
6
cyclopentadienyl ring and retentive nucleophilic displacement at
the benzylic position, which allow for the preparation of a broad
phosphinites, and their ruthenium(II) complexes
7
range of substituted derivatives. We have reported on the synthe-
Initially, the synthesis of
laninol was accomplished in one step from
-, -phenylalanine according to procedures described in the liter-
2
ature, using NaBH –I in dry THF. The ferrocene based amino
D
-,
L
-phenylglycinol and
D-, L-phenyla-
8
sis of new phosphinite ligands and their application in ruthenium-
D
-, -phenylglycine or
L
9
catalyzed transfer hydrogenation reactions. With the aim of
D
L
1
1
designing an efficient and recoverable phosphinite ligands for the
asymmetric transfer hydrogenations of ketones, we designed and
synthesized a series of novel ferrocenyl-phosphinites and their
4
alcohols 1–4 were prepared by a condensation reaction, followed
by reductive amination between ferrocenecarboxaldehyde12 and
the corresponding amino alcohols in the presence of a base catalyst
1
⇑
Corresponding author. Tel.: +90 412 248 8550x3175; fax: +90 412 248 8300.
E-mail address: akinb@dicle.edu.tr (A. Baysal).
as illustrated in Scheme 1. The H NMR spectra of compounds 1–4
showed characteristic features: the a- and b-cyclopentadienyl
0
957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.09.004

1
258
B. Ak et al. / Tetrahedron: Asymmetry 24 (2013) 1257–1264
inite ligands were not affected by the molar ratio of [Ru(
cymene)( -Cl)Cl] or the steric and electronic properties of the do-
nor phosphorus atoms. The initial color change, that is, from clear
g
6-p-
O
NH
R
R
l
R
2
i
*
ii
*
OH
OH
NH2
Fe
*
H
H
NH2
HO
orange to deep red, was attributed to the dimer cleavage most
1
8
probably caused by the phosphinite ligand. All of the complexes
3
1
1
R: D-phenyl 1; L-phenyl 2
R: D-benzyl 3; L-benzyl 4
were isolated as indicated by singlets in the P-{ H} NMR spectra
at d 112.14, 112.46, 112.20, and 111.56 ppm for 9–12, respectively,
in line with the values previously observed for similar com-
NH
iii
R
1
9
31
1
pounds. The P-{ H} NMR spectra of the complexes showed sin-
Fe
*
gle resonances at approximately d 112 ppm with a coordination
1
13
Ph2PO
Ru
NH
R
shift of approximately d 3.0 ppm. In the H and C spectra of com-
plexes 9–12, the characteristic signals of mono- and unsubstituted
Cl
Cl
iv
Fe
*
2
0
1
13
ferrocene unit were observed. The H, C NMR, IR spectroscopic
data, and the elemental analysis data of the complexes were con-
sistent with the proposed structures (see Section 4).
Ph2PO
R: D-phenyl 9; L-phenyl 10
R: D-benzyl 11; L-benzyl 12
R: D-phenyl 5; L-phenyl 6
R: D-benzyl 7; L-benzyl 8
2
.2. Asymmetric transfer hydrogenation of acetophenone
Scheme 1. Reagents and conditions: (i) NaBH
hyde, K CO , CHCl , NaBH PCl, 1 equiv Et
2
for 5–8; (iv) 1/2 equiv [Ru( -p-cymene)(l-Cl)Cl] , toluene for 9–12.
4
–I
2
, THF; (ii) ferrocenecarboxalde-
derivatives with iso-PrOH
2
3
3
4
, 1.5 h, for 1–4; (iii) 1 equiv Ph
2
3
N, toluene
6
g
The encouraging performance of many ferrocene based biden-
2
1
date phosphorus–chelate ligands in recent years has led to a re-
newed interest in the development of chiral monodendate
phosphorus containing ligands for their use in asymmetric hydro-
protons in the amino alcohols with relatively small non-resolved
multiplets appeared at approximately d 4.00–4.50 ppm. The mag-
netic non-equivalence of protons, which is caused by the diastereo-
topicity of the alpha and beta protons of ferrocene, as well as those
of the carbon atoms of the monosubstituted Cp (cyclopentadienyl)
ring was observed. The 13C-{ H} NMR spectra also exhibited the
signals typical for monosubstituted ferrocenes. The structures of
these ferrocene based chiral amino alcohols were consistent
with the data obtained from 1H NMR, C NMR, IR spectra, and
elemental analyses (for further details see Section 4).
2
2
genation reactions. This resurgence in monodendate ligands is
due to the ready accessibility of a range of diverse ligand struc-
tures, and often their lower cost compared to bidendate ligands.23
Additionally, the most important advantage of chiral phosphinite
ligands over the corresponding phosphorus-based ligands is the
ease of preparation, which has led to substantial interest in the
development of highly effective chiral monodendate phosphinite
1
13
24
ligands for asymmetric catalysis. Encouraged by our recent suc-
cess in the development of new chiral and highly active ligands,25
we initiated a study of the synthesis of a series of monodendate
ferrocene based chiral phosphinite ligands, and investigated their
efficiency in Ru(II)-catalyzed asymmetric transfer hydrogenations
(Scheme 2).
Chiral phosphinite ligands 5–8 based on the ferrocenyl group,
were synthesized by hydrogen abstraction from the described fer-
rocene based chiral amino alcohols 1–4, by a base (Et
subsequent reaction with 1 equiv of Ph PCl in anhydrous toluene
under an inert argon atmosphere, respectively (Scheme 1). The
3
N) and the
2
3
1
1
O
HO
H
progress of this reaction was conveniently followed by P-{ H}
NMR spectroscopy. The signal of the starting material PPh Cl at d
1.0 ppm disappeared and a new singlet appeared downfield due
catalyst
2
*
8
3
1
1
to the phosphinite ligands. The P-{ H} NMR spectra of 5–8
showed no unexpected features. The P-{ H} NMR spectra of the
free ligands were
observed for similar compounds, respectively. A solution of the
ligands in CDCl , prepared under anaerobic conditions, was stable
up to 24 h and then decomposed very slowly to give an oxide
iso-PrOH
acetone
31
1
1
3
Scheme 2. Hydrogen transfer from iso-PrOH to acetophenone.
in agreement with the values previously
14
3
In a preliminary study, these chiral complexes 9–12 were tested
as catalyst precursors for the asymmetric transfer hydrogenation
of acetophenone by iso-PrOH and the results are shown in Table 1.
Catalytic experiments were carried out under an Ar atmosphere
using standard Schlenk-line techniques. These systems catalyzed
the reduction of acetophenone to the corresponding alcohol (S)-,
(R)-1-phenylethanol in the presence of KOH as a promoter. To an
iso-PrOH solution of Ru(II)-monodendate phosphinite complex,
an appropriate amount of acetophenone and KOH/iso-PrOH solu-
tions was added at room temperature. The solution was stirred
for several hours and then monitored with capillary GC analysis.
At room temperature, the transfer hydrogenation of acetophenone
1
5
and the hydrolysis product diphenylphosphinous acid, Ph
2
P(O)H.
Furthermore, the P-{ H} NMR spectrum also displayed the for-
mation of PPh PPh and P(O)Ph PPh , as indicated by signals at
approximately d ꢀ15.6 ppm as a singlet and d 35.4 ppm and d
3
1
1
2
2
2
2
1
ꢀ
21.8 ppm as doublets with
J
(PP) 220 Hz, respectively, after
1
6
1
4
2
8 h. The assignment of the H chemical shifts was derived from
D HH-COSY spectra and the appropriate assignment of the
1
3
C
chemical shifts from DEPT and 2D HMQC spectra. Again, the mag-
netic non-equivalence of the protons as well as the carbon atoms of
the monosubstituted Cp ring was observed (see Section 4). All
1
26
products were fully characterized by spectroscopic methods: H,
occurred very slowly with low conversion (up to 15%, 24 h) and
1
3
C NMR, IR spectra, and elemental analysis.
moderate to high enantioselectivity (up to 90% ee) (entries 1–4).
During this period, the color changed from orange to deep red. Car-
rying out this reaction at room temperature and prolonging the
reaction time (72 h) led to a slight decrease in enantioselectivity,
as indicated by the catalytic results collected with 9–12 (entries
All of the ruthenium complexes were readily synthesized in
6
good yields. The starting ruthenium(II) complex, [Ru(
g
-p-cyme-
ne)(
2
l-Cl)Cl] , was prepared from the reaction of commercially
available
diene) with RuCl
a
-phellandrene (5-isopropyl-2-methylcyclohexa-1,3-
1
7
6
d
3
.
Treatment of [Ru(
g
-p-cymene)(
l
-Cl)Cl]
2
1 and 2 ). Furthermore, as can be inferred from Table 1 (entries
with phosphinites 5–8 in 0.5:1 molar ratio in toluene resulted in
the formation of mononuclear complexes 9–12 as orange-red crys-
talline solids. The reactions between Ru(II) precursor and phosph-
5–8) the presence of a base is necessary to observe appreciable
conversions. The choice of base, such as KOH and NaOH, had little
influence on the conversion and enantioselectivity (entries 9 and

B. Ak et al. / Tetrahedron: Asymmetry 24 (2013) 1257–1264
1259
Table 1
Transfer hydrogenation of acetophenone with iso-PrOH catalyzed by Ru-ferrocenyl based monodendate phosphinite complexes 9–12
f
eeg
Configurationh
i
ꢀ1
Entry
Complex
S/C/KOH
Time
Conversion (%)
%
TOF (h
)
1
2
3
4
9a
10
11
12
100:1:5
100:1:5
100:1:5
100:1:5
24 h (72 h)d
24 h (72 h)d
24 h
10 (48)d
15 (45)d
11
85 (81)d
90 (88)d
86
(R)
(S)
(R)
(S)
>5
>5
>5
>5
a
a
a
24 h
9
82
5
6
7
8
9b
10
11
12
100:1
100:1
100:1
100:1
1 h
1 h
1 h
1 h
e
<5
<5
<5
<5
—
—
—
—
—
—
—
—
>5
>5
>5
>5
b
b
b
9c
10
11
12
100:1:5
100:1:5
100:1:5
100:1:5
20 min (20 min)
20 min (20 min)
99 (97)
98 (97)
99
97
e
79 (78)
83 (81)
70
77
e
(R)
(S)
(R)
(S)
297 (291)
294 (291)
198
9
c
e
e
e
1
1
1
0
1
2
c
30 min
30 min
c
194
13
14
15
16
10
10
10
10
100:1:3j
20 min
20 min
20 min
20 min
95
98
94
92
77
83
79
72
(R)
(S)
(R)
(S)
285
294
282
276
k
100:1:5
100:1:7
l
100:1:9m
a
b
c
Reaction conditions: At room temperature; acetophenone/Ru/KOH, 100:1:5.
Refluxing in iso-PrOH; acetophenone/Ru, 100:1, in the absence of base.
Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:5.
At room temperature; acetophenone/Ru/KOH, 100:1:5, (72 h).
Refluxing in iso-PrOH; acetophenone/Ru/NaOH, 100:1:5.
d
e
f
Determined by GC (three independent catalytic experiments).
Determined by capillary GC analysis using a chiral cyclodex B (Agilent) capillary column.
g
h
i
Determined by comparison of the retention times of the enantiomers on the GC traces with literature values, an (S)- or (R)-configuration was obtained in all experiments.
ꢀ1
TOF = (mol product/mol cat.) ꢁ h
.
j
Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:3.
Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:5.
Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:7.
Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:9.
k
l
m
1
0e). In addition, optimization studies of the catalytic reduction of
erties of the ring substituents also influenced the hydrogenation
results. The highest enantioselectivity was found for the transfer
hydrogenation of o-methoxyacetophenone (91% ee). The intro-
acetophenone in iso-PrOH showed that good activity was obtained
with a base/ligand ratio of 5:1 (entries 13–16).
The reduction of acetophenone into (S)- or (R)-1-phenylethanol
could be achieved in high yield by increasing the temperature up to
2
duction of electron-withdrawing substituents, such as F or NO ,
at the para-positions of the aryl ring of the ketone resulted in
improved activity with good enantioselectivity (Table 2, entries
1–4, 13–16). The introduction of electron withdrawing substitu-
ents at the para-position of the aryl ring of the ketone decreased
the electron density of the C@O bond so that the activity was
8
2 °C (Table 1, entries 9–12). Chiral phosphinite ligands containing
a ferrocenyl moiety with an amino (NH) moiety showed much
higher activity and enantioselectivity. A similar tendency was re-
ported in earlier studies,27 indicating that the NH functional moi-
ety in the ligand played an important role in the ruthenium(II)–
ligand catalytic system by H-bonding. The higher activity and
enantioselectivity of the amino containing phosphinite ligand
may also be due to the fact that the NH moiety can stabilize the
catalytic transition state.28 Furthermore, it is noteworthy that the
catalytic systems 9–12 display the differences in reactivity. These
results indicate that the structure of the monodendate phosphinite
ligands is a crucial factor for accelerating the reaction. Compared to
2
9
improved, giving rise to easier hydrogenation.
The lowest
enantioselectivity was observed in the transfer hydrogenation
of p-methoxyacetophenone, which is probably due to the strong
electron-donating effect of the methoxy group on the aryl ring of
the ketone. The introduction of an electron-donating group such
as methoxy group to the p-position decelerates the reaction, but
introduced at the o-position, it increased the rate and improved
the enantioselectivity. These results show that the activity and
enantioselectivity of the Ru(II) catalysts are also sensitive to
the substrate structure.
the other complexes, [(2R)-,(2S)-2-(ferrocenylmethylamino)-2-
6
phenylethyldiphenylphosphinito(dichloro(
g
-p-cymene)ruthe-
nium(II))], 9–10 appear to provide a more effective chiral environ-
ment around the ruthenium atom due to the presence of the
phenyl moiety and the configuration. From these results, it could
be reasonably argued that the absolute configuration of the prod-
uct is governed by the ligand chirality (probably via chirality trans-
fer to the metal).
Due to its efficiency in the transfer hydrogenation of aceto-
phenone, complexes 9–12 were further investigated in the trans-
fer hydrogenation of substituted acetophenone derivatives; the
results are summarized in Table 2. The catalytic reduction of
acetophenone derivatives was tested with the conditions opti-
mized for acetophenone. The results in Table 2 demonstrate that
a range of acetophenone derivatives can be hydrogenated with
good to high enantioselectivities. Complex 10 showed the high-
est activity with good enantioselectivity for most of the ketones
listed in Table 2. Furthermore, the position and electronic prop-
3
. Conclusion
In conclusion, the work presented here explores the scope of
Ru(II)-phosphinite ligands based on ferrocenyl moiety catalysts.
These catalyst systems are effective for the asymmetric transfer
hydrogenation (ATH) of acetophenone derivatives. High yields
and moderate to good enantioselectivities were obtained by
using the complexes as catalysts. The facile synthesis of
the ligands and catalysts provides a useful method for the mod-
ular design of this type of compounds. Furthermore, the sim-
plicity and efficiency make it an excellent choice of catalyst
for the practical preparation of highly valued alcohols via the
catalytic asymmetric transfer hydrogenation of ketones. Further
studies of these ligands in catalytic reactions are currently
underway.

1
260
B. Ak et al. / Tetrahedron: Asymmetry 24 (2013) 1257–1264
Table 2
Asymmetric transfer hydrogenation results for substituted acetophenones catalyzed by Ru-ferrocenyl based monodendate phosphinite complexes 9–12a
O
OH
OH
O
Cat / KOH
R
+
R
+
b
eec (%)
TOFd (hꢀ1
)
Config.e
Entry
Catalyst
Substrate
Product
Time (min)
Conv . (%)
1
2
3
4
9
10
11
12
O
OH
*
15
15
20
20
97
98
98
96
74
80
76
72
388
392
294
288
(R)
(S)
(R)
(S)
F
F
5
6
9
10
O
OH
20
20
98
99
75
80
294
297
(R)
(S)
7
8
11
12
*
30
30
97
98
78
74
194
196
(R)
(S)
Cl
Br
Cl
Br
9
9
10
11
12
O
OH
*
20
20
30
30
98
99
98
99
73
79
74
75
294
297
196
198
(R)
(S)
(R)
(S)
1
1
1
0
1
2
1
1
1
1
3
4
5
6
9
10
11
12
O
OH
15
15
20
20
98
98
98
97
77
81
75
72
392
392
294
291
(R)
(S)
(R)
(S)
*
2
O N
O N
2
1
1
1
2
7
8
9
0
9
10
11
12
OMe O
OMe OH
30
30
60
60
96
99
98
98
80
91
82
73
192
198
98
98
(R)
(S)
(R)
(S)
*
2
2
2
2
1
2
3
4
9
10
11
12
O
OH
60
60
120
120
96
99
98
97
70
79
67
63
96
99
49
49
(R)
(S)
(R)
(S)
*
MeO
MeO
a
b
c
Catalyst (0.005 mmol), substrate (0.5 mmol), iso-PrOH (5 mL), KOH (0.025 mmol %), 82 °C, the concentration of acetophenone is 0.1 M.
The purity of compounds was checked by NMR and GC (three independent catalytic experiments), yields are based on aryl ketone.
Determined by capillary GC analysis using a chiral cyclodex B (Agilent) capillary column (30 m ꢁ 0.32 mm I.D. ꢁ 0.25
lm film thickness).
d
e
ꢀ1
TOF = (mol product/mol cat.) ꢁ h
.
Determined by comparison of the retention times of the enantiomers on the GC traces with the literature values.
4
4
. Experimental
ramp 1.3 °C/min; final temperature, 150 °C; initial time
.2 min; temperature ramp 2.15 °C/min; final temperature,
250 °C; initial time 3.3 min; final time, 44.33 min; injector port
temperature, 200 °C; detector temperature, 200 °C, injection
2
.1. Materials and methods
Unless otherwise mentioned, all reactions were carried out
volume, 2.0 lL.
under an argon atmosphere using conventional Schlenk glass-
ware. Solvents were dried using established procedures and
distilled under argon immediately prior to use. Analytical grade
and deuterated solvents were purchased from Merck. The starting
4
.2. General procedure for the transfer hydrogenation of ketones
Typical procedure for the catalytic hydrogen-transfer reaction:
a solution of ruthenium complexes 9–12 (0.005 mmol), KOH
0.025 mmol), and the corresponding ketone (0.5 mmol) in de-
materials
2 3
D-, L-phenylglycine, D-, L-phenylalanine, PPh Cl, and Et N
were purchased from Fluka and used as received. Ferrocenecarbox-
(
3
0
6
31
aldehyde,
and [Ru(
g
-p-cymene)(
l
-Cl)Cl]
(at 400.1 MHz),
P-{ H} NMR (at 162.0 MHz) spectra were
2
,
were prepared
gassed iso-PrOH (5 mL) was refluxed until the reaction was com-
pleted. Next a sample of the reaction mixture was taken off,
diluted with acetone, and analyzed immediately by GC, conver-
sions obtained are related to the unreacted ketone.
1
13
according to the literature.
00.6 MHz), and
H
C
(at
3
1
1
1
recorded on a Bruker Avance 400 spectrometer, with TMS (tetra-
methylsilane) as an internal reference for 1H NMR and C NMR
13
as the external reference for 31P-{ H} NMR. The IR
1
3
or 85% H PO
4
spectra were recorded on a Mattson 1000 ATI UNICAM FT-IR
spectrometer as KBr pellets. Elemental analysis was carried out
on a Fisons EA 1108 CHNS-O instrument. Melting points were re-
corded by a Gallenkamp Model apparatus with open capillaries.
GC analyses were performed on a Shimadzu GC 2010 Plus Gas
Chromatograph equipped with cyclodex B (Agilent) capillary
4.3. Synthesis of amino alcohols based on the ferrocene backbone
4.3.1. (2R)-2-[(Ferrocenylmethyl)amino]-2-phenylethan-1-ol 1
Ferrocenecarboxaldehyde (856 mg, 4.0 mmol) and
cinol (576 mg, 4.2 mmol) were dissolved in previously dried
chloroform (40 mL; dried over K CO ) and the resulting solution
D-phenylgly-
2
3
column (30 m ꢁ 0.32 mm I.D. ꢁ 0.25
samples of alcohols were obtained by reduction of the correspond-
ing ketones with NaBH and used as authentic samples for ee
determination. The GC parameters for asymmetric transfer
hydrogenation of ketones are as follows; initial temperature,
l
m film thickness). Racemic
was heated at reflux under argon for 90 min. Next, the solution
was allowed to cool to room temperature, the solvent was removed
under reduced pressure and the red–brown residue immediately re-
dissolved in dry methanol (40 mL; distilled from a MeONa solution).
The methanolic solution was cooled in an ice bath and treated slowly
4
5
0 °C; initial time 1.1 min; solvent delay, 4.48 min; temperature
4
with solid NaBH (756 mg, 20 mmol over 30 min). After adding all of

B. Ak et al. / Tetrahedron: Asymmetry 24 (2013) 1257–1264
1261
the NaBH
4
, the mixture was stirred at 0 °C for 1 h and at room tem-
was allowed to cool at room temperature, the solvent was removed
under reduced pressure and the red–brown residue immediately
re-dissolved in dry methanol (40 mL; distilled from a MeONa solu-
tion). The methanolic solution was cooled in an ice bath and treated
perature for a further 90 min. Next, the cooled mixture was
quenched with an aqueous solution of NaOH (10%, 40 mL) and ex-
tracted with CH
2
Cl
2
(2 ꢁ 40 mL). The combined organic layers were
washed with brine (2 ꢁ 40 mL), dried over anhydrous magnesium
sulfate, and evaporated, leaving the crude product as a yellow–
brown solid. Subsequent purification of the residue by column chro-
matography (silica gel, dichloromethane–methanol 10:1) led to the
development of two bands: the first (minor) one containing mostly
ferrocenylmethanol, followed by the major band of the aminoalco-
hol. Careful evaporation of the second fraction afforded pure 1 as
an amber oil, which slowly solidified to a brown solid (yield:
4
slowly with solid NaBH (756 mg, 20 mmol over 30 min). After add-
ing all of the NaBH , the mixture was stirred at 0 °C for 1 h and at
4
room temperature for a further 90 min. Next, the cooled mixture
was quenched with an aqueous solution of NaOH (10%, 40 mL) and
extracted with dichloromethane (2 ꢁ 40 mL). The combined organic
layers were washed with brine (2 ꢁ 40 mL), dried over anhydrous
magnesium sulfate, and evaporated, leavinga crude productas a yel-
low–brown solid. Subsequent purification of the residue by column
chromatography (silica gel, dichloromethane–methanol 10:1) led to
the development of two bands: the first (minor) one containing
mostly ferrocenylmethanol, followed by the major band of the ami-
noalcohol. Careful evaporation of the second fraction afforded pure 3
as an amber oil, which slowly solidified to a brown solid (yield:
2
D
0
1
1
.03 g, 77 %; mp: 78–79 °C); ½
aꢂ
¼ ꢀ42:8 (c 1.2, MeOH); H NMR
(
400.1 MHz, CDCl3, ppm) d: 2.10 (br, 2H, NH and OH), 3.29 (d, 1H,
J = 12.6 Hz, CH
2
NH, (a)), 3.43 (d, 1H, J = 12.6 Hz, CH
.53 (m, 1H, CH OH) (a)), 3.63–3.66 (m, 1H, CH OH) (b)), 3.75–
.79 (m, 1H, –CHNH), 4.01 (m, 5H, C +2H, C ), 4.06 (m, 2H,
); C NMR (100.6 MHz, CDCl3, ppm)
NH), 63.98 (CHNH), 66.58 (CH OH), 67.79, 67.89,
8.09, 68.42 (C ), 68.49 (C ), 85.52 (i-C ), 127.32, 127.75,
28.73 (C ), 140.37 (i-C ); IR (KBr pellet in cm
281, (C-Cp): 3086, (C@C-Cp): 1455, (O–H): 3280; Anal. Calcd for
21NOFe (335.27 g/mol): C, 67.87; N, 4.16; H, 6.29. Found: C,
2
NH, (b)), 3.48–
3
3
C
2
2
5
H
5
5 4
H
13
20
D
1
5
H
4
), 7.12–7.33 (m, 5H, C
6
H
5
1.19 g, 81%; mp: 50–51 °C); ½
a
ꢂ
¼ þ18:6 (c 1.2, MeOH); H NMR
d: 46.29 (CH
2
2
(400.1 MHz, CDCl3, ppm) d: 2.11 (br, 2H, (NH and OH)), 2.83–2.88
6
1
3
C
6
H
5 4
5
H
5
H
5 4
(m, 2H, CH
(a) + CH OH (a)), 3.54 (d, 1H, J = 13.2 Hz, CH
J = 3.8 and 10.6, CH OH (b)), 4.09 (m, 5H, C
(m, 2H, C ), 7.23–7.36 (m, 5H, C
ppm) d: 38.26 (CH Ph) 46.07 (CH
OH), 67.61, 67.64, 67.76, 67.86 (C
126.62, 128.72, 129.20 (C ), 138.52 (i-C
: (N–H): 3268, (C-Cp): 3084, (C@C-Cp): 1448; (O–H): 3305;
Anal. Calcd for C20 23NOFe (349.29 g/mol): C, 68.76; N, 4.02; H,
2
Ph), 3.00–3.06 (m, 1H, CHNH), 3.39–3.45 (m, 2H, CH
NH (b)), 3.70 (dd, 1H,
+ 2H, C ), 4.16
); C NMR (100.6 MHz, CDCl3,
NH), 59.71 (CHNH), 62.38 (CH2-
), 68.35 (C ), 86.85 (i-C
); IR (KBr pellet in
2
NH
ꢀ1
6
H
5
6
H
5
)
m
: (N–H):
2
2
2
5
H
5
5 4
H
1
3
19
H
5
H
4
6 5
H
7.82; N, 4.11; H, 6.24.
2
2
H
5 4
5
H
5
5 4
H )
4
.3.2. (2S)-2-[(Ferrocenylmethyl)amino]-2-phenylethan-1-ol 2
H
6 5
6 5
H
ꢀ
1
Ferrocenecarboxaldehyde (856 mg, 4.0 mmol) and
cinol (576 mg, 4.2 mmol) were dissolved in previously dried chloro-
form (40 mL; dried over K CO ) and the resulting solution was
L-phenylgly-
cm ) m
H
2
3
6.64. Found: C, 68.74; N, 3.99; H, 6.59.
heated at reflux under argon for 90 min. Next, the solution was al-
lowed to cool at room temperature, the solvent was removed under
reduced pressure and the red–brown residue immediately re-dis-
solved in dry methanol (40 mL; distilled from a MeONa solution).
The methanolic solution was cooled in an ice bath and treated slowly
4.3.4. (2S)-2-[(Ferrocenylmethyl)amino]-3-phenylpropan-1-ol 4
Ferrocenecarboxaldehyde (856 mg, 4.0 mmol) and
laninol (635 mg, 4.2 mmol) were dissolved in previously dried chlo-
roform (40 mL; dried over K CO ) and the resulting solution was
L-phenyla-
2
3
with solid NaBH
4
(756 mg, 20 mmol over 30 min). After adding all of
heated at reflux under argon for 90 min. Next, the solution was
allowed to cool to room temperature, the solvent was removed
under reduced pressure and the red–brown residue immediately
re-dissolved in dry methanol (40 mL; distilled from a MeONa solu-
tion). The methanolic solution was cooled in an ice bath and treated
the NaBH , the mixture was stirred at 0 °C for 1 h and at room tem-
4
perature for a further 90 min. Next, the cooled mixture was
quenched with an aqueous solution of NaOH (10%, 40 mL) and ex-
tracted with dichloromethane (2 ꢁ 40 mL). The combined organic
layers were washed with brine (2 ꢁ 40 mL), dried over anhydrous
magnesium sulfate, and evaporated, leaving the crude product as a
yellow–brown solid. Subsequent purification of the residue by col-
umn chromatography (silica gel, dichloromethane–methanol 10:1)
led to the development of two bands: the first (minor) one contain-
ing mostly ferrocenylmethanol, followed by the major band of the
aminoalcohol. Careful evaporation of the second fraction afforded
pure 2 as an amber oil, which slowly solidified to a brown solid
4
slowly with solid NaBH (756 mg, 20 mmol over 30 min). After add-
ing all of the NaBH , the mixture was stirred at 0 °C for 1 h and at
4
room temperature for a further 90 min. Next, the cooled mixture
was quenched with an aqueous solution of NaOH (10%, 40 mL)
and extracted with dichloromethane (2 ꢁ 40 mL). The combined or-
ganic layers were washed with brine (2 ꢁ 40 mL), dried over anhy-
drous magnesium sulfate, and evaporated, leaving the crude
product as a yellow–brown solid. Subsequent purification of the
residue by column chromatography (silica gel, dichloromethane–
methanol 10:1) led to the development of two bands: the first
(minor) one containing mostly ferrocenylmethanol, followed by
the major band of the aminoalcohol. Careful evaporation of the sec-
2
D
0
1
(
yield: 0.98 g, 73%; mp: 78–79 °C); ½
aꢂ
¼ þ42:8 (c 1.2, MeOH); H
NMR (400.1 MHz, CDCl3, ppm) d: 2.34 (br, 2H, NH and OH), 3.39 (d,
1
(
H, J = 13.2 Hz, CH
a)), 3.74 (dd, 1H, J = 4.2 and 11.0 Hz CH
J = 4.4 and 8.8 Hz, –CHNH), 4.10 (m, 5H, C
2
NH, (a)), 3.51–3.63 (m, 2H, CH
OH) (b)), 3.87 (dd, 1H,
+ 2H, C ), 4.18 (m,
); C NMR (100.6 MHz, CDCl3,
NH), 63.98 (CHNH), 66.64 (CH OH), 67.80,
7.90, 68.11, 68.43 (C ), 68.51 (C ), 86.45 (i-C ), 127.34,
27.72, 128.73 (C ), 140.37 (i-C ); IR (KBr pellet in cm
2 2
NH (b) + CH OH
2
5
H
5
5
H
4
ond fraction afforded pure 4 as an amber oil, which slowly solidified
13
20
D
2
5
H, C H
4
), 7.35–7.43 (m, 5H, C
6
H
5
to a brown solid. (Yield: 1.20 g, 82%; mp: 50–51 °C); ½
a
ꢂ
¼ ꢀ18:6 (c
1
ppm) d: 46.31 (CH
6
1
2
2
1.2, MeOH); H NMR (400.1 MHz, CDCl3, ppm) d: 2.01 (br, 2H, NH
and OH), 2.82–2.85 (m, 2H, CH Ph), 3.01–3.05 (m, 1H, CHNH),
3.40 (m, 1H, CH OH (a), 3.43 (d, 1H, J = 13.1 Hz, CH NH (a), 3.54
(d, 1H, J = 12.9 Hz, CH NH (b)), 3.70 (dd, 1H, CH OH (b)), 4.10 (m,
5H, C + 2H, C ), 4.16 (br s, 2H, C ), 7.23–7.36 (m, 5H,
); C NMR (100.6 MHz, CDCl3, ppm) d: 38.28 (CH Ph), 46.05
NH), 59.68 (CHNH), 62.38 (CH OH), 67.60, 67.63, 67.76, 67.85
), 68.35 (C ), 86.88 (i-C ), 126.62, 128.72, 129.20 (C ),
); IR (KBr pellet in cm : (N–H): 3268, (C-Cp):
3089, (C@C-Cp): 1448; (O–H): 3305; Anal. Calcd for C20 23NOFe
5
H
4
5
H
5
5
H
4
2
ꢀ1
6
H
5
6
H
5
)
m:
2
2
(
N–H): 3291, (C-Cp): 3087, (C@C-Cp): 1441, (O–H): 3320; Anal.
Calcd for C19 21NOFe (335.27 g/mol): C, 67.87; N, 4.16; H, 6.29.
Found: C, 67.81; N, 4.10; H, 6.22.
2
2
H
5
H
5
5
H
4
5 4
H
1
3
6
C H
5
2
(CH
2
2
4
.3.3. (2R)-2-[(Ferrocenylmethyl)amino]-3-phenylpropan-1-ol 3
Ferrocenecarboxaldehyde (856 mg, 4.0 mmol) and -phenyla-
laninol (635 mg, 4.2 mmol) were dissolved in previously dried chlo-
roform (40 mL; dried over K CO ) and the resulting solution was
heated at reflux under argon for a further 90 min. Next, the solution
(C
5
H
4
5
H
5
5 4
H
6 5
H
ꢀ1
D
138.52 (i-C
6 5
H
) m
H
2
3
(349.29 g/mol): C, 68.76; N, 4.02; H, 6.64. Found: C, 68.73; N,
4.00; H, 6.58.

1
262
B. Ak et al. / Tetrahedron: Asymmetry 24 (2013) 1257–1264
4
.4. Synthesis of phosphinite ligands based on the ferrocene
J = 12.9 Hz, CH
), 4.14–4.22 (m, 4H, C
and m-C P), 7.60–7.66 (m, 4H, o-C
CDCl3, ppm) d: 38.44 (CH ), 46.73 (CH
J = 8.0 Hz, CHNH), 67.65, 67.70, 67.97, 67.98 (C
71.53 (d, J = 17.1 Hz, CH OP), 87.35 (i-C ), 128.34, 128.59,
129.15 (CH ), 129.42 (d, J = 2.2 Hz, m-carbons of phenyls),
129.51 (s, p-carbons of phenyls), 130.60 (d, J = 21.6 Hz, o-carbons
of phenyls), 137.94 (i-C ), 142.08 (d, J = 17.1 Hz, i-carbons of
phenyls); P-{ H} NMR (162.0 MHz, CDCl , ppm) d: 115.62 (s, O-
: (N–H) = 3322, (C-Cp): 3068,
(C@C-Cp): 1454, (P-Ph): 1435, (O–P): 1026; Anal. Calcd for C32
2
NH (b)), 3.92–3.96 (m, 2H, CH
2
OP), 4.09 (s, 5H,
+ 6H, p
P); C NMR (100.6 MHz,
NH), 59.88 (d,
), 68.41 (C ),
backbone and their ruthenium(II) complexes
5
C H
5
5
H
4
), 7.25–7.50 (m, 5H, C
6 5
H
1
3
6
H
5
6 5
H
4
.4.1. (2R)-2-(Ferrocenylmethylamino)-2-phenylethyl diphenyl-
2
C H
6 5
2
phosphinite 5
5
H
4
5 5
H
(
2R)-2-(Ferrocenylmethylamino)-2-phenylethan-1-ol 1 (100 mg
2
5 4
H
0
.30 mmol) and triethylamine (30.4 mg, 0.30 mmol) were dissolved
2 6 5
C H
in dry toluene (20 mL) under an argon atmosphere. Next PPh
2
Cl
(
66.1 mg, 0.30 mmol) was added dropwise with a syringe to this
6 5
H
3
1
1
solution. The mixture was stirred at room temperature for 30 min.
The white precipitate was then filtered under argon and the remain-
ing organic phase was dried in vacuo to produce a white viscous oily
3
ꢀ
1
2
P(Ph) ); IR (KBr pellet in cm ) m
H
32-
2
D
0
1
compound 5 (yield: 0.135 g, 87%); ½
aꢂ
¼ ꢀ55:6 (c 1.2, MeOH); H
NOPFe (533.43 g/mol): C, 72.05; N, 2.62; H, 6.04. Found: C, 72.02;
N, 2.59; H, 6.01.
NMR (400.1 MHz, CDCl3, ppm) d: 3.32 (d, 1H, J = 13.2 Hz, CH
2
NH
OP),
), 7.32–7.56 (m, 5H,
, ppm) d: 46.37 (CH2-
),
), 127.67,
5
H ), 128.46 (d, J = 7.0 Hz, m-carbons of phen-
(
4
C
a)), 3.50 (d, 1H, J = 13.2 Hz, CH
2
NH (b)), 3.96–3.99 (m, 2H, CH
.12–4.18 (m, 1H, CHNH + 4H C + 5H, C
P); C NMR (100.6 MHz, CDCl
2
5
H
4
5
H
5
4.4.4. (2S)-2-(Ferrocenylmethylamino)-3-phenylpropyl diphen-
ylphosphinite 8
(2S)-2-(Ferrocenylmethylamino)-3-phenylpropan-1-ol 4 (100 mg
0.28 mmol) and triethylamine (29.0 mg, 0.28 mmol) were dis-
solved in dry toluene (20 mL) under an argon atmosphere. Next,
1
3
6
H
5
+ 10H C
6
H
5
3
NH), 63.52 (d, J = 8.0 Hz, CHNH), 67.59, 67.79, 68.02, 68.24 (C
5
H
4
6
8.42 (C
5 5 2 5 4
H ), 74.85 (d, J = 17.11 Hz, CH OP), 87.25 (i-C H
1
27.93, 128.54 (CHC
6
yls), 129.49 (s, p-carbons of phenyls), 130.59 (d, J = 21.6 Hz, o-car-
bons of phenyls), 140.23 (i-C ), 141.69 (t, J = 19.31 Hz, i-carbons
of phenyls); P-{ H} NMR (162.0 MHz, CDCl , ppm) d: 116.30 (s,
: (N–H) = 3323, (C-Cp): 3058,
C@C-Cp): 1454, (P-Ph): 1443, (O–P): 1028; Anal. Calcd for
2
PPh Cl (57.3 mg, 0.28 mmol) was added dropwise with a syringe
6
H
5
to this solution. The mixture was stirred at room temperature for
30 min. The white precipitate was then filtered under argon and
the remaining organic phase was dried in vacuo to produce a white
3
1
1
3
ꢀ
1
2
O-P(Ph) ); IR (KBr pellet in cm ) m
2
D
0
(
viscous oily compound 8 (yield:0.142 g, 93 %); ½
aꢂ
¼ ꢀ25:4 (c 1.2,
1
C
7
31
H
30NOPFe (520.41 g/mol): C, 71.54; N, 2.69; H, 5.81. Found: C,
MeOH); H NMR (400.1 MHz, CDCl3, ppm) d: 2.81–2.86 (m, 1H CH2-
1.52; N, 2.67; H, 5.79.
C
3
6
H
5, (a)), 2.89–2.94 (m, 1H, CH
.52 (d, 1H, J = 12.4 Hz, CH NH (a)), 3.61 (d, 1H, J = 12.4 Hz, CH
OP), 4.05 (br, 5H, C ), 4.10–4.16 (m, 4H,
), 7.19–7.41 (m, 5H, C + 6H, p- and m-C P), 7.56 (m,
P); C NMR (100.6 MHz, CDCl3, ppm) d: 38.16 (CH
), 46.60 (CH NH), 59.77 (d, J = 7.0 Hz, CHNH), 67.67, 67.72,
68.07, 68.36 (C ), 68.46 (C ), 71.20 (d, J = 17.1 Hz, CH OP),
87.25 (i-C ), 128.31, 128.40, 128.53 (CH ), 129.34 (s, p-car-
bons of phenyls), 129.43 (d, J = 7.0 Hz, m-carbons of phenyls),
130.54 (d, J = 21.6 Hz, o-carbons of phenyls), 138.72 (i-C ),
P-{ H} NMR
); IR (KBr pellet in
: (N–H) = 3332, (C-Cp): 3054, (C@C-Cp): 1494, (P-Ph):
1435, (O–P): 1023; Anal. Calcd for C32 32NOPFe (533.43 g/mol):
2
C
6
H
5, (b)), 3.19 (br, 1H, CHNH),
2
2
NH
4
.4.2. (2S)-2-(Ferrocenylmethylamino)-2-phenylethyl diphenyl-
(b)), 3.88 (br, 2H, CH
2
5 5
H
phosphinite 6
C
5
H
4
6
H
5
6 5
H
1
3
(
2S)-2-(Ferrocenylmethylamino)-2-phenylethan-1-ol 2 (100 mg
4H, o-C
H
6
H
5
2 6-
C
0
.30 mmol) and triethylamine (30.4 mg, 0.30 mmol) were dissolved
5
2
in dry toluene (20 mL) under an argon atmosphere. Next, PPh
2
Cl
5
H
4
5
H
5
2
(
66.1 mg, 0.30 mmol) was added dropwise with a syringe to this
5
H
4
2 6 5
C H
solution. The mixture was stirred at room temperature for 30 min.
The white precipitate was then filtered under argon and the remain-
ing organic phase was dried in vacuo to produce a white viscous oily
6
H
5
3
1
1
141.84 (d, J = 18.3 Hz, i-carbons of phenyls);
(162.0 MHz, CDCl3, ppm) d: 114.64 (s, O-P(Ph)
cm ) m
2
D
0
1
compound 6 (yield: 0.140 g, 90 %); ½
aꢂ
¼ þ55:6 (c 1.2, MeOH); H
2
ꢀ
1
NMR (400.1 MHz, CDCl3, ppm) d: 3.30 (d, 1H, J = 13.3 Hz, CH
2
NH
OP),
), 7.38–7.55 (m, 5H,
P); C NMR (100.6 MHz, CDCl3, ppm) d: 46.36 (CH2-
),
), 127.63,
), 128.42 (d, J = 6.00 Hz, m-carbons of phen-
(
a)), 3.47 (d, 1H, J = 13.3 Hz, CH
2
NH (b)), 3.93–3.97 (m, 2H, CH
2
H
4
C
.11–4.16 (m, 1H, CHNH + 4H C + 5H, C
5
H
4
5
H
5
C, 72.05; N, 2.62; H, 6.04. Found: C, 72.00; N, 2.57; H, 6.00.
1
3
6 5 6 5
H + 10H C H
NH), 63.52 (d, J = 7.10 Hz, CHNH), 67.56, 67.75, 67.98, 68.20 (C
5
H
4
4.4.5. (2R)-2-(Ferrocenylmethylamino)-2-phenylethyl diphenyl-
6
6
8.39 (C H
5 5
), 74.85 (d, J = 17.10 Hz, CH
2
OP), 87.31 (i-C
H
5 4
phosphinito(dichloro(
g
-p-cymene)ruthenium(II)) 9
-Cl)Cl] (91 mg, 0.15 mmol) and
6
1
27.90, 128.50 (CHC
6
H
5
At first, [Ru(
g
-p-cymene)(
l
2
yls), 129.46 (s, p-carbons of phenyls), 130.56 (d, J = 22.1 Hz, o-car-
bons of phenyls), 140.27 (i-C ), 141.67 (t, J = 19.01 Hz, i-carbons
of phenyls); P-{ H} NMR (162.0 MHz, CDCl3, ppm) d: 116.27 (s,
(2R)-2-(ferrocenylmethylamino)-2-phenylethyl diphenylphosphi-
nite 5 (156 mg, 0.30 mmol) were dissolved in 20 mL of toluene
and stirred for 1 h at room temperature. The volume was concen-
trated to ca. 1–2 mL under reduced pressure and the addition of
petroleum ether (15 mL) gave 9 as a red solid. The product was col-
lected by filtration and dried in vacuum (yield: 0.197 g, 80 %; mp:
6
H
5
3
1
1
ꢀ
1
2
O-P(Ph) ); IR (KBr pellet in cm ) m: (N–H) = 3325, (C-Cp): 3060,
(
C@C-Cp): 1458, (P-Ph): 1440, (O–P): 1030; Anal. Calcd for C31H
30-
NOPFe (520.41 g/mol): C, 71.54; N, 2.69; H, 5.81. Found: C, 71.50;
N, 2.65; H, 5.77.
2
0
1
113–115 °C); ½
aꢂ
¼ ꢀ43:2 (c 1.2, MeOH); H NMR (400.1 MHz,
D
3 2
CDCl3, ppm) d: 1.07 (d, 6H, J = 7.6 Hz, (CH ) CHPh of p-cymene),
4
.4.3. (2R)-2-(Ferrocenylmethylamino)-3-phenylpropyl diphenyl-
1.79 (s, 3H, CH
3.28 (d, 1H, J = 12.8 Hz, CH
(b)), 3.80–3.89 (m, 2H, CH
+ 5H C ), 4.20 (s, 2H, C
protons of p-cymene), 7.29–7.39 (m, 6H, m- and p-protons of phen-
yls + 5H, (C
), 7.83–7.85 (m, 4H, o-protons of phenyls); 13C NMR
(100.6 MHz, CDCl3, ppm) d: 17.51 (CH -Ph of p-cymene), 21.84,
((CH CH of p-cymene), 30.12 (CH- of p-cymene), 46.31 (CH NH),
62.22 (CHNH), 67.68, 67.92, 68.20, 68.42 (C ), 68.58 (C ),
71.41 (CH OP), 87.00 (i-C ), 87.41, 87.73, 90.39, 90.70 (aromatic
carbons of p-cymene), 97.48, 111.46 (quaternary carbons of p-cym-
ene), 127.73, 127.91, 127.98, (C ), 128.01 (s, m-carbons of phen-
yls), 130.95 (d, J = 11.0 Hz, p-carbons of phenyls), 132.49 (d,
3
-Ph of p-cymene), 2.62 (m, 1H, CH- of p-cymene),
NH (a)), 3.47 (d, 1H, J = 12.8 Hz, CH NH
OP + 1H CHNH), 4.09–4.12 (m, 2H,
), 5.15–5.18 (m, 4H, aromatic
phosphinite 7
2
2
(2R)-2-(Ferrocenylmethylamino)-3-phenylpropan-1-ol 3 (100 mg
2
0
.28 mmol) and triethylamine (29.0 mg, 0.28 mmol) were dis-
5
C H
4
5
H
5
5 4
H
solved in dry toluene (20 mL) under an argon atmosphere. Next,
PPh Cl (57.3 mg, 0.28 mmol) was added dropwise with a syringe
to this solution. The mixture was stirred at room temperature for
0 min. The white precipitate was then filtered under argon and
the remaining organic phase was dried in vacuo to produce a white
2
6 5
H
3
3
3
)
2
2
H
5 4
5 5
H
2
D
0
viscous oily compound 7 (yield: 0.140 g, 92%); ½
aꢂ
¼ þ25:4 (c 1.2,
2
5 4
H
1
MeOH); H NMR (400.1 MHz, CDCl3, ppm) d: 2.84–2.89 (m, 1H,
CH (a)), 2.96–3.01 (m, 1H, CH (b)), 3.22–3.25 (m, 1H,
CHNH), 3.55 (d, 1H, J = 12.9 Hz, CH NH (a)), 3.64 (d, 1H,
2
C H
6 5
C
2 6
H
5
6 5
H
2

B. Ak et al. / Tetrahedron: Asymmetry 24 (2013) 1257–1264
[C42
1263
J = 10.6 Hz, o-carbons of phenyls), 136.33 (d, J = 50.3 Hz, i-carbons
H
46NOPFeRuCl
2
] (839.62 g/mol): C, 60.08; N, 1.66; H, 5.52.
31
1
of phenyls), 138.20 (i-C
H
6 5
); P-{ H} NMR (162.0 MHz, CDCl3,
Found: C, 59.98; N, 1.60; H, 5.45.
ꢀ
1
ppm) d: 112.14 (s, O-P(Ph)
2
); IR (KBr pellet in cm
281, (C-Cp): 3086, (C@C-Cp): 1455, (O–P): 1020, (C@C-Cp):
465; Anal. Calcd for [C41 44NOPFeRuCl ] (826.60 g/mol): C,
) m: (N–H):
3
1
5
4
.4.8. (2S)-2-(Ferrocenylmethyl-amino)-3-phenylpropyl diphe-
H
2
6
nylphosphinito(dichloro(
g
-p-cymene)ruthenium(II)) 12
-p-cymene) ( -Cl)Cl] (87.6 mg, 0.143 mmol) and
2S)-2-(ferrocenylmethylamino)-3-phenylpropyl diphenylphosph-
inite 8 (154.7 mg, 0.28 mmol) were dissolved in 20 mL of toluene
and stirred for 1 h at room temperature. The volume was concen-
trated to ca. 1–2 mL under reduced pressure and the addition of
petroleum ether (15 mL) gave 12 as a red solid. The product was col-
lected by filtration and dried in vacuum (yield: 0.204 g, 85 %; mp:
9.57; N, 1.69; H, 5.36. Found: C, 59.53; N, 1.65; H, 5.32.
6
At first, [Ru(
g
l
2
(
4
.4.6. (2S)-2-(Ferrocenylmethylamino)-2-phenylethyl diphenyl-
6
phosphinito(dichloro(
g
-p-cymene)ruthenium(II)) 10
-Cl)Cl] (91 mg, 0.15 mmol) and
2S)-2-(ferrocenylmethylamino)-2-phenylethyl diphenylphosphi-
6
At first, [Ru(
g
-p-cymene)(
l
2
(
nite 6 (156 mg, 0.30 mmol) were dissolved in 20 mL of toluene
and stirred for 1 h at room temperature. The volume was concen-
trated to ca. 1–2 mL under reduced pressure and addition of petro-
leum ether (15 mL) gave 10 as a red solid. The product was
collected by filtration and dried in vacuo (yield: 0.187 g, 76%;
20
D
1
1
04–106 °C); ½
aꢂ
¼ ꢀ33:9 (c 1.2, MeOH)]; H NMR (400.1 MHz,
3 3 2
CDCl , ppm) d: 0.98 (m, 6H, (CH ) CH of p-cymene), 1.66 (s, 3H, CH3-
Ph of p-cymene)), 2.25 (br, 1H, NH), 2.57 (m, 1H, –CH of p-cymene),
.70 (m, 2H, CH ), 2.97 (m, 1H, CHNH), 3.40 (m, 2H, CH NH),
2
2
C
H
6 5
2
2
D
0
1
mp: 113–115 °C);
(
½
a
ꢂ
¼ þ43:2 (c 1.2, MeOH);
H
NMR
CHPh of p-cymene),
-Ph of p-cymene), 2.52 (m, 1H, CH- of p-cymene),
.22 (br, 1H, CH NH (a)), 3.39 (br, 1H, CH NH (b)), 3.80 (br, 2H,
OP + 1H, CHNH), 4.00–4.14 (m, 4H, C + 5H, C ) 5.08 (br,
H, aromatic protons of p-cymene), 7.26 (br, 6H, m- and p-protons
3.61 (m, 1H, CH OP (a)), 3.71 (m, 1H, CH OP (b)), 3.96 (m, 2H, C H
2
2
5
4
400.1 MHz, CDCl3, ppm) d: 0.97 (br, 6H, (CH )
3 2
+
5
5H, C H
5
); 4.07 (m, 2H, C
p-cymene), 7.25 (m, 5H, CH
of phenyls), 7.82 (m, 4H, o-protons of phenyls);
100.6 MHz, CDCl3, ppm) d: 17.50 CH
CH
5
H
4
), 5.11 (m, 4H, aromatic protons of
C H ); 7.29 (m, 6H, m- and p-protons
1
.71 (s, 3H, CH
3
2 6 5
3
2
2
13
C
NMR
-Ph of p-cymene), 21.80,
CH of p-cymene), 30.11 (CH– of p-cymene), 38.38 (CH Ph),
OH), 67.74, 67.84, 68.12,
CH
2
5
H
4
5 5
H
(
(
4
6
9
3
4
3
)
2
2
1
3
of phenyls + 5H, C
6
H
5
), 7.75 (br, 4H, o-protons of phenyls);
-Ph of p-cymene),
CH of p-cymene), 30.12 (CH- of p-cymene), 46.26
NH), 62.18 (d, J = 7.1 Hz, CHNH), 65.86, 67.73, 67.99, 68.43
), 68.69 (C ), 71.25 (CH OP), 86.90 (i-C ), 87.44, 87.70,
C
6.70 (CH
2
NH), 58.75 (CHNH), 64.42 (CH
), 68.43 (C ), 87.32 (i-C
2
NMR (100.6 MHz, CDCl3, ppm) d: 17.52 CH
1.82 ((CH
3
8.43 (C
5
H
4
5
H
5
5
H
4
), 87.46, 87.74, 90.28,
2
3 2
)
0.40 (aromatic carbons of p-cymene), 97.60, 111.65 (quaternary
), 130.92
d, J = 10.0, m-carbons of phenyls), 132.08 (d, J = 10.1 Hz, p-carbons
of phenyls), 133.12 (d, J = 11.0 o-carbons of phenyls), 136.92 (d,
(CH
2
2 6 5
carbons of p-cymene), 127.82, 127.95, 128.71 (CH C H
(C H
5
4
H
5 5
2
5 4
H
(
9
0.41, 90.73 (aromatic carbons of p-cymene), 97.47, 111.41 (qua-
ternary carbons of p-cymene), 127.98, 128.53, 130.89, 131.05,
31
1
J = 50.3 Hz, i-carbons of phenyls), 137.40 (i-CH
2
C
6
H
5
); P-{ H}
3
1
1
1
32.46, 132.71, 136.03, 136.53 (carbons of phenyls); P-{ H}
NMR (162.0 MHz, CDCl3, ppm) d: 112.46 (s, O-P(Ph) ); IR (KBr pel-
: (N–H): 3291, (C-Cp): 3087, (C@C-Cp): 1441, (P-Ph):
442, (O–P): 1016, (C@C-Cp): 1465; Anal. Calcd for [C41 44NOP-
FeRuCl ] (826.60 g/mol): C, 59.57; N, 1.69; H, 5.36. Found: C,
9.51; N, 1.63; H, 5.30.
NMR (162.0 MHz, CDCl3, ppm) d: 111.56 (s, O-P-(Ph)
2
); IR (KBr pellet
ꢀ1
2
in cm
) m
: 3268, (C-Cp): 3089, (C@C-Cp): 1448, (P-Ph): 1442, (O–P):
46NOPFeRuCl
839.62 g/mol): C, 60.08; N, 1.66; H, 5.52. Found: C, 59.97; N, 1.61;
ꢀ
1
let in cm
) m
1
023, (C@C-Cp): 1465; Anal. Calcd for [C42
H
2
]
1
H
(
2
H, 5.47.
5
Acknowledgement
4
.4.7. (2R)-2-(Ferrocenylmethylamino)-3-phenylpropyl diphenyl-
6
phosphinito(dichloro(
g
-p-cymene)ruthenium(II)) 11
-p-cymene)( -Cl)Cl] (87.6 mg, 0.143 mmol)
(2R)-2-(ferrocenylmethylamino)-3-phenylpropyl diph-
enylphosphinite (154.7 mg, 0.28 mmol) were dissolved in
0 mL of toluene and stirred for 1 h at room temperature. The
Partial support from Dicle University (Project number: DÜBAP-
6
At first, [Ru(
g
l
2
0
9-FF-64) is gratefully acknowledged.
and
7
References
2
volume was concentrated to ca. 1–2 mL under reduced pressure
and the addition of petroleum ether (15 mL) gave 11 as a red so-
lid. The product was collected by filtration and dried in vacuo
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20
(
yield: 0.197 g, 82%; mp: 104–106 °C);
½
a
ꢂ
¼ þ33:9 (c 1.2,
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C H
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(
(
(
br, 1H, CHNH), 3.33 (br, 1H, CH
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br, 4H, C + 5H, C
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2
2
2
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3
H
(
(
5
) 7.80 (d, 4H, J = 6.8 Hz, o-protons of phenyls);
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CH CH of p-cymene), 30.12 (CH- of p-cymene), 38.35 (CH
C NMR
3
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)
2
2
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4
6
9
6.65 (CH
8.41 (C
2
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), 70.36 (CH OP), 87.22 (i-C
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4
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H
5
2
H
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6
94, 2488–2492; (b) Elma, D.; Durap, F.; Aydemir, M.; Baysal, A.; Meriç, N.; Ak,
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(
3
1
1
9. (a) Aydemir, M.; Baysal, A.; Meric, N.; Kayan, C.; To g˘ rul, M.; Gümgüm, B. Appl.
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(i-CH
2
C H
6 5
), 138.35 (d, J = 52.0 Hz, i-carbons of phenyls); P-{ H}
); IR (KBr
: (N–H): 3268, (C-Cp): 3084, (C@C-Cp): 1448,
P-Ph): 1442, (O–P): 1022, (C@C-Cp): 1465; Anal. Calcd for
NMR (162.0 MHz, CDCl3, ppm) d: 112.20 (s, O-P-(Ph)
pellet in cm
(
2
ꢀ1
) m

1
264
B. Ak et al. / Tetrahedron: Asymmetry 24 (2013) 1257–1264
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2
2
dry ferrocene (53.76 mmol) and 150 mL of CH
orthoformate (264.34) was added dropwise to the mixture with stirring. After
the ferrocene was completely dissolved, 30.0 g of anhydrous AlCl was added
2 2
Cl . Next 39.2 g of triethyl
3
slowly, and the reaction mixture was stirred at room temperature for 4 h. The
reaction was quenched with sodium hydrosulphite saturated solution
(200 mL) and the mixture was extracted with diethyl ether (200 mL). After
being concentrated under reduced pressure, the residue was purified by
chromatography on silica gel (petroleum ether:ethyl acetate = 5:1) to afford a
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_
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(
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red solid (7 g) with a yield of 70%. 1H NMR (400 MHz, CDCl
4.61 (s, 2H); 4.80 (s, 2H), 9.96 (s, 1H).
3
) d = 4.28 (s, 5H),
6
Org. Lett. 2007, 9, 5557–5560; (g) Tarraga, A.; Molina, P.; Curiel, D.; Bautista, D.
Tetrahedron: Asymmetry 2002, 13, 1621–1628.
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